Shortened duration of untreated first episode of psychosis: changes in patient characteristics at treatment.

OBJECTIVE: This study examined whether duration of untreated psychosis can be shortened in patients with first episodes of DSM-IV schizophrenia spectrum disorders and whether shorted duration alters patient appearance at treatment. METHOD: Two study groups were ascertained in the same Norwegian health care sector: one from 1993-1994 with usual detection methods and one from 1997-1998 with early detection strategies that included education about psychosis. RESULTS: Patients with early detection had a shorter median duration of untreated psychosis by 21.5 weeks than patients with usual detection. The number with psychosis was greater in the early detection group; the number with schizophrenia was less. Early detection patients had more substance abuse and were younger, better adjusted premorbidly, and less ill. CONCLUSIONS: Early detection can shorten duration of untreated psychosis and help more patients when they are less severely ill. Given the devastation of psychosis, this is a significant treatment advance.     

Risk factors for more severe regional musculoskeletal symptoms: A two‐year prospective study of a general working population

Objective

To quantify the relative contribution of work‐related physical and psychosocial factors, individual factors, and health‐related factors to the development of more severe musculoskeletal pain in the neck and upper limbs and the back and lower limbs.

Methods

In this cohort study of 5,604 workers from industrial and service companies, we collected information on work‐related physical and psychosocial exposures and on individual and health‐related factors. Questionnaires were completed at baseline by 4,006 participants (71.5%) and after 24 months by 3,276 (82%). At followup, participants with no or minor pain were included in Cox regression analyses to determine which factors predicted more severe regional pain.

Results

Of the 4,006 baseline respondents, only 7.7% were free of regional pain. A total of 1,513 participants were free of severe pain at baseline and completed the 24‐month followup. Highly repetitive work predicted arm pain, heavy lifting and prolonged standing predicted low back pain, and heavy pushing or pulling predicted lower limb pain. Low job satisfaction predicted neck/shoulder pain and lower limb pain, whereas other psychosocial work place factors were only of marginal importance. High levels of fear avoidance were associated with arm pain and lower limb pain. A high body mass index was highly associated with lower limb pain.

Conclusion

Very few workers are totally free of pain in musculoskeletal regions, and we question the concept of incidence of musculoskeletal pain. The transition from no or minor pain to more severe pain was influenced by physical and psychosocial work place factors together with individual and health‐related factors.

     

The phagocytic activity of monocytes and polymorphonuclear leucocytes against viral antigens as measured by chemiluminescence in patients with multiple sclerosis

Twenty-two patients with Multiple Sclerosis in different stages of the disease were investigated in a chemiluminescence-assay and compared with a similar number of healthy individuals. The reactivity of peripheral blood monocytes to different viral antigens was followed by measurement of both the immediate oxidative activity and the development of activity through a 85-minutes period. The patients with a progressive course of the disease showed a high activity and reached maximum activity in a shorter time than the other groups, indicating an activation of the monocytes in these patients.--The patients in steady state showed a rather low activity, compared with both the other patient groups and the control group. A possible significance of these findings is discussed. The activity of the polymorphonuclear cells did not show differences in activity between the groups.     

Insulin degludec's ultra‐long pharmacokinetic properties observed in adults are retained in children and adolescents with type 1 diabetes

Insulin degludec (IDeg) is a basal insulin with an ultra‐long pharmacokinetic profile in adults that at steady‐state produces remarkably flat and stable insulin levels; however, no studies have yet reported on the pharmacokinetic properties of IDeg in subjects younger than 18 years of age. This was a single‐centre, randomised, single‐dose, double‐blind, two‐period crossover trial conducted in children (6–11 years), adolescents (12–17 years), and adults (18–65 years) with type 1 diabetes. Subjects received a single subcutaneous dose of 0.4 U/kg IDeg or insulin glargine (IGlar), respectively, on two separate dosing visits, with pharmacokinetic blood sampling up to 72‐h postdose. A total of 37 subjects (12 children, 13 adolescents, and 12 adults) completed the trial. Total exposure of IDeg after a single dose (AUC_{IDeg,0‐∞,SD}) was higher in children compared to adults [estimated ratio children/adults 1.48 (95% confidence interval, CI: 0.98; 2.24)] and in adolescents compared to adults [estimated ratio adolescents/adults 1.33 (95% CI: 1.08; 1.64)]; however, the difference was only statistically significant for the latter comparison. No statistically significant difference in maximum concentration of IDeg (C_max,IDeg,SD) was observed. Estimated ratios for C_max,IDeg,SD were (children/adults) 1.20 (95% CI: 0.90; 1.60) and (adolescents/adults) 1.23 (95% CI: 1.00; 1.51). Simulated mean steady state pharmacokinetic profiles supported a flat and stable IDeg exposure across a 24‐h dosing interval. IDeg was detectable in serum for at least 72 h (end of blood sampling period) in all subjects following single dose. In conclusion, the ultra‐long pharmacokinetic properties of IDeg observed in adults are preserved in children and adolescents with type 1 diabetes.     

L-selectin mediates neutrophil rolling in inflamed venules through sialyl LewisX-dependent and -independent recognition pathways

The glycoprotein (GP) L-selectin initiates adhesive interactions between leukocytes and endothelial cells (EC). It functions as a lymphocyte-lectin homing receptor recognizing carbohydrate determinants of the peripheral lymph node addressing on high endothelial venules. It also mediates neutrophil rolling, the earliest interaction of neutrophils with acutely inflamed venules. Neutrophil L-selectin presents sialyl-LewisX (sLe(X)) as a ligand to P- and E-selectin in vitro, and we have proposed that this is a major mechanism of L- selectin-mediated rolling in vivo. In contrast, the contribution of neutrophil L-selectin as a receptor protein recognizing one (or more) ligand(s) on inflamed EC is unclear. To address this question, an sLe(X)-negative murine pre-B cell line, L1-2, that can neither bind vascular selectins nor roll in inflamed rabbit venules, was transfected with human L-selectin cDNA. L-selectin expression in stable transfectants was sufficient to confer significant rolling in vivo. Rolling was unaffected by neuraminidase treatment but completely blocked by anti-L-selectin monoclonal antibody (MoAb) DREG-56. Thus, L- selectin can initiate leukocyte interactions with EC determinants potentially through recognition of endothelial carbohydrates. In contrast, when human neutrophils were tested, rolling was reduced, but not abolished, by MoAb DREG-56. Likewise, treatment with neuraminidase or anti-sLe(X) MoAbs decreased, but did not abrogate, neutrophil rolling, consistent with residual EC recognition via L-selectin. Combination of MoAb DREG-56 and neuraminidase resulted in almost complete loss of rolling, as did removal of glycosylated L-selectin by chymotrypsin. Together with the demonstrable rolling of L-selectin transfectants, our results support the concept of a bidirectional interaction between L-selectin bearing sLe(X) on neutrophils and activated EC in vivo. These findings also suggest that L-selectin may mediate rolling of lymphocytes that lack carbohydrate ligands for E- or P-selectin, although probably less efficiently than through bidirectional recognition.     

Early identification of non‐remission in first‐episode psychosis in a two‐year outcome study

Simonsen E, Friis S, Opjordsmoen S, Mortensen EL, Haahr U, Melle I, Joa I, Johannessen JO, Larsen TK, Røssberg JI, Rund BR, Vaglum P, McGlashan TH. Early identification of non‐remission in first‐episode psychosis in a two‐year outcome study. Objective: To identify predictors of non‐remission in first‐episode, non‐affective psychosis. Method: During 4 years, we recruited 301 patients consecutively. Information about first remission at 3 months was available for 299 and at 2 years for 293 cases. Symptomatic and social outcomes were assessed at 3 months, 1 and 2 years. Results: One hundred and twenty‐nine patients (43%) remained psychotic at 3 months and 48 patients (16.4%) remained psychotic over 2 years. When we compared premorbid and baseline data for the three groups, the non‐remitted (n = 48), remitted for <6 months (n = 38) and for more than 6 months (n = 207), duration of untreated psychosis (DUP) was the only variable that significantly differentiated the groups (median DUP: 25.5, 14.4 and 6.0 weeks, respectively). Three months univariate predictors of non‐remission were being single, longer DUP, core schizophrenia, and less excitative and more negative symptoms at baseline. Two‐year predictors were younger age, being single and male, deteriorating premorbid social functioning, longer DUP and core schizophrenia. In multivariate analyses DUP, negative and excitative symptoms predicted non‐remission at 3 months, but only DUP predicted at 2 years. Conclusion: Long DUP predicted both 3 month and 2‐year non‐remission rates in first‐episode psychosis.     

GNAS1 T393C polymorphism and disease progression in patients with malignant melanoma

Background: Once metastasized, despite a variety of therapeutic options, the prognosis of patients with malignant melanoma (MM) is still poor. Therefore, the search for reliable markers to identify patients with high risk of disease progression is of high clinical importance. We have recently shown that TT genotypes of the single-nucleotide polymorphism (SNP) T393C in the gene GNAS1 are significantly associated with better outcome in a variety of carcinomas. - Patients: In the present study we assessed whether the T393C SNP is also related to the clinical course in MM. 328 patients with MM were retrospectively genotyped and genotypes were correlated with clinical outcome. - Results: While the allele frequency in the MM group (fC 0.52) did not significantly differ from that of healthy blood donors, the T393C SNP was associated with tumor progression of MM. Carriers of the C-allele showed a significantly more severe tumor progression as estimated from the time period to develop metastasis (HR 2.2, 95% CI 1.1-3.2, p = 0.017). Proportions of 5-year metastasis-free intervals were 87.1% for TT genotypes and 66.0% for C-allele carriers. Moreover, multivariable Cox regression analysis including tumor stage and melanoma subtype proved the T393C polymorphism to be an independent factor for metastasis (p = 0.012). - Conclusions: In summary, the GNAS1 T393C SNP represents a genetic host factor for predicting tumor progression also in patients with MM; genotyping of this SNP may contribute to better define patients who could benefit from an early individualized therapy.     

Clinical epidemiologic first-episode psychosis: 1-year outcome and predictors

OBJECTIVE: To describe 1-year outcome in a large clinical epidemiologic sample of first-episode psychosis and its predictors. METHOD: A total of 301 patients with first-episode psychosis from four healthcare sectors in Norway and Denmark receiving common assessments and standardized treatment were evaluated at baseline, at 3 months, and at 1 year. RESULTS: Substantial clinical and social improvements occurred within the first 3 months. At 1-year 66% were in remission, 11% in relapse, and 23% continuously psychotic. Female gender and better premorbid functioning were predictive of less severe negative symptoms. Shorter DUP was predictive for shorter time to remission, stable remission, less severe positive symptoms, and better social functioning. Female gender, better premorbid social functioning and more education also contributed to a better social functioning. CONCLUSION: This first-episode sample, being well treated, may be typical of the early course of schizophrenia in contemporary centers.