Feasibility of Double-Blind Clinical Trials with Oral Diacetylmorphine: A Randomized Controlled Phase II Study in an Inpatient Setting

The aim of this study was to evaluate the feasibility of conducting double-blind controlled randomized clinical trials using twice-a-day immediate-release oral diacetylmorphine (DAM) in heroin-dependent patients, by means of measuring the capacity of oral DAM to block opiate withdrawal and clinicians' ability to distinguish it from morphine and methadone. This was a randomized, phase II, double-blind, multicenter pilot study comparing immediate-release oral DAM, slow-release oral morphine and oral methadone administered twice a day during 10 days. Forty-five heroin-dependent patients were randomly assigned to these three treatment groups in an inpatient regime. Patients were stabilized with a mean of 350 mg (SD = 193) of immediate-release oral DAM, 108 mg (SD = 46.2) of slow-release oral morphine and 40 mg (SD = 17.9) of methadone. No statistically significant differences were found between any studied medication in clinical outcome. Neither patients nor clinicians were able to identify the administered medication. This study shows the feasibility of double-blind clinical trials using b.i.d. immediate-release oral DAM allowing further phase III clinical trials in the process of introducing oral DAM as a medication for heroin-dependent patients not responding to standard maintenance treatments.     

Health-related quality of life and well-being in adults with idiopathic inflammatory myopathy

Health-related quality of life (HRQoL) and well-being are concepts that attempt to objectively capture a person’s subjective perceptions of vitality and energy. Our objectives were to determine HRQoL and well-being in adult patients diagnosed with inflammatory myopathy who attended at our outpatient clinic and to investigate clinical and biological correlations with these concepts. Sixty-two patients (52 women), with a mean age of 50.7 years, were evaluated in this cross-sectional study—47 with dermatomyositis and 15 with polymyositis. Disease damage and activity were assessed with the International Myositis Assessment and Clinical Studies-validated instruments. Manual muscle testing was used to evaluate muscle strength. Quality of life was evaluated with the WHO instrument (WHO Quality of Life Measure (WHOQOL-BREF)), adapted for use in the Spanish population, and well-being with the WHO-Five Well-Being Index (WHO-5). t tests were conducted to examine differences in HRQoL and well-being outcomes in relation to several disease- and patient-related variables. Correlation analyses were performed with the Pearson correlation coefficient. None of the clinical or biological variables analyzed was significantly associated with a poorer HRQoL or well-being. No differences in HRQoL or WHO-5 well-being score were found between the two myositis subgroups (dermatomyositis vs. polymyositis). Disease activity and muscle weakness were negatively associated with the physical and environmental domains of the HRQoL, respectively (p?<?0.002), but not with well-being. Disease duration did not have a significant impact on HRQoL or well-being. In adult patients with myositis, disease activity and muscle weakness are associated with poorer HRQoL in the physical health and environmental domains, respectively.     

“Pregnancy in adult-onset idiopathic inflammatory myopathy”: Report from a cohort of myositis patients from a single center

Background and purpose

Idiopathic inflammatory myopathies (IIM) are systemic diseases, characterized by the presence of an inflammatory muscle infiltrate. Although more frequent in women, its relationship with pregnancy has not been extensively studied. Our goal was to analyze the interaction between pregnancy and myositis in a cohort of IIM women from a single center.

Methods

A total of 51 patients from a historical cohort of IIM diagnosed between 1983 and 2013 were interviewed with a specific questionnaire. Comparisons between pregnancies occurring before and after the onset of the disease were performed using generalized mixed-effect models with normal and binomial distributions adjusted for confounding factors and clustering.

Results

A total of 102 pregnancies from 51 patients (41 with dermatomyositis and 10 with polymyositis) were analyzed. A total of 14 pregnancies from 8 patients occurred after disease onset; statistically significant (p = 0.02) clinical improvement during gestation was evident in 7 pregnancies (4 patients), 5 of them (from 2 patients) experienced a relapse of IIM symptoms afterwards, while in the rest, there was no influence of pregnancy on the disease. No disease flare associated with pregnancy was observed. Two patients were diagnosed within the first 6 months after delivery and none during pregnancy. No evidence was found to support pregnancy as a trigger for myopathy (p = 0.71).

Conclusions

Pregnancy does not seem to carry a worse prognosis for the mother nor for the fetus in patients with IIM; on the contrary, nearly half of the patients in our series improved clinically when they became pregnant, a relapse of IIM symptoms being common afterwards. Pregnancy does not appear to be a trigger for IIM.     

Testing the temporal stability of individual differences in the acquisition and generalization of fear

We studied the temporal stability of individual differences in the acquisition and generalization of fear. Seventy‐one participants were tested in two almost identical fear‐acquisition and fear‐generalization sessions (separated by 8 months). Acquisition and generalization were measured by the fear‐potentiated startle, the skin conductance response, and online expectancies of the unconditioned stimulus. To control for the effects of previous experience, different stimuli were used for half of the participants in Session 2. Acquisition and generalization did not differ across sessions or as a function of the stimuli used in Session 2, and a significant proportion of individual differences in these processes was stable over time (generalizability coefficients ranged from 0.17 to 0.38). When the same stimuli were used, acquisition measures showed compromised stability. The results are discussed in terms of their theoretical and applied implications.