From the voices of people with haemophilia A and their caregivers: Challenges with current treatment, their impact on quality of life and desired improvements in future therapies.

INTRODUCTION: Haemophilia A is a chronic disease requiring frequent intravenous infusions of recombinant factor VIII. Previous studies have shown that challenges associated with current treatments may have significant impacts on quality of life (QoL) that are as important as the health outcomes conferred by the therapy. Emerging therapeutic innovations offer the potential to mitigate treatment-related challenges, and it is therefore important to develop a better understanding of patient and caregiver experiences with existing haemophilia A treatments in order to characterize the full value of new treatments. AIM: To gather firsthand perspectives from people with haemophilia A (PWHA) and caregivers on the challenges with current treatment, their impact on QoL and desired improvements in future therapies. METHODS: Qualitative insights were gathered from 20 non-inhibitor PWHA or caregivers of PWHA across Canada through one-on-one interviews; insights were further explored through focus group sessions to uncover overarching themes and prioritize issues with current treatments. RESULTS: PWHA and caregivers identified several challenges, including administration of intravenous infusions, coordination of treatment schedules and ensuring adequate medication and supplies. Participants described how these challenges impact psychosocial well-being, physical health, personal/social life and work. Alternate modes of administration and longer-lasting treatment effects were identified as desired improvements over current treatments. CONCLUSION: This study emphasizes the impact that existing haemophilia A treatments have on psychological well-being, employment opportunities and adherence to treatment regimens. These considerations may help to inform decision-making for policymakers and health systems around the true value of new therapies entering the haemophilia market.

Click-evoked otoacoustic emissions: response amplitude is associated with circulating testosterone levels in men.

In rhesus monkeys, the magnitude of the cochlear response to auditory stimuli (click-evoked otoacoustic emissions, [CEOAEs]) is correlated with seasonal changes in circulating testosterone levels. The present study investigated the association between circulating testosterone and CEOAE production in men. CEOAEs were measured in 67 men and 37 women, and saliva was analyzed to quantify bioavailable testosterone. A sex difference in CEOAE response amplitude was found, confirming previous reports. In agreement with the monkey work, seasonal variation in the CEOAE response amplitude also was identified. CEOAEs were greater in summer and fall, the seasons that showed the lowest levels of circulating testosterone. On an individual basis, men who had higher levels of testosterone at the time of assessment exhibited smaller CEOAE response amplitudes. These findings support previous data from rhesus macaques and are consistent with the prospect of an activational effect of testosterone in the human cochlea.

Sex and ear differences in spontaneous and click-evoked otoacoustic emissions in young adults.

Effects of sex and handedness on the production of spontaneous and click-evoked otoacoustic emissions (OAEs) were explored in a non-hearing impaired population (ages 17-25 years). A sex difference in OAEs, either produced spontaneously (spontaneous OAEs or SOAEs) or in response to auditory stimuli (click-evoked OAEs or CEOAEs) has been reported in infants and children, but healthy young adults seldom have been the target of study. In the current data, a robust sexual dimorphism was confirmed, with women producing more numerous and stronger SOAEs, and CEOAEs with greater response amplitude compared to men. A right-ear advantage was found for the number of SOAEs produced and, in women, for SOAE power. Although handedness did not moderate the ear asymmetry in production, exploratory analyses revealed that departures from strong right hand preference were associated in the present sample with reduced numbers or strengths of OAEs. The results are discussed with respect to differential exposure to androgens during prenatal development.

Estradiol and corticosterone independently impair spatial navigation in the Morris water maze in adult female rats.

The independent effects of ovarian and adrenal hormones on spatial place learning were examined in male and female Long-Evans hooded rats. Experimental groups received bilateral ovariectomy (females only) and adrenalectomy (both sexes), followed by hormone administration according to a predetermined schedule. Spatial and reversal training in the Morris water maze were used to measure behavioural performance in locating a hidden platform. General proficiency and strategies use were assessed using search times and time spent in the periphery, respectively. The number of direct and circle swims to the platform was used to assess memory for the location of the hidden platform. Experiment 1 investigated the roles of estradiol and progesterone in spatial navigation in the absence of high levels of adrenal steroids. The female group that received estradiol alone showed longer search times, greater periphery swimming, and fewer direct and circle swims to the target than all other female groups. Experiment 2 investigated the role of corticosterone (CORT) in spatial navigation in the absence of ovarian hormones. Male and female rats that received acute matched doses of exogenous CORT were equally impaired during spatial training. During reversal training, the impairment in search time, periphery swimming, and direct and circle swims persisted in the female CORT group only. Analysis of serum CORT levels in the male and female experimental groups revealed no significant differences. These data suggest that estradiol and CORT can independently impair acquisition of spatial navigation skills and strategies use in adult female rats.