Clinical application of biological markers for treatments of resectable non-small-cell lung cancers

We performed a clinical study to identify biological markers useful for the treatment of resectable non-small-cell lung cancers (NSCLCs). In all, 173 patients were studied. By immunohistochemistry, we evaluated the Ki-67 proliferation index, tumour vascularity, thymidylate synthase (TS), vascular endothelial growth factor (VEGF)-A, VEGF-C, and E (epithelial)-cadherin. Concerning the survival of NSCLC patients, tumour vascularity (P<0.01), VEGF-A status (P=0.03), VEGF-C status (P=0.03), and E-cadherin status (P=0.03) were significant prognostic factors in patients with stage I NSCLCs. The Ki-67 proliferation index (P=0.02) and TS status (P<0.01) were significant prognostic factors in patients with stage II–III NSCLCs. In patients with stage II–III NSCLCs, furthermore, the survival of UFT (a combination of tegafur and uracil)-treated patients with TS-negative tumours was significantly better than those of any other patients. Biological markers associated with tumour angiogenesis or metastasis are useful for the detection of aggressive tumours among early-stage NSCLCs. Postoperative chemotherapy might be necessary in such tumours even in stage I. In contrast, tumour proliferation rate and TS status are useful markers for identifying less aggressive tumours in locally advanced NSCLCs. Thymidylate synthase expression is also a useful marker to evaluate responsiveness of UFT-based chemotherapy for these tumours

The Amsterdam Studies of Acute Psychiatry - II (ASAP-II): a comparative study of psychiatric intensive care units in the Netherlands

Background The number of patients in whom mental illness progresses to stages in which acute, and often forced treatment is warranted, is on the increase across Europe. As a consequence, more patients are involuntarily admitted to Psychiatric Intensive Care Units (PICU). From several studies and reports it has become evident that important dissimilarities exist between PICU's. The current study seeks to describe organisational as well as clinical and patient related factors across ten PICU's in and outside the Amsterdam region, adjusted for or stratified by level of urbanization. Method/Design This paper describes the design of the Amsterdam Studies of Acute Psychiatry II (ASAP-II). This study is a prospective observational cohort study comparing PICU's in and outside the Amsterdam region on various patient characteristics, treatment aspects and recovery related variables. Dissimilarities were measured by means of collecting standardized forms which were filled out in the framework of care as usual, by means of questionnaires filled out by mental health care professionals and by means of extracting data from patient files for every consecutive patient admitted at participating PICU's during a specific time period. Urbanization levels for every PICU were calculated conform procedures as proposed by the Dutch Central Bureau for Statistics (CBS). Discussion The current study may provide a deeper understanding of the differences between psychiatric intensive care units that can be used to promote best practice and benchmarking procedures, and thus improve the standard of care

Detection of cytokeratins 19/20 and guanylyl cyclase C in peripheral blood of colorectal cancer patients

The clinical significance of detecting supposed tumour cell-derived mRNA transcripts in blood using the polymerase chain reaction (PCR) remains unclear. We have used a fully quantitative 5′-nuclease RT-PCR assay to screen for the expression of cytokeratins (ck) 19 and 20 and guanylyl cyclase C (GCC) in the peripheral blood of 21 healthy controls and 27 colorectal cancer patients. Expression of cytokeratin 19 and 20 mRNA was detected in 30% and 100% of samples, respectively, taken from healthy volunteers. There was no apparent difference in ck19 and ck20 mRNA transcription levels between controls and patients, or between patients with different Dukes' stages. While GCC mRNA was detected in only 1/21 control samples, it was expressed in approximately 80% of patients, although again there was no correlation between GCC levels and disease stage. Transcription levels of all three markers varied considerably between samples, even between samples taken from the same person at different times. We conclude that neither ck19 nor ck20 are reliable markers for the detection of colon epithelial cells in peripheral blood and that an evaluation of the usefulness of GCC awaits further longitudinal studies. © 1999 Cancer Research Campaig

Impact of district mental health care plans on symptom severity and functioning of patients with priority mental health conditions: the Programme for Improving Mental Health Care (PRIME) cohort protocol

Background: The Programme for Improving Mental Health Care (PRIME) sought to implement mental health care plans (MHCP) for four priority mental disorders (depression, alcohol use disorder, psychosis and epilepsy) into routine primary care in five low- and middle-income country districts. The impact of the MHCPs on disability was evaluated through establishment of priority disorder treatment cohorts. This paper describes the methodology of these PRIME cohorts. Methods: One cohort for each disorder was recruited across some or all five districts: Sodo (Ethiopia), Sehore (India) , Chitwan (Nepal), Dr. Kenneth Kaunda (South Africa) and Kamuli (Uganda), comprising 17 treatment cohorts in total (N = 2182). Participants were adults residing in the districts who were eligible to receive mental health treatment according to primary health care staff, trained by PRIME facilitators as per the district MHCP. Patients who screened positive for depression or AUD and who were not given a diagnosis by their clinicians (N = 709) were also recruited into comparison cohorts in Ethiopia, India, Nepal and South Africa. Caregivers of patients with epilepsy or psychosis were also recruited (N = 953), together with or on behalf of the person with a mental disorder, depending on the district. The target sample size was 200 (depression and AUD), or 150 (psychosis and epilepsy) patients initiating treatment in each recruiting district. Data collection activities were conducted by PRIME research teams. Participants completed follow-up assessments after 3 months (AUD and depression) or 6 months (psychosis and epilepsy), and after 12 months. Primary outcomes were impaired functioning, using the 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS), and symptom severity, assessed using the Patient Health Questionnaire (depression), the Alcohol Use Disorder Identification Test (AUD), and number of seizures (epilepsy). Discussion: Cohort recruitment was a function of the clinical detection rate by primary health care staff, and did not meet all planned targets. The cross-country methodology reflected the pragmatic nature of the PRIME cohorts: while the heterogeneity in methods of recruitment was a consequence of differences in health systems and MHCPs, the use of the WHODAS as primary outcome measure will allow for comparison of functioning recovery across sites and disorders

The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis

The proto-oncogene RAS, coding for a 21 kDa protein (p21), is mutated in 20% of lung cancer. However, the literature remains controversial on its prognostic significance for survival in lung cancer. We performed a systematic review of the literature with meta-analysis to assess its possible prognostic value on survival. Published studies on lung cancer assessing prognostic value of RAS mutation or p21 overexpression on survival were identified by an electronic search. After a methodological assessment, we estimated individual hazard ratios (HR) estimating RAS protein alteration or RAS mutation effect on survival and combined them using meta-analytic methods. In total, 53 studies were found eligible, with 10 concerning the same cohorts of patients. Among the 43 remaining studies, the revelation method was immunohistochemistry (IHC) in nine and polymerase chain reaction (PCR) in 34. Results in terms of survival were significantly pejorative, significantly favourable, not significant and not conclusive in 9, 1, 31, 2, respectively. In total, 29 studies were evaluable for meta-analysis but we aggregated only the 28 dealing with non-small-cell lung cancer (NSCLC) and not the only one dealing with small-cell-lung cancer (SCLC). The quality scores were not statistically significantly different between studies with or without significant results in terms of survival, allowing us to perform a quantitative aggregation. The combined HR was 1.35 (95% CI: 1.16–1.56), showing a worse survival for NSCLC with KRAS2 mutations or p21 overexpression and, particularly, in adenocarcinomas (ADC) (HR 1.59; 95% CI 1.26–2.02) and in studies using PCR (HR 1.40; 95% CI 1.18–1.65) but not in studies using IHC (HR 1.08; 95% CI 0.86–1.34). RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR

External quality assessment of SARS-CoV-2-sequencing: An ESGMD-SSM pilot trial across 15 European laboratories

Objective: This first pilot on external quality assessment (EQA) of SARS-CoV-2 whole genome sequencing, initiated by the ESCMID Study Group for Genomic and Molecular Diagnostics (ESGMD) and Swiss Society for Microbiology (SSM), aims to build a framework between laboratories in order to improve pathogen surveillance sequencing.Methods: Ten samples with varying viral loads were sent out to 15 clinical laboratories who had free choice of sequencing methods and bioinformatic analyses. The key aspects on which the individual centres were compared on were identification of 1) SNPs and indels, 2) Pango lineages, and 3) clusters between samples.Results: The participating laboratories used a wide array of methods and analysis pipelines. Most were able to generate whole genomes for all samples. Genomes were sequenced to varying depth (up to 100-fold difference across centres). There was a very good consensus regarding the majority of reporting criteria, but there were a few discrepancies in lineage and cluster assignment. Additionally, there were inconsistencies in variant calling. The main reasons for discrepancies were missing data, bioinformatic choices, and interpretation of data.Conclusions: The pilot EQA was an overall success. It was able to show the high quality of participating labs and provide valuable feedback in cases where problems occurred, thereby improving the sequencing setup of laboratories. A larger follow-up EQA should, however, improve on defining the variables and format of the report. Additionally, contamination and/or minority variants should be a further aspect of assessment.</p

Schizophrenic patients without neuropsychological deficits: subgroup, disease severity or cognitive compensation?

Some schizophrenic patients do not show clinically relevant cognitive deficits. The question remains whether this represents the existence of an etiologically different subgroup, a general effect of disease severity or whether their cognitive deficits do not reach a clinical threshold due to a greater cognitive compensation ('brain reserve') capacity. A group of 23 out of 118 first onset patients was identified as cognitively normal (CN). The cognitive profile of these patients was compared with that of 45 healthy controls. Next these patients were compared with the cognitively impaired (0) patients on obstetric complications (OCs), premorbid adjustment, age at onset, Positive and Negative Syndrome Scale ratings, social functioning and substance abuse. In addition both groups were compared on intelligence and educational level as indirect indicators of cognitive compensation capacity. There were no differences in OCs, premorbid adjustment, age at onset, psychopathology or substance abuse between the two patient groups. There was a significant difference in social functioning, which is a consequence rather than a cause of cognitive deficits. However, the CN patients scored significantly higher on measures of intelligence and educational level than the CI patients. This suggests that a difference in cognitive compensation capacity could explain the existence of a CN patient group. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved