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Jason Oke and Tom Fanshawe expose four simple biases that can change our understanding of cancer survival rates and skew comparisons made between countries.
\n \n\n \n \nBackground: Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol formed by heating an e-liquid. People who smoke report using ECs to stop or reduce smoking, but some organisations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit and if they are safe to use for this purpose. This review is an update of a review first published in 2014. Objectives: To evaluate the effect and safety of using electronic cigarettes (ECs) to help people who smoke achieve long-term smoking abstinence. Search methods: We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO for relevant records to January 2020, together with reference-checking and contact with study authors. Selection criteria: We included randomized controlled trials (RCTs) and randomized cross-over trials in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. To be included, studies had to report abstinence from cigarettes at six months or longer and/or data on adverse events (AEs) or other markers of safety at one week or longer. Data collection and analysis: We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow-up, AEs, and serious adverse events (SAEs). Secondary outcomes included changes in carbon monoxide, blood pressure, heart rate, blood oxygen saturation, lung function, and levels of known carcinogens/toxicants. We used a fixed-effect Mantel-Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data from these studies in meta-analyses. Main results: We include 50 completed studies, representing 12,430 participants, of which 26 are RCTs. Thirty-five of the 50 included studies are new to this review update. Of the included studies, we rated four (all which contribute to our main comparisons) at low risk of bias overall, 37 at high risk overall (including the 24 non-randomized studies), and the remainder at unclear risk. There was moderate-certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.25 to 2.27; I2 = 0%; 3 studies, 1498 participants). In absolute terms, this might translate to an additional four successful quitters per 100 (95% CI 2 to 8). There was low-certainty evidence (limited by very serious imprecision) of no difference in the rate of adverse events (AEs) (RR 0.98, 95% CI 0.80 to 1.19; I2 = 0%; 2 studies, 485 participants). SAEs occurred rarely, with no evidence that their frequency differed between nicotine EC and NRT, but very serious imprecision led to low certainty in this finding (RR 1.37, 95% CI 0.77 to 2.41: I2 = n/a; 2 studies, 727 participants). There was moderate-certainty evidence, again limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non-nicotine EC (RR 1.71, 95% CI 1.00 to 2.92; I2 = 0%; 3 studies, 802 participants). In absolute terms, this might again lead to an additional four successful quitters per 100 (95% CI 0 to 12). These trials used EC with relatively low nicotine delivery. There was low-certainty evidence, limited by very serious imprecision, that there was no difference in the rate of AEs between these groups (RR 1.00, 95% CI 0.73 to 1.36; I2 = 0%; 2 studies, 346 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 0.25, 95% CI 0.03 to 2.19; I2 = n/a; 4 studies, 494 participants). Compared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.50, 95% CI 1.24 to 5.04; I2 = 0%; 4 studies, 2312 participants). In absolute terms this represents an increase of six per 100 (95% CI 1 to 14). However, this finding was very low-certainty, due to issues with imprecision and risk of bias. There was no evidence that the rate of SAEs varied, but some evidence that non-serious AEs were more common in people randomized to nicotine EC (AEs: RR 1.17, 95% CI 1.04 to 1.31; I2 = 28%; 3 studies, 516 participants; SAEs: RR 1.33, 95% CI 0.25 to 6.96; I2 = 17%; 5 studies, 842 participants). Data from non-randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate over time with continued use. Very few studies reported data on other outcomes or comparisons and hence evidence for these is limited, with confidence intervals often encompassing clinically significant harm and benefit. Authors' conclusions: There is moderate-certainty evidence that ECs with nicotine increase quit rates compared to ECs without nicotine and compared to NRT. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the degree of effect, particularly when using modern EC products. Confidence intervals were wide for data on AEs, SAEs and other safety markers. Overall incidence of SAEs was low across all study arms. We did not detect any clear evidence of harm from nicotine EC, but longest follow-up was two years and the overall number of studies was small. The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates. Further RCTs are underway. To ensure the review continues to provide up-to-date information for decision-makers, this review is now a living systematic review. We will run searches monthly from December 2020, with the review updated as relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status.
\n \n\n \n \nIn this diagnostic test accuracy systematic review we summarise the evidence on the diagnostic accuracy of blood \u03b1-fetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH) in surveillance for testicular cancer recurrence in adults. We searched four electronic databases for studies that reported the diagnostic accuracy of HCG, AFP, and/or LDH in sufficient detail for sensitivity and specificity to be calculated by extracting a 2 \u00d7 2 table comparing biomarker positivity with testicular cancer recurrence. Screening, data extraction and QUADAS-2 quality assessment were completed by two independent reviewers. From 2406 studies, nine met our inclusion criteria. Eight reported data at the per-patient level. Sample sizes were small (range 5 to 449 patients) and clinical heterogeneity precluded meta-analysis. In most studies the specificity for recurrence with AFP and HCG was high (90\u2013100%) but sensitivity was often relatively low, suggesting that many recurrences would not be detected by tumour markers alone. The diagnostic performance of LDH appears poorer. Studies were methodologically weak, with probable selection, incorporation and partial verification bias, and many studies were excluded for not reporting on recurrence-free patients. Limitations including small sample sizes, high heterogeneity, and inconsistent and incomplete reporting mean these results must be interpreted with caution. Despite inclusion of biomarkers in international surveillance guidance, there remains a lack of high quality evidence about their accuracy, optimal thresholds, and the most effective surveillance strategy in relation to contemporary investigative modalities. Higher quality research using data from modern-day follow-up cohorts is necessary to identify opportunities to reduce unnecessary testing.
\n \n\n \n \nBackground:We aimed to evaluate the analytic performance of 3 rapid HIV viral load assays: The novel Xpert HIV-1 VL XC (Xpert XC), Xpert HIV-1 VL (Xpert VL), and m-PIMA HIV-1/2 VL (m-PIMA).Setting:Two South African clinics.Methods:We conducted a prospective diagnostic accuracy study. Site-laboratory technicians and nurses used the Xpert XC, Xpert VL, and m-PIMA to test plasma samples from people with HIV receiving antiretroviral therapy. We compared results with the Roche cobas HIV-1 reference assay. We determined accuracy to detect viraemia at the World Health Organization (WHO) failure threshold of 1000 copies/mL on all 3 assays, and 50 and 200 copies/mL on the Xpert assays. We assessed the agreement using Bland-Altman plots.Results:We enrolled 140 participants (98 [70%] women, median age 37 years), who provided 189 paired samples at one or more timepoints. We tested 174 samples with the Xpert XC, 188 with the Xpert VL, and 128 with the m-PIMA. At 1000 copies/mL, sensitivity and specificity (95% confidence intervals) were 97% (82 to 100) and 98% (93 to 99) (Xpert XC), 100% (87 to 100) and 96% (91 to 98) (Xpert VL), and 92% (72 to 99) and 99% (93 to 100) (m-PIMA) respectively. At 50 copies/mL, sensitivity and specificity were 93% (81 to 98) and 96% (91 to 99) (Xpert XC), and 95% (84 to 99) and 95% (90 to 98) (Xpert VL) respectively. Mean bias was -0.10 (-0.54 to 0.34) log10copies/mL (Xpert XC), 0.07 (-0.37 to 0.52) log10copies/mL (Xpert VL), and -0.26 (-0.83 to 0.31) log10copies/mL (m-PIMA).Conclusions:In these South African clinics, the accuracy of all 3 assays was clinically acceptable to detect viraemia at the WHO failure threshold, whereas both Xpert assays were also accurate at detecting low-level viraemia.
\n \n\n \n \nBackground: Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). Objectives: To review the efficacy of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation. Search methods: We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('cytisine' or 'Tabex' or 'dianicline' or 'varenicline' or 'nicotine receptor partial agonist') in the title or abstract, or as keywords. The register is compiled from searches of MEDLINE, EMBASE, and PsycINFO using MeSH terms and free text to identify controlled trials of interventions for smoking cessation and prevention. We contacted authors of trial reports for additional information where necessary. The latest update of the specialised register was in May 2015, although we have included a few key trials published after this date. We also searched online clinical trials registers. Selection criteria: We included randomised controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment. Data collection and analysis: We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomisation procedure, concealment of allocation, and completeness of follow-up. The main outcome measured was abstinence from smoking at longest follow-up. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model. Main results: Two trials of cytisine (937 people) found that more participants taking cytisine stopped smoking compared with placebo at longest follow-up, with a pooled risk ratio (RR) of 3.98 (95% confidence interval (CI) 2.01 to 7.87; low-quality evidence). One recent trial comparing cytisine with NRT in 1310 people found a benefit for cytisine at six months (RR 1.43, 95% CI 1.13 to 1.80). One trial of dianicline (602 people) failed to find evidence that it was effective (RR 1.20, 95% CI 0.82 to 1.75). This drug is no longer in development. We identified 39 trials that tested varenicline, 27 of which contributed to the primary analysis (varenicline versus placebo). Five of these trials also included a bupropion treatment arm. Eight trials compared varenicline with nicotine replacement therapy (NRT). Nine studies tested variations in varenicline dosage, and 13 tested usage in disease-specific subgroups of patients. The included studies covered 25,290 participants,\u00a011,801 of whom used varenicline. The pooled RR for continuous or sustained abstinence at six months or longer for varenicline at standard dosage versus placebo was 2.24 (95% CI 2.06 to 2.43; 27 trials, 12,625 people; high-quality evidence). Varenicline at lower or variable doses was also shown to be effective, with an RR of 2.08 (95% CI 1.56 to 2.78; 4 trials, 1266 people). The pooled RR for varenicline versus bupropion at six months was 1.39 (95% CI 1.25 to 1.54; 5 trials, 5877 people; high-quality evidence). The RR for varenicline versus NRT for abstinence at 24 weeks was 1.25 (95% CI 1.14 to 1.37; 8 trials, 6264 people; moderate-quality evidence). Four trials which tested the use of varenicline beyond the 12-week standard regimen found the drug to be well-tolerated during long-term use. The number needed to treat with varenicline for an additional beneficial outcome, based on the weighted mean control rate, is 11 (95% CI 9 to 13). The most commonly reported adverse effect of varenicline was nausea, which was mostly at mild to moderate levels and usually subsided over time. Our analysis of reported serious adverse events occurring during or after active treatment suggests there may be a 25% increase in the chance of SAEs among people using varenicline (RR 1.25; 95% CI 1.04 to 1.49; 29 trials, 15,370 people; high-quality evidence). These events include comorbidities such as infections, cancers and injuries, and most were considered by the trialists to be unrelated to the treatments. There is also evidence of higher losses to follow-up in the control groups compared with the intervention groups, leading to a likely underascertainment of the true rate of SAEs among the controls. Early concerns about a possible association between varenicline and depressed mood, agitation, and suicidal behaviour or ideation led to the addition of a boxed warning to the labelling in 2008. However, subsequent observational cohort studies and meta-analyses have not confirmed these fears, and the findings of the EAGLES trial do not support a causal link between varenicline and neuropsychiatric disorders, including suicidal ideation and suicidal behaviour. The evidence is not conclusive, however, in people with past or current psychiatric disorders. Concerns have also been raised that varenicline may slightly increase cardiovascular events in people already at increased risk of those illnesses. Current evidence neither supports nor refutes such an association, but we await the findings of the CATS trial, which should establish whether or not this is a valid concern. Authors' conclusions: Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and three-fold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion or with NRT. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The most frequently recorded adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Early reports of possible links to suicidal ideation and behaviour have not been confirmed by current research. Future trials of cytisine may test extended regimens and more intensive behavioural support.
\n \n\n \n \nObjectives: To assess whether residential proximity to industrial incinerators in England is associated with increased risk of cancer incidence and mortality. Design: Retrospective study using matched case-control areas. Setting: Five circular regions of radius 10 km near industrial incinerators in England (case regions) and five matched control regions, 1998-2008. Participants: All cases of diseases of interest within the circular areas. Primary and secondary outcome measures: Counts of childhood cancer incidence (<15 years); childhood leukaemia incidence (<15 years); leukaemia incidence; liver cancer incidence; lung cancer incidence; non-Hodgkin's lymphoma incidence; allcause mortality; infant mortality (<1 year) and liver cancer mortality. Results: The estimated relative risks for case circles versus control circles for the nine outcomes considered range from 0.94 to 1.14, and show neither elevated risk in case circles compared to control areas nor elevated risk with proximity to incinerators within case circles. Conclusions: This study applies statistical methods for analysing spatially referenced health outcome data in regions with a hypothesised exposure relative to matched regions with no such exposure. There is no evidence of elevated risk of cancer incidence or mortality in the vicinity of large industrial incinerators in England.
\n \n\n \n \nBackground: We consider the problem of assessing inter-rater agreement when there are missing data and a large number of raters. Previous studies have shown only 'moderate' agreement between pathologists in grading breast cancer tumour specimens. We analyse a large but incomplete data-set consisting of 24177 grades, on a discrete 1-3 scale, provided by 732 pathologists for 52 samples. Methodology/principal findings: We review existing methods for analysing inter-rater agreement for multiple raters and demonstrate two further methods. Firstly, we examine a simple non-chance-corrected agreement score based on the observed proportion of agreements with the consensus for each sample, which makes no allowance for missing data. Secondly, treating grades as lying on a continuous scale representing tumour severity, we use a Bayesian latent trait method to model cumulative probabilities of assigning grade values as functions of the severity and clarity of the tumour and of rater-specific parameters representing boundaries between grades 1-2 and 2-3. We simulate from the fitted model to estimate, for each rater, the probability of agreement with the majority. Both methods suggest that there are differences between raters in terms of rating behaviour, most often caused by consistent over- or under-estimation of the grade boundaries, and also considerable variability in the distribution of grades assigned to many individual samples. The Bayesian model addresses the tendency of the agreement score to be biased upwards for raters who, by chance, see a relatively 'easy' set of samples. Conclusions/significance: Latent trait models can be adapted to provide novel information about the nature of inter-rater agreement when the number of raters is large and there are missing data. In this large study there is substantial variability between pathologists and uncertainty in the identity of the 'true' grade of many of the breast cancer tumours, a fact often ignored in clinical studies. \u00a9 2008 Fanshawe et al.
\n \n\n \n \nAims: To assess the cardiovascular disease (CVD) risk of people with screen-detected Type 2 diabetes and to estimate the risk reduction achievable through early intensive pharmacological intervention. Methods: In ADDITION-Cambridge, diabetic patients were identified among people aged 40-69 years through a stepwise screening procedure including a risk score, random and fasting capillary blood glucose, HbA1c and oral glucose tolerance test. In those without prior macrovascular disease, 10-year CVD risk was computed using UK Prospective Diabetes Study (UKPDS) and Framingham engines. The absolute risk reduction achievable and its plausible range were predicted using relative risk reductions for individual therapies from published trials and sensitivity analysis. Results: Of the 867 individuals with undiagnosed diabetes, 19% had pre-existing CVD, 97% were overweight or obese, 86% had hypertension, 75% had dyslipidaemia, 20% had microalbuminuria and 18% were smokers. Of those with hypertension, 35% were not prescribed drugs and 42% were suboptimally treated. Of participants with dyslipidaemia, 68% were not prescribed medications and 22% were poorly controlled. Median 10-year CVD risk was 34.0% [interquartile range (IQR) 26.2-44.6] in men and 21.5% (IQR 15.7-28.7) in women using the UKPDS engine; 38.6% (IQR 27.8-53.0) in men and 24.6% (IQR 17.2-32.9) in women using Framingham equations. In the most conservative scenario (no additive effect of therapies), the absolute risk reduction achievable through multifactorial therapy ranged from 4.9 to 9.5% (UKPDS) and from 5.4 to 10.5% (Framingham). The corresponding ranges of numbers needed to treat were 11-20 and 10-19. Conclusions: People with screen-detected diabetes have an adverse cardiovascular risk profile, which is potentially modifiable through application of existing treatment recommendations. \u00a9 2008 The Authors.
\n \n\n \n \nBackground & Objectives: The aim of this study was to apply three simple risk - scoring systems to prospectively collected data on all elective open Abdominal Aortic Aneurysm (AAA) operations in the Cambridge Academic Vascular Unit over a 6 - year period (January 1998 to January 2004), to compare their predictive values and to evaluate their validity with respect to prediction of mortality and post-operative complications. Methods: 204 patients underwent elective open infra-renal AAA repair. Data were prospectively collected and risk assessment scores were calculated for mortality and morbidity according to the Glasgow Aneurysm Score (GAS), VBHOM (Vascular Biochemistry and Haematology Outcome Models) and Estimation of Physiologic Ability and Surgical Stress (E-PASS). Results: The mortality rate was 6.3% (13/204) and 59% (121/204) experienced a post-operative complication (30-day outcome). For GAS, VBHOM and E-PASS the receiver operating characteristics (ROC) curve analysis for prediction of in-hospital mortality showed area under the curve (AUC) of 0.84 (95% confidence interval [CI], 0.76 to 0.92; p < 0.0001), 0.82 (95% CI, 0.68 to 0.95; p = 0.0001) and 0.92 (95% CI, 0.87 to 0.97; p < 0.0001) respectively. There were also significant correlations between post-operative complications and length of hospital stay and each of the three scores, but the correlation was substantially higher in the case of E-PASS. Conclusions: All three scoring systems accurately predicted the risk of mortality and morbidity in patients undergoing elective open AAA repair. Among these, E-PASS seemed to be the most accurate predictor in this patient population. \u00a9 2007 European Society for Vascular Surgery.
\n \n\n \n \nAim: To compare the effect of an initial early computed tomography (CT) examination versus standard practice (SP) on the length of hospital stay, diagnostic accuracy, and mortality of adults presenting with acute abdominal pain. Materials and methods: Two hundred and five adults presenting with acute abdominal pain were randomized to undergo an early CT examination or current SP, which comprised supine abdominal and erect chest radiography. One hundred and ninety-eight patients (99 in each arm) were included in the analysis. The primary endpoint was the duration of inpatient stay; secondary endpoints were diagnostic certainty and mortality. Results: There was no significant difference in the length of hospital stay between the two arms (p = 0.20). At randomization 36% (35 of 96) of CT patients and 49% (48 of 98) of SP patients were correctly diagnosed; 24 h after randomization the correct diagnosis had been established in 84% of CT patients and 73% of SP patients. This refinement in diagnostic certainty was significantly better in the CT group (p < 0.001). There was no difference in mortality between the two trial arms (p = 0.31). Conclusion: Early abdominal CT in patients with acute abdominal pain improves diagnostic certainty, but does not reduce the length of hospital stay and 6 month mortality. \u00a9 2007 The Royal College of Radiologists.
\n \n\n \n \nThis paper explores whether and how the behavioral impact of genotype disclosure can be disentangled from the impact of numerical risk estimates generated by genetic tests. Secondary data analyses are presented from a randomized controlled trial of 162 first-degree relatives of Alzheimer's disease (AD) patients. Each participant received a lifetime risk estimate of AD. Control group estimates were based on age, gender, family history, and assumed \u03b54-negative apolipoprotein E (APOE) genotype; intervention group estimates were based upon the first three variables plus true APOE genotype, which was also disclosed. AD-specific self-reported behavior change (diet, exercise, and medication use) was assessed at 12 months. Behavior change was significantly more likely with increasing risk estimates, and also more likely, but not significantly so, in \u03b54-positive intervention group participants (53% changed behavior) than in control group participants (31%). Intervention group participants receiving \u03b54-negative genotype feedback (24% changed behavior) and control group participants had similar rates of behavior change and risk estimates, the latter allowing assessment of the independent effects of genotype disclosure. However, collinearity between risk estimates and \u03b54-positive genotypes, which engender high-risk estimates, prevented assessment of the independent effect of the disclosure of an \u03b54 genotype. Novel study designs are proposed to determine whether genotype disclosure has an impact upon behavior beyond that of numerical risk estimates. \u00a9 Copyright 2008, Mary Ann Liebert, Inc.
\n \n\n \n \nThe aim of this study was to determine the incidence of facial clefting in Cambridge, UK, using multiple resources of ascertainment and to relate the findings to antenatal ultrasound screening (AUS) detection rates.AUS records from an obstetric ultrasound department, post-natal records from the regional craniofacial unit, and autopsy reports of foetuses over 16 weeks' gestational age from a regional pathology department from 1993 to 1997 were retrospectively reviewed. Cross-referencing between the three data sets identified all cases of facial clefts.Of 23577 live and stillbirths, 30 had facial clefts. AUS detected 17 of these. Sixteen of the 30 had isolated facial clefts. Others had associated anomalies, chromosomal defects, or syndromes. Percentages and confidence intervals were calculated from the above data. Twenty-one resulted in live births, seven terminations, and two foetal deaths. Overall, detection rate by AUS was 65 per cent [67 per cent isolated cleft lip, 93 per cent cleft lip and palate (CLP), and 22 per cent isolated cleft palate], with no false positives. The incidence of facial clefts was 0.127 per cent (95 per cent confidence interval 0.089-0.182 per cent); the incidence for isolated CLP was lower than previously reported: 0.067 per cent (0.042-0.110 per cent). With one exception, all terminations were in foetuses with multiple anomalies.The figures presented will enable joint CLP clinics to give parents information of termination rates. The study allows pre-pregnancy counselling of families previously affected by clefting about the reliability of AUS detection rates. \u00a9 2011 The Author.
\n \n\n \n \nBackground: The Estimation of Physiologic Ability and Surgical Stress (E-PASS) score was designed on the premise that the balance between the patient's physiologic reserve capacity and the surgical stress inflicted at operation was important in the occurrence of postoperative complications. The aim of this study was to assess its value in predicting mortality and morbidity after open elective abdominal aortic aneurysm (AAA) repair. Methods: E-PASS data items were collected prospectively in a group of 204 patients undergoing elective open AAA repair over a 6-year period. The operative morbidity and mortality rates were compared with the preoperative risk score (PRS), surgical stress score (SSS) and comprehensive risk score (CRS) of E-PASS. The group comprised 180 (88%) males and the median age was 73 (range 44 to 86) years. Results: There were 13 (6%) deaths and 121 (59%) experienced a postoperative complication. As the PRS, SSS and CRS increased, the incidence of postoperative morbidity and mortality significantly increased (P < .0001). Overall mean CRS was .52 (\u00b1.27). Mean CRS in the groups of patients who survived and died were .49 (\u00b1.24) and .98 (\u00b126), respectively. PRS, SSS, and CRS all had extremely good predictive power for both mortality and morbidity as demonstrated by high areas under the receiver operator curve (range .799 to .953). CRS also showed a strong statistically significant association with the severity of postoperative complication (P < .0001) and length of hospital stay (P < .0001). Conclusions: The E-PASS model appears to be a promising method of predicting death and the development of postoperative complications in patients undergoing elective open AAA surgery. It requires further validation in arterial surgery at different geographical locations. \u00a9 2007 Excerpta Medica Inc. All rights reserved.
\n \n\n \n \nThe aim of this study was to evaluate survival and success rates following autotransplantation of permanent maxillary canine teeth. Sixty-three cases of maxillary canine autotransplantation from 49 subjects (mean age at transplantation 21.8 years, range 13-42.1 years) undertaken between 1977 and 2003 were collected as part of an audit project of transplantation success. All maxillary canines had complete root development at the time of transplantation. The sample was divided into two groups, a matched case-control study to compare 27 unilateral transplanted canines with the non-transplanted canine on the contralateral side, and all 63 transplanted canines with no controls. Teeth were assessed clinically using established criteria for success: tooth presence for survival and resorption, mobility, probing pocket depth (PPD), gingival bleeding, vitality, and colour. Radiographic investigation for success assessed internal and external inflammatory resorption (including the amount) bone levels and any signs of pathology. Data were described with descriptive statistics and analytical tests were used to assess frequencies of occurrence.The survival rate was 83 per cent with an average duration of 14.5 years in situ. Thirty-eight per cent of the transplants were deemed successful. There were statistically significant associations between the transplanted and non-transplanted teeth in PPD (P = 0.006), gingival bleeding (P = 0.006), vitality (P = 0.004), and colour (P = 0.002). Autotransplantation of impacted maxillary canines can be successful in the long term and may be indicated in selected cases. Although the rate for complete success in this study was low (no signs of resorption, mobility, and sound periodontal tissues), the survival rate can be considered favourable when evaluating autotransplantation as a treatment option for grossly malpositioned canines with little scope for orthodontic alignment. \u00a9 2010 The Author.
\n \n\n \n \nBackground: Transjugular liver biopsy (TJLB) can be performed to obtain more than two cores safely. This advantage has not been evaluated in terms of diagnostic accuracy or grading/staging evaluation. Aim: To evaluate whether three separate cores of TJLB provide more histological information compared with two or one cores. Methods: Twenty-three patients, who had three separate passes, with each core \u22657mm in length using a 19G Tru-cut needle, were evaluated. Each TJLB was blindly coded; the pathologist randomly assessed: (a) each core separately covering the other two, (b) two cores simultaneously covering the third and (c) the three cores together for diagnostic yield, inflammation and fibrosis. Results: The mean TJLB length was 32\u00b15.5mm. In 12 one-core (52%) and 18 2-core (78%) assessments, diagnosis (mainly cirrhosis) was made correctly in each core. The within-patient standard deviations for one-core vs two-core assessment were similar for grading (0.42 and 0.47, respectively), but higher for staging (0.39 and 0.15, respectively). Staging was underestimated in assessing one-core and less for two cores compared to three cores. Conclusion: Three non-fragmented cores (each core \u22657mm in length) of TJLB can be considered a minimum requirement for histological assessment, giving better reproducibility in diagnosis as well as for inflammation and fibrosis. \u00a9 2007 Blackwell Munksgaard.
\n \n\n \n \nBackground: We investigated cell cycle kinetics of nodular lesions in cirrhosis to differentiate hepatocellular carcinoma (HCC) from its precursor lesions. Methods: Twelve small HCC, 10 regenerative (RN), six large regenerative (LRN), and five dysplastic nodules (DN), identified in explant cirrhotic livers of five consecutive patients transplanted at Royal Free Hospital in 2002. Immunoperoxidase for MCM2, geminin and Ki67 was performed and the percentage of positive cells counted. Result: The proportion of cells expressing MCM2 was more than those expressing Ki67, which in turn was more than those expressing geminin (overall median=16%, 2% and 0.5%, respectively, P<0.001). There was a statistically significant trend of increasing Ki67 expression (P=0.006), from RN to HCC; this trend was not statistically significant for geminin (P=0.18) or MCM2 (P=0.51). The median percentage of cells expressing Ki67 was 1% in RN, 0.5% in LRN, 2.2% in DN and 5.4% in HCC. The combination of these markers identified four different cell kinetics patterns: 'resting' (GO cells: MCM2 - ve, Ki67 - ve, geminin - ve); 'licensed' (MCM2 +ve, Ki67 -ve, geminin -ve); 'slowly growing' (G1 phase arrest, MCM2 +ve, Ki67 +ve, low (0.4%) geminin) and expanding (MCM2 +ve, Ki67 +ve, geminin +ve) nodules. Conclusions: The combination of MCM2, geminin and Ki67 could represent a valuable tool in the understanding of HCC progression in cirrhosis. \u00a9 2006 Blackwell Munksgaard.
\n \n\n \n \nThe objective was to evaluate the effect of an assessment strategy using the computer decision support system (the GRAIDS software), on the management of familial cancer risk in British general practice in comparison with best current practice. The design included cluster randomised controlled trial, and involved forty-five general practice teams in East Anglia, UK. Randomised to GRAIDS (Genetic Risk Assessment on the Internet with Decision Support) support (intervention n=23) or comparison (n=22). Training in the new assessment strategy and access to the GRAIDS software (GRAIDS arm) was conducted, compared with an educational session and guidelines about managing familial breast and colorectal cancer risk (comparison) were mailed. Outcomes were measured at practice, practitioner and patient levels. The primary outcome measure, at practice level, was the proportion of referrals made to the Regional Genetics Clinic for familial breast or colorectal cancer that were consistent with referral guidelines. Other measures included practitioner confidence in managing familial cancer (GRAIDS arm only) and, in patients: cancer worry, risk perception and knowledge about familial cancer. There were more referrals to the Regional Genetics Clinic from GRAIDS than comparison practices (mean 6.2 and 3.2 referrals per 10 000 registered patients per year; mean difference 3.0 referrals; 95% confidence interval (CI) 1.2-4.8; P=0.001); referrals from GRAIDS practices were more likely to be consistent with referral guidelines (odds ratio (OR)=5.2; 95% CI 1.7-15.8, P=0.006). Patients referred from GRAIDS practices had lower cancer worry scores at the point of referral (mean difference -1.44 95% CI -2.64 to -0.23, P=0.02). There were no differences in patient knowledge about familial cancer. The intervention increased GPs' confidence in managing familial cancer. Compared with education and mailed guidelines, assessment including computer decision support increased the number and quality of referrals to the Regional Genetics Clinic for familial cancer risk, improved practitioner confidence and had no adverse psychological effects in patients. Trials are registered under N0181144343 in the UK National Research Register. \u00a9 2007 Cancer Research UK.
\n \n\n \n \nThe DNA replication (or origin) licensing machinery ensures precise duplication of the genome and contributes to the regulation of proliferative capacity in metazoa. Using an in vitro fibroblast model system coupled to a cell-free DNA replication assay, we have studied regulation of the origin licensing pathway during exit from and re-entry into the mitotic cell cycle. We show that in the quiescent state (G0) loss of proliferative capacity is achieved in part through down-regulation of the replication licensing factors Cdc6 and Mcm2-7. The origin licensing repressor geminin is absent in quiescent fibroblasts, suggesting that this powerful inhibitor of the licensing machinery is not required to suppress proliferative capacity in G0. Geminin expression is induced at a late stage in the G0-S transition post pre-RC assembly. Ectopic geminin can block re-acquisition of DNA replication competence during re-entry into the cell cycle, indicating that geminin levels must be tightly down-regulated for escape from G0. Analysis of geminin levels in thyroid shows that geminin expression is suppressed in anatomical compartments/tissues harbouring quiescent cells, confirming our in vitro data. Spatio-temporal control of geminin expression may therefore be of particular relevance for multi-potential stem cells which cycle infrequently. In support of this hypothesis, we have identified a unique population of cells in the putative stem cell niche of intestinal epithelium that are unlicensed and lack geminin expression, a prerequisite for successful re-entry into cycle. Our data argue that the prolonged cell cycle times observed for intestinal stem cells could be due to exit of progenitor cells from cycle into an unlicensed \"out-of-cycle\" state, a powerful mechanism by which rapidly proliferating tissues may resist genotoxic insult. \u00a9 2005 Elsevier Inc. All rights reserved.
\n \n\n \n \nObjectives: To compare patients' enablement and satisfaction after teaching and non-teaching consultations. To explore patients' views about the possible impact that increased community based teaching of student doctors in their practice may have on the delivery of service and their attitudes towards direct involvement with students. Design: Observational study using validated survey instruments (patient enablement index-PEI, and consultation satisfaction questionnaire-CSQ) administered after teaching consultations and non-teaching consultations. Ten focus groups (two from each practice), comprising five with patients participating in prearranged teaching sessions and five with patients not participating in these. Setting: Five general practices in west Suffolk and southern Norfolk, England, that teach student doctors on the Cambridge graduate medical course. Participants: 240 patients attending teaching consultations (response rate 82%, 196 patients) and 409 patients attending non-teaching consultations (response rate 72%, 294 patients) received survey instruments. Ten focus groups with a total of 34 patients participating in prearranged teaching sessions and 20 patients not participating in these. Main outcome measures: Scores on the patient enablement index and consultation satisfaction questionnaire, analysed at the level of all patients, allowing for age, sex, general practitioner, and practice, and at the level of the individual general practitioner teacher. Qualitative analysis of focus group data. Results: Patients' enablement or satisfaction was not reduced after teaching consultations compared with non-teaching consultations (mean difference in scores on the patient enablement index and consultation satisfaction questionnaire with adjustment for confounders 2.24% and 1.70%, respectively). This held true for analysis by all patients and by general practitioner teacher. Qualitative data showed that patients generally supported the teaching of student doctors in their practice. However, this support was conditional on receiving sufficient information about reasons for doctors' absence, the characteristics of students, and the nature of teaching planned. Many patients viewed their general practice as different from hospital and expected greater control over students' presence during their consultations. Conclusions: Patients' enablement and satisfaction are not impaired by students' participation in consultations. Patients generally support the teaching of student doctors in their general practice but expect to be provided with sufficient information and to have a choice about participation, so they can give informed consent Recognising this when organising general practice based teaching is important.
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