Parent satisfaction before and after implementing of a developmental screening tool in nine well-baby clinics in Norway.

AIM: The aim of the study was to compare parental satisfaction items before and after the implementation of The Ages & Stages Questionnaires (ASQ) as part of the health check-up. METHODS: ASQ was implemented in regular health check-ups of infants up to two years of age in 9 Norwegian well-baby clinics. After the infant's two years' health check-ups, a questionnaire-based survey among 652 families before and 562 families after intervention was conducted. Descriptive analyses and ordinal logistic regression were used to report and compare parental satisfaction items before and after the project. RESULTS: Parents reported high satisfaction with well-baby services both before and after the implementation of ASQ, and ninety-six per cent recommended other well-baby clinics to use ASQ. Some significant differences appeared, before the implementation of ASQ, parents were more satisfied with the support they received regarding parenting and child development in general and information about the child's physical health. After ASQ was implemented, parents were significantly more satisfied with the information they received about 'the child's mental health'. CONCLUSION: Developmental screening in well-baby clinics in Norway is acceptable among parents with young children. The use of standardised instruments must not come at the expense of listening to parents' concerns.

A comparison of CT based measures of skeletal muscle mass and density from the Th4 and L3 levels in patients with advanced non-small-cell lung cancer.

BACKGROUND: Muscle mass and density assessed from CT-images at the L3 level are prognostic for survival and predict toxicity in cancer patients. However, L3 is not always included on routine CT-scans. We aimed to investigate whether images at the Th4 level may be used instead. METHODS: Patients from three chemotherapy trials in advanced NSCLC were eligible (n = 1305). Skeletal muscle area (cm2), skeletal muscle index (SMI, cm2/m2) and skeletal muscle density (SMD) at Th4 and L3 levels were assessed from baseline CT-scans. SMI and SMD at the Th4 and L3 level were transformed into z-scores and the agreement between scores was investigated by Bland-Altman plots and estimated by intra-class correlation analyses. Linear regression was used to test if Th4 SMI and SMD z-scores predicted L3 SMI and SMD z-scores. RESULTS: CT-images from 401 patients were analysable at both levels. There was a moderate agreement between Th4 and L3 SMI z-scores with an intra-class correlation of 0.71 (95% CI 0.64-0.77) for men and 0.53 (95% CI 0.41-0.63) for women. Regression models predicting L3 SMI z-scores from Th4 SMI z-scores showed coefficients of 0.71 (95% CI 0.62-0.80) among men and 0.53 (95% CI 0.40-0.66) among women. R-squares were 0.51 and 0.28, respectively, indicating moderate agreement. A similar, moderate agreement between Th4 and L3 SMD z-scores was observed. CONCLUSION: There was only moderate agreement between muscle measures from Th4 and L3 levels, indicating that missing data from the L3 level cannot be replaced by analysing images at the Th4 level.

Muscle mass and association to quality of life in non-small cell lung cancer patients.

BACKGROUND: Cancer wasting is characterized by muscle loss and may contribute to fatigue and poor quality of life (QoL). Our aim was to investigate associations between skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) and selected QoL outcomes in advanced non-small cell lung cancer (NSCLC) at diagnosis. METHODS: Baseline data from patients with stage IIIB/IV NSCLC and performance status 0-2 enrolled in three randomized trials of first-line chemotherapy (n = 1305) were analysed. Associations between SMI (cm2 /m2 ) and SMD (Hounsfield units) based on computed tomography-images at the third lumbar level and self-reported physical function (PF), role function (RF), global QoL, fatigue, and dyspnoea were investigated by linear regression using flexible non-linear modelling. RESULTS: Complete data were available for 734 patients, mean age 65 years. Mean SMI was 47.7 cm2 /m2 in men (n = 420) and 39.6 cm2 /m2 in women (n = 314). Low SMI values were non-linearly associated with low PF and RF (men P = 0.016/0.020, women P = 0.004/0.012) and with low global QoL (P = 0.001) in men. Low SMI was significantly associated with high fatigue (P = 0.002) and more pain (P = 0.015), in both genders, but not with dyspnoea. All regression analyses showed poorer physical outcomes below an SMI breakpoint of about 42-45 cm2 /m2 for men and 37-40 cm2 /m2 for women. In both genders, poor PF and more dyspnoea were significantly associated with low SMD. CONCLUSIONS: Low muscle mass in NSCLC negatively affects the patients' PF, RF, and global QoL, possibly more so in men than in women. However, muscle mass must be below a threshold value before this effect can be detected.

Skeletal muscle radiodensity is prognostic for survival in patients with advanced non-small cell lung cancer.

BACKGROUND & AIMS: Recent research indicates that severe muscular depletion (sarcopenia) is frequent in cancer patients and linked to cachexia and poor survival. Our aim was to investigate if measures of skeletal muscle hold prognostic information in advanced non-small cell lung cancer (NSCLC). METHODS: We included NSCLC patients with disease stage IIIB/IV, performance status 0-2, enrolled in three randomised trials of first-line chemotherapy (n = 1305). Computed tomography (CT) images obtained before start of treatment were used for body composition analyses at the level of the third lumbar vertebra (L3). Skeletal muscle mass was assessed by measures of the cross sectional muscle area, from which the skeletal muscle index (SMI) was obtained. Skeletal muscle radiodensity (SMD) was measured as the mean Hounsfield unit (HU) of the measured muscle area. A high level of mean HU indicates a high SMD. RESULTS: Complete data were available for 734 patients, mean age 65 years. Both skeletal muscle index (SMI) and muscle radiodensity (SMD) varied largely. Mean SMI and SMD were 47.7 cm2/m2 and 37.4 HU in men (n = 420), 39.6 cm2/m2 and 37.0 HU in women (n = 314). Multivariable Cox regression analyses, adjusted for established prognostic factors, showed that SMD was independently prognostic for survival (Hazard ratio (HR) 0.98, 95% CI 0.97-0.99, p = 0.001), whereas SMI was not (HR 0.99, 95% CI 0.98-1.01, p = 0.329). CONCLUSION: Low SMD is associated with poorer survival in advanced NSCLC. Further research is warranted to establish whether muscle measures should be integrated into routine practice to improve prognostic accuracy.

Medical benefits in young adulthood: a population-based longitudinal study of health behaviour and mental health in adolescence and later receipt of medical benefits.

OBJECTIVES: To examine the extent to which smoking, alcohol, physical activity and mental health problems in 15-16-year-olds are associated with receipt of medical benefits in young adulthood, after adjustment for confounders. DESIGN: Prospective population-based cohort survey linked to national registers. PARTICIPANTS: In the 'Youth studies' from the Norwegian Institute of Public Health, 15 966 10th graders in 6 Norwegian counties answered a health behaviour and mental health questionnaire; 88% were linked to National Insurance Administration Registers (FD-Trygd). OUTCOME MEASURE: Time to receipt of medical benefits, based on FD-Trygd. Follow-up was from age 18 years until participants were aged 22-26 years. METHOD: We performed Cox regression analyses to examine the extent to which variations in health behaviour and mental health problems during 10th grade were associated with receipt of medical benefits during follow-up. RESULTS: Daily smoking at age 15-16 years was associated with a significant increase in hazard of receiving health benefits at follow-up compared with not smoking for boys, HR (95% CI) 1.56 (1.23 to 1.98), and for girls 1.47 (1.12 to 1.93). Physical activity was associated with a decrease in hazard compared with inactivity from 23% to 53% in boys and from 21% to 59% in girls, while use of alcohol showed a mixed pattern. The hazard for benefits use rose with increasing levels of emotional symptoms, peer problems, conduct problems and hyperactivity-inattention problems (Strengths and Difficulties Questionnaire) at 15-16 years among both genders. CONCLUSIONS: Health behaviour and mental health problems in adolescence are independent risk factors for receipt of medical benefits in young adulthood.

Contemporary external validation of the Leibovich model for prediction of progression after radical surgery for clear cell renal cell carcinoma.

OBJECTIVE: The aim of this study was to externally validate in an up-to-date setting the predictive ability of the model for recurrence after radical treatment of clear cell renal cell carcinoma (CCRCC) published by Leibovich in 2003. MATERIALS AND METHODS: The study included a total of 386 consecutive patients with CCRCC between January 1997 and May 2013, treated with partial or radical nephrectomy. All patients were scored with points between 0 and 11, and further subdivided into low-, intermediate- and high-risk groups according to the original paper. Well-recognized statistical methods for the evaluation of Cox's proportional hazard-based prognostic models were applied. To validate the discriminative ability, Harrell's concordance (c) index and hazard ratios (HRs) between risk groups were used, and calibration was graphically explored. RESULTS: The 10 year recurrence-free survival rates for the low-, intermediate- and high-risk groups were 87.3%, 63.8% and 19.8%, respectively Harrell's c index was 0.864. The HRs across risk groups for the intermediate- and high-risk groups were 5.29 and 21.56, respectively, with the low-risk group as a reference category. A gross comparison of the survival estimates between the patients showed an overall similarity. However, differences within the intermediate- and high-risk groups were seen in the first year of follow-up. CONCLUSIONS: The Leibovich model seems to discriminate well between risk groups, but for the intermediate- and high-risk groups the calibration is not optimal. This study validates the model in a present-day Nordic patient population. The model can be used as a risk stratification tool for follow-up after radical treatment of CCRCC.

Mental health problems in the 10th grade and non-completion of upper secondary school: the mediating role of grades in a population-based longitudinal study.

BACKGROUND: School drop-out is a problem all over the world with adverse life-course consequences. The aim of this paper is to study how internalising and externalising problems in the 10th grade are associated with non-completion of upper secondary school, and to examine the mediating role of grade points in the 10th grade across general academic and vocational tracks in upper secondary school. We also study the impact of health behaviour. METHODS: Population-based health surveys were linked with Norwegian registries on education and sociodemographic factors (n = 10 931). Mental health was assessed by the self-report Strengths and Difficulties Questionnaire. Logistic regression was used to analyse the relations between mental health and health behaviour in 10th grade and non-completion of upper secondary school. The mediating effect of grade points was studied by causal mediation analysis. RESULTS: Adolescents not completing upper secondary school reported more externalising problems and girls more internalising problems in the 10th grade, after adjustments. Smoking and physical inactivity increased the odds of non-completion of upper secondary school. Causal mediation analyses showed that a reduction in externalising problems of 10 percentage points led to lower rates of non-completion of 4-5 percentage points, and about three-quarters of this total effect was mediated by grades. For internalising problems the total effect was significant only for girls (1 percentage point), and the mediated effect of grades was about 30%. The effect of mental health problems on school dropout was mainly the same in both vocational and general tracks. CONCLUSIONS: Assuming a causal relationship from mental health problems to school performance, this study suggests that externalising problems impair educational attainment. A reduction of such problems may improve school performance, reduce school drop-out and reduce the adverse life-course consequences.

Ureteroscopy with and without safety guide wire: should the safety wire still be mandatory?

BACKGROUND AND PURPOSE: Although the evidence is sparse, most urologists advise the insertion of a safety guide wire (SGW) alongside the ureteroscope whenever performing ureteroscopy (URS). The aim of the study was to compare the results of ureteroscopic treatment for ureteral stones at the Oslo University Hospital (OUH), where the SGW is routinely used, with the results at the Haukeland University Hospital (HUH), where the SGW is routinely omitted. The primary goal was to evaluate the success rates of passing the ureteroscope through the orifice, the ability to access the ureteral stone, and the ability to place a ureteral stent when needed after the endoscopy. The secondary goals were to compare the perioperative complication rates and stone-free rates at the two hospitals. MATERIALS AND METHODS: A retrospective review of 500 URS for ureteral calculi at each of the two hospitals, during 2004-2010, was performed. Relevant data were extracted from the medical records. The exact chi-squared, Mann-Whitney U, and independent-samples t-tests were used comparing the results at the two hospitals. RESULTS: An SGW was used in 480 (96.2%) of the URS procedures at OUH and in 7 (1.4%) at HUH. No significant differences were found between the two hospitals in the success rates of passing the ureteroscope through the orifice, in the ability to access the ureteral calculus, or in the ability to place a ureteral stent when needed after the endoscopy. There were no significant differences in the number of intraoperative complications, but postendoscopic ureteral stenosis occurred more often at OUH (3.4%) than at HUH (1.2%), p=0.039. The overall stone-free rate was higher at HUH (85.9%) compared to OUH (77.1%), p=0.001. CONCLUSION: No superior results were found at the hospital with the routine use of an SGW. It may be questioned if the SGW still should be considered mandatory.

A safety guidewire influences the pushing and pulling forces needed to move the ureteroscope in the ureter: a clinical randomized, crossover study.

BACKGROUND AND PURPOSE: It is generally advised to keep a safety guidewire (SGW) in the ureter alongside the ureteroscope during endoscopy of the upper urinary tract, but little is known of how the SGW influences the forces exerted on the ureteroscope in the ureter. The purpose of this study was to investigate whether the presence of an SGW during ureteroscopy (URS) in a normal clinical setting will influence the pushing and pulling forces exerted on a semirigid ureteroscope. PATIENTS AND METHODS: In a 1-year period (2010-2011), 40 patients admitted to Haukeland University Hospital for endoscopic treatment of renal pelvic stone disease were included in a clinical randomized crossover trial measuring the forces needed to move a semirigid ureteroscope during URS. A digital force meter was connected to the ureteroscope to perform the force measurements. The pushing and pulling forces were measured at four locations during URS with and without an SGW. The patients were randomized to whether the first series of force measurements should be with or without SGW. Paired-samples t tests were used comparing the forces in the two series. RESULTS: Significantly higher forces were found both when inserting and retracting the semirigid endoscope when an SGW was used compared with times when an SGW was omitted. The mean percentage increase in the forces with an SGW in place varied between 51.8% and 112.5% across locations and directions. A limitation is that the study has been performed with a semirigid ureteroscope only. CONCLUSION: An SGW substantially increased the resistance against moving a semirigid ureteroscope up and down the ureter. The SGW may thus be an obstacle to the ureteroscopic procedure and may even increase the risk of harming the ureter in some patients.

A novel method to measure the mechanical pushing and pulling forces during ureteroscopy in a normal clinical setting.

BACKGROUND AND PURPOSE: The forces needed to move the ureteroscope up and down the urinary tract may injure the ureter, but a method to measure these forces in patients is lacking. The purpose of the study was to develop and test a novel method for measuring the pushing and pulling forces exerted on a semirigid ureteroscope during ureteroscopy (URS) in a clinical setting. MATERIALS AND METHODS: During 2010 to 2011, 20 patients planned for retrograde flexible URS or percutaneous lithotripsy for renal pelvic stones were recruited to a study measuring the forces exerted on a semirigid ureteroscope during retrograde URS. A coupling device was constructed to connect a digital force meter to a standard semirigid ureteroscope. The pushing and pulling forces, given in Newton (N), were measured at four defined locations in the ureter. The experiment was repeated twice to evaluate the reproducibility of the results. Paired-samples t test and Intraclass Correlation Coefficient (ICC) addressed the reproducibility of the results. RESULTS: The force meter did not disturb the endoscopic procedure, and the force measurements were performed as intended. The results were reproducible at repeated measurements, with the ICC ranging from minimum 0.737 to maximum 0.812 at the different measuring locations in the ureter. The mean forces needed for insertion of the ureteroscope increased from 4.4 N (±3.6 N) at the distal part of the ureter to 9.7 N (±7.3 N) at the proximal part with large interpatient variation. Similar but smaller forces were found for retraction. CONCLUSION: The present method is proven to reliably measure forces exerted on the ureteroscope in a clinical setting. This opens the opportunity for further force studies on endoscopic procedures to make URS safer.

Gamma knife treatment of growing vestibular schwannoma in Norway: a prospective study.

PURPOSE: Gamma Knife radiosurgery (GKRS) has been increasingly used in the treatment of vestibular schwannoma (VS). Very few studies relate tumor control and post-treatment growth rates to pretreatment growth rates. METHODS AND MATERIALS: We prospectively included 45 consecutive VS patients who were initially treated conservatively and then received GKRS between 2000 and 2007 because of demonstrated tumor growth. Pretreatment and post-treatment tumor volumes were estimated. Patients underwent audiograms, reported their symptoms, and responded to the Short Form General Health Survey (SF-36) questionnaire on each visit. RESULTS: Volume doubling times before and after treatment were 1.36 years (95% confidence intervals, 1.14-1.68) and -13.1 years (95% confidence intervals, -111.0 to -6.94), respectively. Tumor control, defined as a post-GKRS growth rate ≤ 0, was achieved in 71.1% of patients, with highest odds for tumor control among older patients and those with larger tumors. The 5-year retreatment-free survival rate was 93.9% (95% confidence intervals, 76.5-98.5). None of the clinical endpoints investigated showed statistically significant changes after GKRS, but improvement was seen in a few SF-36 parameters. CONCLUSIONS: GKRS alters the natural course of the tumor by reducing growth. Mathematic models yield poorer tumor control rates than those found by clinical assessment. Symptoms were unaffected by treatment, but quality of life was improved.

Growth of untreated vestibular schwannoma: a prospective study.

OBJECT: Small vestibular schwannomas (VSs) are often conservatively managed and treated only upon growth. Growth is usually reported in mm/year, but describing the growth of a 3D structure by a single diameter has been questioned. As a result, VS growth dynamics should be further investigated. In addition, baseline clinical parameters that could predict growth would be helpful. In this prospective study the authors aimed to describe growth dynamics in a cohort of conservatively managed VSs. They also compared different growth models and evaluated the ability of baseline parameters to predict future growth. METHODS: Between 2000 and 2006, 178 consecutive patients with unilateral de novo small-sized VSs identified among the Norwegian population of 4.8 million persons were referred to a tertiary care center and were included in a study protocol of conservative management. Tumor size was defined by MR imaging-based volume estimates and was recorded along with clinical data at regular visits. Mixed-effects models were used to analyze the relationships between observations. Three growth models were compared using statistical diagnostic tests: a mm/year-based model, a cm(3)/year-based model, and a volume doubling time (VDT)-based model. A receiver operating characteristic curve analysis was used to determine a cutoff for the VDT-based model for distinguishing growing and nongrowing tumors. RESULTS: A mean growth rate corresponding to a VDT of 4.40 years (95% CI 3.49-5.95) was found. Other growth models in this study revealed mean growth rates of 0.66 mm/year (95% CI 0.47-0.86) and 0.19 cm(3)/year (95% CI 0.12-0.26). Volume doubling time was found to be the most realistic growth model. All baseline variables had p values > 0.09 for predicting growth. CONCLUSIONS: Based on the actual measurements, VDT was the most correct way to describe VS growth. The authors found that a cutoff of 5.22 years provided the best value to distinguish growing from nongrowing tumors. None of the investigated baseline predictors were usable as predictors of growth.

Conservative management of vestibular schwannoma--a prospective cohort study: treatment, symptoms, and quality of life.

BACKGROUND: One hundred ninety-three patients with sporadic unilateral vestibular schwannoma given conservative management were enrolled in a prospective study. OBJECTIVE: To evaluate the efficacy of conservative management and to determine the effect of an initial conservative management on the quality of life (QOL) and severity of audio vestibular symptoms. METHODS: The patients underwent magnetic resonance imaging scans, clinical examination, and QOL assessment by 2 validated questionnaires, the Short Form-36 (SF-36) and Glasgow Benefit Inventory (GBI). Using regression analysis of clustered data, we analyzed possible associations between tumor growth and symptoms and tested whether our earlier finding that vertigo is associated with reduced QOL could be verified. RESULTS: The median follow-up time was 43 months (range, 9-115 months; SD, 21.48 months). Results are based on 703 clinical controls and 642 (SF-36) and 638 (GBI) questionnaires. Seven patients were lost to follow-up. Approximately 40% of patients were in need of treatment during follow-up. We found a statistically significant association between tinnitus and vertigo and tumor growth. Vertigo was found to significantly reduce QOL. There was a significant drop in the Social Function subscales of both SF-36 and GBI, possibly attributable to progressive hearing loss. Otherwise, there was no overall trend toward any change in QOL during the observation period. In addition, QOL seemed to be little affected by treatment. CONCLUSION: There was a small but statistically significant improvement in vestibular complaints and no change in the occurrence of tinnitus. Except for hearing loss caused by surgery, treatment did not affect symptoms or QOL significantly. Growth was associated with the occurrence of tinnitus and balance problems.

A prospective observational study of the effect of platelet transfusions on levels of platelet-derived cytokines, chemokines and interleukins in acute leukaemia patients with severe chemotherapy-induced cytopenia.

BACKGROUND: Platelet concentrates contain soluble mediators derived from both platelets and contaminating leukocytes. During platelet transfusion these mediators are transferred, and transfusion-induced modulation of the cytokine network may then occur, possibly contributing to transfusion reactions, immunomodulation, or affecting residual leukemic cells. In this prospective observational study, we investigate the effect of platelet transfusion on the systemic levels of platelet-derived cytokines, chemokines and interleukins in an unselected group of acute leukaemia patients with severe chemotherapy-induced cytopenia. STUDY DESIGN AND METHODS: We investigated 31 platelet transfusions involving pre-storage, white blood cell-reduced, gamma-irradiated or pathogen-inactivated, photochemically-treated platelet concentrates received by 10 unselected patients. Peripheral blood plasma samples were collected before, immediately after, one hour, and 24 hours after the transfusions. Sampling from platelet concentrates was performed immediately before transfusion. A total of 31 soluble mediators were examined. Ten healthy controls matched for age and gender were included. RESULTS: Despite heterogeneity in patients and platelet concentrates, significantly increased plasma concentrations were detected for the platelet-derived mediators, platelet-derived growth factor, ß-thromboglobulin, transforming growth factor-ß (TGF-ß), CCL5, and CXCL4, 1 hour and/or immediately after platelet transfusions. The plasma levels of vascular endothelial growth factor and soluble CD40 ligand were not altered by platelet transfusion. Certain interleukins (IL-1ß, IL-2, IL-4, IL-6, IL-9, and IL-12), as well as interferon-γ showed a minor, transient decrease in systemic plasma levels during the first hour following transfusion. CONCLUSION: Platelet transfusions modulate the systemic cytokine network in acute leukaemia patients with severe, chemotherapy-induced cytopenia.

Serum folate is significantly correlated with plasma cysteine concentrations in healthy industry workers.

BACKGROUND: A low concentration of serum folate is associated with an increased risk of cardiovascular disease. Extracellular cysteine is involved in aging, cancer and cardiovascular disease. The relationship between serum folate and plasma cysteine is poorly understood. Therefore, we investigated this relationship in industry workers, whose health has economic implications. METHODS: The concentration of serum folate was determined by the Access ImmunoAssay System Sanofi Pasteur. Plasma cysteine and homocysteine were measured by an ion-pair HPLC method. The concentrations of serum triglycerides were determined by an enzymatic colorimetric method. RESULTS: We detected a positive correlation between the concentration of serum folate and plasma cysteine, whereas the concentration of serum folate was negatively correlated with plasma homocysteine and serum triglycerides. In a multiple regression analysis with adjustment for age, BMI and smoking, serum folate as the dependent variable exhibited a strong relationship with plasma cysteine, and a negative relationship with plasma homocysteine and serum triglycerides. CONCLUSION: We observed significant correlations between serum folate, plasma cysteine and serum triglyceride concentrations in industry workers, implying that folate may modulate key aspects of the body's cysteine and lipid metabolism.

Increased intracellular growth of Mycobacterium avium in HIV-1 exposed monocyte-derived dendritic cells.

Dendritic cells (DC) are the most potent antigen-presenting cells, and form a link between the innate and adaptive immune system. They sample the periphery of the body for antigens and present them to T cells to elicit a proper immune response. It has been shown that dendritic cells phagocytose mycobacteria, but there have been conflicting reports as to whether the bacteria are capable of intracellular replication in DCs. Mycobacterium avium is a facultative intracellular bacterium, part of the Mycobacterium avium complex (MAC) of mycobacteria and are commonly seen as opportunistic pathogens in patients infected by Human immunodeficiency virus type 1 (HIV-1). To clarify the issue of whether DCs are capable of controlling the intracellular growth of M. avium and whether this control is lost upon HIV-1 exposure, we investigated the intracellular replication of M. avium in monocyte-derived dendritic cells and compared it to bacterial growth in dendritic cultures exposed to HIV-1 for 24 h. Our results show that exposure of DCs to HIV-1 promotes or facilitates the intracellular growth of M. avium.

Type 1 plasminogen activator inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC) and its impact on angiogenesis, progression and patient survival after radical nephrectomy.

BACKGROUND: To examine the expression of type 1 plasminogen inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC), and its possible association with microvessel density (MVD), the expression of thrombospondin-1 (TSP-1), nuclear grade, tumour stage, continuously coded tumour size (CCTS) and to assess the value of PAI as a prognostic marker in 162 patients with CCRCC treated with radical nephrectomy. METHODS: A total of 172 consecutive patients with CCRCC treated with radical nephrectomy were enrolled in the study. The expression of PAI-1, TSP-1 and factor VIII were analysed on formalin-fixed, paraffin-embedded tissues without knowledge of the clinical outcome. Ten cases, where PAI-1 immunohistochemistry was not possible due to technical problems and lack of material, were excluded. Sixty-nine patients (43%) died of RCC, while 47 patients (29%) died of other diseases. Median follow-up was 13.8 years for the surviving 46 patients (28%). RESULTS: Nine percent of the tumours showed PAI-1 positivity. High expression of PAI-1 was significantly inversely correlated with TSP-1 (p = 0.046) and directly with advanced stage (p = 0.008), high NG (3+4) (p = 0.002), tumour size (p = 0.011), microvessel density (p = 0.049) and disease progression (p = 0.002). In univariate analysis PAI-1 was a significant prognosticator of cancer-specific survival (CSS) (p < 0.001). Multivariate analysis revealed that TNM stage (p < 0.001), PAI-1 (p = 0.020), TSP-1 (p < 0.001) and MVD (p = 0.007) were independent predictors of CSS. CONCLUSIONS: PAI-1 was found to be an independently significant prognosticator of CSS and a promoter of tumour angiogenesis, aggressiveness and progression in CCRCC.

A 12-year population-based study of psychosis in Parkinson disease.

OBJECTIVE: To investigate the prevalence, incidence, risk factors, and concomitants of Parkinson disease (PD)-associated psychosis (PDP) in a population-based prevalent cohort. DESIGN: Prospective longitudinal cohort study. SETTING: Community-based study in southwestern Norway. PARTICIPANTS: Two hundred thirty community-based PD patients were followed up prospectively for 12 years. Reassessments were conducted at 4 and 8 years and then annually. MAIN OUTCOME MEASURES: Severity of PDP was measured by the Unified Parkinson Disease Rating Scale thought disorder (UPDRS-TD) item. Patients with a UPDRS-TD score of 2 or more or those taking antipsychotic drugs owing to psychotic symptoms were categorized at each visit as having PDP. Generalized estimating equations were applied to investigate baseline risk factors for incident PDP and clinical and demographic concomitants of PDP during 12 years. RESULTS: By study's end, 137 patients (60%) had developed hallucinations or delusions. The incidence rate of PDP was 79.7 per 1000 person-years. Higher age at onset, higher baseline levodopa-equivalent doses, probable rapid eye movement (REM) sleep behavior disorder at baseline, and follow-up time were independent risk factors of incident PDP. Significant concomitant features of patients with PDP during the 12-year study period were low activities of daily living function (UPDRS II), dementia, high levodopa-equivalent dose, and probable REM sleep behavior disorder. CONCLUSIONS: Psychotic symptoms affect most patients with PD, with increased risk in those with higher age at onset, need for high doses of dopaminergic drugs, and probable REM sleep behavior disorder. This risk factor pattern and the observed associations with increased disability and dementia place PDP within a symptom complex signaling a malignant disease course.

High-dose preoperative chemoradiotherapy in esophageal cancer patients does not increase postoperative pulmonary complications: correlation with dose-volume histogram parameters.

PURPOSE: To investigate the association of high-dose preoperative chemoradiotherapy (CRT) and dose-volume histogram (DVH) parameters of lungs with incidence of postoperative pulmonary complications and to identify predictive clinical factors of pulmonary complications. METHODS: Data of 65 patients were collected retrospectively. Thirty-five patients underwent transthoracic esophagectomy (TTE) alone and 30 received cisplatin and 5-fluorouracil, concomitant with radiotherapy, median dose 66Gy, and followed by TTE. From the DVH for each lung alone and for both lungs together as one organ we generated total lung volume, mean radiotherapy dose, relative and absolute volumes receiving more than a threshold dose, and relative and absolute volumes receiving less than a threshold dose. Postoperative pulmonary complications were defined as pneumonia or respiratory failure. RESULTS: Sixty percent of the patients in the TTE alone group had postoperative pulmonary complications versus 63% in the CRT+TTE group. Postoperative mortality was 8.6% and 16.7% in the respective patient groups (p=NS). None of the DVH parameters was associated with postoperative pulmonary complications. Squamous cell carcinoma was an adverse factor related to increased postoperative pulmonary complications. CONCLUSION: High-dose preoperative CRT was not associated with increased postoperative pulmonary complications in this cohort of esophageal cancer patients.

Effects of in vitro HIV-1 infection on mycobacterial growth in peripheral blood monocyte-derived macrophages.

Coinfection with human immunodeficiency virus type 1 (HIV-1) and opportunistic mycobacteria, especially Mycobacterium tuberculosis, is a cause of high morbidity and mortality worldwide. Both mycobacteria and HIV-1 may infect macrophages, and thus, coinfection may generate conditions that reciprocally influence the intracellular replication of the pathogens. Elucidation of the interaction between HIV-1 and mycobacteria in their common target cell is important for understanding pathogenesis in coinfected individuals. In this study, we investigated the effects of in vitro HIV-1 infection on the growth of M. tuberculosis, M. avium, and M. paratuberculosis in human peripheral blood monocyte-derived macrophages. Interestingly, HIV-1 infection induced a greater bacterial burden in coinfected cell cultures for all of the mycobacterial species tested and specifically induced accelerated growth of M. tuberculosis with a reduced mean generation time. The interaction of HIV-1 and M. tuberculosis was especially detrimental to the host cell, causing a significant synergistic reduction in macrophage viability. Also, in M. tuberculosis/HIV-1-coinfected cultures, increased levels of interleukin-1beta (IL-1beta), IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor were observed and viral replication was enhanced. Overall, the present data suggest that HIV-1 infection of macrophages may impair their ability to contain mycobacterial growth. Furthermore, coinfection with HIV-1 and M. tuberculosis seems to give rise to synergistic effects at the cellular level that mutually enhance the replication of both pathogens. This may, in part, contribute to the increased morbidity and mortality seen in coinfected individuals.