Neuroendocrine assessment of serotonergic, dopaminergic, and noradrenergic functions in alcohol-dependent individuals

Background: Alcohol dependence has been associated with reduced function of serotonin, dopamine as well as noradrenaline activities in several neuroendocrine studies. To our knowledge, there is, however, no study investigating all these 3 systems with the use of neuroendocrine methods in one and the same alcohol‐dependent individual. Methods: Alcohol‐dependent individuals (n = 42) and controls (n = 28) participated in the neuroendocrine test series. Central serotonergic neurotransmission was assessed by the prolactin (PRL) response to citalopram (CIT). The postsynaptic DRD2 function was measured by the growth hormone (GH) response to apomorphine (APO) and the postsynaptic α2‐adrenoceptor function by GH response to clonidine (CLON). Results: In the alcohol‐dependent individuals, the PRL concentrations were significantly lower at the time points 240 minutes and 300 minutes after CIT administration and mean delta PRL value was significantly reduced by 45% in comparison with controls. There were no significant differences in APO‐GH and CLON‐GH concentrations at any time points or in mean delta GH values between the groups. An impaired monoaminergic profile, including all 3 systems, was significantly more frequent in alcohol‐dependent individuals than controls (43% vs. 6% respectively). Conclusions: The monoaminergic dysfunction was restricted to an impairment of the serotonergic system, suggesting that this system is especially vulnerable to long‐term and excessive alcohol consumption. Moreover, impaired monoaminergic profiles, including low responses in 2 or 3 systems, were more frequently observed in alcohol‐dependent individuals than in controls. Such impaired profiles may be of clinical importance, but further studies are needed.     

Rapid salvage treatment with virus-specific T cells for therapy-resistant disease

Background.?Viral infections are major complications after allogeneic hematopoietic stem cell transplantation (HSCT). During posttransplant immunosuppression the regular T-cell control is compromised. Even if treatment strategies against infections caused by herpes viruses such as cytomegalovirus, Epstein-Barr virus, and adenovirus have improved, the mortality rate is still considerable. If primary antiviral therapy fails or cannot be tolerated, adoptive therapy with virus-specific cytotoxic T cells (CTL) can be utilized. Methods.?In this study, we used virus-specific CTLs to treat 8 patients suffering from severe viral infections after allogeneic HSCT. Using positive selection with HLA multimers and magnetic beads, we isolated CTLs from both frozen donor material as well as third-party donors within hours. Results.?At 90 days after CTL infusions 7 out of 8 patients were still living. CTLs infused from third-party donors were detected in 5 of 6 patients up to 76 days after infusion. No graft-versus-host disease associated with CTL infusions was observed. Conclusions.?Our separation approach offers a rapid alternative for adoptive CTL therapy if primary antiviral treatment strategies fail. Because no prolonged expansion steps are needed, this method may be used for early treatment of patients suffering from life-threatening infectious complications.     

Therapeutic Drug Monitoring of Venlafaxine in an Everyday Clinical Setting: Analysis of Age,Sex and Dose Concentration Relationships

Venlafaxine is a commonly used antidepressant agent. We aimed to provide detailed information on the associations between venlafaxine dose and concentrations of venlafaxine, by patient age and sex. From a therapeutic drug monitoring (TDM) database located at Odense University Hospital, Denmark, we identified all adults for whom the treating physician had requested clinical advice on the TDM result for venlafaxine between 2002 and 2012. We identified 1077 TDM samples of venlafaxine from 334 males and 743 females (median age 45 years), and the median daily dose was 225 mg. Median plasma concentration of venlafaxine and o‐desmethylvenlafaxine (ODV) was 306 nmol/L and 861 nmol/L, respectively. The median dose‐corrected serum level for venlafaxine was 1.49 nmol/L/mg., while the dose‐corrected serum level of men and women were 1.21 nmol/L/mg and 1.60 nmol/L/mg, respectively. The dose‐corrected sum of venlafaxine and ODV was 8.91 nmol/L/mg (IQR 6.56–12.26) versus 5.52 nmol/L/mg (IQR 4.16–7.52) for patients above 64 years and below the age of 65 years, respectively. Dose‐corrected plasma concentrations of venlafaxine and ODV are increased to a clinically significant degree in patients above the age of 64, and initiation of venlafaxine therapy in the elderly should be made cautiously and supported by drug measurements.     

Suffering in silence: a qualitative study of older adults’ experiences of living with long-term musculoskeletal pain at home

Long-term musculoskeletal pain is a major, disabling, and often undertreated health problem among the increasing number of older adults worldwide. However, there is limited knowledge of community-dwelling older adults’ experiences of living with this type of pain. The aim of the study was to deepen the understanding of the phenomenon: how older adults experience living with long-term musculoskeletal pain at home. The study design was an inductive qualitative Reflective Lifeworld Research approach grounded in phenomenological epistemology. Data were obtained from 20 community-dwelling older adults, aged 72–97 years. Data were collected through open-ended interviews and analyzed to understand the meanings of the phenomenon. The essence of the phenomenon entailed suffering in silence and encompassed the following constituents: loneliness and restrictions in daily living; ways to endure and distract from pain; not being taken seriously; fear of the future; and valuing joy and meaning in life. Living with long-term musculoskeletal pain restricts access to the world and leads to a suffering in silence. Finding ways to endure and distract from pain and to focus on issues that give joy and meaning in life is predominant in efforts to balance restraints from pain in life. Suffering is reinforced by loneliness, a sense of not being taken seriously by health care providers and fear of an uncertain future. It is necessary to foster increased attentiveness and sensitivity in meeting the needs of each older adult and provide a care that alleviates suffering and preserves and promotes health and well-being.     

The meanings of place and space in forensic psychiatric care – A qualitative study reflecting patients’ point of view

The outcome of care for patients sentenced to forensic psychiatric care is of importance not only for the patient but also for society, in preventing new crimes. In recent years, a person‐centered perspective is influencing the care, recognizing the design of the physical environment as a therapeutic resource. To capture the complexity of patients’ experience of the physical environment, a qualitative approach is needed. The aim of this study was to investigate the meanings of the patient room as a place and space in forensic psychiatric in‐patient care from the patients’ perspective. An explorative qualitative design was chosen, data were collected by photovoice; a combination of photographs, taken by the patients, followed by interviews. Eleven (N = 11) patients were interviewed. The interviews were analysed by a thematic analysis method. Four themes emerged from the data revealing the meanings of the patient room as a place and space: (i) striving towards normality; (ii) being anchored and protected; (iii) being at‐home and homeness; and (iv) being in communion and meaningfulness. The findings show that the physical environment has a say in patients’ basic needs and a role in maintaining normality. Substandard reveals a lack of respect and dignity towards this patient group. Involving patients in the design process of new facilities can be a way to make progress.