C-reactive protein predicts mortality in patients referred for coronary angiography and symptoms of heart failure with preserved ejection fraction

AIMS Heart failure with preserved ejection fraction (HFpEF) has a different pathophysiological background compared to heart failure with reduced ejection fraction (HFrEF). Tailored risk prediction in this separate heart failure group with a high mortality rate is of major importance. Inflammation may play an important role in the pathogenesis of HFpEF because of its significant contribution to myocardial fibrosis. We therefore aimed to assess the predictive value of C-reactive protein (CRP) in patients with HFpEF. METHODS AND RESULTS Plasma levels of CRP were determined in 459 patients with HFpEF in the LUdwigshafen Risk and Cardiovascular Health (LURIC) study using a high-sensitivity assay. During a median follow-up of 9.7 years 40% of these patients died. CRP predicted all-cause mortality with an adjusted hazard ratio (HR) of 1.20 [95% confidence interval (CI) 1.02-1.40, P = 0.018] and cardiovascular mortality with a HR of 1.32 (95% CI 1.08-1.62, P = 0.005) per increase of one standard deviation. CRP was a significantly stronger mortality predictor in HFpEF patients than in a control group of 522 HFrEF patients (for interaction, P = 0.015). Furthermore, CRP added prognostic value to N-terminal pro B-type natriuretic peptide (Nt-proBNP): the lowest 5-year mortality rate of 6.8% was observed for patients in the lowest tertile of Nt-proBNP as well as CRP. The mortality risk peaked in the group combining the highest values of Nt-proBNP and CRP with a 5-year rate of 36.5%. CONCLUSION It was found that CRP was an independent and strong predictor of mortality in HFpEF. This observation may reflect immunological processes with an adverse impact on the course of HFpEF.

Association Between Drinking Goal and Alcohol Use One Year After Residential Treatment: A Multicenter Study

This study examined whether patients’ drinking goals at admission to and discharge from 12 residential alcohol use disorder treatment programs were associated with alcohol-related outcomes at 1-year follow-up. Detoxified patients (N D 289) completed assessments at admission, after treatment, and at 1-year follow-up. Drinking goals of abstinence, conditional abstinence (in principle abstinence but potential occurrence of lapses or drinking, when urges are strong), and controlled drinking changed during treatment and predicted the 1-year follow-up outcomes (abstinence, number of standard drinks, and number of days to the first alcohol use). Goals at discharge had a better predictive value. The goal of abstinence at discharge had better outcomes than conditional abstinence; the poorest had controlled drinking.

Effects of acupuncture on sensory perception: a systematic review and meta-analysis.

BACKGROUND The effect of acupuncture on sensory perception has never been systematically reviewed; although, studies on acupuncture mechanisms are frequently based on the idea that changes in sensory thresholds reflect its effect on the nervous system. METHODS Pubmed, EMBASE and Scopus were screened for studies investigating the effect of acupuncture on thermal or mechanical detection or pain thresholds in humans published in English or German. A meta-analysis of high quality studies was performed. RESULTS Out of 3007 identified articles 85 were included. Sixty five studies showed that acupuncture affects at least one sensory threshold. Most studies assessed the pressure pain threshold of which 80% reported an increase after acupuncture. Significant short- and long-term effects on the pressure pain threshold in pain patients were revealed by two meta-analyses including four and two high quality studies, respectively. In over 60% of studies, acupuncture reduced sensitivity to noxious thermal stimuli, but measuring methods might influence results. Few but consistent data indicate that acupuncture reduces pin-prick like pain but not mechanical detection. Results on thermal detection are heterogeneous. Sensory threshold changes were equally frequent reported after manual acupuncture as after electroacupuncture. Among 48 sham-controlled studies, 25 showed stronger effects on sensory thresholds through verum than through sham acupuncture, but in 9 studies significant threshold changes were also observed after sham acupuncture. Overall, there is a lack of high quality acupuncture studies applying comprehensive assessments of sensory perception. CONCLUSIONS Our findings indicate that acupuncture affects sensory perception. Results are most compelling for the pressure pain threshold, especially in pain conditions associated with tenderness. Sham acupuncture can also cause such effects. Future studies should incorporate comprehensive, standardized assessments of sensory profiles in order to fully characterize its effect on sensory perception and to explore the predictive value of sensory profiles for the effectiveness of acupuncture.

Positive affect moderates the effect of negative affect on cardiovascular disease-related hospitalizations and all-cause mortality after cardiac rehabilitation

BACKGROUND Little is known as to whether negative emotions adversely impact the prognosis of patients who undergo cardiac rehabilitation. We prospectively investigated the predictive value of state negative affect (NA) assessed at discharge from cardiac rehabilitation for prognosis and the moderating role of positive affect (PA) on the effect of NA on outcomes. METHODS A total of 564 cardiac patients (62.49 ± 11.51) completed a comprehensive three-month outpatient cardiac rehabilitation program, filling in the Global Mood Scale (GMS) at discharge. The combined endpoint was cardiovascular disease (CVD)-related hospitalizations plus all-cause mortality at follow-up. Cox regression models estimated the predictive value of NA, as well as the moderating influence of PA on outcomes. Survival models were adjusted for sociodemographic factors, traditional cardiovascular risk factors, and severity of disease. RESULTS During a mean follow-up period of 3.4 years, 71 patients were hospitalized for a CVD-related event and 15 patients died. NA score (range 0-20) was a significant and independent predictor (hazard ratio (HR) 1.091, 95% confidence interval (CI) 1.012-1.175; p = 0.023) with a three-point higher level in NA increasing the relative risk by 9.1%. Furthermore, PA interacted significantly with NA (p < 0.001). The relative risk of poor prognosis with NA was increased in patients with low PA (p = 0.012) but remained unchanged in combination with high PA (p = 0.12). CONCLUSION The combination of NA with low PA was particularly predictive of poor prognosis. Whether reduction of NA and increase of PA, particularly in those with high NA, improves outcome needs to be tested.

Derivation and validation of multimarker prognostication for normotensive patients with acute symptomatic pulmonary embolism.

RATIONALE Not all patients with acute pulmonary embolism (PE) have a high risk of an adverse short-term outcome. OBJECTIVES This prospective cohort study aimed to develop a multimarker prognostic model that accurately classifies normotensive patients with PE into low and high categories of risk of adverse medical outcomes. METHODS The study enrolled 848 outpatients from the PROTECT (PROgnosTic valuE of Computed Tomography) study (derivation cohort) and 529 patients from the Prognostic Factors for Pulmonary Embolism (PREP) study (validation cohort). Investigators assessed study participants for a 30-day complicated course, defined as death from any cause, hemodynamic collapse, and/or adjudicated recurrent PE. MEASUREMENTS AND MAIN RESULTS A complicated course occurred in 63 (7.4%) of the 848 normotensive patients with acute symptomatic PE in the derivation cohort and in 24 patients (4.5%) in the validation cohort. The final model included the simplified Pulmonary Embolism Severity Index, cardiac troponin I, brain natriuretic peptide, and lower limb ultrasound testing. The model performed similarly in the derivation (c-index of 0.75) and validation (c-index of 0.85) cohorts. The combination of the simplified Pulmonary Embolism Severity Index and brain natriuretic peptide testing showed a negative predictive value for a complicated course of 99.1 and 100% in the derivation and validation cohorts, respectively. The combination of all modalities had a positive predictive value for the prediction of a complicated course of 25.8% in the derivation cohort and 21.2% in the validation cohort. CONCLUSIONS For normotensive patients who have acute PE, we derived and validated a multimarker model that predicts all-cause mortality, hemodynamic collapse, and/or recurrent PE within the following 30 days.

A novel universal DNA labeling and amplification system for rapid microarray-based detection of 117 antibiotic resistance genes in Gram-positive bacteria.

A rapid and simple DNA labeling system has been developed for disposable microarrays and has been validated for the detection of 117 antibiotic resistance genes abundant in Gram-positive bacteria. The DNA was fragmented and amplified using phi-29 polymerase and random primers with linkers. Labeling and further amplification were then performed by classic PCR amplification using biotinylated primers specific for the linkers. The microarray developed by Perreten et al. (Perreten, V., Vorlet-Fawer, L., Slickers, P., Ehricht, R., Kuhnert, P., Frey, J., 2005. Microarray-based detection of 90 antibiotic resistance genes of gram-positive bacteria. J.Clin.Microbiol. 43, 2291-2302.) was improved by additional oligonucleotides. A total of 244 oligonucleotides (26 to 37 nucleotide length and with similar melting temperatures) were spotted on the microarray, including genes conferring resistance to clinically important antibiotic classes like β-lactams, macrolides, aminoglycosides, glycopeptides and tetracyclines. Each antibiotic resistance gene is represented by at least 2 oligonucleotides designed from consensus sequences of gene families. The specificity of the oligonucleotides and the quality of the amplification and labeling were verified by analysis of a collection of 65 strains belonging to 24 species. Association between genotype and phenotype was verified for 6 antibiotics using 77 Staphylococcus strains belonging to different species and revealed 95% test specificity and a 93% predictive value of a positive test. The DNA labeling and amplification is independent of the species and of the target genes and could be used for different types of microarrays. This system has also the advantage to detect several genes within one bacterium at once, like in Staphylococcus aureus strain BM3318, in which up to 15 genes were detected. This new microarray-based detection system offers a large potential for applications in clinical diagnostic, basic research, food safety and surveillance programs for antimicrobial resistance.

Pulmonary veins to left atrium cycle length gradient predicts procedural and clinical outcomes of persistent atrial fibrillation ablation.

BACKGROUND Rapid pulmonary vein (PV) activity has been shown to maintain paroxysmal atrial fibrillation (AF). We evaluated in persistent AF the cycle length (CL) gradient between PVs and the left atrium (LA) in an attempt to identify the subset of patients where PVs play an important role. METHODS AND RESULTS Ninety-seven consecutive patients undergoing first ablation for persistent AF were studied. For each PV, the CL of the fastest activation was assessed over 1 minute (PVfast) using Lasso recordings. The PV to LA CL gradient was quantified by the ratio of PVfast to LA appendage (LAA) AF CL. Stepwise ablation terminated AF in 73 patients (75%). In the AF termination group, the PVfast CL was much shorter than the LAA CL resulting in lower PVfast/LAA ratios compared with the nontermination group (71±10% versus 92±7%; P<0.001). Within the termination group, PVfast/LAA ratios were notably lower if AF terminated after PV isolation or limited adjunctive substrate ablation compared with patients who required moderate or extensive ablation (63±6% versus 75±8%; P<0.001). PVfast/LAA ratio <69% predicted AF termination after PV isolation or limited substrate ablation with 74% positive predictive value and 95% negative predictive value. After a mean follow-up of 29±17 months, freedom from arrhythmia recurrence off-antiarrhythmic drugs was achieved in most patients with PVfast/LAA ratios <69% as opposed to the remaining population (80% versus 43%; P<0.001). CONCLUSIONS The PV to LA CL gradient may identify the subset of patients in whom persistent AF is likely to terminate after PV isolation or limited substrate ablation and better long-term outcomes are achieved.

Circulating microRNA profiling in patients with advanced non-squamous NSCLC receiving bevacizumab/erlotinib followed by platinum-based chemotherapy at progression (SAKK 19/05).

OBJECTIVES Molecular subclassification of non small-cell lung cancer (NSCLC) is essential to improve clinical outcome. This study assessed the prognostic and predictive value of circulating micro-RNA (miRNA) in patients with non-squamous NSCLC enrolled in the phase II SAKK (Swiss Group for Clinical Cancer Research) trial 19/05, receiving uniform treatment with first-line bevacizumab and erlotinib followed by platinum-based chemotherapy at progression. MATERIALS AND METHODS Fifty patients with baseline and 24 h blood samples were included from SAKK 19/05. The primary study endpoint was to identify prognostic (overall survival, OS) miRNA's. Patient samples were analyzed with Agilent human miRNA 8x60K microarrays, each glass slide formatted with eight high-definition 60K arrays. Each array contained 40 probes targeting each of the 1347 miRNA. Data preprocessing included quantile normalization using robust multi-array average (RMA) algorithm. Prognostic and predictive miRNA expression profiles were identified by Spearman's rank correlation test (percentage tumor shrinkage) or log-rank testing (for time-to-event endpoints). RESULTS Data preprocessing kept 49 patients and 424 miRNA for further analysis. Ten miRNA's were significantly associated with OS, with hsa-miR-29a being the strongest prognostic marker (HR=6.44, 95%-CI 2.39-17.33). Patients with high has-miR-29a expression had a significantly lower survival at 10 months compared to patients with a low expression (54% versus 83%). Six out of the 10 miRNA's (hsa-miRN-29a, hsa-miR-542-5p, hsa-miR-502-3p, hsa-miR-376a, hsa-miR-500a, hsa-miR-424) were insensitive to perturbations according to jackknife cross-validation on their HR for OS. The respective principal component analysis (PCA) defined a meta-miRNA signature including the same 6 miRNA's, resulting in a HR of 0.66 (95%-CI 0.53-0.82). CONCLUSION Cell-free circulating miRNA-profiling successfully identified a highly prognostic 6-gene signature in patients with advanced non-squamous NSCLC. Circulating miRNA profiling should further be validated in external cohorts for the selection and monitoring of systemic treatment in patients with advanced NSCLC.

Is surgery in acute aortic dissection type A still contraindicated in the presence of preoperative neurological symptoms?

OBJECTIVES Severe neurological deficit (ND) due to acute aortic dissection type A (AADA) was considered a contraindication for surgery because of poor prognosis. Recently, more aggressive indication for surgery despite neurological symptoms has shown acceptable postoperative clinical results. The aim of this study was to evaluate early and mid-term outcomes of patients with AADA presenting with acute ND. METHODS Data from 53 patients with new-onset ND who received surgical repair for AADA between 2005 and 2012 at our institution were retrospectively reviewed. ND was defined as focal motor or sensory deficit, hemiplegia, paraplegia, convulsions or coma. Neurological symptoms were evaluated preoperatively using the Glasgow Coma Scale (GCS) and modified Rankin Scale (mRS), and at discharge as well as 3-6 months postoperatively using the mRS and National Institutes of Health Stroke Scale. Involvement of carotid arteries was assessed in the pre- and postoperative computed tomography. Logistic regression analysis was performed to detect predictive factors for recovery of ND. RESULTS Of the 53 patients, 29 (54.7%) showed complete recovery from focal ND at follow-up. Neurological symptoms persisted in 24 (45.3%) patients, of which 8 (33%) died without neurological assessment at follow-up. Between the two groups (patients with recovery and those with persisting ND), there was no significant difference regarding the duration of hypothermic circulatory arrest (28 ± 14 vs 36 ± 20 min) or severely reduced consciousness (GCS <8). Multivariate analysis showed significant differences for the preoperative mRS between the two groups (P < 0.007). A high preoperative mRS was associated with persistence of neurological symptoms (P < 0.02). Cardiovascular risk factors, age or involvement of supra-aortic branches were not predictive for persistence of ND. CONCLUSION More than half of our patients recovered completely from ND due to AADA after surgery. Severity of clinical symptoms had a predictive value. Patients suffering from AADA and presenting with ND before surgery should not be excluded from emergency surgery.

Post-therapeutic response evaluation by a combination of endoscopy and CT scan in esophagogastric adenocarcinoma after chemotherapy: better than its reputation.

BACKGROUND Neoadjuvant chemotherapy is an accepted standard of care for locally advanced esophagogastric cancer. As only a subgroup benefits, a response-based tailored treatment would be of interest. The aim of our study was the evaluation of the prognostic and predictive value of clinical response in esophagogastric adenocarcinomas. METHODS Clinical response based on a combination of endoscopy and computed tomography (CT) scan was evaluated retrospectively within a prospective database in center A and then transferred to center B. A total of 686/740 (A) and 184/210 (B) patients, staged cT3/4, cN0/1 underwent neoadjuvant chemotherapy and were then re-staged by endoscopy and CT before undergoing tumor resection. Of 184 patients, 118 (B) additionally had an interim response assessment 4-6 weeks after the start of chemotherapy. RESULTS In A, 479 patients (70 %) were defined as clinical nonresponders, 207 (30 %) as responders. Median survival was 38 months (nonresponders: 27 months, responders: 108 months, log-rank, p < 0.001). Clinical and histopathological response correlated significantly (p < 0.001). In multivariate analysis, clinical response was an independent prognostic factor (HR for death 1.4, 95 %CI 1.0-1.8, p = 0.032). In B, 140 patients (76 %) were nonresponders and 44 (24 %) responded. Median survival was 33 months, (nonresponders: 27 months, responders: not reached, p = 0.003). Interim clinical response evaluation (118 patients) also had prognostic impact (p = 0.008). Interim, preoperative clinical response and histopathological response correlated strongly (p < 0.001). CONCLUSION Preoperative clinical response was an independent prognostic factor in center A, while in center B its prognostic value could only be confirmed in univariate analysis. The accordance with histopathological response was good in both centers, and interim clinical response evaluation showed comparable results to preoperative evaluation.

A retrospective comparative exploratory study on two methylentetrahydrofolate reductase (MTHFR) polymorphisms in esophagogastric cancer: the A1298C MTHFR polymorphism is an independent prognostic factor only in neoadjuvantly treated gastric cancer patients.

BACKGROUND Methylentetrahydrofolate reductase (MTHFR) plays a major role in folate metabolism and consequently could be an important factor for the efficacy of a treatment with 5-fluorouracil. Our aim was to evaluate the prognostic and predictive value of two well characterized constitutional MTHFR gene polymorphisms for primarily resected and neoadjuvantly treated esophagogastric adenocarcinomas. METHODS 569 patients from two centers were analyzed (gastric cancer: 218, carcinoma of the esophagogastric junction (AEG II, III): 208 and esophagus (AEG I): 143). 369 patients received neoadjuvant chemotherapy followed by surgery, 200 patients were resected without preoperative treatment. The MTHFR C677T and A1298C polymorphisms were determined in DNA from peripheral blood lymphozytes. Associations with prognosis, response and clinicopathological factors were analyzed retrospectively within a prospective database (chi-square, log-rank, cox regression). RESULTS Only the MTHFR A1298C polymorphisms had prognostic relevance in neoadjuvantly treated patients but it was not a predictor for response to neoadjuvant chemotherapy. The AC genotype of the MTHFR A1298C polymorphisms was significantly associated with worse outcome (p = 0.02, HR 1.47 (1.06-2.04). If neoadjuvantly treated patients were analyzed based on their tumor localization, the AC genotype of the MTHFR A1298C polymorphisms was a significant negative prognostic factor in patients with gastric cancer according to UICC 6th edition (gastric cancer including AEG type II, III: HR 2.0, 95% CI 1.3-2.0, p = 0.001) and 7th edition (gastric cancer without AEG II, III: HR 2.8, 95% CI 1.5-5.7, p = 0.003), not for AEG I. For both definitions of gastric cancer the AC genotype was confirmed as an independent negative prognostic factor in cox regression analysis. In primarily resected patients neither the MTHFR A1298C nor the MTHFR C677T polymorphisms had prognostic impact. CONCLUSIONS The MTHFR A1298C polymorphisms was an independent prognostic factor in patients with neoadjuvantly treated gastric adenocarcinomas (according to both UICC 6th or 7th definitions for gastric cancer) but not in AEG I nor in primarily resected patients, which confirms the impact of this enzyme on chemotherapy associated outcome.

Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions.

OBJECTIVE To systematically review evidence on genetic risk factors for carbamazepine (CBZ)-induced hypersensitivity reactions (HSRs) and provide practice recommendations addressing the key questions: (1) Should genetic testing for HLA-B*15:02 and HLA-A*31:01 be performed in patients with an indication for CBZ therapy to reduce the occurrence of CBZ-induced HSRs? (2) Are there subgroups of patients who may benefit more from genetic testing for HLA-B*15:02 or HLA-A*31:01 compared to others? (3) How should patients with an indication for CBZ therapy be managed based on their genetic test results? METHODS A systematic literature search was performed for HLA-B*15:02 and HLA-A*31:01 and their association with CBZ-induced HSRs. Evidence was critically appraised and clinical practice recommendations were developed based on expert group consensus. RESULTS Patients carrying HLA-B*15:02 are at strongly increased risk for CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in populations where HLA-B*15:02 is common, but not CBZ-induced hypersensitivity syndrome (HSS) or maculopapular exanthema (MPE). HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported from Asian countries only, including China, Thailand, Malaysia, and India. HLA-B*15:02 is rare among Caucasians or Japanese; no HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported so far in these groups. HLA-A*31:01-positive patients are at increased risk for CBZ-induced HSS and MPE, and possibly SJS/TEN and acute generalized exanthematous pustulosis (AGEP). This association has been shown in Caucasian, Japanese, Korean, Chinese, and patients of mixed origin; however, HLA-A*31:01 is common in most ethnic groups. Not all patients carrying either risk variant develop an HSR, resulting in a relatively low positive predictive value of the genetic tests. SIGNIFICANCE This review provides the latest update on genetic markers for CBZ HSRs, clinical practice recommendations as a basis for informed decision making regarding the use of HLA-B*15:02 and HLA-A*31:01 genetic testing in patients with an indication for CBZ therapy, and identifies knowledge gaps to guide future research. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Clinical herniation – how to improve differentiation between WFNS grade IV and V

Objective: Current data show a favorable outcome after poor grade subarachnoid hemorrhage (SAH) in up to 50% of patients. This limits the use of the WFNS scale for drawing treatment decisions. We therefore analyzed how clinical signs of herniation might improve the existing WFNS grading. Therefore we compared the current WFNS grading and a modified WFNS grading with respect to outcome. Method: We performed a retrospective study including 182 poor grade SAH patients. Patients were graded according to the original WFNS scale and additionally into a modified classification the “WFNS herniation” (WFNSh grade IV: no herniation; grade V clinical signs of herniation). Outcome was compared between these two grading systems with respect to the dichotomized modified Rankin scale after 6 months. Results: The WFNS and WFNSh showed a positive predictive value (PPV) for poor outcome of 74.3% (OR 3.79, 95% confidence interval [CI]=1.94, 7.54) and 85.7% (OR 8.27, 95% CI=3.78, 19.47), respectively. With respect to mortality the PPV was 68.3% (OR 3.9, 95% CI=2.01, 7.69) for the WFNS grade V and 77.9% (OR 6.22, 95% CI=3.07, 13.14) for the WFNSh grade V. Conclusions: Using positive clinical signs of herniation instead of “no response to pain stimuli” (motor Glasgow Coma Scale Score) can improve WFNS V grading. Using this modification, prediction of poor outcome or death improves.

Impact of development of job control and task-related stressors on resigned job attitude.

With more experience in the labor market, some job characteristics increase, some decrease. For example, among young employees who just entered the labor market, job control may initially be low but increase with more routine and experience. Job control is a job resource that is valued in itself and is positively associated with job satisfaction; but job control also helps dealing with stressors at work. There is little research on correlated changes, but the existing evidence suggests a joint development over time. However, even less is known about the relevance of such changes for employees. Usually, research tends to use mean levels to predict mean levels in outcomes but development in job control and stressors may be as relevant for job satisfaction as having a certain level in those job characteristics. Job satisfaction typically is regarded as a positive attitude towards one’s work. What has received less attention is that some employees may lower their expectations if their job situation does not reflect their needs, resulting in a resigned attitude towards one’s job. The present study investigates the development of job control and task-related stressors over ten years and tests the predictive value of changes in job control and task-related stressors for resigned attitude towards one’s job. We used data from a Swiss panel study (N=356) ranging over ten years. Job control, task-related stressors (an index consisting of time pressure, concentration demands, performance constraints, interruptions, and uncertainty about tasks), and resigned attitude towards one’s job were assessed in 1998, 1999, 2001, and 2008. Latent growth modeling revealed that growth rates of job control and task-related stressors were not correlated with one another. We predicted resigned attitude towards one’s job in 2008 a) by initial levels, and b) by changes in job control and stressors, controlling for resigned attitude in 1998. There was some prediction by initial levels (job control: β = -.15, p < .05; task-related stressors: β = .12, p = .06). However, as expected, changes in control and stressors predicted resigned attitude much better, with β = -.37, p < .001, for changes in job control, and β = .31, p < .001, for changes in task-related stressors. Our data confirm the importance of having low levels of task-related stressors and higher levels of job control for job attitudes. However, development in these job characteristics seems even more important than initial levels.

What is the best time point to identify patients at risk of developing persistent low back pain?

BACKGROUND Early identification of patients at risk of developing persistent low back pain (LBP) is crucial. OBJECTIVE Aim of this study was to identify in patients with a new episode of LBP the time point at which those at risk of developing persistent LBP can be best identified.METHODS: Prospective cohort study of 315 patients presenting to a health practitioner with a first episode of acute LBP. Primary outcome measure was functional limitation. Patients were assessed at baseline, three, six, twelve weeks and six months looking at factors of maladaptive cognition as potential predictors. Multivariate logistic regression analysis was performed for all time points. RESULTS The best time point to predict the development of persistent LBP at six months was the twelve-week follow-up (sensitivity 78%; overall predictive value 90%). Cognitions assessed at first visit to a health practitioner were not predictive. CONCLUSIONS Maladaptive cognitions at twelve weeks appear to be suitable predictors for a transition from acute to persistent LBP. Already three weeks after patients present to a health practitioner with acute LBP cognitions might influence the development of persistent LBP. Therefore, cognitive-behavioral interventions should be considered as early adjuvant LBP treatment in patients at risk of developing persistent LBP.