Validation of the Vascular quality of life questionnaire - 6 for clinical use in patients with lower limb peripheral arterial disease.

BACKGROUND: The VascuQoL-6 (VQ-6) health-related quality of life questionnaire, a short version of the disease-specific VascuQoL-25, was developed for clinical practice and use in vascular registries. The study purpose was to evaluate the validity and reliability of VQ-6. METHODS: VQ-6 was translated to Norwegian with linguistic validation and face value evaluation, and consecutive patients with intermittent claudication (IC) or critical limb ischemia (CLI) were included. All patients completed VQ-6 and Short Form-36 (SF-36), and were evaluated with ankle-brachial index (ABI) measurement pre- and post-exercise, a constant load treadmill test and clinical consultation at baseline and after 4 weeks. Correlation analysis, change statistics and receiver operator characteristics (ROC) curves were used to evaluate reliability, validity and responsiveness to change. RESULTS: One hundred seventy-one patients with peripheral arterial disease (PAD) were included, 70 (41%) female. 147 (86%) of the patients suffered from IC. The reliability of VQ-6 was good, Cronbachs-α 0.82. The ability of VQ-6 to differentiate between IC and CLI was good, area under the curve (AUC) 0.754. There was good correlation between SF-36 physical domains and component scores and VQ-6 score (r = 0.55-0.62) and excellent responsiveness to change after treatment, standard response mean (SRM) 1.12. The clinical anchors of ABI at rest, treadmill walking performance and Fontaine class improvement were less responsive to change than VQ-6, SF-36 and the vascular surgeon's evaluation. CONCLUSIONS: VQ-6 is reliable and valid, and can be used to evaluate PAD treatment in clinical practice and in vascular registries. Further research is necessary to determine the clinically important change over time. TRIAL REGISTRATION: ISRCTN14846962 (retrospectively registered).

A retrospective analysis of cardiovascular outcomes in patients treated with ASV.

OBJECTIVES: The effect of long-term adaptive servo-ventilation (ASV) on cardiovascular mortality and admission rates in patients with chronic heart failure (CHF) and Cheyne-Stokes respiration (CSR) has not been much studied. The aim of this study was primarily to investigate whether ASV therapy significantly reduced these parameters. DESIGN: We included 75 CHF patients on optimal medication and CSR ≥25% of sleeping time, in New York Heart Association (NYHA) classes II-IV and left ventricular ejection fraction (LVEF) ≤ 45%. Thirty-one patients were treated with ASV for >3-18 months and 44 patients served as a control group. RESULTS: Seven deaths (16%) in the control group and one death (3%) in the ASV treatment group had cardiovascular etiology. There was no significant difference between the two groups regarding cardiovascular death (log rank p = 0.07; HR 0.18 (95% CI 0.02-1.44), p = 0.11) and combined cardiovascular death or readmissions, but there was a trend toward better outcome regarding cardiovascular event-free survival (log rank p = 0.06; HR 0.53 (95% CI 0.27-1.05). CONCLUSIONS: In CHF patients with CSR, 18 months ASV treatment did not significantly affect cardiovascular death or combined cardiovascular death or hospital admissions. But there was a trend toward better combined outcome.

Additional functional outcomes after endovascular treatment for intermittent claudication.

Background Endovascular treatment (EVT) for intermittent claudication (IC) is performed in selected patients where conservative treatment and training fail. Treatment outcomes reported in vascular registries (survival, limb-survival, and re-intervention rate) are inadequate for low-risk patients with IC. Additional measurements of blood flow reduction and functional impairment clarify the indication for treatment and facilitate outcome evaluation. Purpose To analyze the additional outcome information on peripheral arterial pressures and walking capacity obtained from a local registry of EVT. Material and Methods Patients with IC treated with endovascular technique (angioplasty or stent) were prospectively entered into a local registry in addition to the national registry (NORKAR), with information on arterial pressures (ankle brachial index [ABI]) and treadmill performance (maximum walking distance [MWD]). Results A total of 242 consecutive patients (41% women; median age, 70 years) receiving the first treatment between July 2010 and December 2012 were included, 61% with aorto-iliac lesions. After 3 months, mean ABI increased from 0.62 (0.59-0.64) to 0.85 (0.83-0.87). The median MWD increased from 160 m to 410 m. Sixty-two percent reached the test maximum of 10 min. The improvement in ABI and MWD persisted after 1 year. When preoperative ABI was moderately reduced (0.5-0.9), ABI was normal in 61% after 3 months and in 55% after 1 year. When preoperative ABI was low (<0.5), ABI was normal in 43% both after 3 months and 1 year. Conclusion ABI and walking capacity were important outcome variables and improved after EVT. ABI improvement was better for patients with moderately reduced preoperative ABI than with low ABI.

Three-month treatment with adaptive servoventilation improves cardiac function and physical activity in patients with chronic heart failure and cheyne-stokes respiration: a prospective randomized controlled trial.

BACKGROUND: Cheyne-Stokes respiration frequently occurs in patients with congestive heart failure (CHF). Adaptive servoventilation (ASV) is a novel therapy with potential benefits. This prospective randomized trial investigated the effects of ASV on myocardial function and physical capacity. METHODS: Patients with severe CHF, despite optimal cardiac medication and/or left ventricular ejection fraction (LVEF) ≤40% and Cheyne-Stokes breathing for >25% of sleeping time were included. Fifty-one patients, age 57-81 years (4 were women), were randomized to either an ASV or a control group; 30 patients completed the study (15 from each group). The primary end point was any change in LVEF. The secondary end points were alterations in physical capacity according to the 6-min walk test or the New York Heart Association (NYHA) class. RESULTS: In the ASV-treatment group, LVEF improved from baseline (32 ± 11%) to study end (36 ± 13%), p = 0.013. The 6-min walk test improved from 377 ± 115 to 430 ± 123 m (p = 0.014) and the NYHA class from 3.2 (3.0-3.0) to 2.0 (2.0-3.0) (p < 0.001). No changes occurred in the control group. CONCLUSION: Three months of ASV treatment improved LVEF and physical capacity in CHF patients with Cheyne-Stokes respiration. These results suggest that ASV may be a beneficial supplement to standard medication in these patients.

mRNA expression of adipocytokines and glucocorticoid-related genes are associated with downregulation of E-cadherin mRNA in colorectal adenocarcinomas.

BACKGROUND: There is a consistently reported relationship between the incidence of colon cancer and obesity. It is thought that adipose tissue, particularly visceral fat, which secretes systemic factors that alter immunological, metabolic and endocrine milieu and promotes insulin resistance by producing adipocytokines, is important in cancer progression. Systemic high concentrations of adipocytokines, such as tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and glucocorticoid metabolism-related genes have been associated with gastrointestinal cancer. However, limited information exists about the expression of these cytokines within tumour tissue. MATERIAL AND METHODS: mRNA expression of TNF-α, IL-6,IL-8, IL-10, IL-1RN, glucocorticoid receptor alpha (GR-α), 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), plasminogen activator inhibitor-1 (PAI-1), Slug, vimentin, Snail and E-cadherin was analysed in paired samples of tumour tissue and normal mucosa in 60 surgical patients for Dukes B and C colorectal adenocarcinomas using quantitative reverse transcription PCR and microarray technology. The mRNA expression level of analysed genes was compared between tumour tissue and normal mucosa from the same patients, and a correlation to mRNA expression of E-cadherin in the same tissue samples was also performed. RESULTS: A highly significant difference in mRNA expression level of several of the analysed genes was observed between tumour tissue and the normal intestinal mucosa. Inverse correlation between mRNA expression of 11ßHSD1, IL-6, GR-α and PAI-1 on one hand and mRNA expression of E-cadherin on the other hand was observed. CONCLUSION: Results show that the adipocytokines and glucocorticoid metabolism-related genes are overexpressed in colorectal adenocarcinomas, and expression of these genes is associated with the downregulation of E-cadherin mRNA, connecting these genes to carcinogenesis and progression of colorectal cancer.

HPV genotype distribution according to severity of cervical neoplasia.

OBJECTIVE: To analyse the HPV genotype profile and the presence of multiple HPV infections according to severity of cervical intraepithelial neoplasia. METHODS: From a population of 424,143 women in Norway, we included all women (n=643) with histologically confirmed cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and evaluable HPV test during 2005 and 2006. Histology revealed CIN2 in 135 women, CIN3/ACIS in 495, and invasive carcinoma in 13 women. HPV genotyping was performed on cell suspensions from cervix by linear array which differentiates 37 HPV genotypes. RESULTS: HPV was detected in 98.4% (633/643) of the women, of whom 52.5% (338/643) were infected with more than one HPV genotype. HPV16 was most common, being detected in 51.2% (329/643) of all cases, followed by HPV31, 33, 52, 18, and 51. Overall, HPV 16 or 18 were detected in 58.0% (373/643), with 34.7% (223/643) without concurrence of other high-risk genotypes. HPV16 and HPV33 as single infections were more common in women with CIN3+ as compared to CIN2 (age-adjusted odds ratio=5.93, 95% CI=2.73-12.87, and age-adjusted odds ratio=4.53, 95% CI=1.42-14.46, respectively). Concurrent infection with other HPV genotypes did not significantly alter the associations to CIN3+ for HPV16 or HPV33. A single HPV infection, other than HPV16, 18, 31, or 33, was used as the reference. HPV18 or multiple HPV infections not including HPV16 or HPV33 were not associated with the severity of cervical neoplasia. CONCLUSION: HPV16 and HPV33 appear to have a higher oncogenic potential than other HPV genotypes.

Performance of human papillomavirus DNA and mRNA testing strategies for women with and without cervical neoplasia.

In the present study we investigated the cross-sectional positivity for DNA and E6/E7 mRNA from high-risk human papillomavirus (HPV) types in 643 women with high-grade cervical neoplasia (135 cases of cervical intraepithelial neoplasia grade 2 [CIN2], 495 cases of CIN3/adenocarcinoma in situ [ACIS], and 13 cases of invasive carcinoma) and in 736 women with normal cytology by using the Amplicor and PreTect HPV-Proofer assays. In addition, genotyping was performed using Linear Array for women with normal cytology and a positive HPV test and in all women with histologically confirmed CIN2+. In women with normal cytology, 8.3% (61/736) were Amplicor positive and 3.3% (24/736) were PreTect HPV-Proofer positive (P < 0.001). Concordant results between the Amplicor and PreTect HPV-Proofer tests were present in 90.3% (665/736). In women with CIN2+ lesions 96.4% (620/643) were positive by Amplicor, 98.4% (633/643) by linear array, and 64.1% (412/643) by PreTect HPV-Proofer. Concordant results for the three HPV assays were present in 63.8%. The genotype profile detected by linear array and PreTect HPV-Proofer showed substantial agreement for HPV types 16, 18, 33, and 45. HPV type 16 and/or 18 was detected in 58.8% (378/643) of the women with high-grade neoplasia. Detection of E6/E7 mRNA by PreTect HPV-Proofer increased with severity of the cervical lesion. Detection of HPV DNA, however, was not associated with histology grade. In conclusion, the detection of HPV varied according to the assay used, and the concordance between the tests was poor. Our results indicate that mRNA testing may be a biomarker for progression of cervical neoplasia, but the optimal genotype mix remains to be determined.

Construction of an evidence-based, graduated training curriculum for D-box, a webcam-based laparoscopic basic skills trainer box.

BACKGROUND: Surgical training programs are now including simulators as training tools for teaching laparoscopic surgery. The aim of this study was to develop a standardized, graduated, and evidence-based curriculum for the newly developed D-box (D-box Medical, Lier, Norway) for training basic laparoscopic skills. METHODS: Eighteen interns with no laparoscopic experience completed a training program on the D-box consisting of 8 sessions of 5 tasks with assessment on a sixth task. Performance was measured by the use of 3-dimensional electromagnetic tracking of hand movements, path length, and time taken. Ten experienced surgeons (>100 laparoscopic surgeries, median 250) were recruited for establishing benchmark criteria. RESULTS: Significant learning curves were obtained for all construct valid parameters for tasks 4 (P < .005) and 5 (P < .005) and reached plateau levels between the fifth and sixth session. Within the 8 sessions of this study, between 50% and 89% of the interns reached benchmark criteria on tasks 4 and 5. CONCLUSIONS: Benchmark criteria and an evidence-based curriculum have been developed for the D-box. The curriculum is aimed at training and assessing surgical novices in basic laparoscopic skills.

A tale of two trainers: virtual reality versus a video trainer for acquisition of basic laparoscopic skills.

BACKGROUND: This study aimed to assess the transferability of basic laparoscopic skills between a virtual reality simulator (MIST-VR) and a video trainer box (D-Box). METHODS: Forty-six medical students were randomized into 2 groups, training on MIST-VR or D-Box. After training with one modality, a crossover assessment on the other was performed. RESULTS: When tested on MIST-VR, the MIST-VR group showed significantly shorter time (90.3 seconds vs 188.6 seconds, P <.001), better economy of movements (4.40 vs 7.50, P <.001), and lower score (224.7 vs 527.0, P <.001). However, when assessed on the D-Box, there was no difference between the groups for time (402.0 seconds vs 325.6 seconds, P = .152), total hand movements (THC) (289 vs 262, P = .792), or total path length (TPL) (34.9 m vs 34.6 m, P = .388). CONCLUSION: Both simulators provide significant improvement in performance. Our results indicate that skills learned on the MIST-VR are transferable to the D-Box, but the opposite cannot be demonstrated.

Evaluation of suitable reference genes for normalization of real-time reverse transcription PCR analysis in colon cancer.

BACKGROUND: Real-time reverse transcription PCR (qRT-PCR) is frequently used for gene expression quantification due to its methodological reproducibility and sensitivity. The gene expression is quantified by normalization to one or more reference genes which are presumed stably expressed throughout a given experiment. The aim of this study was to validate a standardized experimental setup to identifying reference genes for normalization of qRT-PCR in the metastatic and non-metastatic colon cancer. METHODS: In this study, expression of 16 commonly used reference genes was quantified in tumour tissue and individual-matched normal mucosa in 18 non-metastatic colon cancer patients and 20 colon cancer patients with distant metastases using TaqMan Low Density Array (TLDA). The expression stability was determined and compared by means of geNorm and NormFinder. RESULTS: Two pairs of genes, HPRT1/PPIA and IPO8/PPIA, were identified to be suitable to normalize gene expression data in metastatic and non-metastatic colon cancer patients, according to geNorm and NormFinder respectively. CONCLUSION: We propose a standardized approach of finding the most suitable reference gene(s) in every qRT-PCR experiment using TLDA.

Rectal visceral sensitivity in women with irritable bowel syndrome without psychiatric comorbidity compared with healthy volunteers.

BACKGROUND: Psychiatric comorbidity and visceral hypersensitivity are common in patients with irritable bowel syndrome (IBS), but little is known about visceral sensitivity in IBS patients without psychiatric disorders. AIM: We wanted to examine rectal visceral sensitivity in IBS patients without comorbid psychiatric disorders, IBS patients with phobic anxiety and healthy volunteers. METHODS: A total of thirty-eight female, non-constipated IBS patients without psychiatric disorders and eleven female IBS patients with phobic anxiety were compared to nine healthy women using a barostat double random staircase method. The non-psychiatric patients were divided into those with diarrhoea predominant symptoms and those with alternating stool habits. RESULTS: The IBS patients without psychiatric disorders had normal visceral pressure thresholds. However, in the diarrhoea predominant subgroup, the volume discomfort threshold was reduced while it was unchanged in those with alternating stool habits. The phobic IBS patients had similar thresholds to the healthy volunteers. The rectal tone was increased in the non-psychiatric IBS patients with diarrhoea predominant symptoms and in the IBS patients with phobic anxiety. CONCLUSIONS: Non-constipated IBS patients without psychiatric disorders had increased visceral sensitivity regarding volume thresholds but normal pressure thresholds. Our study suggests that the lowered volume threshold was due to increased rectal tone.

Autonomic function at rest and in response to emotional and rectal stimuli in women with irritable bowel syndrome.

Our aim was to study autonomic function in patients with Irritable bowel syndrome (IBS) without constipation and psychiatric comorbidity. Respiratory sinus arrhythmia (RSA) (representing cardiac vagal activity), skin conductance (representing sympathetic activity) and heart rate were measured at baseline and as a response to emotional stress and rectal discomfort in 33 women with IBS and 21 healthy women. Baseline heart rate was higher in the patients than in the healthy volunteers. Both groups had decreased RSA and increased heart rate and skin conductance level when exposed to emotional stress, but the autonomic responses did not differ significantly between the groups. At discomfort threshold the patients had increased heart rate response and skin conductance amplitude when compared to the healthy volunteers. Correlations between autonomic responses and the depression subscale of the Hospital Anxiety and Depression (HAD) score differed markedly between the diarrhea-predominant IBS patients and the IBS patients with alternating stool habits.

Visceral sensitivity in irritable bowel syndrome and healthy volunteers: reproducibility of the rectal barostat.

The reproducibility of rectal visceral sensitivity using the barostat double-random staircase method was evaluated. We tested 15 healthy women and 18 women with irritable bowel syndrome twice. Pressure, volume, and tension were measured at first sensation of gas, stool, and discomfort. There was no significant difference between test and retest. Three different indexes were used as measures of reproducibility. The intraclass correlation coefficients, considered to demonstrate acceptable reproducibility when higher than 0.80, ranged from 0.76 to 0.93 in the healthy volunteers and from 0.53 to 0.88 in the patients. The pooled coefficients of variation ranged from 10 to 24% in the healthy volunteers and from 11 to 49% in the patients. The repeatability coefficients are also given. The results indicate that barostat visceral sensitivity measurements in the rectum may be applicable when comparing groups of subjects.

[Irritable bowel syndrome--a multifactorial disease in children and adults]. / Irritabel tarm-syndrom multifaktoriell lidelse hos barn og voksne.

Irritable bowel syndrome is the most frequent gastrointestinal disorder in Norway. Though there has been huge research activity in the field, no proven single aetiology or effective treatment has emerged. Consensus-based clinical diagnostic criteria have not yet brought diagnostic clarity. Possibly, there are dysfunctions in the processing of sensory stimuli in the "brain-gut" axis that may cause visceral hypersensitivity and secondary motility changes. In some patients, a multifactorial explanation of the mechanisms is useful, including stressful life events or other psychological factors. Psychiatric co-morbidity is probably the most important maintaining factor. Irritable bowel syndrome may serve as a model for the study of the interaction between biological, psychological and social factors in functional disorders. A good therapeutic relationship between the physician and the patient is an important element in the treatment approach.