Tachyphylaxis and reproducibility of desmopressin response in perioperative persons with nonsevere hemophilia A: implications for clinical practice.

Background: Desmopressin is frequently used perioperatively in persons with nonsevere hemophilia A. However, increase in factor (F)VIII:C after desmopressin use is interindividually highly variable. Tachyphylaxis has only been reported in test setting for persons with hemophilia A, with a remaining response of approximately 70% after a second dose compared with that after a first dose. Objectives: To study tachyphylaxis of FVIII:C response after multiple administration(s) of desmopressin in perioperative persons with nonsevere hemophilia A. Methods: We studied FVIII:C levels after desmopressin before (day 0 [D0]) and on days 1 (D1) and 2 (D2) after surgery in 26 patients of the DAVID and Little DAVID studies. We studied tachyphylaxis by comparing the responses at D1 and D2 with that at D0. We also assessed the reproducibility of the D0 response in comparison to an earlier performed desmopressin test. Results: The median absolute FVIII:C increase was 0.50 IU/mL (0.35-0.74; n = 23) at D0, 0.21 IU/mL (0.14-0.28; n = 17) at D1, and 0.23 IU/mL (0.16-0.30; n = 11) at D2. The median percentage of FVIII increase after the second administration (D1) compared with the first (D0) was 42.9% (29.2%-52.5%; n = 17) and that of the third (D2) compared with the first (D0) was 36.4% (23.7%-46.9%; n = 11). The FVIII:C desmopressin response at D0 was comparable with the desmopressin test response in 74% of the patients. Conclusion: Tachyphylaxis in the surgical setting was considerably more pronounced than previously reported, with FVIII:C at D1 and D2 of 36% to 43% of the initial response. Our results may have important implications for monitoring repeated desmopressin treatment when used perioperatively.

The course of sexual interest and enjoyment in head and neck cancer patients treated with primary (chemo)radiotherapy.

INTRODUCTION: The aim of this prospective study was to investigate the course of sexual interest and enjoyment in relation to sociodemographic and clinical factors, health-related quality of life (HRQOL), and symptoms of psychological distress in head and neck cancer (HNC) patients treated with primary (chemo)radiotherapy. METHODS: HNC patients (n = 354) completed patient-reported outcome measures (PROMs) on HRQOL (EORTC QLQ-C30 and QLQ-H&N35, including the sexuality subscale covering less sexual interest and enjoyment), and psychological distress (HADS) pretreatment, at 6-week follow-up and at 3-, 6-, 12-, 18-, and 24-month follow-up (i.e., after treatment). Linear mixed models were used to analyze the course of sexuality from pretreatment to 24-month follow-up, and to investigate its relation to sociodemographic and clinical factors, HRQOL, and psychological distress as measured at baseline, and to investigate the course of sexuality from 6- to 24-month follow-up in relation to these factors measured at 6-month follow-up. RESULTS: Before start of treatment, 37% of patients reported having less sexuality, which increased to 60% at 6-week follow-up, and returned to baseline level from 12-month follow-up onwards. Older age (p = 0.037) and trouble with social contact (p < 0.001), weight loss (p = 0.013), and constipation (p = 0.041) before treatment were associated with less sexuality over time. Female gender (p = 0.021) and poor social functioning (p < 0.001) at 6-month follow-up were associated with less sexuality from 6- to 24-month follow-up. DISCUSSION: Less sexuality is often reported in HNC patients treated with (chemo)radiotherapy. Using PROMs in clinical practice may help identify patients who might benefit from supportive care targeting sexuality.

Desmopressin in haemophilia: The need for a standardised clinical response and individualised test regimen.

INTRODUCTION: Due to interindividual variation in desmopressin response, non-severe haemophilia A patients require desmopressin testing prior to therapeutic treatment. However, adequate response or frequency of blood sampling is not standardised in international guidelines. Consequently, various definitions and blood sampling protocols are currently applied. Interestingly, sustainability of desmopressin response is not incorporated into these definitions. AIM: To study desmopressin response rates in a cohort of non-severe haemophilia A patients using currently accepted desmopressin response definitions. This, in order to formulate a standardised, uniform response which includes information on sustainability and to design a standardised blood sampling protocol. METHODS: Currently used desmopressin responses in non-severe haemophilia A patients were derived from a literature search. Actual desmopressin response rates were individualised in 105 non-severe HA patients from the Erasmus University Medical Centre and classified according to current varying definitions. RESULTS: Five response definitions were evaluated, three of which included only factor VIII (FVIII):C cut-off levels and two also incorporated FVIII:C-fold increase over baseline. FVIII: C-fold increase showed no association with desmopressin response sustainability. FVIII: C 1 hour after infusion (<0.30, ≥0.30-0.49, ≥0.50-0.79 and ≥0.80 IU/mL) was, however, indicative of desmopressin response after 6 hours. CONCLUSION: We suggest standardised desmopressin response based on clinically relevant FVIII:C levels, e.g. 0.30 and 0.50 IU/mL. In addition, patients with <0.30 IU/mL FVIII:C after 1 hour (non-responder) or ≥0.80 IU/mL (sustained responder) do not require subsequent blood sampling. However, patients with ≥0.30-0.79 IU/mL FVIII:C after 1 hour should undergo blood sampling after 6 hours to additionally determine response sustainability.

Speech-language therapy for adolescents with written-language difficulties: the South African context.

OBJECTIVE: To investigate whether privately practising speech-language therapists in South Africa are fulfilling their role of identification, assessment and intervention for adolescents with written-language and reading difficulties. Further needs concerning training with regard to this population group were also determined. METHOD: A survey study was conducted, using a self-administered questionnaire. Twenty-two currently practising speech-language therapists who are registered members of the South African Speech-Language-Hearing Association (SASLHA) participated in the study. RESULTS: The respondents indicated that they are aware of their role regarding adolescents with written-language difficulties. However, they feel that South-African speech-language therapists are not fulfilling this role. Existing assessment tools and interventions for written-language difficulties are described as inadequate, and culturally and age inappropriate. Yet, the majority of the respondents feel that they are adequately equipped to work with adolescents with written-language difficulties, based on their own experience, self-study and secondary training. The respondents feel that training regarding effective collaboration with teachers is necessary to establish specific roles, and to promote speech-language therapy for adolescents among teachers. CONCLUSION: Further research is needed in developing appropriate assessment and intervention tools as well as improvement of training at an undergraduate level.

An index for quantifying deviations from normal gait.

A method is derived to calculate the amount by which a subject's gait deviates from an average normal profile, and to represent this deviation as a single number. The method uses principal component analysis to derive a set of 16 independent variables from 16 selected gait variables. The sum of the square of these 16 independent variables is interpreted as the deviation of the subject's gait from normal. Statistical tests of the method's validity and an initial demonstration of its clinical utility are included. It is found that using this index, increasing clinical involvement corresponds to increasing index score.

Cadaveric modeling of the pronator teres rerouting tendon transfer.

The purpose of this study is to report the biomechanics of the supination effect of the pronator teres rerouting procedure and to determine the optimum insertion point for the transfer using a cadaveric model. Pronator teres rerouting procedures were performed on 5 fresh-frozen above-elbow cadaver specimens mounted in a forearm rotation mounting frame. The pronator teres was detached from its native insertion and tested at 6 insertions on the radius. The amount of rotation of the forearm was measured after loading of the pronator teres muscle for each insertion site. The experiments were repeated by placing the pronator teres 1 cm proximal to the 6 experimental insertion sites for a total testing of 12 insertions. The results of this study show that placement of the pronator teres through the interosseous membrane, around the radius, with reinsertion onto the volar surface produced the greatest amount of forearm supination. Rerouting of the pronator teres tendon produces supination through a windlass effect when the tendon is rerouted through an interosseous window and reinserted onto its original insertion or onto the volar surface of the radius. Placement of the insertion 1 cm proximal on the radius did not affect the amount of forearm supination compared with 6 original insertion sites.

Lengths of hamstrings and psoas muscles during crouch gait: effects of femoral anteversion.

Recent studies of muscle lengths measured by means of gait analysis data and musculoskeletal models have suggested that in many cases of crouch gait in patients with cerebral palsy, the hamstrings are of normal length and the psoas muscles are short. In these studies, however muscle lengths were calculated by applying kinematic data from a child's joint to a normal adult model. Children with cerebral palsy and other disorders generally do not have normal bone architecture but instead have muscle attachment points and muscle paths altered by osseous deformities. In this study, we explored the consequences of using normal adult musculoskeletal models to calculate hamstring and psoas lengths for children with cerebral palsy. Specifically, for a group of subjects with cerebral palsy who walk with a crouch gait, we investigated the changes in muscle lengths that arise when a patient-specific representation of clinically measured femoral anteversion was added to a model of normal musculoskeletal geometry. The calculation of psoas muscle length was found to be very sensitive to femoral anteversion whereas the calculation of hamstrings length was found to be relatively insensitive to this osseous deformity.

The use of inverse dynamics solutions in direct dynamics simulations.

Previous attempts to use inverse dynamics solutions in direct dynamics simulations have failed to replicate the input data of the inverse dynamics problem. Measurement and derivative estimation error, different inverse dynamics and direct dynamics models, and numerical integration error have all been suggested as possible causes of inverse dynamics simulation failure. However, using a biomechanical model of the type typically used in gait analysis applications for inverse dynamics calculations of joint moments, we produce a direct dynamics simulation that exactly matches the measured movement pattern used as input to the inverse dynamic problem. This example of successful inverse dynamics simulation demonstrates that although different inverse dynamics and direct dynamics models may lead to inverse dynamics simulation failure, measurement and derivative estimation error do not. In addition, inverse dynamics simulation failure due to numerical integration errors can be avoided. Further, we demonstrate that insufficient control signal dimensionality (i.e., freedom of the control signals to take on different "shapes"), a previously unrecognized cause of inverse dynamics simulation failure, will cause inverse dynamics simulation failure even with a perfect model and perfect data, regardless of sampling frequency.

Extra reactivities detected in flow-cytometry-positive, CDC-negative crossmatches are definable HLA specificities.

In this preliminary study, additional reactions were detected in sera that were not found by T-AHG-CDC. The reactions had definable HLA specificities. In our laboratory, the procedures described in this article had the following relative sensitivities for detecting class I HLA alloantibody specificities: FC = B-AHG-CDC greater than T-AHG-CDC greater than B-CDC greater than T-CDC. This study supports the concept that some FC-positive crossmatches, negative by T-AHG-CDC, can be associated with reduced renal allograft survival, since many of the additional reactions detected by FC appear to be due to HLA Class I antibodies.