Contribution to the rheological testing of pharmaceutical semisolids

Rheological behaviour of pharmaceutical semisolid preparations significantly affects manufacturing process, administration, stability, homogeneity of incorporated drug, accuracy of dosing, adhesion in the place of application, drug release, and resulting therapeutic effect of the product. We performed test of consistency by penetrometry, rotational, oscillation and creep tests, and squeeze and tack tests of model samples to introduce methods suitable for characterization and comparison of semisolids in practice. Penetrometry is a simple method allowing sorting the semisolids to low and high stress-resistant materials but deficient for rheological characterization of semisolids. Value of yield stress, generally considered to be appropriate feature of semisolids, is significantly influenced by the method of testing and the way of evaluation. The hysteresis loops of model semisolids revealed incomplete thixotropy, therefore, three-step thixotropy test was employed. Semisolids showed nonlinear response in the creep phase of tests and partial recovery of structure by storing energy in the recovery phase. Squeeze and tack tests seem to be convenient ways for comparison of semisolids. Our study can contribute to a better understanding of different flow behaviour of semisolids given by different physicochemical properties of excipients and can bring useful approaches to evaluation and comparison of semisolids in practice.     

Dreaming the impossible dream? An exploratory study on the expectations of Dutch clients with multiple problems concerning the co-production of public services

Currently, many policymakers try to encourage client involvement during the public service delivery process and make it a co-production. Clients are encouraged to act as active agents and embrace an integrated approach to address their problems to empower them. However, different studies have raised questions regarding to what extent these ambitions are appropriate for clients with vulnerabilities, such as clients with multiple problems. Aiming to further explore this issue, we studied the expectations of clients with multiple problems concerning the co-production of public services. We interviewed 46 clients with multiple problems at the start of their support trajectory. All 46 participants lived in five districts in Rotterdam, the Netherlands, and were recruited via community-based primary care teams. Our study indicates that co-production ambitions might not resonate with clients with multiple problems. The study shows that these clients’ expectations are driven by their feelings of being overwhelmed and stressed out by their situation, feelings of being a victim of circumstances, bad experiences with public services in the past, their evaluation of what counts as a problem and the envisioned solutions. These clients expect public service providers to take over, fix their main problem(s) and not interfere with other aspects of their lives (not an integrated approach). Although participants seek a ‘normal’ life with, e.g., a house, work, partner, children, holidays, a pet, and no stress (a white picket fence life) as ideal, they do not feel that this is attainable for them. More insight into the rationale behind these expectations could help to bridge the gap between policymakers’ ambitions and clients’ expectations.     

Disconnectedness from the here-and-now: a phenomenological perspective as a counteract on the medicalisation of death wishes in elderly people

When elderly people are ideating on manners to end their lives, because they feel life is over and no longer worth living, it is important to understand their lived experiences, thoughts and behaviour in order to appropriately align care, support and policy to the needs of these people. In the literature, the wish to die in elderly people is often understood from a medical, psychopathological paradigm, referred to as cognitive impairment, depressive disorder, pathological bereavement, and suicidality. In this paper, we evaluate this dominant paradigm by considering three serious limitations, namely: (1) the risk of epistemic transformation; (2) the risk of reduction; and (3) the risk of obscuring the social and cultural embeddedness. Drawing on insights from our empirical–phenomenological research on the issue of elderly and the self-chosen death, this paper argues for a phenomenological perspective to counteract the medicalisation of death wishes in elderly people.     

Pubarche and serum dehydroepiandrosterone sulphate levels in children with Prader–Willi syndrome

Context Premature pubarche (PP) is reported in children with Prader–Willi Syndrome (PWS). Pubarche is preceded by adrenarche – an increase in serum levels of adrenal androgens, most specifically dehydroepiandrosterone sulphate (DHEAS). Objectives To assess DHEAS levels, the age at and progression of pubarche and the prevalence of PP in children with PWS. Design/Patients In the Dutch PWS Cohort Study, 120 children (6 months–17 years) are prospectively followed. Their age at onset of pubarche and various pubic hair stages and prevalence of PP were determined. Serum DHEAS levels were assessed in 97 children. Results Median serum DHEAS levels were significantly higher in children with PWS than in healthy age‐matched controls at ages 3–6 years (girls: P = 0·004 and boys: P = 0·010) and 6–10 years (girls: P = 0·045 and boys: P = 0·001). Age and gender significantly influenced DHEAS levels in children with PWS. The median [P10–P90] age at onset of pubarche in children with PWS was significantly younger than in healthy peers, 9·04[6·75–11·84] years in PWS girls (P < 0·0001) and 10·31 [8·65–12·29] years in PWS boys (P = 0·003). The prevalence of PP in children with PWS was 30·0% in girls and 16·1% in boys. Conclusions Compared to healthy children, children with PWS have significantly higher DHEAS levels from 3 to 10 years of age. They are younger at onset of pubarche and have a higher prevalence of premature pubarche. DHEAS levels in PWS are influenced by age and gender. Our findings indicate earlier maturation of the zona reticularis of the adrenal glands in children with PWS.     

Antidepressant use and risk of central nervous system metastasis

Selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants, were found to increase central nervous system (CNS) metastasis in mice. Our study investigated in humans whether antidepressants, and specifically SSRIs, increased the relative odds of CNS metastasis. We identified 189 cases of CNS metastasis amongst breast cancer, melanoma, and non-Hodgkin lymphoma subjects who were diagnosed with CNS metastasis or infiltration between January 1, 2005 and September 30, 2013 and 756 controls (patients without CNS metastasis or infiltration). Using logistic regression, we estimated the relative odds of CNS metastasis associated with antidepressant use adjusting for relevant covariates. The prevalence of antidepressants was 28.6?% in cases and 27.5?% in controls, whereas SSRIs were used in 16.9?% of cases and 17.3?% of controls. Among all patients, antidepressants were not associated with CNS metastasis or infiltration. No consistent patterns of association were observed in the analyses of other cancer subsets or exposure measures, with the possible exception of an increased risk of CNS metastasis associated with ‘any SSRI use’ among breast cancer patients (OR?=?1.73, 95?% CI?=?0.75, 4.04). We did not observe clear patterns of association, which may be due in part to the small sample size in many of our analyses.