Impact of sepsis on risk of postoperative arterial and venous thromboses: large prospective cohort study

OBJECTIVES To evaluate the impact of preoperative sepsis on risk of postoperative arterial and venous thromboses. DESIGN Prospective cohort study using the National Surgical Quality Improvement Program database of the American College of Surgeons (ACS-NSQIP). SETTING Inpatient and outpatient procedures in 374 hospitals of all types across the United States, 2005-12. PARTICIPANTS 2,305,380 adults who underwent surgical procedures. MAIN OUTCOME MEASURES Arterial thrombosis (myocardial infarction or stroke) and venous thrombosis (deep venous thrombosis or pulmonary embolism) in the 30 days after surgery. RESULTS Among all surgical procedures, patients with preoperative systemic inflammatory response syndrome or any sepsis had three times the odds of having an arterial or venous postoperative thrombosis (odds ratio 3.1, 95% confidence interval 3.0 to 3.1). The adjusted odds ratios were 2.7 (2.5 to 2.8) for arterial thrombosis and 3.3 (3.2 to 3.4) for venous thrombosis. The adjusted odds ratios for thrombosis were 2.5 (2.4 to 2.6) in patients with systemic inflammatory response syndrome, 3.3 (3.1 to 3.4) in patients with sepsis, and 5.7 (5.4 to 6.1) in patients with severe sepsis, compared with patients without any systemic inflammation. In patients with preoperative sepsis, both emergency and elective surgical procedures had a twofold increased odds of thrombosis. CONCLUSIONS Preoperative sepsis represents an important independent risk factor for both arterial and venous thromboses. The risk of thrombosis increases with the severity of the inflammatory response and is higher in both emergent and elective surgical procedures. Suspicion of thrombosis should be higher in patients with sepsis who undergo surgery.

Prospective randomised comparison of diagnostic confidence and image quality with normal-dose and low-dose CT pulmonary angiography at various body weights.

OBJECTIVES To find a threshold body weight (BW) below 100 kg above which computed tomography pulmonary angiography (CTPA) using reduced radiation and a reduced contrast material (CM) dose provides significantly impaired quality and diagnostic confidence compared with standard-dose CTPA. METHODS In this prospectively randomised study of 501 patients with suspected pulmonary embolism and BW <100 kg, 246 were allocated into the low-dose group (80 kVp, 75 ml CM) and 255 into the normal-dose group (100 kVp, 100 ml CM). Contrast-to-noise ratio (CNR) in the pulmonary trunk was calculated. Two blinded chest radiologists independently evaluated subjective image quality and diagnostic confidence. Data were compared between the normal-dose and low-dose groups in five BW subgroups. RESULTS Vessel attenuation did not differ between the normal-dose and low-dose groups within each BW subgroup (P = 1.0). The CNR was higher with the normal-dose compared with the low-dose protocol (P < 0.006) in all BW subgroups except for the 90-99 kg subgroup (P = 0.812). Subjective image quality and diagnostic confidence did not differ between CT protocols in all subgroups (P between 0.960 and 1.0). CONCLUSIONS Subjective image quality and diagnostic confidence with 80 kVp CTPA is not different from normal-dose protocol in any BW group up to 100 kg. KEY POINTS • 80 kVp CTPA is safe in patients weighing <100 kg • Reduced radiation and iodine dose still provide high vessel attenuation • Image quality and diagnostic confidence with low-dose CTPA is good • Diagnostic confidence does not deteriorate in obese patients weighing <100 kg.

Total Tumor Volume and Alpha Fetoprotein for selection of transplant candidates with hepatocellular carcinoma: A prospective validation.

The selection of liver transplant candidates with hepatocellular carcinoma (HCC) is currently validated based on Milan criteria. The use of extended criteria has remained a matter of debate, mainly because of the absence of prospective validation. The present prospective study recruited patients according to the previously proposed Total Tumor Volume (TTV ≤115 cm(3) )/alpha fetoprotein (AFP ≤400 ng/ml) score. Patients with AFP >400 ng/ml were excluded, and as such the Milan group was modified to include only patients with AFP <400 ng/ml; these patients were compared to patients beyond Milan, but within TTV/AFP. From January 2007 to March 2013, 233 patients with HCC were listed for liver transplantation. Of them, 195 patients were within Milan, and 38 beyond Milan but within TTV/AFP. The average follow-up from listing was 33,9 ±24,9 months. The risk of drop-out was higher for patients beyond Milan but within TTV/AFP (16/38, 42,1%), than for patients within Milan (49/195, 25,1%, p=0,033). In parallel, intent-to-treat survival from listing was lower in the patients beyond Milan (53,8% vs. 71,6% at four years, p<0,001). After a median waiting time of 8 months, 166 patients were transplanted, 134 patients within Milan criteria, and 32 beyond Milan but within TTV/AFP. They demonstrated acceptable and similar recurrence rates (4,5% vs. 9,4%, p=0,138) and post-transplant survivals (78,7% vs. 74,6% at four years, p=0,932). CONCLUSION Based on the present prospective study, HCC liver transplant candidate selection could be expanded to the TTV (≤115 cm(3) )/AFP (≤400 ng/ml) criteria in centers with at least 8-month waiting time. An increased risk of drop-out on the waiting list can be expected but with equivalent and satisfactory post-transplant survival. This article is protected by copyright. All rights reserved.

Rumination mediates the prospective effect of low self-esteem on depression: A five-wave longitudinal study

Previous research supports the vulnerability model of low self-esteem and depression, which states that low self-esteem operates as a prospective risk factor for depression. However, it is unclear which processes mediate the effect of low self-esteem. To test for the mediating effect of rumination, the authors used longitudinal mediation models, which included exclusively prospective effects and controlled for autoregressive effects of the constructs. Data came from 663 individuals (aged 16 to 62 years), who were assessed 5 times over an 8-month period. The results indicated that low self-esteem predicted subsequent rumination, which in turn predicted subsequent depression, and that rumination partially mediated the prospective effect of low self-esteem on depression. These findings held for both men and women, and for both affective-cognitive and somatic symptoms of depression. Future studies should test for the mediating effects of additional intrapersonal and interpersonal processes.

Switch to etravirine for HIV-positive patients receiving statin treatment: a prospective study

BACKGROUND Life style changes and statins are the cornerstones in management of dyslipidemia in HIV-infected patients. Replacement of an antiretroviral therapy (ART) component is a proposed therapeutic strategy to reduce cardiovascular risk. In dyslipidemic HIV-positive patients, we assessed the efficacy of replacing boosted protease inhibitor (bPI) or efavirenz (EFV) by etravirine (ETR) as an alternative to statin therapy. MATERIALS AND METHODS A prospective, open-label, multicentre, 12-week study of HIV-infected patients on ART including bPI or EFV, and statin treatment. Four weeks after statin interruption, bPI or EFV were switched to ETR (400 mg, 8 weeks) if serum low-density lipoprotein cholesterol (LDL-c) was ≥ 3 mmol/L. The primary endpoint was the proportion of patients on ETR with no indication for statin treatment at study completion. Serum levels of HIV-RNA, lipids, and biomarkers of cardiovascular disease were also measured. (ClinicalTrialsgov: NCT01543035). RESULTS The 31 included patients had a HIV1-RNA <50 copies/mL (median age, 52 years; median CD4, 709 cell/mL; median LDL-c, 2.89 mmol/L), 68% were on EFV, 32% on bPI. At week 4, 27 patients switched to ETR. At study completion, 15 patients (56%) on ETR did not qualify for statin treatment. After the ETR switch, serum levels of the cardiovascular biomarkers sICAM and MCP1/CCL2 decreased by 11.2% and 18.9%, respectively, and those of CCL5/RANTES and tissue inhibitor of metalloproteinase-1 increased by 14.3% and 13.4%, respectively, indicating reduced cardiovascular risk. There were no notable treatment-related adverse events. CONCLUSIONS Replacing bPI or EFV by ETR is a viable strategy to obviate primary prevention statin treatment. This article is protected by copyright. All rights reserved.

Quality of life after pulmonary embolism: Prospective validation of the German version of the PEmb-QoL questionnaire.

BACKGROUND The Pulmonary Embolism Quality of Life questionnaire (PEmb-QoL) is a 40-item questionnaire to measure health-related quality of life in patients with pulmonary embolism. It covers six 6 dimensions: frequency of complaints, limitations in activities of daily living, work-related problems, social limitations, intensity of complaints, and emotional complaints. Originally developed in Dutch and English, we prospectively validated a German version of the PEmb-QoL. METHODS A forward-backward translation of the English version of the PEmb-QoL into German was performed. German-speaking consecutive adult patients aged ≥18 years with an acute, objectively confirmed pulmonary embolism discharged from a Swiss university hospital (01/2011-06/2013) were recruited telephonically. Established psychometric tests and criteria were used to evaluate the acceptability, reliability, and validity of the German PEmb-QoL questionnaire. To assess the underlying dimensions, an exploratory factor analysis was performed. RESULTS Overall, 102 patients were enrolled in the study. The German version of the PEmb-QoL showed a good internal consistency (Cronbach's alpha ranging from 0.72 to 0.96), item-total (0.53-0.95) and inter-item correlations (>0.4), and test-retest reliability (intra-class correlation coefficients 0.59-0.89) for the dimension scores. A moderate correlation of the PEmb-QoL with SF-36 dimension and summary scores (0.21-0.83) indicated convergent validity, while low correlations of PEmb-QoL dimensions with clinical characteristics (-0.16-0.37) supported discriminant validity. The exploratory factor analysis suggested four underlying dimensions: limitations in daily activities, symptoms, work-related problems, and emotional complaints. CONCLUSION The German version of the PEmb-QoL questionnaire is a valid and reliable disease-specific measure for quality of life in patients with pulmonary embolism.

Biological variation of established and novel biomarkers for atherosclerosis: Results from a prospective, parallel-group cohort study.

BACKGROUND Biomarkers are a promising tool for the management of patients with atherosclerosis, but their variation is largely unknown. We assessed within-subject and between-subject biological variation of biomarkers in peripheral artery disease (PAD) patients and healthy controls, and defined which biomarkers have a favorable variation profile for future studies. METHODS Prospective, parallel-group cohort study, including 62 patients with stable PAD (79% men, 65±7years) and 18 healthy control subjects (44% men, 57±7years). Blood samples were taken at baseline, and after 3-, 6-, and 12-months. We calculated within-subject (CVI) and between-subject (CVG) coefficients of variation and intra-class correlation coefficient (ICC). RESULTS Mean levels of D-dimer, hs-CRP, IL-6, IL-8, MMP-9, MMP-3, S100A8/A9, PAI-1, sICAM-1, and sP-selectin levels were higher in PAD patients than in healthy controls (P≤.05 for all). CVI and CVG of the different biomarkers varied considerably in both groups. An ICC≥0.5 (indicating moderate-to-good reliability) was found for hs-CRP, D-Dimer, E-selectin, IL-10, MCP-1, MMP-3, oxLDL, sICAM-1 and sP-selectin in both groups, for sVCAM in healthy controls and for MMP-9, PAI-1 and sCD40L in PAD patients. CONCLUSIONS Single biomarker measurements are of limited utility due to large within-subject variation, both in PAD patients and healthy subjects. D-dimer, hs-CRP, MMP-9, MMP-3, PAI-1, sP-selectin and sICAM-1 are biomarkers with both higher mean levels in PAD patients and a favorable variation profile making them most suitable for future studies.

Loads and loads and loads: the influence of prospective load, retrospective load, and ongoing task load in prospective memory

In prospective memory tasks different kinds of load can occur. Adding a prospective memory task can impose a load on ongoing task performance. Adding ongoing task load (OTL) can affect prospective memory performance. The existence of multiple target events increases prospective load (PL) and adding complexity to the to-be-remembered action increases retrospective load (RL). In two experiments, we systematically examined the effects of these different types of load on prospective memory performance. Results showed an effect of PL on costs in the ongoing task for categorical targets (Experiment 2), but not for specific targets (Experiment 1). RL and OTL both affected remembering the retrospective component of the prospective memory task. We suggest that PL can enhance costs in the ongoing task due to additional monitoring requirements. RL and OTL seem to impact the division of resources between the ongoing task and retrieval of the retrospective component, which may affect disengagement from the ongoing task. In general, the results demonstrate that the different types of load affect prospective memory differentially.

Long-term results of a prospective randomised trial assessing the impact of readaptation of the dorsolateral peritoneal layer following extended pelvic lymph node dissection and cystectomy.

OBJECTIVE To evaluate the long term oncological and functional outcomes after readaptation of the dorsolateral peritoneal layer following pelvic lymph node dissection (PLND) and cystectomy . PATIENTS AND METHODS A randomised, single-center, single-blinded, two-arm trial was conducted on 200 consecutive cystectomy patients who underwent PLND and cystectomy for bladder cancer (

Effect of large doses of parenteral vitamin D on glycaemic control and calcium/phosphate metabolism in patients with stable type 2 diabetes mellitus: a randomised, placebo-controlled, prospective pilot study.

OBJECTIVE Vitamin D (D₃) status is reported to correlate negatively with insulin production and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). However, few placebo-controlled intervention data are available. We aimed to assess the effect of large doses of parenteral D3 on glycosylated haemoglobin (HbA(₁c)) and estimates of insulin action (homeostasis model assessment insulin resistance: HOMA-IR) in patients with stable T2DM. MATERIALS AND METHODS We performed a prospective, randomised, double-blind, placebo-controlled pilot study at a single university care setting in Switzerland. Fifty-five patients of both genders with T2DM of more than 10 years were enrolled and randomised to either 300,000 IU D₃ or placebo, intramuscularly. The primary endpoint was the intergroup difference in HbA(₁c) levels. Secondary endpoints were: changes in insulin sensitivity, albuminuria, calcium/phosphate metabolism, activity of the renin-aldosterone axis and changes in 24-hour ambulatory blood pressure values. RESULTS After 6 months of D₃ supply, there was a significant intergroup difference in the change in HbA(₁c) levels (relative change [mean ± standard deviation] +2.9% ± 1.5% in the D₃ group vs +6.9% ± 2.1% the in placebo group, p = 0.041) as HOMA-IR decreased by 12.8% ± 5.6% in the D₃ group and increased by 10% ± 5.4% in the placebo group (intergroup difference, p = 0.032). Twenty-four-hour urinary albumin excretion decreased in the D₃ group from 200 ± 41 to 126 ± 39, p = 0.021). There was no significant intergroup difference for the other secondary endpoints. CONCLUSIONS D₃ improved insulin sensitivity (based on HOMA-IR) and affected the course of HbA(₁c) positively compared with placebo in patients with T2DM.

Stent placement vs. balloon angioplasty for popliteal artery treatment: two-year results of a prospective, multicenter, randomized trial.

PURPOSE To investigate the 2-year technical and clinical results of primary nitinol stent placement in comparison with percutaneous transluminal angioplasty (PTA) in the treatment of de novo lesions of the popliteal artery. METHODS The ETAP study (Endovascular Treatment of Atherosclerotic Popliteal Artery Lesions: balloon angioplasty vs. primary stenting; www.ClinicalTrials.gov identifier NCT00712309) is a prospective, randomized trial that enrolled 246 patients (158 men; mean age 72 years) who were randomly assigned to receive a nitinol stent (n=119) or PTA (n=127) for lesions averaging 42.3 mm in length. The results of the primary study endpoint were published. Secondary outcome measures and endpoints included primary patency (freedom from duplex-detected target lesion restenosis), target lesion revascularization (TLR), secondary patency, changes in ankle-brachial index and Rutherford class, and event-free survival (freedom from target limb amputation, TLR, myocardial infarction, and death). RESULTS In total, 183 patients (89 stent and 94 PTA) were available for the 2-year analysis. The primary patency rate was significantly higher in the stent group (64.2%) than in the PTA group (31.3%, p=0.0001). TLR rates were 22.4% and 59.5%, respectively (p=0.0001). When provisional stent placement in the PTA arm was not considered as TLR and loss in patency, the differences prevailed between the study groups but were not significant (64.2% vs. 56.1% for primary patency, respectively; p=0.44). A significant improvement in ABI and Rutherford category was observed at 2 years in both groups. CONCLUSION In treatment of obstructive popliteal artery lesions, provisional stenting reveals equivalent patency in comparison to primary stenting. However, the 2-year results of this trial suggest the possibility of a shift toward higher patency rates in favor of primary stenting.

After-effects and after-effects and after-effects of after-effects: The multiple side effects of prospective memory

In a prospective memory task responding to a prospective memory target involves switching between ongoing and prospective memory task which can result in a slowing of subsequent ongoing task performance (i.e., an after-effect). Moreover, a slowing can also occur when prospective memory targets occur after the prospective memory task is deactivated (i.e., another after-effect). In this study, we investigated both after-effects within the same study. Moreover, we also tested whether the latter after-effects even occur on subsequent ongoing task trials. The results show, in fact, after-effects of all kinds. Thus, (1) correctly responding to prospective memory targets results in after-effects, a so far neglected cost on ongoing task performance, (2) responding to deactivated prospective memory targets also slows down performance, probably due to the involuntary retrieval of the intention, and (3) this slowing is present even on subsequent ongoing task trials, suggesting that even deactivated intentions are sufficient to induce a conflict that requires subsequent adaptation. Overall, these results indicate that performance slowing in a prospective memory experiment includes various kinds of sources, not only monitoring cost, and these sources may be understood best in terms of conflict adaptation.

The impact of absolute importance and processing overlaps on prospective memory performance

Prospective memory is the ability to remember an intention at an appropriate moment in the future. Prospective memory tasks can be more or less important. Previously, importance was manipulated by emphasizing the importance of the prospective memory task relative to the ongoing task it was embedded in. This resulted in better prospective memory performance but also ongoing task costs. In the present study, we simply instructed one group of participants that the prospective memory task was important (i.e., absolute importance instruction) and compared them to a group with relative importance instructions and a control group. The results showed that absolute importance lead to an increase in prospective memory performance without enhancing ongoing task costs, whereas relative importance resulted in both increased prospective memory performance and ongoing task costs. Thus, prospective memory can be enhanced without ongoing task costs, which is particularly crucial for safety-work contexts.

Application, tolerance and safety of fondaparinux therapy in a German hospital: a prospective single-centre experience.

INTRODUCTION The pentasaccharide fondaparinux is widely approved for prophylaxis and treatment of thromboembolic diseases and therapy of acute coronary syndrome. It is also used off-label in patients with acute, suspected or antecedent heparin-induced thrombocytopenia (HIT). The aim of this prospective observational cohort study was to document fondaparinux' prescription practice, tolerance and therapy safety in a representative mixed German single-centre patient cohort. PATIENTS AND METHODS Between 09/2008 - 04/2009, 231 consecutive patients treated with fondaparinux were enrolled. Medical data were obtained from patient's records. The patients were clinically screened for thrombosis (Wells score), sequelae of HIT (4T's score), and bleeding complications (ISTH-criteria) and subjected to further assessment (i.e. sonography, HIT-diagnostics), if necessary. The mortality rate was assessed 30 days after therapy start. RESULTS Overall, 153/231 patients had a prophylactic, 74/231 patients a therapeutic, and 4/231 patients a successive prophylactic/therapeutic indication. In 11/231 patients fondaparinux was used due to suspected/antecedent HIT, in 5/231 patients due to a previous cutaneous delayed-type hypersensitivity to heparins. Other indications were rare. Three new/progressive thromboses were detected. No cases of HIT, major bleedings, or fatalities occurred. CONCLUSIONS Fondaparinux was well tolerated and was safe in prophylaxis and therapy; prescriptions mostly followed the current approval guidelines and were rarely related to HIT-associated indications (<5% of prescriptions), which is in contrast to previous study results in the U.S. (>94% of prescriptions were HIT-associated). A trend towards an individualised fondaparinux use based on the compound's inherent properties and the patients' risk profiles, i.e., antecedent HIT, bone fractures, heparin allergy, was observed.

Complementary passive hydrotherapy WATSU (WaterShiatsu) in the rehabilitation of a severely traumatized accident survivor – A prospective case report

Introduction: The implementation of complementary and alternative therapies into conventional treatment schemes is gaining popularity. However, their use is widely depending on patients’ drive. This case-report focuses on a patient’s experience of the integration of WATSU (WaterShiatsu) in rehabilitative care. Methods: Patient: A 52 year old woman survived a severe motorcycle-accident in which she sustained several fractures on the right side of her body, including ribs, pelvis, and femur. After discharge from stationary care, she independently added WATSU to her rehabilitative regimen. Treatment approach: WATSU is a passive form of hydrotherapy in warm water that aims at relaxation, pain relief, and a sense of secureness. In the reported case, an experienced WATSU-therapist who is also trained in physiotherapy and psychosomatics delivered weekly sessions of one hour duration. Measures used: Qualitative data were collected by patient’s diary. Also the therapist’s notes including The Patient Specific Functional Scale (PSFS) were considered. Results: The patient associated WATSU with trunk mobilization (followed by ameliorated breath), reconciliation with her body, and emotional discharge. She ascribed WATSU lasting effects on her body-image. The therapist employed WATSU for careful mobilization and to equalize awareness throughout the body. The PSFS displayed continuous improvement in all categories except usage of public transportation. Due to complications (elevated inflammation markers) only 6 of 8 scheduled sessions were administered. Conclusions: WATSU was experienced helpful in approaching conditions that are difficult to address by conventional physiotherapy. In early rehabilitation, additional medical/physiotherapeutic skills of contributing complementary therapists are advocated.