Knowledge translation in rehabilitation settings in low, lower-middle and upper-middle-income countries: a scoping review.

PURPOSE: This review aims to identify the barriers and facilitators to knowledge use and Knowledge Translation (KT) strategies in rehabilitation in low, lower-middle, and upper-middle-income countries (LMICs). MATERIALS AND METHODS: A scoping review of studies of KT in rehabilitation in LMICs contexts using the Arksey and O'Malley Framework was conducted. A comprehensive search of MEDLINE and 10 other databases was undertaken to identify studies conducted primarily in LMICs. RESULTS: From the initial 15.606 titles identified; 27 articles were included for final analysis. Our analysis identified the following themes: Professional culture and context; KT interventions; and the conceptualization and application of KT and Evidence Based Practice (EBP). Individual-level barriers to KT included lack of skills, knowledge about EBP and English language, lack of motivation, and decision-making power. Facilitators to KT included positive attitudes and motivation. Organization-level barriers included lack of time, lack of financial resources, limited access to scientific journals, and applicability of research to rural settings. Facilitators included adequate financial and physical resources, a supportive management environment, and the existence of training and continuing education programs. CONCLUSION: This review identified common and unique barriers and facilitators to KT in LMICs when compared to KT studies conducted in high-income settings.IMPLICATIONS FOR REHABILITATIONKnowledge Translation from academic institutions to rehabilitation clinical practice in low and upper-middle-income countries is important to support evidence-based practice and patient outcomes.Barriers at the individual level include professionals' ability to understand English and knowledge of the evidence-based practice.Organization-level barriers included lack of time to access and implement new practices, lack of financial and personal resources, limited access to scientific journals, and applicability of research to rural settings.Training and continuing education programs are needed to support rehabilitation professionals' efforts to achieve the application of evidence-based practice in clinical practice.

State-wide utilization and performance of traditional and cell-free DNA-based prenatal testing pathways: the Victorian Perinatal Record Linkage (PeRL) study.

OBJECTIVES: To perform individual record linkage of women undergoing screening with cell-free DNA (cfDNA), combined first-trimester screening (CFTS), second-trimester serum screening (STSS), and/or prenatal and postnatal cytogenetic testing with the aim to (1) obtain population-based estimates of utilization of prenatal screening and invasive diagnosis, (2) analyze the performance of different prenatal screening strategies, and (3) report the residual risk of any major chromosomal abnormality following a low-risk aneuploidy screening result. METHODS: This was a retrospective study of women residing in the state of Victoria, Australia, who underwent prenatal screening or invasive prenatal diagnosis in 2015. Patient-funded cfDNA referrals from multiple providers were merged with state-wide results for government-subsidized CFTS, STSS and invasive diagnostic procedures. Postnatal cytogenetic results from products of conception and infants up to 12 months of age were obtained to ascertain cases of false-negative screening results and atypical chromosomal abnormalities. Individual record linkage was performed using LinkageWizTM . RESULTS: During the study period, there were 79 140 births and 66 166 (83.6%) women underwent at least one form of aneuploidy screening. Linkage data were complete for 93.5% (n = 61 877) of women who underwent screening, and of these, 73.2% (n = 45 275) had CFTS alone, 20.2% (n = 12 486) had cfDNA alone; 5.3% (n = 3268) had STSS alone, 1.3% (n = 813) had both CFTS and cfDNA, and < 0.1% (n = 35) had both STSS and cfDNA. CFTS had a combined sensitivity for trisomies 21 (T21), 18 (T18) and 13 (T13) of 89.57% (95% CI, 82.64-93.93%) for a screen-positive rate (SPR) of 2.94%. There were 12 false-negative results in the CFTS pathway, comprising 10 cases of T21, one of T18 and one of T13. cfDNA had a combined sensitivity for T21, T18 and T13 of 100% (95% CI, 95.00-100%) for a SPR of 1.21%. When high-risk cfDNA results for any chromosome (including the sex chromosomes) and failed cfDNA tests were treated as screen positives, the SPR for cfDNA increased to 2.42%. The risk of any major chromosomal abnormality (including atypical abnormalities) detected on prenatal or postnatal diagnostic testing after a low-risk screening result was 1 in 1188 for CFTS (n = 37) and 1 in 762 for cfDNA (n = 16) (P = 0.13). The range of chromosomal abnormalities detected after a low-risk cfDNA result included pathogenic copy-number variants (n = 6), triploidy (n = 3), rare autosomal trisomies (n = 3) and monosomy X (n = 2). CONCLUSIONS: Our state-wide record-linkage analysis delineated the utilization and clinical performance of the multitude of prenatal screening pathways available to pregnant women. The sensitivity of cfDNA for T21, T18 and T13 was clearly superior to that of CFTS. While there was no statistically significant difference in the residual risk of any major chromosomal abnormality after a low-risk CFTS or cfDNA result, there were fewer live infants diagnosed with a major chromosomal abnormality in the cfDNA cohort. These data provide valuable population-based evidence to inform practice recommendations and health policies. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

A geographic hot spot of Ichthyophonus infection in the southern Salish Sea, USA.

The prevalence of Ichthyophonus infection in Pacific herring Clupea pallasii was spatially heterogeneous in the southern Salish Sea, Washington State, USA. Over the course of 13 mo, 2232 Pacific herring were sampled from 38 midwater trawls throughout the region. Fork length was positively correlated with Ichthyophonus infection at all sites. After controlling for the positive relationship between host size and Ichthyophonus infection, the probability of infection was approximately 6-fold higher in North Hood Canal than in Puget Sound and the northern Straits (12 vs. 2% predicted probability for a 100 mm fish and 30 vs. 7% predicted probability for a 180 mm fish). Temporal changes in Ichthyophonus infection probability were explained by seasonal differences in fish length, owing to Pacific herring life history and movement patterns. Reasons for the spatial heterogeneity remain uncertain but may be associated with density-dependent factors inherent to the boom-bust cycles that commonly occur in clupeid populations.

Prenatal diagnostic testing and atypical chromosome abnormalities following combined first-trimester screening: implications for contingent models of non-invasive prenatal testing.

OBJECTIVES: To investigate by means of a population-based analysis of a cohort of women who underwent combined first-trimester screening (CFTS), changes in uptake of invasive prenatal diagnosis according to risk of trisomy 21 (T21) on CFTS, and prevalence and methods for ascertainment of atypical chromosome abnormalities. METHODS: This was a retrospective cohort study using state-wide prenatal datasets from Victoria, Australia. A three-step approach was taken to analyze the data: (1) linkage of records between serum screening and diagnostic results; (2) comparison of rates of diagnostic testing according to CFTS T21 risk result category in a 2014-2015 cohort with those of a historical 2002-2004 cohort; (3) detailed analysis of atypical abnormalities in the 2014-2015 group according to CFTS T21 risk result, individual serum analyte level and other indications for invasive diagnostic testing. RESULTS: In 2014-2015, there were 100 418 CFTS results issued for 146 776 births (68.4%). The overall prevalence of atypical chromosome abnormalities in the entire CFTS cohort was 0.10% and was highest in those with CFTS T21 risk > 1 in 10 (4.6%), or serum analyte levels < 0.2 multiples of the median (MoM) (6.9% for pregnancy-associated plasma protein-A (PAPP-A) and 5.2% for beta-human chorionic gonadotropin (ß-hCG)). Almost half (49.2%) of women with PAPP-A < 0.2 MoM had a risk for T21 on CFTS of less than 1 in 100. The majority (55%) of atypical abnormalities occurred in women with CFTS T21 risk below 1 in 300, and were most commonly detected on ultrasound examination (47.1%). CONCLUSION: Concerns regarding missed diagnoses of atypical chromosome abnormalities when non-invasive prenatal testing is offered after a result of high risk on CFTS can be mitigated if invasive diagnostic testing is offered to those women with CFTS T21 risk of > 1 in 100, serum PAPP-A or ß-hCG < 0.2 MoM, or ultrasound-detected abnormality. This has implications for contingent models of screening. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

The development and integrity of equine pre-antral follicles cultured in vitro with follicle-stimulating hormone (FSH) supplementation.

This study investigated the effects of different concentrations of FSH (10, 50, 100 and 200 ng/ml) in supplemented MEM+ on the development of equine pre-antral follicles that were cultured in vitro for 2 or 6 days. The ovaries (n = 5) from mares in seasonal anoestrus were collected from a local abattoir. Ten ovarian tissue fragments of approximately 3 × 3 × 1 mm were obtained from each animal. The fragments were cultured in situ for 2 days (D2) or 6 days (D6) in MEM+ or MEM+ supplemented with FSH at four different concentrations, establishing the following 11 groups: control (D0); MEM + (D2); MEM + (D6); MEM + 10 ng/ml of FSH (D2); MEM + 10 ng/ml of FSH (D6); MEM + 50 ng/ml of FSH (D2); MEM + 50 ng/ml of FSH (D6); MEM + 100 ng/ml of FSH (D2); MEM + 100 ng/ml of FSH (D6); MEM + 200 ng/ml of FSH (D2); and MEM + 200 ng/ml of FSH (D6). Follicles were observed in only 9.65% (388 of 4,018) of the histological sections. Of the 861 follicles evaluated, 488 were in the primordial stage, and 373 were in various developmental stages; 59.7% were morphologically normal. Regarding the integrity of the pre-antral follicles, the groups with 100 ng/ml FSH of 2-days culture as well as 50, 100 and 200 ng/ml FSH of 6-days culture provided the best results. In conclusion, the in vitro culture of abattoir-derived equine ovarian fragments presented better morphological integrity when supplemented with FSH for 6 days, in comparison with the MEM culture group. However, no clear effects were observed with FSH regarding the promotion of activation from a primordial to a developing follicle.

Regional distribution and integrity of equine ovarian pre-antral follicles.

The goal of this study was to determine the distribution of pre-antral follicles in the ovarian parenchyma of mares. For Experiment 1, each ovary was cut longitudinally at the greater curvature, performing two hemiovaries. After that, six fragments from each hemiovary were obtained, resulting in 12 fragments, which were divided into the innermost region of the parenchyma, the middle region and the outermost region. All the three obtained sections were cut transversally to obtain two fragments from each one. For Experiment 2, each ovary also submitted to a longitudinal cut on the greater curvature, forming two hemiovaries. Each hemiovary was sectioned into four symmetrical fragments, resulting in eight fragments per ovary. The fragments were related as being near to or far from the ovulatory fossa. The fragments of both experiments were immediately fixed in Carnoy for 12 hr and kept in 70% ethanol for 24 hr. Follicles were classified according to the stages of development and for morphological integrity according to oocyte morphology and granulosa cells. After the histological assessment, a total of 1,130 follicles were visualized from Experiment 1, being 1,054 (93.3%) primordial follicles and 76 (4.7%) follicles in development. The innermost region had the highest percentage of pre-antral follicles compared to the other regions (p < .05). The middle and outermost regions showed higher percentages of intact primordial and developing follicles than the innermost region (p < .05). Considering Experiment 2, 938 follicles were found, being 894 (95.3%) primordial and 44 (4.7%) follicles in development. The region near the ovulatory fossa presented higher (58.7%; 551 of 938) follicular concentration compared to the region far from the ovulatory fossa (41.3%; 387 of 938; p < .05). As a conclusion, distribution of pre-antral follicles in the equine ovary has a specific pattern through the parenchyma. Also, the follicular integrity differed in the studied ovarian areas.

Influence of visual and auditory biofeedback on partial body weight support treadmill training of individuals with chronic hemiparesis: a randomized controlled clinical trial.

BACKGROUND: Stroke is an important causal factor of deficiency and functional dependence worldwide. OBJECTIVE: To determine the immediate effects of visual and auditory biofeedback, combined with partial body weight supported (PBWS) treadmill training on the gait of individuals with chronic hemiparesis. DESIGN: Randomized controlled trial. SETTING: Outpatient rehabilitation hospital. POPULATIONS: Thirty subjects with chronic hemiparesis and ability to walk with some help. METHODS: Participants were randomized to a control group that underwent only PBWS treadmill training; or experimental I group with visual biofeedback from the display monitor, in the form of symbolic feet as the subject took a step; or experimental group II with auditory biofeedback associated display, using a metronome at 115% of the individual's preferred cadence. They trained for 20 minutes and were evaluated before and after training. Spatio-temporal and angular gait variables were obtained by kinematics from the Qualisys Motion Analysis system. RESULTS: Increases in speed and stride length were observed for all groups over time (speed: F=25.63; P<0.001; stride length: F=27.18; P<0.001), as well as changes in hip and ankle range of motion - ROM (hip ROM: F=14.43; P=0.001; ankle ROM: F=4.76; P=0.038), with no time*groups interaction. Other spatio-temporal and angular parameters remain unchanged. CONCLUSIONS: Visual biofeedback and auditory biofeedback had no influence on PBWS treadmill training of individuals with chronic hemiparesis, in short term. Additional studies are needed to determine whether, in long term, the biofeedback will promote additional benefit to the PBWS treadmill training. CLINICAL REHABILITATION IMPACT: The findings of this study indicate that visual and auditory biofeedback does not bring immediate benefits on PBWS treadmill training of individuals with chronic hemiparesis. This suggest that, for additional benefits are achieved with biofeedback, effects should be investigated after long-term training, which may determine if some kind of biofeedback is superior to another to improve the hemiparetic gait.

The impact of socioeconomic position on severe maternal morbidity outcomes among women in Australia: a national case-control study.

OBJECTIVE: Studies in other developed countries have suggested that socioeconomic position may be a risk factor for poorer pregnancy outcomes. This analysis aimed to explore the independent impact of socioeconomic position on selected severe maternal morbidities among women in Australia. DESIGN: A case-control study using data on severe maternal morbidities associated with direct maternal death collected through the Australasian Maternity Outcomes Surveillance System. SETTING: Australia. POPULATION: 623 cases, 820 controls. METHODS: Logistic regression analysis to investigate differences in outcomes among different socioeconomic groups, classified by Socio-Economic Indexes for Areas (SEIFA) quintile. MAIN OUTCOME MEASURES: Severe maternal morbidity (amniotic fluid embolism, placenta accreta, peripartum hysterectomy, eclampsia or pulmonary embolism). RESULTS: SEIFA quintile was statistically significantly associated with maternal morbidity, with cases being twice as likely as controls to reside in the most disadvantaged areas (adjusted OR 2.00, 95%CI 1.29-3.10). Maternal age [adjusted odds ratio (aOR) 2.20 for women aged 35 or over compared with women aged 25-29, 95%CI 1.64-3.15] and previous pregnancy complications (aOR 1.30, 95%CI 1.21-1.87) were significantly associated with morbidity. A parity of 1 or 2 was protective (aOR 0.58, 95%CI 0.43-0.79), whereas previous caesarean delivery was associated with maternal morbidity (aOR 2.20 for women with one caesarean delivery, 95%CI 1.44-2.85, compared with women with no caesareans). CONCLUSION: The risk of severe maternal morbidity among women in Australia is significantly increased by social disadvantage. This study suggests that future efforts in improving maternity care provision and maternal outcomes in Australia should include socioeconomic position as an independent risk factor for adverse outcome.

Experiences, utilisation and outcomes of maternity care in England among women from different socio-economic groups: findings from the 2010 National Maternity Survey.

OBJECTIVE: The objective of this analysis was to explore the healthcare-seeking behaviours and experiences of maternity care among women from different socio-economic groups in order to improve understanding of why socially disadvantaged women have poorer maternal health outcomes in the UK. DESIGN: Secondary analysis of a national survey of women conducted 3 months after they had given birth. SETTING: England. SAMPLE: A total of 5332 women. METHODS: Logistic regression analysis to investigate differences in outcomes among different socio-economic groups, classified by the Index of Multiple Deprivation (IMD). MAIN OUTCOME MEASURES: Healthcare-seeking behaviours, outcomes and experiences of maternity care. RESULTS: With each increase in IMD quintile (decrease in socio-economic position), women were shown to be 25% (adjusted odds ratio [aOR] 0.75; 95% confidence interval [95% CI] 0.63-0.90) less likely to have had any antenatal care and 15% (aOR 0.85; 95% CI 0.80-0.90) less likely to have had a routine postnatal check-up. They were 4% (aOR 1.04; 95% CI 0.99-1.10) more likely to have had an antenatal hospital admission, 7% (aOR 1.07; 95% CI 0.99-1.16) more likely to have been transferred during labour and 4% (aOR 1.04; 95% CI 0.99-1.09) more likely to have had a caesarean birth, although these results were not statistically significant. With decreasing socio-economic position women were more likely to report that they were not treated respectfully or spoken to in a way they could understand by doctors and midwives. CONCLUSIONS: This analysis suggests the need for a focusing of professionals and services towards pregnant women from lower socio-economic groups and more targeted maternal public health education towards socially disadvantaged women.

Effects of treadmill training with partial body weight support and the proprioceptive neuromuscular facilitation method on hemiparetic gait: a randomized controlled study.

BACKGROUND: Gait disturbance is common after stroke; however, there is no consensus regarding the optimal therapeutic rehabilitation of hemiparetic gait. AIM: To compare the effects of the treadmill training with partial body-weight support (TPBWS) and Proprioceptive Neuromuscular Facilitation (PNF) method on gait of subjects with chronic stroke. DESIGN: Randomized clinical trial, comparing two experimental groups (comparative study). SETTING: Laboratory for Human Movement Analysis of UFRN. POPULATION: Twenty-three subjects, with a mean age of 56.7±8.0 years and a mean time since the onset of the stroke of 27.7±20.3 months, able to walk with personal assistance or assistive devices. METHODS: Two experimental groups underwent gait training based on PNF method (N.=11) or using the TPBWS (N.=12), for twelve sessions. Evaluation of motor function (using the STREAM and motor FIM), and kinematic gait analysis were carried out before and after the interventions. RESULTS: Increases in the STREAM scores (F=49.189, P<0.001) and in motor FIM scores (F=7.093, P=0.016), as well as improvement in symmetry ratio-swing time of the paretic leg/swing time of non-paretic leg--(F=7.729, P=0.012), were observed for both groups. Speed, stride length and double-support time showed no change after training. Differences between groups were observed only for the maximum ankle dorsiflexion over the swing phase (F=6.046, P=0.024), which showed an increase for the PNF group. Other angular parameters remain unchanged. CONCLUSION: Improvement in motor function and in gait symmetry was observed for both groups, suggesting similarity of interventions. However, the sample size should be carefully considered in generalizing the results to other populations. CLINICAL REHABILITATION IMPACT: The results showed some equivalence between these two approaches with regard to motor recovery, functionality and temporal symmetry of hemiparetic gait, suggesting that the cost-effectiveness of each treatment may have a important role in this choice.

The influence of treadmill inclination on the gait of ambulatory hemiparetic subjects.

INTRODUCTION: This study evaluated the influence of the degree of treadmill belt inclination for training of ambulatory patients with hemiparetic stroke. METHODS: Twelve patients were instructed to walk at 5 different levels of inclination (0%-8%) while harness-secured on the treadmill. The gait velocity was kept constant during all conditions. Dependent variables were heart rate, gait cycle-dependent parameters, and electromyographic activation patterns of the weight-bearing muscles. RESULTS: Heart rate increased across all inclination levels, stride length increased and cadence decreased, whereas swing symmetry improved due to shortening of the relative swing phase of the affected side at the 6% and 8% inclination levels. No change in the activation pattern of the leg muscles was found. CONCLUSION: An inclination up to at least 8% can be accommodated for treadmill training by ambulatory stroke patients. For a given belt speed, heart rate increased without exceeding critical levels and patients walked with a more symmetric pattern. This protocol appeared to be safe in this selected group of subjects.

Differential detection of Hammondia hammondi from Toxoplasma gondii using polymerase chain reaction.

Hammondia hammondi and Toxoplasma gondii are two related coccidian parasites, with cats as definitive hosts and warm-blooded animals as intermediate hosts. It is difficult to differentiate them by morphological and serological parameters. In the present study, primers were designed to specifically amplify the ITS-1 region of H. hammondi to differentiate it from T. gondii. Attempts were made to detect the presence of H. hammondi DNA in the tissues of mice infected with H. hammondi alone, as well as from mixed infections with T. gondii, using the newly designed primers. The de novo primers effectively amplified the H. hammondi-specific target fragment from all samples containing H. hammondi, including those with concomitant T. gondii infection. Further, the primers did not amplify any fragment from the related parasites like T. gondii, Neospora caninum and Hammondia heydorni. The new primers provide simple and efficient means to differentially diagnose H. hammondi from T. gondii even in samples containing both parasites, thus obviating the need for other labourious techniques like mouse bioassay and in vitro cultivation.

A influencia da estimulacao eletrica funcional associada ao treinamento em esteira com suporte parcial de peso na marcha de Hemipareticos / Influence on hemiparetic patients gait abilities from electrial functional stimulation during treadmill training with partial weight support

Avaliar os efeitos do treino em esteira eletrica com suporte parcial de peso associado a estimulacao eletrica funcional na marcha de sujeitos hemiplegicos por meio da analise de variaveis espaco-temporais. Metodo: para tal proposito foi utilizado o sistema A1-B-A2,no qual A1 e A2 correspondem ao treinamento em esteira eletrica com suporte parcial de peso e B, ao mesmo treinamento associado a estimulacao eletrica funcional. participaram deste estudo dois pacientes hemiparetcos cronicos que foram submetidos a treinamento durante 45 minutos, tres vezes por semana durante 9 semanas...

Cardiovascular functional disorder and stress among patients having neck-shoulder symptoms.

OBJECTIVES: To investigate if autonomic nervous system function, reflected in cardiovascular variables, among patients with neck-shoulder symptoms (tension neck group (T)) differed from that in a symptom free control group (C), and to establish its relation with pain and psychological stress. METHODS: Twelve women with tension neck and nine controls in secretarial jobs were studied. They underwent an orthostatic test, deep breathing test, Valsalva manoeuvre, isometric handgrip test, and muscular endurance test. Pain was measured using visual analogue scales, and psychological stress by the Modified Somatic Perception Questionnaire (MSPQ). Plasma endothelin-1 (ET-1) was measured using high pressure liquid chromatography and radioimmunoassay. RESULTS: Signs of psychological stress were significantly (p < 0.001) more common in group T than in group C. Mean resting heart rate in group T (77.8 (SE 2.9) beats/min; range 64-100) was significantly greater than that in group C (63.8 (3.1) beats/min; range 52-80) (p < 0.01). In the orthostatic test, the overall changes in R-R intervals during the first 40 heart beats after standing up and during seven minutes of testing differed significantly between the groups (p < 0.001, < 0.05, respectively). The increase in diastolic blood pressure in the three minute isometric handgrip test was significantly less in group T (19.4 (3.5) mm Hg; range -5 to 35) than in group C (30 (3.4) mm Hg; range 15-50) (p < 0.05). The MSPQ score in the study group (n = 21) correlated positively with resting heart rate (r = 0.462, p < 0.05) and negatively with increase in diastolic blood pressure (r = -0.514, p < 0.05). Plasma concentrations of ET-1 did not differ between the groups. CONCLUSION: Increased sympathetic activity was found among patients having neck-shoulder symptoms. Local mechanisms may have influenced the cardiovascular changes observed during isometric testing in these patients.

Quantification of plasma lipids and apolipoproteins in British Halflop rabbits. A comparison between normocholesterolemic rabbits, hypercholesterolemic rabbits (modified WHHL rabbits) and rabbits fed an atherogenic diet.

We have established isolation methods and developed electroimmunoassays for rabbit apolipoprotein A-I (apo A-I), apo B, apo C-III and apo E. The assays were used to characterize a hyperlipidemic strain of the British Halflop rabbits (BHL rabbits), obtained after cross-breeding with WHHL rabbits and referred to as modified WHHL rabbits, and to investigate the changes in the apolipoprotein levels induced by feeding normal BHL rabbits an atherogenic diet (0.25% cholesterol and 3% coconut oil). The modified WHHL rabbits were characterized by increased levels of apo B, apo C-III and apo E as well as cholesterol, phospholipids and triacylglycerol as compared to chow-fed BHL rabbits, while the apo A-I levels were only half of those found in the chow-fed animals. The modified WHHL rabbits had virtually no low density lipoprotein (LDL) receptor activity and a low fractional catabolic rate (FCR) of LDL. These results indicate that the modified WHHL rabbit has the homozygous form of the LDL receptor deficiency. The BHL rabbits fed the atherogenic diet showed increased levels of cholesterol, triacylglycerol, apo B, apo C-III and apo E, as compared to those of the chow-fed BHL rabbits. The apo E and apo C-III reached levels in the range of or even higher than those of the modified WHHL rabbits. The apo A-I levels on the other hand did not differ from those of the chow-fed rabbits. Feeding an atherogenic diet led to a decrease in the FCR of LDL to a level similar to that found in the modified WHHL rabbits.

Intravenous and subcutaneous administration of desmopressin (DDAVP) to hemophiliacs: pharmacokinetics and factor VIII responses.

When desmopressin (DDAVP) is given to mild and moderate hemophiliacs intravenously (i.v.) or subcutaneously (s.c.), there is a very large between-patient variability for peak levels of factor VIII coagulant activity (VIII:C). To evaluate whether or not between-patient variability is related to DDAVP levels achieved in plasma, we measured drug levels in 14 hemophilic volunteers (VIII:C 2 to 31 U/dL) who were randomly given 0.3 micrograms/Kg of i.v. or s.c. DDAVP and crossed-over to the other treatment after an interval of 15-30 days. Peak DDAVP levels (Cmax) were higher for i.v. DDAVP (p less than 0.02), times to peak levels (tmax) were shorter for i.v. DDAVP (p less than 0.001). There was no difference between the i.v. and s.c. routes for plasma DDAVP time curve (AUC) and half-life (t 1/2), but there was much larger variability for pharmacokinetic parameters with i.v. than with s.c. DDAVP. Post-DDAVP VIII:C increased 3.4 +/- 1.6 fold (i.v.) and 3.3 +/- 1.3 fold (s.c.) over baseline levels, with no significant correlation between peak VIII:C and DDAVP levels for either route of administration. These findings establish the s.c. route of DDAVP administration to be bioequivalent in effect to the i.v. route, albeit with less variability. At the DDAVP dosage used in this study and currently recommended for therapy, the VIII:C response is neither a function of the rate of absorption of the compound nor of the magnitude of its plasma concentration.