Mental health services use by melanoma patients receiving adjuvant interferon: association of pre-treatment mental health care with early discontinuation.

BACKGROUND: Although high-dose interferon (hd-ifn) is the sole approved adjuvant systemic treatment for melanoma in many jurisdictions, it is toxic. We sought to assess the population-level effects of hd-ifn toxicity, particularly neuropsychiatric toxicity, hypothesizing that such toxicity would have the greatest effect on mental health services use in advanced resected melanoma. METHODS: This retrospective population-based registry study considered all melanoma patients receiving adjuvant hd-ifn in Ontario during 2008-2012. Toxicity was investigated through health services use compatible with hd-ifn toxicity (for example, mental health physician billings). Using stage data reported from cancer centres about a subset of patients (stages iib-iiic), a propensity-matched analysis compared such service use in patients who did and did not receive hd-ifn. Associations between early hd-ifn discontinuation and health services use were examined. RESULTS: Of 718 melanoma patients who received hd-ifn, 12% were 65 years of age and older, and 83% had few or no comorbidities. One third of the patients experienced 1 or more toxicity-associated health care utilization events within 1 year of starting hd-ifn. Of 420 utilization events, 364 (87%) were mental health-related, with 54% being family practitioner visits, and 39% being psychiatrist visits. In the propensity-matched analysis, patients receiving hd-ifn were more likely than untreated matched controls to use a mental health service (p = 0.01), with 42% of the control group and 51% of the hd-ifn group using a mental health service in the period spanning the 12 months before to the 24 months after diagnosis. In the multivariable analysis, early drug discontinuation was more likely in the presence of pre-existing mental health issues (odds ratio: 2.0; 95% confidence limits: 1.1, 3.4). CONCLUSIONS: Stage iib-iiic melanoma patients carry a substantial burden of mental health services use whether or not receiving hd-ifn, highlighting an important survivorship issue for these patients. High-dose interferon is associated with more use of mental health services, and pre-treatment use of mental health services is associated with treatment discontinuation. That association should be kept in mind when hd-ifn is being considered.

Labeling of monoclonal antibodies with samarium-153 for combined radioimmunoscintigraphy and radioimmunotherapy.

The labeling of a monoclonal antibody K-1-21 with 153Sm has been investigated using the bifunctional chelate cyclic diethylenetriaminepentaacetic acid (DTPA) anhydride. Labeling efficiencies greater than 60% were obtained using high specific activity [153Sm]chloride and a cDTPAa:MAb conjugation ratio of 20:1. The resultant labeled antibody had a s.a. greater than 150 MBq.mg-1 and a % retained immunoreactivity greater than 90%. Imaging and biodistribution studies in a rat model demonstrated that specific uptake of 153Sm-K-1-21 into s.c. implants of the target antigen could be clearly detected in scintigrams at 6 days p.i. The specific uptake (1.90 +/- 0.45% ID/g, 19.95 +/- 2.20 Implant:Blood ratio) compared favorably to 131I- and 111In-labeled K-1-21 (2.52 +/- 0.20 and 3.33 +/- 0.20% ID/g, 7.69 +/- 0.45 and 10.10 +/- 0.60 I:B, respectively). Labeling of MAbs with 153Sm for combined scintigraphy/therapy is feasible at clinically appropriate specific activities using cDTPAa, with the resultant conjugates retaining immunoreactivity and in vivo antigen localization.

Changes in corticomotor representations induced by prolonged peripheral nerve stimulation in humans.

OBJECTIVE: Manipulation of afferent input can induce reorganization within the sensorimotor cortex which may have important functional consequences. Here we investigate whether prolonged peripheral nerve stimulation can induce reorganization within the human motor cortex. METHODS: Using transcranial magnetic stimulation, we mapped the scalp representation of the corticospinal projection to hand muscles in 8 normal subjects before and after 2h of simultaneous repetitive electrical stimulation of the ulnar and radial nerves at the wrist. Control mapping experiments were conducted in 6 subjects. RESULTS: Following nerve stimulation, larger motor-evoked potentials were evoked from more scalp sites. The induced changes were most apparent in first dorsal interosseous, but were also seen in other hand muscles. The increases in area of the representational maps were accompanied by changes in the location of the optimal site for evoking responses in first dorsal interosseous, and changes in the centres of gravity of the maps. CONCLUSIONS: Prolonged afferent stimulation induces an increase in excitability of the corticospinal projection. This is accompanied by a significant shift in the centre of gravity of the stimulated muscles which we propose is evidence of a non-uniform expansion in their cortical representation.

Genome-Wide Analyses of Working-Memory Ability: A Review.

Working memory, a theoretical construct from the field of cognitive psychology, is crucial to everyday life. It refers to the ability to temporarily store and manipulate task-relevant information. The identification of genes for working memory might shed light on the molecular mechanisms of this important cognitive ability and-given the genetic overlap between, for example, schizophrenia risk and working-memory ability-might also reveal important candidate genes for psychiatric illness. A number of genome-wide searches for genes that influence working memory have been conducted in recent years. Interestingly, the results of those searches converge on the mediating role of neuronal excitability in working-memory performance, such that the role of each gene highlighted by genome-wide methods plays a part in ion channel formation and/or dopaminergic signaling in the brain, with either direct or indirect influence on dopamine levels in the prefrontal cortex. This result dovetails with animal models of working memory that highlight the role of dynamic network connectivity, as mediated by dopaminergic signaling, in the dorsolateral prefrontal cortex. Future work, which aims to characterize functional variants influencing working-memory ability, might choose to focus on those genes highlighted in the present review and also those networks in which the genes fall. Confirming gene associations and highlighting functional characterization of those associations might have implications for the understanding of normal variation in working-memory ability and also for the development of drugs for mental illness.

Autosomal dominant craniometaphyseal dysplasia with atypical features.

Craniometaphyseal dysplasia (CMD) is a rare genetic disorder of bone modelling characterised by hyperostosis and sclerosis of the craniofacial bones, and abnormal modelling of the metaphyses. Clinically, autosomal dominant (AD) CMD is characterised by facial distortion and cranial-nerve compression. The goals of surgical treatment for AD CMD are cosmetic recontouring of the sclerotic craniofacial bones, correction of nasal obstruction and correction or prevention of neurological manifestations. We describe the successful correction of AD CMD craniofacial manifestations in an individual with atypical findings, and outline an approach for correcting the craniofacial deformities associated with this rare disorder.

Self-reported alcohol use among women of childbearing age and their knowledge of alcohol warning labels and signs.

OBJECTIVE: To examine the prevalence of self-reported alcohol use among women of childbearing age and their ability to recall information about pregnancy risk contained in warning labels on alcoholic beverage containers and warning signs posted in places where liquor is sold. DESIGN: A telephone survey was conducted with adults using a dual-frame procedure. Specifically, approximately one third of the total sample were contacted by random-digit dialing, and the remainder were obtained from listed residential telephone numbers. Also, poststratification weighting was done using estimates of age, ethnic, and sex groups to approximate the 1990 adult population of Illinois. SETTING: A total of 4987 adults with known residence (excluding those without residences and/or telephones and those living in institutions or group quarters) in Illinois participated in a survey during the spring and summer of 1990. PARTICIPANTS: A total of 1515 women of childbearing age (18 through 45 years old) participated in the survey. A random subsample of approximately half were asked questions regarding warning labels and signs; the other half were omitted from the investigation, which yielded the final sample of 748. MAIN OUTCOME MEASURES: The two main outcome measures were self-reported alcohol use and ability to recall information about pregnancy risk contained in warning labels and signs. RESULTS: Pregnant women were significantly less likely than nonpregnant women to report using alcohol in the past 30 days. Approximately one fourth of all women were able to recall information about pregnancy risk contained in warning labels and signs. CONCLUSIONS: Alcohol warning labels and signs seem to be reaching a minority of women; this was uniform across several sociodemographic subpopulations, with few exceptions.

The effect of circulating antigen on radioimmunodetection and monoclonal antibody localisation: studies in a normal rat model.

The effect of circulating antigen (human kappa light chains (LC] on radioimmunoscintigraphy was examined in a normal rat model. Rats were implanted subcutaneously with kappa (test) and lambda (control) LC coupled to sepharose beads (500 micrograms LC/ml swollen gel). When 131I-labelled monoclonal antibody, K-1-21 was injected, clear images of specific antibody localisation to the kappa implant were seen 6 days later. The kappa implant: blood ratio (K:B) was 7.69 +/- 0.45, which represented an implant uptake of 2.52 +/- 0.20 percent injected dose per gram (%ID/g). When 131I-K-1-21 was preincubated with 125I-kappa LC at ratios of up to 1:10 antibody: antigen, (w/w) before injection; or if antigen was given daily by bolus injection or continuously infused via an osmotic pump, very clear specific images of antibody localisation to the kappa implant were still obtained. There was, however, a decline in the absolute uptake of label by the kappa implant. The greatest change was observed following continuous antigen infusion, when kappa implant uptake fell to 1.26 +/- 0.1 %ID/g. Nevertheless, the K:B ratio was still maintained at 6.8 +/- 0.2, due to increased clearance of antibody from the blood. Thus, in this case, where antigen and antibody might be expected to form small, soluble immune complexes, there was no major deleterious effect on radioimmunoscintigraphy.