Psychotic experiences are associated with health anxiety and functional somatic symptoms in preadolescence

Background: Health anxiety (HA) is an increasing public health problem related to increased health service costs, and associated with functional somatic symptoms (FSS) and considerable personal suffering. Abnormal bodily experiences which may resemble HA and FSS are common in psychotic disorders, but a potential link between HA and psychosis vulnerability in childhood is largely unexplored. The current study estimates the association between subclinical psychotic experiences (PE) and HA and FSS in a general population cohort of preadolescents. Methods: The study population consisted of 1,572 11–12-year-old children from the Copenhagen Child Cohort 2000. PE were comprehensibly assessed as either present or not present using the Kiddie Schedule of Affective Disorders and Schizophrenia psychosis section. HA and FSS were assessed by self-report on validated questionnaires. Additional variables on general psychopathology, puberty, and chronic somatic illness were also obtained. Results: Psychotic experiences were associated with the top 10% high scores of HA (Odds Ratio (OR) 3.2; 95% CI: 2.1–4.8) and FSS (OR 4.6; 95% CI: 3.1–6.9) in univariate analyses. After mutual adjustment, the association was reduced to (HA: OR 2.3; 95% CI: 1.5–3.5; FSS: OR 3.7; 95% CI: 2.4–4.7), suggesting interdependence. Further adjustment for potential confounders and general psychopathology only reduced the associations slightly: HA OR 2.2 (95% CI: 1.4–3.4); FSS OR 3.3 (95% CI: 2.1–5.2). Secondary analyses of subdimensions of HA showed that PE were associated with fears (OR 3.0; 95% CI: 2.0–4.6) and daily impact of HA symptoms (OR 5.0; 95% CI: 3.4–7.5), but not help seeking (OR 1.2; 95% CI: 0.7–2.1). Conclusions: This is the first study to investigate the associations between PE and HA and FSS, respectively. PE were significantly associated with HA and FSS over and above general psychopathology in preadolescence. Individuals with PE expressed high levels of health-related fears and daily impact, but no corresponding help-seeking behavior

The predictive validity of the Strengths and Difficulties Questionnaire in preschool age to identify mental disorders in preadolescence

The Strengths and Difficulties Questionnaire (SDQ) is a brief, widely used instrument to screen for mental health problems in children and adolescents. The SDQ predictive algorithms developed for the SDQ, synthesize information from multiple informants regarding psychiatric symptoms and their impact on daily life. This study aimed to explore the validity of the SDQ predictive algorithms used in preschool age to predict mental disorders in preadolescence. The study population comprises 1176 children from the Copenhagen Child Cohort 2000 (CCC2000) assessed at age 5-7 years by the SDQ and reassessed at 11-12 years with the Development and Well Being Assessment (DAWBA) for evaluation of ICD-10 mental disorders. Odds Ratios (ORs), sensitivities, specificities, positive predictive values (PPVs) and negative predictive values (NPVs) were calculated for the SDQ predictive algorithms regarding ICD-10 diagnoses of hyperkinetic-inattentive-, behavioural- and emotional disorders. Significant ORs ranging from 2.3-36.5 were found for the SDQ predictive algorithms in relation to the corresponding diagnoses. The highest ORs were found for hyperkinetic and inattentive disorders, and the lowest for emotional disorders. Sensitivities ranging from 4.5-47.4, specificities ranging from 83.0-99.5, PPVs ranging from 5.0-45.5 and NPVs ranging from 90.6-99.0 were found for the SDQ predictive algorithms in relation to the diagnoses. The results support that the SDQ predictive algorithms are useful for screening at preschool-age to identify children at an increased risk of mental disorders in preadolescence. However, early screening with the SDQ predictive algorithms cannot stand alone, and repeated assessments of children are needed to identify, especially internalizing, mental health problems

Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to crizotinib: a case report

BACKGROUND: Anaplastic lymphoma kinase-positive non-small cell lung carcinoma patients are generally highly responsive to the dual anaplastic lymphoma kinase and MET tyrosine kinase inhibitor crizotinib. However, they eventually acquire resistance to this drug, preventing the anaplastic lymphoma kinase inhibitors from having a prolonged beneficial effect. The molecular mechanisms responsible for crizotinib resistance are beginning to emerge, e.g., in some anaplastic lymphoma kinase-positive non-small cell lung carcinomas the development of secondary mutations in this gene has been described. However, the events behind crizotinib-resistance currently remain largely uncharacterized. Thus, we report on an anaplastic lymphoma kinase-positive non-small cell lung carcinoma patient with concomitant occurrence of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations upon development of crizotinib-resistance. CASE PRESENTATION: A 61-year-old Caucasian never-smoking male was diagnosed with anaplastic lymphoma kinase -positive pulmonary adenocarcinoma, stage T4N3M1b. Treatment with crizotinib initially resulted in complete objective response in the thorax and partial response in the abdomen, but after 8 months of therapy the patient acquired resistance and progressed. Biopsies from new metastases revealed development of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations concomitant with the original anaplastic lymphoma kinase gene rearrangement and without signs of anaplastic lymphoma kinase fusion gene amplification or secondary anaplastic lymphoma kinase mutations. CONCLUSION: To our knowledge, this is the first report of an anaplastic lymphoma kinase-positive pulmonary adenocarcinoma, which upon emergence of crizotinib resistance acquired 2 new somatic mutations in the epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog genes, respectively, concomitant with the original anaplastic lymphoma kinase rearrangement. Thus, these 3 driver mutations, usually considered mutually exclusive, may coexist in advanced non-small cell lung carcinoma that becomes resistant to crizotinib, presumably because heterogeneous tumor clones utilize epidermal growth factor receptor and/or V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog signaling to circumvent the inhibition of anaplastic lymphoma kinase-mediated signaling by crizotinib. The identification of new targetable somatic mutations by tumor re-biopsy may help clarify the mechanism behind the development of the acquired crizotinib resistance and pave the way for combined strategies involving multiple targeted therapies

Perioperative oxygen fraction – effect on surgical site infection and pulmonary complications after abdominal surgery: a randomized clinical trial. Rationale and design of the PROXI-Trial

<p>Abstract</p> <p>Background</p> <p>A high perioperative inspiratory oxygen fraction may reduce the risk of surgical site infections, as bacterial eradication by neutrophils depends on wound oxygen tension. Two trials have shown that a high perioperative inspiratory oxygen fraction (Fi<smcaps>O</smcaps>₂= 0.80) significantly reduced risk of surgical site infections after elective colorectal surgery, but a third trial was stopped early because the frequency of surgical site infections was more than doubled in the group receiving Fi<smcaps>O</smcaps>₂= 0.80. It has not been settled if a high inspiratory oxygen fraction increases the risk of pulmonary complications, such as atelectasis, pneumonia and respiratory failure. The aim of our trial is to assess the potential benefits and harms of a high perioperative oxygen fraction in patients undergoing abdominal surgery.</p> <p>Methods and design</p> <p>The PROXI-Trial is a randomized, patient- and assessor blinded trial of perioperative supplemental oxygen in 1400 patients undergoing acute or elective laparotomy in 14 Danish hospitals. Patients are randomized to receive either 80% oxygen (Fi<smcaps>O</smcaps>₂= 0.80) or 30% oxygen (Fi<smcaps>O</smcaps>₂= 0.30) during surgery and for the first 2 postoperative hours. The primary outcome is surgical site infection within 14 days. The secondary outcomes are: atelectasis, pneumonia, respiratory failure, re-operation, mortality, duration of postoperative hospitalization, and admission to intensive care unit. The sample size allows detection of a 33% relative risk reduction in the primary outcome with 80% power.</p> <p>Discussion</p> <p>This trial assesses benefits and harms of a high inspiratory oxygen fraction, and the trial may be generalizable to a general surgical population undergoing laparotomy.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier: NCT00364741.</p