Prophylactic treatment for severe haemophilia: comparison of an intermediate-dose to a high-dose regimen

A multicentre study was performed in Sweden and the Netherlands, comparing effects of two prophylactic regimens in 128 patients with severe haemophilia, born 1970-90. 42 Swedish patients (high-dose prophylaxis), were compared with 86 Dutch patients (intermediate-dose prophylaxis). Patients were evaluated at the date of their last radiological score according to Pettersson. Annual clotting factor consumption and bleeding frequency were registered for a period of three years before evaluation. Patients in the high-dose group were younger at evaluation (median 15.2 vs. 17.9 years), started prophylaxis earlier (median 2 vs. 5 years), and used 2.19 times more clotting factor kg-1 year-1. Patients treated with high-dose prophylaxis had fewer joint bleeds (median 0.3 year-1 vs. 3.3 year-1) and the proportion of patients without arthropathy as measured by the Pettersson score was higher (69% vs. 32%), however, the age-adjusted difference in scores (median 0 points vs. 4 points) was small and at present not statistically significant. Clinical scores and quality of life were similar. These findings suggest that, compared with intermediate-dose prophylaxis, high-dose prophylaxis significantly increases treatment costs and reduces joint bleeds over a period of 3 years, but only slightly reduces arthropathy after 17 years of follow-up.     

The effects of postponing prophylactic treatment on long-term outcome in patients with severe hemophilia

To prevent hemophilic arthropathy, prophylactic treatment of children with severe hemophilia should be started before joint damage has occurred. However, treatment is expensive, and the burden of regular venipunctures in young children is high. With the aim of providing information on starting prophylaxis on the basis of individual patient characteristics, the effect of postponing prophylaxis on long-term arthropathy was studied in a cohort of 76 patients with severe hemophilia born between 1965 and 1985. The median age at first joint bleed was 2.2 years (range, 0.2-5.8). Prophylaxis was started at a median age of 6 years (interquartile range [IQR], 4-9), and the median annual clotting factor use on prophylaxis was 1750 IU/kg/y (31 IU/kg/wk). Hemophilic arthropathy was measured by the Pettersson score (maximum, 78 points). At a median age of 19 years, the median Pettersson score was 7 points (IQR, 0-17). After 2 decades of follow-up, the Pettersson score was 8% higher (95% confidence interval, 1%-16%) for every year prophylaxis was postponed after the first joint bleed. This effect was independent of age at Pettersson score, age at first joint bleed, and prophylactic dose used. In conclusion, most patients have their first joint bleed after the age of 2 years. Patients who start prophylaxis soon after the first joint bleed show little arthropathy in adulthood. The longer the start of prophylaxis is postponed after the first joint bleed, the higher the risk of developing arthropathy.     

Future directions in intravascular ultrasound: from micro-motors to imaging guidewire systems

Intravascular ultrasound imaging requires both a small transducer assembly and catheter delivery system with optimal flexibil- ity and steerability. At this moment, multiele- ment electronic arrays provide an optimal catheter delivery system but the transducer assembly is both complicated and expensive while the image quality remains rather fair. Most intravascular ultrasound systems use mechanically rotated ultrasound beam generated by a single element. These systems provide good image quality but the need of a drive shaft restricts both the flexibility and steer ability of the catheter delivery system (Table I). In addition, the drive shaft behaves like spring and due to the curved trajectory of the catheter tube in the vascular system, a complicated frictional interaction will occur. The shaft will show a tendency to wind and unwind during one revolution, yielding a certain unpredictability of the angular position of the scanning head relative to that of the proximal system (Fig. 1).1     

1002-LB: ACE Polymorphism in asthmatic patients

Aim

The aim of the this study was to analyse if there is an association between angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism (287 base pairs, on chromosome 17q23, intron 16) with asthma severity . ACE plays a vital role in the renin-angiotensin-system (RAS) which regulates blood pressure by converting angiotensin I into a powerfull vasoconstrictor angiotensin II and could also have a role in bronchoconstriction and airway remodeling in asthmatic disease.

Methods

Asthmatic patients: n = 22;were compared with a control group of n = 206 healthy blood donors. The insertion/deletion (I/D) polymorphism was determined by PCR- Polymerase chain reaction. Control of asthma assessed by validated instrument (ACQ7 and PAQLQ). Statistical analysis was performed with PASW 18, establishing a significance level of p< 0.05. All patients signed an informed consent.

Results

The mean age of the 22 asthmatics was 42.86 ± 20.8 years; 9 females and 13 males; all caucasians; 20 atopic and 2 nonatopic. The mean age of the control-group (n = 206) was 41.05 ± 11.85 years; 70 females and 136 males. In asthmatics the frequencies of the D- Allele (ACE-D) is 0.591 and of the IAllele (ACE-I) is 0.409; in controls: 0.675 and 0.325 respectively. There is no statistical differences between these groups (p = 0.340). Genotypes in the asthmatics- DD: 45.4%; ID: 27.3%; II: 27,3%; in control group- DD:48.1%; ID:38.8%; II: 13.1%. There is no statistical differences between these groups (p = 0,175). In asthmatics, there is no statistical differences in genotype frequencies (p > 0.05) between : atopics and non atopics; controlled and uncontrolled asthma; males and females; and in the different age-groups.

Conclusions

The role of ACE insertion/deletion (I/D) polymorphism, in asthmatic patients is a controversy risk factor to the severity of asthma, but we think that we need a larger sample to infer about its role in remodeling, vascular tonus and bronchoconstriction.     

When do combinatorial mechanisms apply in the production of inflected words?

A central question for theories of inflected word processing is to determine under what circumstances compositional procedures apply. Some accounts (e.g., the dual-mechanism model; Clahsen, 1999 Clahsen, H. 1999. Lexical entries and rules of language: A multidisciplinary study of German inflections. Behavioral and Brain Sciences, 22: 991–1060. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) propose that compositional processes only apply to verbs that take productive affixes. For all other verbs, inflected forms are assumed to be stored in the lexicon in a nondecomposed manner. This account makes clear predictions about the consequences of disruption to the lexical access mechanisms involved in the spoken production of inflected forms. Briefly, it predicts that nonproductive forms (which require lexical access) should be more affected than productive forms (which, depending on the language task, may not). We tested these predictions through the detailed analysis of the spoken production of a German-speaking individual with an acquired lexical impairment resulting from a stroke. Analyses of response accuracy, error types, and frequency effects revealed that combinatorial processes are not restricted to verbs that take productive inflections. On this basis, we propose an alternative account, the stem-based assembly model (SAM), which posits that combinatorial processes may be available to all stems and not only to those that combine with productive affixes.     

Working memory and emotional interpretation bias in a sample of Syrian refugee adolescents

The number of adolescent refugees around the world has been continuously increasing over the past few years trying to escape war and terror, among other things. Such experience not only increases the risk for mental health problems including anxiety, depression, and post-traumatic stress disorder (PTSD), but also may have implications for socio-cognitive development. This study tested cognitive-affective processing in refugee adolescents who had escaped armed conflict in Syria and now resided in Istanbul, Turkey. Adolescents were split into a high trauma (n = 31, 12 girls, mean age = 11.70 years, SD = 1.15 years) and low trauma (n = 27, 14 girls, mean age = 11.07 years, SD = 1.39 years) symptom group using median split, and performed a working memory task with emotional distraction to assess cognitive control and a surprise faces task to assess emotional interpretation bias. The results indicated that high (vs. low) trauma symptom youth were ~ 20% worse correctly remembering the spatial location of a cue, although both groups performed at very low levels. However, this finding was not modulated by emotion. In addition, although all youths also had a ~ 20% bias toward interpreting ambiguous (surprise) faces as more negative, the high (vs. low) symptom youth were faster when allocating such a face to the positive (vs. negative) emotion category. The findings suggest the impact of war-related trauma on cognitive-affective processes essential to healthy development.

     

Influence of Preoperative Mechanical Allodynia on Predicting Postoperative Pain after Root Canal Treatment: A Prospective Clinical Study

IntroductionOdontogenic pain can manifest as pulpal pain, periapical pain (mechanical allodynia), or both. This study aimed to assess the changes in the intensity of mechanical allodynia (MA) and to identify predictors of postoperative pain after root canal treatment (RCT).MethodsIn total, 579 consecutive patients who required RCT were enrolled; we included patients with asymptomatic pulpal diagnoses to avoid any effects of preoperative spontaneous pain on postoperative pain and to evaluate MA independently. Using a visual analog scale (VAS), patients separately indicated the intensity of spontaneous pain, tenderness to percussion, and pain on biting; these measurements were performed before treatment (preoperative pain), at the beginning of each visit (postpreparation pain), and daily for 1 week after RCT (postobturation pain). For analytical purposes, patients were subdivided into 2 groups based on the intensity of preoperative MA (none to mild [VAS <4] or moderate to severe [VAS ≥4]) to evaluate changes in MA and predictive factors of moderate to severe postoperative pain. A generalized estimating equation, repeated-measures analysis of variance, and logistic regression analysis were used.ResultsAlthough the intensity of MA was significantly higher in the moderate to severe group after the initiation of RCT (P < .05), 93% of them experienced alleviation in MA, and 30% of patients in the none to mild group experienced an increase in MA. After adjusting for clinical variables, moderate to severe preoperative MA and the presence of necrotic pulp were significantly correlated with moderate to severe postoperative pain with an odds ratio of 4.107 and 0.286, respectively.ConclusionsModerate to severe preoperative MA was a predictive factor of postoperative pain in patients undergoing RCT.     

Facile Synthesis of Well‐Defined Telechelic Alkyne‐Terminated Polystyrene in Polar Media Using ATRP With Mixed Fe/Cu Transition Metal Catalyst

The synthesis of polystyrene (PS) by atom transfer radical polymerization using the Fe(0)/CuBr₂ catalytic system in dimethylformamide is reported. The effects of temperature, ligand, initiator structure, and monomer to solvent ratio on the polymerization kinetics are evaluated. PS with high molecular weight, low polydispersity, and telechelic structure are achieved and successfully used for further reinitiation or the copper(I)‐catalyzed Huisgen 1,3‐dipolar cycloaddition click reaction between alkyne‐ and azide‐terminated PS. For the first time, suitable styrene polymerization rates are achieved using this cost‐effective and environmentally attractive catalytic system. This method can be very useful in macromolecular engineering to afford PS‐based materials with well‐controlled structure.