Individualized prophylaxis for optimizing hemophilia care: can we apply this to both developed and developing nations?

Prophylaxis is considered optimal care for hemophilia patients to prevent bleeding and to preserve joint function thereby improving quality of life (QoL). The evidence for prophylaxis is irrefutable and is the standard of care in developed nations. Prophylaxis can be further individualized to improve outcomes and cost effectiveness. Individualization is best accomplished taking into account the bleeding phenotype, physical activity/lifestyle, joint status, and pharmacokinetic handling of specific clotting factor concentrates, all of which vary among individuals. Patient acceptance should also be considered. Assessment tools (e.g. joint status imaging and function studies/scores, QoL) for determining and monitoring risk factors and outcome, as well as population PK profiling have been developed to assist the individualization process. The determinants of optimal prophylaxis include (1) factor dose/dosing frequency, hence, cost/affordability (2) bleeding triggers (physical activity/lifestyle, chronic arthropathy and synovitis) and (3) bleeding rates. Altering one determinant results in adjustment of the other two. Thus, the trough level to protect from spontaneous bleeding can be increased in patients who have greater bleeding risks; and prophylaxis to achieve zero joint bleeds is achievable through optimal individualization. Prophylaxis in economically constrained nations is limited by the ill-affordability of clotting factor concentrates. However, at least 5 studies on children and adults from Thailand, China and India have shown superiority of low dose (~5–10 IU kg^?1 2-3× per week) prophylaxis over episodic treatment in terms of bleed reduction, and quality of life, with improved physical activity, independent functioning, school attendance and community participation. In these nations, the prophylaxis goals should be for improved QoL rather than “zero bleeds” and perfect joints. Prophylaxis can still be individualized to affordability. Higher protective trough level can be achieved by using smaller doses given more frequently without an increase in consumption/cost. The bleeding trigger can also be down-regulated by avoiding unnecessary injury, and by engaging in judicious strengthening exercises appropriate to the joint status to improve balance and joint stabilization. Central to the success of prophylaxis are clinics with comprehensive care that provide the necessary professional expertise, support, and counseling, to educate patients, families, and other healthcare professionals, and to support research for improved hemophilia care.     

Lactulose: A Simple Sugar in a Complex Encephalopathy

Hepatic encephalopathy is a common encephalopathy and one of the very few that are treatable. Lactulose has remained a standard pharmaceutical intervention and is listed as one of the World Health Organization’s Essential Medicines. The discovery of lactulose, the acid dialysis proof of concept, and the role of Bircher are not well known. This historical vignette reviews the gradual understanding of the complex liver–brain connection, the effective treatment of hepatic stupor with lactulose, and the immediate relevance of lactulose to the practice of consultative neurocritical care.     

Increasing Valid Profiles in Phallometric Assessment of Sex Offenders with Child Victims: Combining the Strengths of Audio Stimuli and Synthetic Characters

Penile plethysmography (PPG) is a measure of sexual interests that relies heavily on the stimuli it uses to generate valid results. Ethical considerations surrounding the use of real images in PPG have further limited the content admissible for these stimuli. To palliate this limitation, the current study aimed to combine audio and visual stimuli by incorporating computer-generated characters to create new stimuli capable of accurately classifying sex offenders with child victims, while also increasing the number of valid profiles. Three modalities (audio, visual, and audiovisual) were compared using two groups (15 sex offenders with child victims and 15 non-offenders). Both the new visual and audiovisual stimuli resulted in a 13% increase in the number of valid profiles at 2.5 mm, when compared to the standard audio stimuli. Furthermore, the new audiovisual stimuli generated a 34% increase in penile responses. All three modalities were able to discriminate between the two groups by their responses to the adult and child stimuli. Lastly, sexual interest indices for all three modalities could accurately classify participants in their appropriate groups, as demonstrated by ROC curve analysis (i.e., audio AUC = .81, 95% CI [.60, 1.00]; visual AUC = .84, 95% CI [.66, 1.00], and audiovisual AUC = .83, 95% CI [.63, 1.00]). Results suggest that computer-generated characters allow accurate discrimination of sex offenders with child victims and can be added to already validated stimuli to increase the number of valid profiles. The implications of audiovisual stimuli using computer-generated characters and their possible use in PPG evaluations are also discussed.     

Visual Attention and Key Word Sign in Children with Autism Spectrum Disorder

The aim of this study was to examine the relationship between children’s visual attention to, and acquisition of, Key Word Sign (KWS). Our hypothesis was that children’s visual attention to the clinician’s modelling would be associated with their acquisition and production of KWS. A multiple baseline single case experimental design with additional exploratory analyses was used to examine the effect of visual attention on sign acquisition among three preschool children with ASD. This paper extends from the previous intervention study (see Tan et al. 2014) by examining visual attention as a potential factor underpinning individual differences in sign acquisition documented in the initial study. All three children visually attended to the clinician’s modelling of KWS, and acquired signs to varying degrees following the introduction of KWS intervention. A weak, non-significant correlation was found between the children’s amount of visual attention and their production of signs. The results provide preliminary evidence for a lack of association between children’s amount of ‘looking’ and ‘doing’ during KWS intervention. Replication and examination of other factors impacting on KWS intervention outcomes is required.     

Ex Vivo Expansion or Manipulation of Stem Cells to Improve Outcome of Umbilical Cord Blood Transplantation

The outcome of umbilical cord blood transplantation for adult patients with hematologic malignancies now rivals that of matched unrelated donor transplantation. However, delayed hematopoietic and immunologic recovery remains a source of significant morbidity and mortality. Multiple strategies are now being studied to overcome these limitations. One strategy involves ex vivo expansion of the umbilical cord blood unit prior to transplantation. A second strategy involves exposure of the umbilical cord blood graft to compounds aimed at improving homing and engraftment following transplantation. Such a strategy may also address the problem of slow hematopoietic recovery as well as the increased risk of graft failure. Many of these strategies are now being tested in late phase multi-center clinical trials. If proven cost-effective and efficacious, they may alter the landscape of donor options for allogeneic stem cell transplantation.