15 research outputs found
Cohort profile : demographic and clinical characteristics of the MILESTONE longitudinal cohort of young people approaching the upper age limit of their child mental health care service in Europe
Purpose: The presence of distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) impacts continuity of mental health treatment for young people. However, we do not know the extent of discontinuity of care in Europe nor the effects of discontinuity on the mental health of young people. Current research is limited, as the majority of existing studies are retrospective, based on small samples or used non-standardised information from medical records. The MILESTONE prospective cohort study aims to examine associations between service use, mental health and other outcomes over 24 months, using information from self, parent and clinician reports. Participants: Seven hundred sixty-three young people from 39 CAMHS in 8 European countries, their parents and CAMHS clinicians who completed interviews and online questionnaires and were followed up for 2 years after reaching the upper age limit of the CAMHS they receive treatment at. Findings to date: This cohort profile describes the baseline characteristics of the MILESTONE cohort. The mental health of young people reaching the upper age limit of their CAMHS varied greatly in type and severity: 32.8% of young people reported clinical levels of self-reported problems and 18.6% were rated to be âmarkedly illâ, âseverely illâ or âamong the most extremely illâ by their clinician. Fifty-seven per cent of young people reported psychotropic medication use in the previous half year. Future plans: Analysis of longitudinal data from the MILESTONE cohort will be used to assess relationships between the demographic and clinical characteristics of young people reaching the upper age limit of their CAMHS and the type of care the young person uses over the next 2 years, such as whether the young person transitions to AMHS. At 2 years follow-up, the mental health outcomes of young people following different care pathways will be compared. Trial registration number: NCT03013595
Demographic, clinical, and service-use characteristics related to the clinicianâs recommendation to transition from child to adult mental health services
Purpose:
The service configuration with distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) may be a barrier to continuity of care. Because of a lack of transition policy, CAMHS clinicians have to decide whether and when a young person should transition to AMHS. This study describes which characteristics are associated with the cliniciansâ advice to continue treatment at AMHS.
Methods:
Demographic, family, clinical, treatment, and service-use characteristics of the MILESTONE cohort of 763 young people from 39 CAMHS in Europe were assessed using multi-informant and standardized assessment tools. Logistic mixed models were fitted to assess the relationship between these characteristics and cliniciansâ transition recommendations.
Results:
Young people with higher clinician-rated severity of psychopathology scores, with self- and parent-reported need for ongoing treatment, with lower everyday functional skills and without self-reported psychotic experiences were more likely to be recommended to continue treatment. Among those who had been recommended to continue treatment, young people who used psychotropic medication, who had been in CAMHS for more than a year, and for whom appropriate AMHS were available were more likely to be recommended to continue treatment at AMHS. Young people whose parents indicated a need for ongoing treatment were more likely to be recommended to stay in CAMHS.
Conclusion:
Although the decision regarding continuity of treatment was mostly determined by a small set of clinical characteristics, the recommendation to continue treatment at AMHS was mostly affected by service-use related characteristics, such as the availability of appropriate services
Synthesis and Biological Evaluation (in Vitro and in Vivo) of Cyclic ArginineâGlycineâAspartate (RGD) PeptidomimeticâPaclitaxel Conjugates Targeting Integrin α<sub>V</sub>ÎČ<sub>3</sub>
A small
library of integrin ligandâpaclitaxel conjugates <b>10</b>â<b>13</b> was synthesized with the aim of
using the tumor-homing <i>cyclo</i>[DKP-RGD] peptidomimetics
for site-directed delivery of the cytotoxic drug. All the paclitaxelâRGD
constructs <b>10</b>â<b>13</b> inhibited biotinylated
vitronectin binding to the purified α<sub>V</sub>ÎČ<sub>3</sub> integrin receptor at low nanomolar concentration and showed
in vitro cytotoxic activity against a panel of human tumor cell lines
similar to that of paclitaxel. Among the cell lines, the cisplatin-resistant
IGROV-1/Pt1 cells expressed high levels of integrin α<sub>V</sub>ÎČ<sub>3</sub>, making them attractive to be tested in in vivo
models. <i>cyclo</i>[DKP-<i>f</i>3-RGD]-PTX <b>11</b> displayed sufficient stability in physiological solution
and in both human and murine plasma to be a good candidate for in
vivo testing. In tumor-targeting experiments against the IGROV-1/Pt1
human ovarian carcinoma xenotransplanted in nude mice, compound <b>11</b> exhibited a superior activity compared with paclitaxel,
despite the lower (about half) molar dosage used
Design, Synthesis, and Biological Evaluation of Novel cRGDâPaclitaxel Conjugates for Integrin-Assisted Drug Delivery
The efficacy of taxane-based antitumor therapy is limited
by several
drawbacks which result in a poor therapeutic index. Thus, the development
of approaches that favor selective delivery of taxane drugs (e.g.,
paclitaxel, PTX) to the disease area represents a truly challenging
goal. On the basis of the strategic role of integrins in tumor cell
survival and tumor progression, as well as on integrin expression
in tumors, novel molecular conjugates were prepared where PTX is covalently
attached to either cyclic AbaRGD (Azabicycloalkane-RGD) or AmproRGD
(Aminoproline-RGD) integrin-recognizing matrices via structurally
diverse connections. Receptor-binding assays indicated satisfactory-to-excellent
α<sub>V</sub>ÎČ<sub>3</sub> binding capabilities for most
conjugates, while <i>in vitro</i> growth inhibition assays
on a panel of human tumor cell lines revealed outstanding cell sensitivity
values. Among the nine conjugate ensemble, derivative <b>21</b>, bearing a robust triazole ring connected to ethylene glycol units
by an amide function and showing excellent cell sensitivity properties,
was selected for <i>in vivo</i> studies in an ovarian carcinoma
model xenografted in immunodeficient mice. Remarkable antitumor activity
was attained, superior to that of PTX itself, which was associated
with a marked induction of aberrant mitoses, consistent with the mechanism
of action of spindle poisons. Overall, the novel cRGD-PTX conjugates
disclosed here represent promising candidates for further advancement
in the domain of targeted antitumor therapy