Les Inhibiteurs Faibles du Facteur VIII Chez les Hémophiles A

Sans résumé     

Effect of hysterectomy on colonoscopy completion rate

BACKGROUND:

Several studies show that colonoscopies are technically more difficult to perform in women than men, especially in women who have undergone abdominal and gynecological surgeries. A review of the literature indicates an increased rate of noncompletion of colonoscopies in most cases; however, no studies have investigated the procedural complication rate, sedation requirements and perception of pain in colonoscopies.

OBJECTIVE:

To determine whether women who have undergone a previous hysterectomy have a higher noncompletion rate when undergoing a colonoscopy, and to assess whether there is a higher percentage of complications. Furthermore, the present study also aimed to ascertain whether these women required more sedation and whether their perception of pain is greater than that of women who did not undergo previous abdominal surgeries.

METHODS:

The present study was a prospective cohort study of women, 45 to 80 years of age, who underwent colonoscopy (n=508). A total of 229 patients were eligible for the study; they completed a questionnaire, and were subsequently divided into control and hysterectomy groups. Gastroenterologists performed all procedures. After colonoscopy, the patient and endoscopist completed a pain perception questionnaire. Cecal intubation rates were also recorded.

RESULTS:

No significant difference for cecal intubation rates were detected between the two groups (95.7% and 98.7% in hysterectomy and control groups, respectively; P=0.176). The crude OR for the success rate was 0.29 (95% CI 0.05 to 1.90). There was no significant difference between groups regarding sedation or the type of colonoscope. No correlation between the gastroenterologists’ evaluation of pain and patients’ pain was observed.

CONCLUSION:

Hysterectomy did not significantly diminish the cecal intubation rate, and there was no detectable difference in pain perception or sedative dose. Colonoscopy remains an excellent screening and diagnostic tool for all women.     

On the use of the outcome variable “small for gestational age” when gestational age is a potential mediator: a maternal asthma perspective

Background

The variable “small for gestational age,” frequently defined as birth weight below the 10th percentile in a gestational age and sex-normalized population, is nowadays generally perceived as a more adequate measure than birth weight or low birth weight (birth weight?<?2500 g) to capture fetal growth. However, the use of small for gestational age rather than birth weight or low birth weight as an outcome (dependent) variable may have important impacts on the interpretation of analyses aimed at estimating the causal effect of an exposure of interest on infants. We hypothesized potential differences in both types of effects estimated (direct or total) and in ability to control for confounding bias.

Methods

We first examined the use of outcome variables birth weight and small for gestational age to get insights on modeling practices within the field of maternal asthma. Using directed acyclic graph simulations where gestational age was a potential mediator, we then compared estimated exposure effects in regression models for birth weight, low birth weight, and small for gestational age. Graphs with and without confounding were considered.

Results

Our simulations showed that the variable small for gestational age captures the direct effect of exposure on birth weight, but not the indirect effect of exposure on birth weight through gestational age. Interestingly, exposure effect estimates from small for gestational age models were found unbiased whenever exposure effect estimates from birth weight models were affected by collider bias due to conditioning on gestational age in the models.

Conclusions

The sole consideration of the outcome small for gestational age in a study may lead to suboptimal understanding and quantification of the underlying effect of an exposure on birth weight-related measures. Instead, our results suggest that both outcome variables (low) birth weight and small for gestational age should minimally be considered in studies investigating perinatal outcomes.

     

Quality-adjusted survival analysis shows differences in outcome after immunosuppression or bone marrow transplantation in aplastic anemia

Bone marrow transplantation (BMT) and immunosuppression (IS) have improved the prognosis of aplastic anemia; both treatments have specific advantages and drawbacks but similar survival rates. Analysis of additional endpoints may help in treatment decisions. In a single-center study, patients with aplastic anemia treated with IS (n=155) or BMT (n=52) were compared for survival, event-free survival, and quality-adjusted time without symptoms and toxicity (Q-TWiST). Probability of overall and event-free survival at 15 years was similar among both groups (BMT 51±15% and 25±14%, IS 53±10% and 27±8%), with more early deaths in the transplant group and more late deaths in the IS group. There were differences in terms of mean duration of seven analyzed health states: time with symptoms from treatment-related toxicity (IS 0.36 years, BMT 0.27), transfusion dependency (IS 0.66 years, BMT 0.1 years), partial remission (IS 3.27 years, BMT 1.42), and secondary clonal disorder (IS 0.68 years, BMT 0.04) was significantly longer for IS compared to BMT (p0.001). Patients treated with BMT spent more time with extensive chronic graft-versus-host disease (GvHD) (IS 0 years, BMT 0.96, p<0.023) and in CR without drugs (IS 1.22 years, BMT 2.43, p=0.056). In conclusion, survival, event-free survival, and Q-TWiST are similar. BMT-treated patients had longer periods free from symptoms, while IS-treated patients needed closer medical care, transfusion support, and medications.     

Connexin channels provide a target to manipulate brain endothelial calcium dynamics and blood�Cbrain barrier permeability

The cytoplasmic Ca²⁺ concentration ([Ca²⁺]_i) is an important factor determining the functional state of blood–brain barrier (BBB) endothelial cells but little is known on the effect of dynamic [Ca²⁺]_i changes on BBB function. We applied different agonists that trigger [Ca²⁺]_i oscillations and determined the involvement of connexin channels and subsequent effects on endothelial permeability in immortalized and primary brain endothelial cells. The inflammatory peptide bradykinin (BK) triggered [Ca²⁺]_i oscillations and increased endothelial permeability. The latter was prevented by buffering [Ca²⁺]_i with BAPTA, indicating that [Ca²⁺]_i oscillations are crucial in the permeability changes. Bradykinin-triggered [Ca²⁺]_i oscillations were inhibited by interfering with connexin channels, making use of carbenoxolone, Gap27, a peptide blocker of connexin channels, and Cx37/43 knockdown. Gap27 inhibition of the oscillations was rapid (within minutes) and work with connexin hemichannel-permeable dyes indicated hemichannel opening and purinergic signaling in response to stimulation with BK. Moreover, Gap27 inhibited the BK-triggered endothelial permeability increase in in vitro and in vivo experiments. By contrast, [Ca²⁺]_i oscillations provoked by exposure to adenosine 5′ triphosphate (ATP) were not affected by carbenoxolone or Gap27 and ATP did not disturb endothelial permeability. We conclude that interfering with endothelial connexin hemichannels is a novel approach to limiting BBB-permeability alterations.