Ramucirumab plus paclitaxel or FOLFIRI in platinum-refractory advanced or metastatic gastric or gastroesophageal junction adenocarcinoma-experience at two centres.

BACKGROUND: Ramucirumab is a VEGFR-2 antibody that has proven to prolong overall survival (OS) in patients with pretreated metastatic gastric/gastrooesophageal junction (GEJ) adenocarcinoma. We present data from patients treated with ramucirumab and paclitaxel or FOLFIRI after failure of at least one platinum- and 5-FU-containing chemotherapy (CHT) regimen. METHODS: In this retrospective two-center study, 56 patients with metastatic gastric cancer (47%) or adenocarcinoma of the GEJ (53%) were treated with paclitaxel and ramucirumab (n=38) as second-line (75%) or beyond second-line (25%) therapy. FOLFIRI-ramucirumab (FOLFIRI-R) (n=16) was given to patients with a short interval between taxane-based perioperative CHT and occurrence of metastatic disease or to those ineligible for paclitaxel. RESULTS: The median progression-free survival (PFS) and OS for patients treated with paclitaxel-ramucirumab (pacl-R) were 2.9 (95% CI: 2.3-3.6) and 4.4 (4.1-4.7) months, respectively, and those for patients treated with FOLFIRI-R were 5.9 (95% CI: 0.35-11.4) and 8.3 (6.6-10) months, respectively (P=0.05). We observed a trend towards prolonged PFS after perioperative taxane-based FLOT CHT (n=12) with FOLFIRI-R compared with pacl-R. Adverse events were manageable, with neutropenia and polyneuropathy (PNP) being the most common events. More than two treatment lines were given to 48.2% of patients. CONCLUSIONS: The use of ramucirumab in combination with FOLFIRI showed favourable PFS and OS in patients with prior treatments with platinum and/or taxane-based agents and allows further treatment lines after progression. In patients with taxane pretreatment or persistent high-grade PNP, the combination of FOLFIRI-R might be a promising combination.

Attention deficit hyperactivity disorder (ADHD): an affect-processing and thought disorder?

In the literature on child and adolescent psychoanalysis attention deficit hyperactivity disorder (ADHD) is described as complex syndrome with wide-ranging psychodynamic features. Broadly speaking, the disorder is divided into three categories: 1. a disorder in early object relations leading to the development of a maniform defence organization in which object-loss anxieties and depressed affects are not worked through via symbolization but are organized in a body-near manner; 2. a triangulation disorder in which the cathexis of the paternal position is not stable; structures providing little support alternate with excessive arousal, affect regulation is restricted; 3. current emotional stress or a traumatic experience. I suggest taking a fresh look at ADHD from a psychoanalytic vantage point. With respect to the phenomenology of the disorder, the conflict-dynamic approach should be supplemented by a perspective regarding deficits in α-function as constitutive for ADHD. These deficits cause affect-processing and thought disorders compensated for (though not fully) by the symptomatology. At a secondary level, a vicious circle develops through the mutual reinforcement of defective processing of sense data and affects into potential thought content, on the one hand, and secondary, largely narcissistic defence processes on the other. These considerations have major relevance for the improved understanding of ADHD and for psychoanalytic technique.

What can actigraphy add to the concept of labschool design in clinical trials?

Pharmacological intervention with methylphenidate (MPH) is very common and helpful in the treatment of attention-deficit/ hyperactivity disorder (ADHD). It ameliorates inattention, impulsivity and hyperactivity and improves psychosocial functioning. The core symptoms of ADHD are problematic mainly in demanding structured situations such as in the classroom. It was argued that MPH does not only lead to a decrease of hyperactivity in these situations but may also result in a general dampening of motor activity during non-structured leisure time. Unfortunately, only few clinical trials have investigated this practically important issue and thus it is still a matter of debate. It follows that many parents hesitate to accept psychotropic drugs for their children. To elucidate this problem in the current study, not only overall behavioral ratings (half-day blocks) but also day-long actigraphy was applied during an analogue classroom setting, where structured and non-structured situations alternated over time. Fourty-nine children with ADHD were assessed for treatment effects of once-daily extended-release and twice daily immediate-release methylphenidate (MPH) as well as placebo. Both MPH regimes yielded improved behavioral ratings during morning and afternoon, while actigraphy showed reduced motor activity in structured situations, but not during leisure time. Furthermore, the movement information obtained with actigraphy during structured situations could be differentiated from the one gained with overall behavioral ratings. Thus, while behavioral ratings provide a valid estimate of the overall symptomatology, additional information gathered with actigraphy may help to differentiate the impact of medication on hyperactive movement in different situations during the day. This may reflect a more valid picture of a child's real life and improve the quality of clinical trials. Thus, both methods may be regarded as complementary for the assessment of drug effects in children with ADHD and should be a standard of further laboratory school protocols in clinical trials.

Basic symptoms in the general population and in psychotic and non-psychotic psychiatric adolescents.

OBJECTIVE: Cognitive-perceptive 'basic symptoms' are used complementary to ultra-high-risk criteria in order to predict onset of psychosis in the pre-psychotic phase. The aim was to investigate the prevalence of a broad selection of 'basic symptoms' in a representative general adolescent population sample (GPS; N=96) and to compare it with adolescents first admitted for early onset psychosis (EOP; N=87) or non-psychotic psychiatric disorders (NP; N=137). METHODS: Subjects were assessed with the Bonn Scale for the Assessment of Basic Symptoms (BSABS). Prevalence of at least one 'basic symptom' and mean numbers were compared across the three groups. Logistic regression was used to predict group membership by BSABS subscales; risk ratios were calculated to identify 'basic symptoms' which best discriminated between groups. RESULTS: The prevalence of at least any one 'basic symptom' was 30.2% in GPS compared to 81% in NP and 96.5% in EOP. Correct classification of EOP when compared to GPS was high (94.0%) and lower when compared to NP (78.6%). Cognitive symptoms discriminated best between EOP and NP. CONCLUSION: Alike other prodromal- and psychotic-like experiences, 'basic symptoms' are prevalent in the general adolescent population, yet at a lower rate compared to EOP and NP. The usage of 'at least one basic symptom' as a screening criterion for youth at risk of developing a psychotic disorder is not recommended in the general population or in unselected psychiatrically ill adolescents. However, particularly cognitive 'basic symptoms' may be a valuable criteria to be included in future 'at risk' studies in adolescents.

Stability of soluble adhesion molecules, selectins, and C-reactive protein at various temperatures: implications for epidemiological and large-scale clinical studies.

BACKGROUND: We assessed the impact of sample storage conditions on soluble vascular cell adhesion molecules (sVCAM), soluble intracellular adhesion molecules (sICAM-1), soluble (s)E-selectin, C-reactive protein (CRP), and sP-selectin. METHODS: Markers were measured by ELISA in venous blood from 10 healthy volunteers on aliquots stored as plasma or whole blood at 4, 21, or 30 degrees C for 1-5 days and after 1-5 freeze-thaw cycles. We compared results on these samples to results for samples processed immediately and stored at -80 degrees C. Statistical models assessed time-related effects and effects of postprocessing conditions. RESULTS: Using an upper limit of 10% variation from baseline with P >0.05, we found that stability duration in plasma was 5 days for sVCAM-1 and sICAM-1 and at least 2 days for sE-selectin at 4, 21, and 30 degrees C and 5 days for CRP at 4 and 21 degrees C and 1 day at 30 degrees C. Stability duration in whole blood was 5 days for sVCAM-1 and sICAM-1 and at least 2 days for sE-selectin at 4, 21, and 30 degrees C and 5 days for CRP at 4 and 21 degrees C and 2 days at 30 degrees C. sP-selectin was not stable in plasma or whole blood. sICAM-1, sVCAM-1, CRP, and sE-selectin were stable after 5 freeze-thaw cycles. CONCLUSIONS: sVCAM-1, sICAM-1, and CRP are stable in plasma or whole blood at 4 and 21 degrees C for at least 3 days and sE-selectin for 2 days. sP-selectin is not stable and therefore requires immediate assay.

Comparative efficacy of once-a-day extended-release methylphenidate, two-times-daily immediate-release methylphenidate, and placebo in a laboratory school setting.

BACKGROUND: Given the dosing limitations of methylphenidate short-acting preparations in treating ADHD, galenics with longer release of the substance were developed mainly to avoid drug intake during school hours. OBJECTIVES: This investigation was conducted to assess the efficacy and the duration of action of a new extended-release formulation of methylphenidate (Medikinet retard) as a once-daily treatment for children with attention-deficit hyperactivity disorder (ADHD). METHOD: This was a randomized, double-blind, crossover multicentre study with three treatment conditions: once-daily extended-release methylphenidate, twice-daily immediate-release methylphenidate and placebo given to 79 children (8-14 years old) with ADHD. Daily assessments in an analogue classroom setting included blind ratings of attention and deportment and a performance measure (math test) obtained 5 times over an 8-hour period. Secondary measures included an ADHD rating scale, based on DSMIV/ ICD-10 separately rated for the morning and the afternoon. RESULTS: Both active treatment conditions displayed significant time course effects and were superior to placebo in improving all efficacy measures. Once a day extended-release methylphenidate was not different from the same dose of twice daily immediate-release methylphenidate. CONCLUSIONS: These data provide support for the benefit of this novel, once-daily methylphenidate preparation in the treatment of ADHD. The longer duration of action of Medikinet Retard has the potential to simplify psychostimulant treatment, thus reducing dose diversion and eliminating the need for in-school administration.

Creatine monohydrate supplementation on body weight and percent body fat.

Seventeen active males (age 22.9 +/- 4.9 year) participated in a study to examine the effects of creatine monohydrate supplementation on total body weight (TBW), percent body fat, body water content, and caloric intake. The TBW was measured in kilograms, percent body fat by hydrostatic weighing, body water content via bioelectrical impedance, and caloric intake by daily food log. Subjects were paired and assigned to a creatine or placebo group with a double-blind research design. Supplementation was given for 4 weeks (30 g a day for the initial 2 weeks and 15 g a day for the final 2 weeks). Subjects reported 2 days a week for supervised strength training of the lower extremity. Significant increases before and after the study were found in TBW (90.42 +/- 14.74 to 92.12 +/- 15.19 kg) and body water content (53.77 +/- 1.75 to 57.15 +/- 2.01 L) for the creatine group (p = 0.05). No significant changes were found in percent body fat or daily caloric intake in the creatine group. No significant changes were noted for the placebo group. These findings support previous research that creatine supplementation increases TBW. Mean percent body fat and caloric intake was not affected by creatine supplementation. Therefore weight gain in lieu of creatine supplementation may in part be due to water retention.

[Maturation, separation and social integration. Some developmental psychology aspects of childhood sports]. / Reifung, Ablösung und soziale Integration. Einige entwicklungspsychologische Aspekte des Kindersports.

The unfolding of motorical and social experiences with one's own body is a core element of ego-development and identity in childhood and adolescence. This paper describes essential elements of this process in different age stages. Especially in adolescence, the maturational and separational development are determined by the complex interaction between integration into the peer group and separation from adults, between search for appreciation and oppositional tendencies. On the one hand sport plays an important role for many adolescents during this process. On the other hand adolescent conflicts have a great impact on practising sport. These considerations are illustrated by two case vignettes.