Von Willebrand factor propeptide and pathophysiological mechanisms in European and Iranian patients with type 3 von Willebrand disease enrolled in the 3WINTERS-IPS study

Background Type 3 von Willebrand disease (VWD) is a severe bleeding disorder caused by the virtually complete absence of von Willebrand factor (VWF). Pathophysiological mechanisms of VWD like defective synthesis, secretion, and clearance of VWF have previously been evaluated using ratios of VWF propeptide (VWFpp) over VWF antigen (VWF:Ag) and factor (F)VIII coagulant activity (FVIII:C) over VWF:Ag. Objective To investigate whether the VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios may also be applied to understand the pathophysiological mechanism underlying type 3 VWD and whether VWFpp is associated with bleeding severity. Methods European and Iranian type 3 patients were enrolled in the 3WINTERS-IPS study. Plasma samples and buffy coats were collected and a bleeding assessment tool was administered at enrolment. VWF:Ag, VWFpp, FVIII:C, and genetic analyses were performed centrally, to confirm patients' diagnoses. VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios were compared among different variant classes using the Mann-Whitney test. Median differences with 95% confidence intervals (CI) were estimated using the Hodges-Lehmann method. VWFpp association with bleeding symptoms was assessed using Spearman's rank correlation. Results Homozygosity/compound heterozygosity for missense variants showed higher VWFpp level and VWFpp/VWF:Ag ratio than homozygosity/compound heterozygosity for null variants ([VWFpp median difference, 1.4 IU/dl; 95% CI, 0.2-2.7; P = .016]; [VWFpp/VWF:Ag median difference, 1.4; 95% CI, 0-4.2; P = .054]). FVIII:C/VWF:Ag ratio was similarly increased in both. VWFpp level did not correlate with the bleeding symptoms (r = .024; P = .778). Conclusions An increased VWFpp/VWF:Ag ratio is indicative of missense variants, whereas FVIII:C/VWF:Ag ratio does not discriminate missense from null alleles. The VWFpp level was not associated with the severity of bleeding phenotype.Peer reviewe

The effect of 810-nm low-level laser therapy on pain caused by orthodontic elastomeric separators

The purpose of this study was to assess the effect of 810-nm (DMC Equipamentos, Sao Carlos, Brazil) continuous wave low-level laser therapy (LLLT) on the pain caused by orthodontic elastomeric separators. Thirty-seven orthodontic patients (12 male and 25 female, aged 11–32 years, mean age = 24.97 years) participated in the study, including 20 subjects aged 18 years or more, and 17 under 18 years of age. Four elastomeric separators (Dentarum, Springen, Germany) were placed for the first permanent molars (distal and mesial), either for maxillary (22 patients) or mandibular (15 patients) arches; one quadrant was randomly selected and used as a placebo group (received no laser irradiation). After separator placement for each quadrant, patients received 10 doses (2 J/cm2, 100 mW, 20 s) of laser irradiation on the buccal side (at the cervical third of the roots), for distal and mesial of the second premolars and first permanent molars, as well as distal of second permanent molars (five doses). The same procedure was repeated for the lingual or palatal side (five doses). After 24 h, patients returned to the clinic and received another 10 doses of laser irradiation on the same quadrant. Postseparation pain level recorded on a 10-cm visual analog scale for both jaws immediately (hour 0), and after 6, 24, 30 h, as well as on days 3, 4, 5, 6, and 7. Significant differences in the pain perception (PP) were found between the laser and placebo groups at 6, 24, 30 h, and day 3 of the experiment (P < 0.05). Friedman’s test of multiple comparisons revealed significant differences in the PP among various time intervals for laser (chi-square = 173.407, P = 0.000) and placebo (chi-square = 184.712, P = 0.000) groups. In both groups, pain was highest at 6 and 30 h after placing elastomeric separators. No gender differences were observed in both groups. More pain was recorded in the mandible (P < 0.05) at 24 (laser group) and 30 h (both groups) after starting the experiment. The PP was significantly higher (P < 0.05) for the group aged 18 years or more, only at days 3 [both groups] and 4 [laser group only] of the experiment. The 810-nm continuous wave LLLT significantly reduced the PP in the first 3 days after orthodontic separation. However, the mean postseparation PP in both groups was low and wide ranges of PP scores were observed

The analgesic effect of benzocaine mucoadhesive patches on orthodontic pain caused by elastomeric separators, a preliminary study

Objectives: To study the effect of benzocaine mucoadhesive patches (20%) on orthodontic pain caused by elastomeric separators. Subjects and methods. A split-mouth design was used in 30 patients (12 female, 18 male, aged 23 ± 3.75 years). They were instructed to apply benzocaine and placebo patches randomly for right or left first permanent molars of maxillary/mandibular arches for 20 min and repeat this procedure every 6 h with a similar type patch. A 10 cm Visual Analogue Scale (VAS) was used for pain perception assessment in patients who were given benzocaine (benzocaine group) or placebo (placebo group) patches. Pain perception (VAS) was recorded immediately after separator placement and after 2, 6, 12, 18, 24, 48 and 72 h. Results. The mean VAS (SD) for the placebo and benzocaine groups were 2.28 (1.08) and 1.63 (0.67), respectively. The pain peaked at 24 h. Significant pain perception differences were observed between groups at 2, 18, 24, 48 and 72 h. Pain perception was not different between genders or jaws investigated (p > 0.05). The Friedman test revealed significant differences in pain perception among various time intervals for benzocaine (χ 2 = 99.84, p = 0.000) and placebo (χ 2 = 102.361, p = 0.000) groups. Significant negative correlations (ρ) were found only between pain perception scores and patient's ages in the placebo group at 18 (−0.438), 24 (−0.526), 48 (−0.565) and 72 h (−0.458). Conclusion. The recorded mean VAS values were relatively low; however, the benzocaine 20% patches significantly reduced the post-separation orthodontic pain

The effect of 810-nm low-level laser therapy on pain caused by orthodontic elastomeric separators

Abstract The purpose of this study was to assess the effect of 810-nm (DMC Equipamentos, Sao Carlos, Brazil) continuous wave low-level laser therapy (LLLT) on the pain caused by orthodontic elastomeric separators. Thirty-seven orthodontic patients (12 male and 25 female, aged 11-32 years, mean age=24.97 years) participated in the study, including 20 subjects aged 18 years or more, and 17 under 18 years of age. Four elastomeric separators (Dentarum, Springen, Germany) were placed for the first permanent molars (distal and mesial), either for maxillary (22 patients) or mandibular (15 patients) arches; one quadrant was randomly selected and used as a placebo group (received no laser irradiation). After separator placement for each quadrant, patients received 10 doses (2 J/cm 2 , 100 mW, 20 s) of laser irradiation on the buccal side (at the cervical third of the roots), for distal and mesial of the second premolars and first permanent molars, as well as distal of second permanent molars (five doses). The same procedure was repeated for the lingual or palatal side (five doses). After 24 h, patients returned to the clinic and received another 10 doses of laser irradiation on the same quadrant. Postseparation pain level recorded on a 10-cm visual analog scale for both jaws immediately (hour0), and after 6, 24, 30 h, as well as on days3, 4, 5, 6, and 7. Significant differences in the pain perception (PP) were found between the laser and placebo groups at 6, 24, 30 h, and day3 of the experiment (P&lt;0.05). Friedman&apos;s test of multiple comparisons revealed significant differences in the PP among various time intervals for laser (chi-square=173.407, P= 0.000) and placebo (chi-square = 184.712, P=0.000) groups. In both groups, pain was highest at 6 and 30 h after placing elastomeric separators. No gender differences were observed in both groups. More pain was recorded in the mandible (P&lt;0.05) at 24 (laser group) and 30 h (both groups) after starting the experiment. The PP was significantly higher (P&lt;0.05) for the group aged 18 years or more, only at days3 [both groups] and 4 [laser group only] of the experiment. The 810-nm continuous wave LLLT significantly reduced the PP in the first 3 days after orthodontic separation. However, the mean postseparation PP in both groups was low and wide ranges of PP scores were observed