Recurrence pattern after [(18)F]fluoroethyltyrosine-positron emission tomography-guided radiotherapy for high-grade glioma: a prospective study.

PURPOSE: To assess the failure pattern observed after (18)F fluoroethyltyrosine (FET) planning after chemo- and radiotherapy (RT) for high-grade glioma. METHODS: All patients underwent prospectively RT planning using morphological gross tumour volumes (GTVs) and biological tumour volumes (BTVs). The post-treatment recurrence tumour volumes (RTVs) of 10 patients were transferred on their CT planning. First, failure patterns were defined in terms of percentage of RTV located outside the GTV and BTV. Second, the location of the RTV with respect to the delivered dose distribution was assessed using the RTV's DVHs. Recurrences with >95% of their volume within 95% isodose line were considered as central recurrences. Finally, the relationship between survival and GTV/BTV mismatches was assessed. RESULTS: The median percentages of RTV outside the GTV and BTV were 41.8% (range, 10.5-92.4) and 62.8% (range, 34.2-81.1), respectively. The majority of recurrences (90%) were centrally located. Using a composite target volume planning formalism, the degree of GTV and BTV mismatch did not correlate with survivorship. CONCLUSIONS: The observed failure pattern after FET-PET planning and chemo-RT is primarily central. The target mismatch-survival data suggest that using FET-PET planning may counteract the possibility of BTV-related progression, which may have a detrimental effect on survival.

Improvements in readiness to change and drinking in primary care patients with unhealthy alcohol use: a prospective study.

BACKGROUND: The course of alcohol consumption and cognitive dimensions of behavior change (readiness to change, importance of changing and confidence in ability to change) in primary care patients are not well described. The objective of the study was to determine changes in readiness, importance and confidence after a primary care visit, and 6-month improvements in both drinking and cognitive dimensions of behavior change, in patients with unhealthy alcohol use. METHODS: Prospective cohort study of patients with unhealthy alcohol use visiting primary care physicians, with repeated assessments of readiness, importance, and confidence (visual analogue scale (VAS), score range 1-10 points). Improvements 6 months later were defined as no unhealthy alcohol use or any increase in readiness, importance, or confidence. Regression models accounted for clustering by physician and adjusted for demographics, alcohol consumption and related problems, and discussion with the physician about alcohol. RESULTS: From before to immediately after the primary care physician visit, patients (n = 173) had increases in readiness (mean +1.0 point), importance (+0.2), and confidence (+0.5) (all p < 0.002). In adjusted models, discussion with the physician about alcohol was associated with increased readiness (+0.8, p = 0.04). At 6 months, many participants had improvements in drinking or readiness (62%), drinking or importance (58%), or drinking or confidence (56%). CONCLUSION: Readiness, importance and confidence improve in many patients with unhealthy alcohol use immediately after a primary care visit. Six months after a visit, most patients have improvements in either drinking or these cognitive dimensions of behavior change.

Tibial or hip BMD predict clinical fracture risk equally well: results from a prospective study in 700 elderly Swiss women.

SUMMARY: In a randomly selected cohort of Swiss community-dwelling elderly women prospectively followed up for 2.8 +/- 0.6 years, clinical fractures were assessed twice yearly. Bone mineral density (BMD) measured at tibial diaphysis (T-DIA) and tibial epiphysis (T-EPI) using dual-energy X-ray absorptiometry (DXA) was shown to be a valid alternative to lumbar spine or hip BMD in predicting fractures. INTRODUCTION: A study was carried out to determine whether BMD measurement at the distal tibia sites of T-EPI and T-DIA is predictive of clinical fracture risk. METHODS: In a predefined representative cohort of Swiss community-dwelling elderly women aged 70-80 years included in the prospective, multi-centre Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture risk (SEMOF) study, fracture risk profile was assessed and BMD measured at the lumbar spine (LS), hip (HIP) and tibia (T-DIA and T-EPI) using DXA. Thereafter, clinical fractures were reported in a bi-yearly questionnaire. RESULTS: During 1,786 women-years of follow-up, 68 clinical fragility fractures occurred in 61 women. Older age and previous fracture were identified as risk factors for the present fractures. A decrease of 1 standard deviation in BMD values yielded a 1.5-fold (HIP) to 1.8-fold (T-EPI) significant increase in clinical fragility fracture hazard ratio (adjusted for age and previous fracture). All measured sites had comparable performance for fracture prediction (area under the curve range from 0.63 [LS] to 0.68 [T-EPI]). CONCLUSION: Fracture risk prediction with BMD measurements at T-DIA and T-EPI is a valid alternative to BMD measurements at LS or HIP for patients in whom these sites cannot be accessed for clinical, technical or practical reasons.

Health impact of sport and exercise in emerging adult men: a prospective study.

PURPOSE: Health benefits of sport and exercise are well documented in children, adolescents and adults, but little is known about emerging adulthood-a period of life characterized by significant demographic and developmental changes. The present study aimed to assess the health impact of changes in sport and exercise levels during that specific period of life. METHODS: The analysis used baseline and 15-month follow-up data (N = 4,846) from the cohort study on substance use risk factors. Associations between baseline exercise levels or changes in exercise levels and health indicators (i.e., health-related quality of life, depression, body mass index, alcohol dependence, nicotine dependence and cannabis use disorder) were measured using chi-squared tests and ANOVA. Direction of effects was tested using cross-lagged analysis. RESULTS: At baseline, all health indicator scores were observed to be better for regular exercisers than for other exercise levels. At follow-up, participants who had maintained regular exercise over time had better scores than those who had remained irregular exercisers or had discontinued, but their scores for health-related quality of life and depression were close to those of participants who had adopted regular exercise after the baseline questionnaire. Cross-lagged analysis indicated that regular exercise at baseline was a significant predictor of health-related quality of life and substance use dependence at follow-up, but was itself predicted only by health-related quality of life. CONCLUSIONS: From a health promotion perspective, this study emphasizes how important it is for emerging adult men to maintain, or adopt, regular sport and exercise.

Axillary Lymph Node Dissection for Sentinel Lymph Node Micrometastases May Be Safely Omitted in Early-Stage Breast Cancer Patients: Long-Term Outcomes of a Prospective Study.

OBJECTIVES: To evaluate the long-term disease-free and overall survival of patients with sentinel lymph node (SLN) micrometastases, in whom a completion axillary lymph node dissection (ALND) was systematically omitted. BACKGROUND: The use of step sectioning and immunohistochemistry for SLN analysis results in a more accurate histopathologic examination and a higher detection rate of micrometastases. However, the clinical relevance and therapeutic implications of SLN micrometastases remain a matter of debate. METHODS: In this prospective study, 236 SLN biopsies were performed in 234 consecutive early-stage breast cancer patients (T1, T2 </= 3 cm, cN0 M0) between 1998 and 2002. The SLN were examined by step sectioning and stained with hematoxylin and eosin and immunohistochemistry. None of the patients with negative SLN or SLN micrometastases (International Union Against Cancer classification, >.2 mm to </=2 mm) underwent a completion ALND or radiation to the axilla. Long-term overall and disease-free survivals were compared between patients with negative SLN and those with SLN micrometastases by log rank tests. RESULTS: The SLN was negative in 55% of patients (123 of 224). SLN micrometastases were detected in 27 patients (27 of 224, 12%). After a median follow-up of 77 months (range, 24-106 months), neither locoregional recurrences nor distant metastases occurred in any of the 27 patients with SLN micrometastases. There were no statistically significant differences for overall (P = .656), locoregional (P = .174), and axillary and distant disease-free survival (P = .15) between patients with negative SLN and SLN micrometastases. CONCLUSIONS: This analysis of unselected patients provides evidence that a completion level I and II ALND may be safely omitted in early-stage breast cancer patients with SLN micrometastases.

Targeting burn prevention in the paediatric population : a prospective study of children's burns in the Lausanne area.

QUESTION UNDER STUDY: Domestic accidents are an important problem in paediatric medicine. This study was designed to gain a better understanding of burn mechanisms and target prevention. METHODS: Children treated for burn lesions in the Department of Paediatric Surgery between August 2004 and August 2005 were included in this prospective study. The burn mechanisms, the children's ages and the circumstances in which children were burned as well as their home environment variables were analyzed. RESULTS: The current study included eighty-nine patients, aged between 2 months and 15 years. Seventy-eight percent were less than 5 years old. More than half were boys. Hot liquid scalding was the most frequent mechanism. There does not seem to be an increased risk in the immigrant population or in low economic status families. In most cases, an adult person was present at time of injury. CONCLUSIONS: If we were to describe the highest "at risk" candidate for a burn in our region, it would be a boy aged 15 months to 5 years who is burned by a cup of hot liquid on his hand, at home, around mealtime, in the presence of one or both parents. Reduced attention in the safe domestic setting is probably responsible.

High-density electric source imaging (esi) in focal epilepsy: a prospective study of 150 operated patients

Purpose: EEG is mandatory in the diagnosis of the epilepsy syndrome. However, its potential as imaging tool is still under estimated. In the present study, we aim to determine the prerequisites of maximal benefit of electric source imaging (ESI) to localize the irritative zone in patients with focal epilepsy. Methods: One hundred fifty patients suffering from focal epilepsy and with minimum 1 year postoperative follow-up were studied prospectively and blinded to the underlying diagnosis. We evaluated the influence of two important factors on sensitivity and specificity of ESI: the number of electrodes (low resolution, LR-ESI: <30 versus high resolution, HR-ESI: 128-256 electrodes), and the use of individual MRI (i-MRI) versus template MRI (t-MRI) as the head model. Findings: ESI had a sensitivity of 85% and a specificity of 87% when HR-ESI with i-MRI was used. Using LR-ESI, sensitivity decreased to 68%, or even 57% when only t-MRI was available. The sensitivity of HR-ESI/i-MRI compared favorably with those of MRI (76%), PET (69%) and ictal/interictal SPECT (64%). Interpretation: This study on a large patient group shows excellent sensitivity and specificity of ESI if 128 EEG channels or more are used for ESI and if the results are coregistered to the patient's individual MRI. Localization precision is as high as or even higher than established brain imagery techniques. HR-ESI appears to be a valuable additional imaging tool, given that larger electrode arrays are easily and rapidly applied with modern EEG equipment and that structural MRI is nearly always available for these patients.

Pregnancy outcome following maternal exposure to statins: a multicenter prospective study

Introduction Statin use in women of childbearing age is increasingly common. However, published data on pregnancy outcome after exposure to statins are scarce and conflicting. This contribution addresses the safety of statin use during pregnancy.Materials and Methods In a multi-centre (n = 11), prospective study we compared the outcomes of 249 women exposed during the 1st trimester of pregnancy to simvastatin (n = 124), atorvastatin (n = 67), pravastatin (n = 32), rosuvastatin (n = 18), fl uvastatin (n = 7) or cerivastatin (n = 1) with a control group exposed to agents known to be non-teratogenic (n = 249). Data were collected by members of the European Network of Teratology Information Services during individual risk counselling.Results The difference in the rate of major birth defects between the statinexposed and the control group was statistically insignificant (4.0% versus 2.7% OR 1.5; 95% CI 0.5-4.5, p = 0.44). The crude rate of spontaneous abortions (12.8% versus 7.1%, OR 1.9, 95% CI 1.0-3.6, p = 0.04) was higher in the exposed group. However, after adjustment to maternal age and gestational age at initial contact, the difference became insignificant. The rate of elective pregnancy-termination (8.8% versus 4.4%, p = 0.05) was higher and the rate of live births was lower in the exposed group (77.9% versus 88.4%, p = 0.002). Prematurity was more frequent in exposed pregnancies (16.1% versus 8.5%; OR 2.1, 95% CI 1.1- 3.8, p = 0.02). Nonetheless, gestational age at birth (median 39 weeks, IQR 37-40 versus 39 weeks, IQR 38-40, p = 0.27) and birth weight (median 3280 g, IQR 2835-3590 versus 3250 g, IQR 2880- 3600, p = 0.95) did not differ between exposed and non-exposed pregnancies.Conclusion This study did not detect a teratogenic effect of statins. Its statistical power however is not sufficient to reverse the recommendation of treatment discontinuation during pregnancy.

Bulky DNA adducts, 4-aminobiphenyl-haemoglobin adducts and diet in the European Prospective Investigation into Cancer and Nutrition (EPIC) prospective study

In contrast to some extensively examined food mutagens, for example, aflatoxins, N-nitrosamines and heterocyclic amines, some other food contaminants, in particular polycyclic aromatic hydrocarbons (PAH) and other aromatic compounds, have received less attention. Therefore, exploring the relationships between dietary habits and the levels of biomarkers related to exposure to aromatic compounds is highly relevant. We have investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort the association between dietary items (food groups and nutrients) and aromatic DNA adducts and 4-aminobiphenyl-Hb adducts. Both types of adducts are biomarkers of carcinogen exposure and possibly of cancer risk, and were measured, respectively, in leucocytes and erythrocytes of 1086 (DNA adducts) and 190 (Hb adducts) non-smokers. An inverse, statistically significant, association has been found between DNA adduct levels and dietary fibre intake (P = 0·02), vitamin E (P = 0·04) and alcohol (P = 0·03) but not with other nutrients or food groups. Also, an inverse association between fibre and fruit intake, and BMI and 4-aminobiphenyl-Hb adducts (P = 0·03, 0·04, and 0·03 respectively) was observed. After multivariate regression analysis these inverse correlations remained statistically significant, except for the correlation adducts v. fruit intake. The present study suggests that fibre intake in the usual range can modify the level of DNA or Hb aromatic adducts, but such role seems to be quantitatively modest. Fibres could reduce the formation of DNA adducts in different manners, by diluting potential food mutagens and carcinogens in the gastrointestinal tract, by speeding their transit through the colon and by binding carcinogenic substances.

Efficacy, safety and pharmacokinetic of once-daily boosted saquinavir (1500/100 mg) together with 2 nucleos(t)ide reverse transcriptase inhibitors in real life: a multicentre prospective study.

BACKGROUND. Ritonavir-boosted saquinavir (SQVr) is nowadays regarded as an alternative antiretroviral drug probably due to several drawbacks, such as its high pill burden, twice daily dosing and the requirement of 200 mg ritonavir when given at the current standard 1000/100 mg bid dosing. Several once-daily SQVr dosing schemes have been studied with the 200 mg SQV old formulations, trying to overcome some of these disadvantages. SQV 500 mg strength tablets became available at the end of 2005, thus facilitating a once-daily regimen with fewer pills, although there is very limited experience with this formulation yet. METHODS. Prospective, multicentre study in which efficacy, safety and pharmacokinetics of a regimen of once-daily SQVr 1500/100 mg plus 2 NRTIs were evaluated under routine clinical care conditions in either antiretroviral-naïve patients or in those with no previous history of antiretroviral treatments and/or genotypic resistance tests suggesting SQV resistance. Plasma SQV trough levels were measured by HPLV-UV. RESULTS. Five hundred and fourteen caucasian patients were included (47.2% coinfected with hepatitis C and/or B virus; 7.8% with cirrhosis). Efficacy at 52 weeks (plasma RNA-HIV <50 copies/ml) was 67.7% (CI95: 63.6 - 71.7%) by intention-to-treat, and 92.2% (CI95: 89.8 - 94.6%) by on-treatment analysis. The reasons for failure were: dropout or loss to follow-up (18.4%), virological failure (7.8%), adverse events (3.1%), and other reasons (4.6%). The high rate of dropout may be explained by an enrollment and follow-up under routine clinical care condition, and a population with a significant number of drug users. The median SQV Cmin (n = 49) was 295 ng/ml (range, 53-2172). The only variable associated with virological failure in the multivariate analysis was adherence (OR: 3.36; CI95, 1.51-7.46, p = 0.003). CONCLUSIONS. Our results suggests that SQVr (1500/100 mg) once-daily plus 2 NRTIs is an effective regimen, without severe clinical adverse events or hepatotoxicity, scarce lipid changes, and no interactions with methadone. All these factors and its once-daily administration suggest this regimen as an appropriate option in patients with no SQV resistance-associated mutations.

Complicated intra-abdominal infections in a worldwide context: an observational prospective study (CIAOW Study).

Despite advances in diagnosis, surgery, and antimicrobial therapy, mortality rates associated with complicated intra-abdominal infections remain exceedingly high. The World Society of Emergency Surgery (WSES) has designed the CIAOW study in order to describe the clinical, microbiological, and management-related profiles of both community- and healthcare-acquired complicated intra-abdominal infections in a worldwide context. The CIAOW study (Complicated Intra-Abdominal infection Observational Worldwide Study) is a multicenter observational study currently underway in 57 medical institutions worldwide. The study includes patients undergoing surgery or interventional drainage to address complicated intra-abdominal infections. This preliminary report includes all data from almost the first two months of the six-month study period. Patients who met inclusion criteria with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study. 702 patients with a mean age of 49.2 years (range 18-98) were enrolled in the study. 272 patients (38.7%) were women and 430 (62.3%) were men. Among these patients, 615 (87.6%) were affected by community-acquired IAIs while the remaining 87 (12.4%) suffered from healthcare-associated infections. Generalized peritonitis was observed in 304 patients (43.3%), whereas localized peritonitis or abscesses was registered in 398 (57.7%) patients.The overall mortality rate was 10.1% (71/702). The final results of the CIAOW Study will be published following the conclusion of the study period in March 2013.

Existential values transformation in all organ transplantation: A qualitative prospective study.

Organ transplantation offers a treatment of choice for patients suffering from end stage illnesses. The aim of this IRB approved prospective qualitative study was to analyze patients’ psychological concerns from their inclusion on the waiting list for first organ transplantation (TX) (T1; N=71; kidney, K=30; liver, Li=11; lung, Lu=15; heart, H=15) and six months after TX (T2; N=49; K=15; Li=10; Lu=14; H=10). Semi-structured interviews were conducted at home or in a place selected by patients. Qualitative pattern analysis (QUAPA) of the verbatim transcriptions was applied. T1 (K) Patients maintained an apparent normality (87%), building emotional protection (23%), and developing a fatalist attitude towards life (43%). (Li) Physical limits were set to spare energy until TX (73%). Illness led to reevaluation of life values (66%). (Lu) Physical and psychological self-protection was prioritized when health declined (67%). Modified life values, fatalism (33%) and spirituality (27 %) were mentioned. (H) Patients husbanded physical (80%) and psychological (67%) resources and self-protection. Modified life values and fatalist attitude towards life were reported (40%). T2 (K) New perspective on life was described, with increase of empathy towards others (20%). (Li) Positive identity and life values modifications (60%), greater openness towards others, closeness to significant ones (30%) and a more self-centered attitude (30%) prioritizing the essential (20%) were reported. Lack of respect of life values generated anger (40%). (Lu) Setting existential priorities and increase in spirituality (64%), along with the development of new life values, greater openness to others (57%) and closeness to significant ones (21%) were underlined. Lack of respect of human values induced negative feelings (36%). Self-centered attitudes, setting limits to other people were mentioned (29%). (H) Change in life values with setting life priorities was reported (70%) with increase in spirituality, and the lack of respect of life values generated anger (50%). Self-centered attitudes were reported (60%). TX not only comes with positive physical benefits, but also with positive existential values and psychological transformation, and the development of a more altruistic attitude and humanistic values.

Are some hypertensive patients overtreated? A prospective study of ambulatory blood pressure recording.

Ambulatory blood pressure (BP) was recorded in hypertensive patients whose physicians had been asked to reduce diastolic pressure measured in the office to 90 mm Hg or less. 34 hypertensive patients with a diastolic pressure measured by their physician of 95 mm Hg or more despite antihypertensive therapy had their treatment changed with the aim of achieving this pre-set goal within 3 months. At the beginning and the end of the study, ambulatory BP was monitored during the daytime with a portable non-invasive recorder. The results of the ambulatory recordings were not made available to the physicians until completion of the study. In half the patients the ambulatory diastolic pressure was already 90 mm Hg or less at the start. In these patients, treatment adjustment did not further decrease ambulatory BP. In contrast, patients who initially had an ambulatory diastolic pressure above 90 mm Hg had a significantly decreased ambulatory BP at the end of the study. Intensifying the therapy of hypertensive patients who have a normal ambulatory BP may result in overtreatment without any real gain in BP control.

Molecular characterization of 39 de novo sSMC: contribution to prognosis and genetic counselling, a prospective study.

Small supernumerary marker chromosomes (sSMCs) are structurally abnormal chromosomes that cannot be characterized by karyotype. In many prenatal cases of de novo sSMC, the outcome of pregnancy is difficult to predict because the euchromatin content is unclear. This study aimed to determine the presence or absence of euchromatin material of 39 de novo prenatally ascertained sSMC by array-comparative genomic hybridization (array-CGH) or single nucleotide polymorphism (SNP) array. Cases were prospectively ascertained from the study of 65,000 prenatal samples [0.060%; 95% confidence interval (CI), 0.042-0.082]. Array-CGH showed that 22 markers were derived from non-acrocentric markers (56.4%) and 7 from acrocentic markers (18%). The 10 additional cases remained unidentified (25.6%), but 7 of 10 could be further identified using fluorescence in situ hybridization; 69% of de novo sSMC contained euchromatin material, 95.4% of which for non-acrocentric markers. Some sSMC containing euchromatin had a normal phenotype (31% for non-acrocentric and 75% for acrocentric markers). Statistical differences between normal and abnormal phenotypes were shown for the size of the euchromatin material (more or less than 1 Mb, p = 0.0006) and number of genes (more or less than 10, p = 0.0009). This study is the largest to date and shows the utility of array-CGH or SNP array in the detection and characterization of de novo sSMC in a prenatal context.