Assertive community treatment in the Netherlands: a randomized controlled trial

OBJECTIVE: Assertive community treatment is rapidly implemented by many European mental health services, but recently the evidence base has been questioned. Positive results of randomized trials in the USA were not replicated in the UK. The question is whether the UK findings are representative for other European countries with modern mental health services. METHOD: Open randomized controlled trial of long-term severely mentally ill patients [Health of the Nation Outcome Scales (HoNOS) total score >or=15], assigned to assertive community treatment (n = 59) or to standard community mental health care (n = 59). Primary outcome: sustained contact; housing stability and admission days. This trial is registered as an International Standard Randomized Clinical Trial, number ISRCTN 11281756. RESULTS: Assertive community treatment was significantly better in sustaining contact with patients, but not in reducing admission days. No differences in housing stability, psychopathology, social functioning or quality of life were found. CONCLUSION: The results are in agreement with UK studies. However, the sustained contact potential of assertive community treatment is important, as too many patients are lost in standard care.     

Truncation of activated leukocyte cell adhesion molecule: a gateway to melanoma metastasis

Progression of human cutaneous primary melanoma is, among others, accompanied by de novo expression of activated leukocyte cell adhesion molecule (ALCAM/CD166) and enhanced activity of proteolytic cascades in the invasive, vertical growth phase (VGP) of lesions. The homophilic cell adhesion function of wild-type ALCAM mediates homotypic clustering of melanoma cells and would, thus, antagonize cell release from the primary tumor, an early prerequisite for metastasis. Stable transfection of a transmembrane, amino-terminally truncated ALCAM (DeltaN-ALCAM) into metastatic cells diminished cell clustering mediated by wild-type ALCAM. We have addressed the biological effects of DeltaN-ALCAM on tumorigenicity and found that the relief of cell clustering constraints promoted motility in vitro and the transition from expansive tumor growth to tissue invasion in reconstructed skin in culture. In a transplant tumor model, the changes were reflected in reduced subcutaneous tumor growth and in accelerated, spontaneous lung metastasis. These data indicate that the intact cell adhesion function of ALCAM may both favor primary tumor growth and represent a rate-limiting step for tissue invasion from VGP melanoma. ALCAM induction could, thus, provide an attractive target for proteolysis as a part of a more complex cellular program that couples growth and migration and facilitates dissemination.     

Feasibility and safety of multiple daily insulin injections in general medicine wards

AimIntravenous insulin improves clinical outcome in patients hospitalized in intensive care units. Whether glucose control with multiple daily subcutaneous insulin injections (MDI) is beneficial in patients hospitalized in general medical wards is unknown. We tested the feasibility, safety and efficacy of glucose control with MDI in diabetic patients hospitalized in a general medicine ward.MethodsEighty-eight adults with diabetes mellitus were studied in an internal medicine department. All patients were treated with subcutaneous pre-meal insulin analogue and Glargin insulin. A conservative and an intensified protocol was tested.ResultsMean daily glucose levels decreased in the conservatively treated patients from 275 ± 71 mg/dl at day 1 to 197.0 ± 60 mg/dl at day 4 of hospitalization p = 0.0001 and in the intensified protocol to 191 ± 38 mg/dl already on day 1 remaining stable throughout the hospitalization. A mean daily glucose < 180 mg% was reached by day 2 in 48% of patients in the intensified and in 32% in the conservative groups. Only one serious event of hypoglycemia was noted in the intensified group.ConclusionIntensive insulin treatment with MDI is feasible, safe and efficacious in general medicine wards.     

The Influence of Testosterone Combined with a PDE5-inhibitor on Cognitive,Affective, and Physiological Sexual Functioning in Women Suffering from Sexual Dysfunction

IntroductionWomen with female sexual dysfunction have a reduced sensitivity to sexual stimuli. Activation of central mechanisms may open a window for phosphodiesterase type 5 inhibitors (PDE5) to be effective; as a consequence, the combination of testosterone and a PDE5 inhibitor will restore sexual function.AimTo demonstrate that the combination of testosterone and vardenafil will increase the sensitivity for sexual stimuli and will improve the desire and arousal components of the sexual response.MethodsIn a double-blind randomly assigned placebo-controlled crossover design, 28 women with desire and/or arousal disorder underwent four different drug treatments on four separate experimental days. A masked version of the emotional Stroop task with sexual and nonsexual words was used to measure sensitivity for sexual content. Neutral and erotic film fragments were used to determine genital–physiological and subjective reactions.Main Outcome MeasuresA masked version of the emotional Stroop task, vaginal pulse amplitude. For subjective measurement, responses were collected continuously with a lever and two self-report measures were used.ResultsIn two subgroups, which were differentiated on the basis of their initial preconscious attentional bias for sexual cues, a different sexual response profile was found. In an initially low-attention group, preconscious attentional bias for sexual cues increased under the testosterone condition. In these women, the combination of testosterone and vardenafil caused an improvement in genital response and subjective indices of sexual functioning. In the group that had initially a high attention for sexual cues, preconscious attentional bias for sexual cues decreased under the condition of testosterone. In these women, the combination of testosterone and vardenafil had no effect on any of the indices of their sexual functioning.ConclusionIn women suffering from low sexual desire—associated with low attention for sexual cues—the combination of testosterone and vardenafil may be a promising new treatment. van der Made F, Bloemers J, Yassem WE, Kleiverda G, Everaerd W, van Ham D, Olivier B, Koppeschaar H, and Tuiten A. The influence of testosterone combined with a PDE5-inhibitor on cognitive, affective, and physiological sexual functioning in women suffering from sexual dysfunction. J Sex Med 2009;6:777–790.     

Pharmacokinetics of a Prototype Formulation of Sublingual Testosterone and a Buspirone Tablet,Versus an Advanced Combination Tablet of Testosterone and Buspirone in Healthy Premenopausal Women

The study aimed to compare the kinetics of two novel combination drug products for Female Sexual Interest/Arousal Disorder (FSIAD). Thirteen women received testosterone via the sublingual route followed 2.5 hours later by a buspirone tablet, versus a single combination tablet swallowed at once. The first clinical prototype consisted of a sublingual solution containing testosterone (0.5 mg) complexed with cyclodextrin and a tablet containing 10 mg buspirone, in a gelatin capsule to ensure blinding during the clinical studies. The innovative fixed-combination tablet consists of an inner-core component of 10 mg buspirone coated with a polymeric time-delay coating and an outer polymeric coating containing testosterone with hydroxypropyl-beta cyclodextrin. We observed an immediate testosterone pulse absorption from both formulations. We also demonstrated that there was adequate absorption of buspirone (>80 % relative to the conventional tablet) and a time delay in release of buspirone of 3.3 hours, close to the 3.0 hours of the reference formulation that showed clinical efficacy in early proof-of-principle studies. The newly developed combination tablet fulfils its design criteria and is a convenient tablet for further clinical studies in FSIAD.     

Necrotizing fasciitis caused by Salmonella enteritidis

A 57-year-old immunocompromized female developed a necrotizing fasciitis with sepsis a few days after abdominal complaints and diarrhoea. Surgery was performed because of progressive worsening of the patient's situation and during surgery the decision was made to perform an amputation. After surgery the patient was brought to the intensive care department for a few days. She recovered from her sepsis within a few days. Cultures showed Salmonella enteritidis.