Screening and Stepped Care Targeting Psychological Distress in Patients With Metastatic Colorectal Cancer: The TES Cluster Randomized Trial.

BACKGROUND: This study evaluated the effectiveness of a screening and stepped care program (the TES program) in reducing psychological distress compared with care as usual (CAU) in patients with metastatic colorectal cancer starting with first-line systemic palliative treatment. PATIENTS AND METHODS: In this cluster randomized trial, 16 hospitals were assigned to the TES program or CAU. Patients in the TES arm were screened for psychological distress with the Hospital Anxiety and Depression Scale and the Distress Thermometer/Problem List (at baseline and 10 and 18 weeks). Stepped care was offered to patients with distress or expressed needs, and it consisted of watchful waiting, guided self-help, face-to-face problem-solving therapy, or referral to specialized mental healthcare. The primary outcome was change in psychological distress over time, and secondary outcomes were quality of life, satisfaction with care, and recognition and referral of distressed patients by clinicians. Linear mixed models and effect sizes were used to evaluate differences. RESULTS: A total of 349 patients were randomized; 184 received the TES program and 165 received CAU. In the TES arm, 60.3% of the patients screened positive for psychological distress, 26.1% of which entered the stepped care program (14.7% used only watchful waiting and 11.4% used at least one of the other treatment steps). The observed low use of the TES program led us to pursue a futility analysis, which showed a small conditional power and therefore resulted in halted recruitment for this study. No difference was seen in change in psychological distress over time between the 2 groups (effect size, -0.16; 95% CI, -0.35 to 0.03; P>.05). The TES group reported higher satisfaction with the received treatment and better cognitive quality of life (all P<.05). CONCLUSIONS: As a result of the low use of stepped care, a combined screening and treatment program targeting psychological distress in patients with metastatic colorectal cancer did not improve psychological distress. Our results suggest that enhanced evaluation of psychosocial concerns may improve aspects of patient well-being.

Warranty period of coronary computed tomography angiography and [15O]H2O positron emission tomography in symptomatic patients.

AIMS: Data on the warranty period of coronary computed tomography angiography (CTA) and combined coronary CTA/positron emission tomography (PET) are scarce. The present study aimed to determine the event-free (warranty) period after coronary CTA and the potential additional value of PET. METHOD AND RESULTS: Patients with suspected but not previously diagnosed coronary artery disease (CAD) who underwent coronary CTA and/or [15O]H2O PET were categorized based upon coronary CTA as no CAD, non-obstructive CAD, or obstructive CAD. A hyperaemic myocardial blood flow (MBF) ≤ 2.3 mL/min/g was considered abnormal. The warranty period was defined as the time for which the cumulative event rate of death and non-fatal myocardial infarction (MI) was below 5%. Of 2575 included patients (mean age 61.4 ± 9.9 years, 41% male), 1319 (51.2%) underwent coronary CTA only and 1237 (48.0%) underwent combined coronary CTA/PET. During a median follow-up of 7.0 years 163 deaths and 68 MIs occurred. The warranty period for patients with no CAD on coronary CTA was ≥10 years, whereas patients with non-obstructive CAD had a 5-year warranty period. Patients with obstructive CAD and normal hyperaemic MBF had a 2-year longer warranty period compared to patients with obstructive CAD and abnormal MBF (3 years vs. 1 year). CONCLUSION: As standalone imaging, the warranty period for normal coronary CTA is ≥10 years, whereas patients with non-obstructive CAD have a warranty period of 5 years. Normal PET yielded a 2-year longer warranty period in patients with obstructive CAD.

The Dynamic Relationship Between Invasive Microvascular Function and Microvascular Injury Indicators, and Their Association With Left Ventricular Function and Infarct Size at 1-Month After Reperfused ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: The invasive microvascular function indices, coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR), exhibit a dynamic pattern after ST-segment-elevation myocardial infarction. The effects of microvascular injury on the evolution of the microvascular function and the prognostic significance of the evolution of microvascular function are unknown. We investigated the relationship between the temporal changes of CFR and IMR, and cardiovascular magnetic resonance-derived microvascular injury characteristics in reperfused ST-segment-elevation myocardial infarction patients, and their association with 1-month left ventricular ejection fraction and infarct size (IS). METHODS: In 109 ST-segment-elevation myocardial infarction patients who underwent angiography for primary percutaneous coronary intervention (PPCI) and at 1-month follow-up, invasive assessment of CFR and IMR were performed in the culprit artery during both procedures. Cardiovascular magnetic resonance was performed 2 to 7 days after PPCI and at 1 month and provided assessment of left ventricular ejection fraction, IS, microvascular obstruction, and intramyocardial hemorrhage. RESULTS: CFR and IMR significantly changed over 1 month (both, P<0.001). The absolute IMR change over 1 month (ΔIMR) showed association with both microvascular obstruction and intramyocardial hemorrhage presence (both, P=0.01). ΔIMR differed between patients with/without microvascular obstruction (P=0.02) and with/without intramyocardial hemorrhage (P=0.04) but not ΔCFR for both. ΔIMR demonstrated association with both left ventricular ejection fraction and IS at 1 month (P<0.001, P=0.001, respectively), but not ΔCFR for both. Receiver-operating characteristics curve analysis of ΔIMR showed a larger area under the curve than post-PPCI CFR and IMR, and ΔCFR to be associated with both 1-month left ventricular ejection fraction >50% and extensive IS (the highest quartile). CONCLUSIONS: In reperfused ST-segment-elevation myocardial infarction patients, CFR and IMR significantly improved 1 month after PPCI; the temporal change in IMR is closely related to the presence/absence of microvascular damage and IS. ΔIMR exhibits a stronger association for 1-month functional outcome than post-PPCI CFR, IMR, or ΔCFR.

DNA hypermethylation analysis in sputum of asymptomatic subjects at risk for lung cancer participating in the NELSON trial: argument for maximum screening interval of 2†years.

AIMS: Lung cancer is the major contributor to cancer mortality due to metastasised disease at time of presentation. The current study investigated DNA hypermethylation of biomarkers RASSF1A, APC, cytoglobin, 3OST2, FAM19A4, PHACTR3 and PRDM14 in sputum of asymptomatic high-risk individuals from the NELSON lung cancer low-dose spiral CT screening trial to detect lung cancer at preclinical stage. METHODS: Subjects were selected with (i) lung cancer in follow-up (cases; n=65), (ii) minor cytological aberrations (controls; n=120) and (iii) a random selection of subjects without cytological aberrations (controls; n=99). Median follow-up time for controls was 80 months. Cut-off values were based on high specificity to assess diagnostic value of the biomarkers. RESULTS: RASSF1A may denote presence of invasive cancer because of its high specificity (93% (95% CI 89% to 96%); sensitivity 17% (95% CI 4% to 31%), with best performance in a screening interval of 2 years. The panel of RASSF1A, 3OST2 and PRDM14 detected 28% (95% CI 11% to 44%) of lung cancer cases within 2 years, with specificity of 90% (95% CI 86% to 94%). Sputum cytology did not detect any lung cancers. CONCLUSIONS: In a lung cancer screening setting with maximum screening interval of 2 years, DNA hypermethylation analysis in sputum may play a role in the detection of preclinical disease, but complementary diagnostic markers are needed to improve sensitivity.

Four-year follow-up of poly-L-lactic Acid cages for lumbar interbody fusion in goats.

BACKGROUND: New applications of bioabsorbable polymer implants demand for histologic evaluation because a host tissue response is elicited and late complications after polymer implantation have been reported. Furthermore, in load-bearing regions an accelerated polymer degradation and foreign body reaction may be observed. METHODS: Lumbar interbody fusion procedures were performed using poly-L-lactic acid (PLLA) and titanium cages in 43 goats. At 3, 6, 12, 24, 36, and 48 months after surgery, sequential histologic analysis of instrumented motion segments, lymph nodes, and nervous structures was performed. Blood samples were retrieved for laboratory analysis. RESULTS: No adverse local or distant histologic or systemic effects were observed during the absorption of the poly-L-lactic acid cages. Interbody fusion was maintained, and only a very mild inflammatory response was observed. In half the specimens complete absorption was observed, and in the remaining specimens an estimated 1-10% of the original PLLA was present at the 3-year follow-up. At the 4-year follow-up, five out of seven PLLA specimens showed no PLLA particles under polarized light microscopy. In the remaining two specimens an estimated 1% of the original PLLA could be observed. CONCLUSIONS: Poly-L-lactic acid cages are feasible for lumbar interbody fusion, and the biocompatibility under high load bearing conditions is excellent during the complete absorption of the PLLA interbody fusion cages.

Additional value of CSF amyloid-beta 40 levels in the differentiation between FTLD and control subjects.

To determine the additional value of cerebrospinal fluid (CSF)amyloid-beta1-40 (Abeta40) next to amyloid-beta1-42 (beta42), total tau (Tau), and tau phosphorylated at threonine-181 (pTau) to distinguish patients with frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), and controls, we measured CSF levels of Abeta40, Abeta42, pTau, and Tau in 55 patients with FTLD, 60 with AD, and 40 control subjects. Logistic regression was used to identify biomarkers that best distinguished the groups. Additionally, a decision tree (cost=test method; Matlab 7.7) was used to predict diagnosis selecting the best set of biomarkers with the optimal cut-off. Logistic regression showed that Abeta42 and pTau CSF levels provided optimal distinction between AD and FTLD. A combination of Abeta42, Tau, and Abeta40 optimally discriminated FTLD from controls and AD from controls. The decision tree used Abeta42 (cut-off 578 pg/ml) to identify AD (positive predictive value (PPV) 97%), followed by Tau(cut-off 336 pg/ml) to identify FTLD (PPV 67%), and in the last step,Abeta40 (cut-off 10 ng/ml) was used to differentiate controls (PPV68%). Applying CSF Abeta40 levels in the model, the PPV of diagnosis increased to 75% as opposed to 70% when only Abeta42 and Tau were used. CSF Abeta40 levels added to the conventional CSF biomarkers increases the potential to discriminate subjects with dementia from controls. Our findings favor the implementation of CSF Abeta40 in differential diagnosis between FTLD, AD, and control subjects.

Prevention of cervical cancer: where immunology meets diagnostics.

Based on the insight that cervical cancer is caused by high-risk human papillomavirus (hrHPV) types, two new directions of cervical cancer prevention have emerged: primary prevention by prophylactic vaccination against hrHPV types 16 and 18, and secondary prevention by cervical screening with HPV DNA testing. These "current views" elaborate on both prevention modes in the context of public health. It is argued that within the next decades using current vaccines the most effective way of prevention and control of cervical cancer requires an integrated vaccination-screening approach, including routine prophylactic vaccination to pre-pubertal women and adapted cervical screening for older women.