Pneumocystis jirovecii genotype associated with increased death rate of HIV-infected patients with pneumonia.

Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations have been associated with failure of sulfa prophylaxis; their effect on the outcome of patients with P. jirovecii pneumonia (PCP) remains controversial. P. jirovecii DHPS polymorphisms and genotypes were identified in 112 cases of PCP in 110 HIV-infected patients by using PCR single-strand conformation polymorphism. Of the 110 patients observed, 21 died; 18 of those deaths were attributed to PCP. Thirty-three percent of the PCP cases involved a P. jirovecii strain that had 1 or both DHPS mutations. The presence or absence of DHPS mutations had no effect on the PCP mortality rate within 1 month, whereas P.jirovecii type 7 and mechanical ventilation at PCP diagnosis were associated with an increased risk of death caused by PCP. Mechanical ventilation at PCP diagnosis was also associated with an increased risk of sulfa treatment failure at 5 days.

Diagnostic delay in Crohn's disease is associated with a complicated disease course and increased operation rate.

OBJECTIVES: The impact of diagnostic delay (a period from appearance of first symptoms to diagnosis) on the clinical course of Crohn's disease (CD) is unknown. We examined whether length of diagnostic delay affects disease outcomes. METHODS: Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (68%), regional hospitals (14%), and private practices (18%). The frequencies of occurrence of bowel stenoses, internal fistulas, perianal fistulas, and CD-related surgery (intestinal and perianal) were analyzed. RESULTS: A total of 905 CD patients (53.4% female, median age at diagnosis 26 (20-36) years) were stratified into four groups according to the quartiles of diagnostic delay (0-3, 4-9, 10-24, and ≥25 months, respectively). Median diagnostic delay was 9 (3-24) months. The frequency of immunomodulator and/or antitumor necrosis factor drug use did not differ among the four groups. The length of diagnostic delay was positively correlated with the occurrence of bowel stenosis (odds ratio (OR) 1.76, P=0.011 for delay of ≥25 months) and intestinal surgery (OR 1.76, P=0.014 for delay of 10-24 months and OR 2.03, P=0.003 for delay of ≥25 months). Disease duration was positively associated and non-ileal disease location was negatively associated with bowel stenosis (OR 1.07, P<0.001, and OR 0.41, P=0.005, respectively) and intestinal surgery (OR 1.14, P<0.001, and OR 0.23, P<0.001, respectively). CONCLUSIONS: The length of diagnostic delay is correlated with an increased risk of bowel stenosis and CD-related intestinal surgery. Efforts should be undertaken to shorten the diagnostic delay.

Coping with continuous human disturbance in the wild: insights from penguin heart rate response to various stressors.

ABSTRACT: BACKGROUND: A central question for ecologists is the extent to which anthropogenic disturbances (e.g. tourism) might impact wildlife and affect the systems under study. From a research perspective, identifying the effects of human disturbance caused by research-related activities is crucial in order to understand and account for potential biases and derive appropriate conclusions from the data. RESULTS: Here, we document a case of biological adjustment to chronic human disturbance in a colonial seabird, the king penguin (Aptenodytes patagonicus), breeding on remote and protected islands of the Southern ocean. Using heart rate (HR) as a measure of the stress response, we show that, in a colony with areas exposed to the continuous presence of humans (including scientists) for over 50 years, penguins have adjusted to human disturbance and habituated to certain, but not all, types of stressors. When compared to birds breeding in relatively undisturbed areas, birds in areas of high chronic human disturbance were found to exhibit attenuated HR responses to acute anthropogenic stressors of low-intensity (i.e. sounds or human approaches) to which they had been subjected intensely over the years. However, such attenuation was not apparent for high-intensity stressors (i.e. captures for scientific research) which only a few individuals experience each year. CONCLUSIONS: Habituation to anthropogenic sounds/approaches could be an adaptation to deal with chronic innocuous stressors, and beneficial from a research perspective. Alternately, whether penguins have actually habituated to anthropogenic disturbances over time or whether human presence has driven the directional selection of human-tolerant phenotypes, remains an open question with profound ecological and conservation implications, and emphasizes the need for more knowledge on the effects of human disturbance on long-term studied populations.

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.

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.

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.

The effect of workplace smoking bans on heart rate variability and pulse wave velocity of non-smoking hospitality workers

OBJECTIVES: To investigate the effect of a change in second-hand smoke (SHS) exposure on heart rate variability (HRV) and pulse wave velocity (PWV), this study utilized a quasi-experimental setting when a smoking ban was introduced. METHODS: HRV, a quantitative marker of autonomic activity of the nervous system, and PWV, a marker of arterial stiffness, were measured in 55 non-smoking hospitality workers before and 3-12 months after a smoking ban and compared to a control group that did not experience an exposure change. SHS exposure was determined with a nicotine-specific badge and expressed as inhaled cigarette equivalents per day (CE/d). RESULTS: PWV and HRV parameters significantly changed in a dose-dependent manner in the intervention group as compared to the control group. A one CE/d decrease was associated with a 2.3 % (95 % CI 0.2-4.4; p = 0.031) higher root mean square of successive differences (RMSSD), a 5.7 % (95 % CI 0.9-10.2; p = 0.02) higher high-frequency component and a 0.72 % (95 % CI 0.40-1.05; p < 0.001) lower PWV. CONCLUSIONS: PWV and HRV significantly improved after introducing smoke-free workplaces indicating a decreased cardiovascular risk.

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.

Ponctions et infiltrations articulaires [Arthrocentesis and joint infiltration]

Cet article se veut être un condensé des bases nécessaires à la pratique d'une ponction et, ou infiltration articulaire, des indications principales aux complications potentielles en passant par la description de la procédure et de ses contre-indications. La ponction du genou fait l'objet d'une description plus détaillée. Les données permettant de justifier une façon particulière de procéder ont spécifiquement été recherchées dans la littérature (Cochrane et Medline, termes de recherche : arthrocentesis ; joint aspiration). Le détail de ces données, comme par exemple le résultat d'études, ne trouve pas sa place dans ce résumé mais fait l'objet d'une publication à part. What should be known in order to practice safely a joint aspiration and/or infiltration is summarized in the following article. This summary includes various aspects, such as the indications and contraindications, the procedure itself, and the possible complications. The arthrocentesis of the knee is described in more details. Data in support of a specific modus operandi have been searched for in Cochrane and Pubmed (key words: arthrocentesis, joint aspiration). Only the conclusions of this research are exposed in this summary. A more comprehensive article will be published

May absorbable suture anchors increase the rate of recurrent dislocations after shoulder stabilization?

Introduction: Absorbable anchors are frequently used in shoulder surgery. Mechanisms of absorption induce a local inflammatory reaction. It is not clear if this process may disturb healing of the capsule and ligaments. The purpose of the study was to compare the rate of recurrent dislocation following open shoulder stabilization when using absorbable or non-absorbable suture anchors. Methods: Between 1999 and 2003, 83 open Bankart repairs were performed by the same surgeon. All patients had recurrent traumatic anterior shoulder instability. All had preoperative arthro-MRI or arthro-CT which did not reveal any significant bony Bankart lesion or rotatorcuff tear. Thirty-four patients were treated with absorbable anchors (Panalok®) and sutures (Panacryl®) and 49 with non-absorbable anchors (Mitek GII®) and sutures (Ethibond®). The same surgical technique and rehabilitation protocol were used. The incidence of sports ability and recurrent instability were recorded. We defined instability as true dislocation. Results: Five patients on 34 were lost to follow-up in the absorbable group and 7 on 49 in the non-absorbable group. The mean age of absorbable group was 25 years (range, 17-39 years). At a mean follow-up of 66 months (range, 54-76 months), 86% could resume sports activity. Five patients on 29 (17%) reported recurrent instability and two did need revision surgery. The mean age in non-absorbable group was 28 year (range, 18-47 years). At a mean follow-up of 78 months (range, 49-82 months), 93% could resume sports activity. Three patients on 42 (7%) reported recurrent instability and one did need revision surgery. Conclusion: This clinical study showed a clear tendency to a higher recurrence rate of dislocation when using absorbable suture anchors (17% in absorbable vs 7% in non-absorbable group). It is known that Panacryl® may be responsible for a major local inflammatory response. However, it is still unclear if this could be the failure etiology. Consequently, we prefer to use systematically non-absorbable sutureanchors for shoulder stabilization.