Despite many studies of the likely survival outcome of individual patients with colorectal cancer, our knowledge of this subject remains poor. Until recently, we had virtually no understanding of ...individual responses to therapy, but the discovery of the KRAS mutation as a marker of probable failure of epidermal growth factor receptor (EGFR)-targeted therapy is a first step in the tailoring of treatment to the individual. With the application of molecular analyses, as well as the ability to perform high-throughput screens, there has been an explosive increase in the number of markers thought to be associated with prognosis and treatment outcome in this disease. In this Review, we attempt to summarize the sometimes confusing findings, and critically assess those markers already in the public domain.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Examined associations between effortful control temperament and externalizing problems in 220 3-year-old boys and girls, controlling for co-occurring cognitive and social risk factors. We also ...considered possible additive and/or interactive contributions of child dispositional anger and psychosocial adversity, and whether relations between effortful control and early externalizing problems were moderated by child gender. Individual differences in children's effortful control abilities, assessed using behavioral and parent rating measures, were negatively associated with child externalizing problems reported by mothers, fathers, and preschool teachers. These associations were not overshadowed by other cognitive or social risk factors, or by other relevant child temperament traits such as proneness to irritability. Further analyses revealed that associations between externalizing problem behavior and effortful control were specific to components of child problem behavior indexing impulsive-inattentive symptoms. Thus, children's effortful control skills were important correlates of children's early disruptive behavior, a finding that may provide insight into the developmental origins of chronic behavioral maladjustment.
Summary Background The aim of the QUASAR trial was to determine the size and duration of any survival benefit from adjuvant chemotherapy for patients with colorectal cancer at low risk of recurrence, ...for whom the indication for such treatment is unclear. Methods After apparently curative resections of colon or rectal cancer, 3239 patients (2963 91% with stage II node negative disease, 2291 71% with colon cancer, median age 63 IQR 56–68 years) enrolled between May, 1994, and December, 2003, from 150 centres in 19 countries were randomly assigned to receive chemotherapy with fluorouracil and folinic acid (n=1622) or to observation (with chemotherapy considered on recurrence; n=1617). Chemotherapy was delivered as six 5-day courses every 4 weeks or as 30 once-weekly courses of intravenous fluorouracil (370 mg/m2 ) with high-dose (175 mg) L-folinic acid or low-dose (25 mg) L-folinic acid. Until 1997, levamisole (12 courses of 450 mg over 3 days repeated every 2 weeks) or placebo was added. After 1997, patients who were assigned to receive chemotherapy were given fluorouracil and low-dose folinic acid only. The primary outcome was all-cause mortality. Analyses were done by intention to treat. This trial is registered with the International Clinical Trial Registry, number ISRCTN82375386. Findings At the time of analysis, 61 (3·8%) patients in the chemotherapy group and 50 (3·1%) in the observation group had missing follow-up. After a median follow-up of 5·5 (range 0–10·6) years, there were 311 deaths in the chemotherapy group and 370 in the observation group; the relative risk of death from any cause with chemotherapy versus observation alone was 0·82 (95% CI 0·70–0·95; p=0·008). There were 293 recurrences in the chemotherapy group and 359 in the observation group; the relative risk of recurrence with chemotherapy versus observation alone was 0·78 (0·67–0·91; p=0·001). Treatment efficacy did not differ significantly by tumour site, stage, sex, age, or chemotherapy schedule. Eight (0·5%) patients in the chemotherapy group and four (0·25%) in the observation group died from non-colorectal cancer causes within 30 weeks of randomisation; only one of these deaths was deemed to be possibly chemotherapy related. Interpretation Chemotherapy with fluorouracil and folinic acid could improve survival of patients with stage II colorectal cancer, although the absolute improvements are small: assuming 5-year mortality without chemotherapy is 20%, the relative risk of death seen here translates into an absolute improvement in survival of 3·6% (95% CI 1·0–6·0).
The present study examined the stability of young men’s intimate partner violence (IPV) over a 12-year period as a function of relationship continuity or discontinuity. Multiwave measures of IPV ...(physical and psychological aggression) were obtained from 184 men at risk for delinquency and their women partners. The effects of relationship continuity versus transitions on change in IPV were examined using multilevel analyses. In general, men’s IPV decreased over time. Men’s physical aggression in their early 20s predicted levels of physical aggression about 7 years later, and men’s psychological aggression in their early 20s predicted levels of psychological aggression about 10–12 years later. As hypothesized, higher stability in IPV was found for men who stayed with the same partners, whereas men experiencing relationship transitions showed greater change. The IPV of new partners was linked to the changes in men’s IPV that occurred with repartnering. There was less change in men’s IPV over time as men changed partners less frequently.
We developed quantitative gene expression assays to assess recurrence risk and benefits from chemotherapy in patients with stage II colon cancer.
We sought validation by using RNA extracted from ...fixed paraffin-embedded primary colon tumor blocks from 1,436 patients with stage II colon cancer in the QUASAR (Quick and Simple and Reliable) study of adjuvant fluoropyrimidine chemotherapy versus surgery alone. A recurrence score (RS) and a treatment score (TS) were calculated from gene expression levels of 13 cancer-related genes (n = 7 recurrence genes and n = 6 treatment benefit genes) and from five reference genes with prespecified algorithms. Cox proportional hazards regression models and log-rank methods were used to analyze the relationship between the RS and risk of recurrence in patients treated with surgery alone and between TS and benefits of chemotherapy.
Risk of recurrence was significantly associated with RS (hazard ratio HR per interquartile range, 1.38; 95% CI, 1.11 to 1.74; P = .004). Recurrence risks at 3 years were 12%, 18%, and 22% for predefined low, intermediate, and high recurrence risk groups, respectively. T stage (HR, 1.94; P < .001) and mismatch repair (MMR) status (HR, 0.31; P < .001) were the strongest histopathologic prognostic factors. The continuous RS was associated with risk of recurrence (P = .006) beyond these and other covariates. There was no trend for increased benefit from chemotherapy at higher TS (P = .95).
The continuous 12-gene RS has been validated in a prospective study for assessment of recurrence risk in patients with stage II colon cancer after surgery and provides prognostic value that complements T stage and MMR. The TS was not predictive of chemotherapy benefit.
Objective: Multidimensional Treatment Foster Care (MTFC) has been found to reduce delinquency among girls in juvenile justice through 2-year follow-up. Given that such girls are at elevated risk for ...suicide and depression into adulthood, we tested MTFC effects on long-term trajectories of suicidal ideation and depressive symptoms. Method: Girls (N = 166; mean SD age = 15.3 1.2 years; 68% White) with a recent criminal referral who were mandated to out-of-home care were enrolled in 2 sequential cohorts. Girls were randomized to receive MTFC (n = 81) or group care (GC) treatment as usual (TAU; n = 85); the second MTFC cohort also received modules targeting substance use and risky sexual behavior. Depressive symptoms and suicidal ideation were assessed repeatedly through early adulthood (mean SD follow-up = 8.8 2.9 years). Suicide attempt history was assessed in early adulthood. Results: Girls assigned to MTFC showed significantly greater decreases in depressive symptoms across the long-term follow-up than GC girls (π = −.86, p < .05). Decreases in suicidal ideation rates were slightly stronger in MTFC than in GC as indicated by a marginal main effect (odds ratio OR = .92, p < .10) and a significant interaction that favored MTFC in the second cohort relative to the first (OR = .88, p < .01). There were no significant MTFC effects on suicide attempt. Conclusions: MTFC decreased depressive symptoms and suicidal thinking beyond the decreases attributable to time and TAU. Thus, MTFC has further impact on girls' lives than originally anticipated.
The Interpersonal Needs Questionnaire (INQ) for assessing thwarted belongingness (TB) and perceived burdensomeness (PB) has not been validated with community adolescents. We translated and ...administered the INQ to 307 Slovenian adolescents twice over 2–3 months and found that the 15‐item version (INQ‐15) did not fit without modification. TB and PB scales correlated with concurrent and later suicide ideation and lifetime suicide attempt history. The latent PB factor was associated with concurrent and later ideation controlling for TB, age, gender, depressive symptoms, binge drinking, and peer victimization. Suicide ideation and binge drinking were independently related to attempt history. Assessing and intervening on PB and binge drinking may be promising approaches to suicide prevention with community adolescents.
The DoMore-v1-CRC marker was recently developed using deep learning and conventional haematoxylin and eosin-stained tissue sections, and was observed to outperform established molecular and ...morphological markers of patient outcome after primary colorectal cancer resection. The aim of the present study was to develop a clinical decision support system based on DoMore-v1-CRC and pathological staging markers to facilitate individualised selection of adjuvant treatment.
We estimated cancer-specific survival in subgroups formed by pathological tumour stage (pT<4 or pT4), pathological nodal stage (pN0, pN1, or pN2), number of lymph nodes sampled (≤12 or >12) if not pN2, and DoMore-v1-CRC classification (good, uncertain, or poor prognosis) in 997 patients with stage II or III colorectal cancer considered to have no residual tumour (R0) from two community-based cohorts in Norway and the UK, and used these data to define three risk groups. An external cohort of 1075 patients with stage II or III R0 colorectal cancer from the QUASAR 2 trial was used for validation; these patients were treated with single-agent capecitabine. The proposed risk stratification system was evaluated using Cox regression analysis. We similarly evaluated a risk stratification system intended to reflect current guidelines and clinical practice. The primary outcome was cancer-specific survival.
The new risk stratification system provided a hazard ratio of 10·71 (95% CI 6·39–17·93; p<0·0001) for high-risk versus low-risk patients and 3·06 (1·73–5·42; p=0·0001) for intermediate versus low risk in the primary analysis of the validation cohort. Estimated 3-year cancer-specific survival was 97·2% (95% CI 95·1–98·4; n=445 41%) for the low-risk group, 94·8% (91·7–96·7; n=339 32%) for the intermediate-risk group, and 77·6% (72·1–82·1; n=291 27%) for the high-risk group. The guideline-based risk grouping was observed to be less prognostic and informative (the low-risk group comprised only 142 13% of the 1075 patients).
Integrating DoMore-v1-CRC and pathological staging markers provided a clinical decision support system that risk stratifies more accurately than its constituent elements, and identifies substantially more patients with stage II and III colorectal cancer with similarly good prognosis as the low-risk group in current guidelines. Avoiding adjuvant chemotherapy in these patients might be safe, and could reduce morbidity, mortality, and treatment costs.
The Research Council of Norway.
Cleared blood glucose monitors (BGMs) for personal use may not always deliver levels of accuracy currently specified by international and U.S. regulatory bodies. This study's objective was to assess ...the accuracy of 18 such systems cleared by the U.S. Food and Drug Administration representing approximately 90% of commercially available systems used from 2013 to 2015.
A total of 1,035 subjects were recruited to have a capillary blood glucose (BG) level measured on six different systems and a reference capillary sample prepared for plasma testing at a reference laboratory. Products were obtained from consumer outlets and tested in three triple-blinded studies. Each of the three participating clinical sites tested a different set of six systems for each of the three studies in a round-robin. In each study, on average, a BGM was tested on 115 subjects. A compliant BG result was defined as within 15% of a reference plasma value (for BG ≥100 mg/dL 5.55 mmol/L) or within 15 mg/dL (0.83 mmol/L) (for BG <100 mg/dL 5.55 mmol/L). The proportion of compliant readings in each study was compared against a predetermined accuracy standard similar to, but more lenient than, current regulatory standards. Other metrics of accuracy included the overall compliance proportion; the proportion of extreme outlier readings differing from the reference value by >20%; modified Bland-Altman analysis including average bias, coefficient of variation, and 95% limits of agreement; and proportion of readings with no clinical risk as determined by the Surveillance Error Grid.
The different accuracy metrics produced almost identical BGM rankings. Six of the 18 systems met the predetermined accuracy standard in all three studies, 5 systems met it in two studies, and 3 met it in one study. Four BGMs did not meet the accuracy standard in any of the three studies.
Cleared BGMs do not always meet the level of analytical accuracy currently required for regulatory clearance. This information could assist patients, professionals, and payers in choosing products and regulators in evaluating postclearance performance.
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