The purpose was to determine the accuracy of polyp measurement by endoscopy and CT. A colonic phantom was constructed containing 12 simulated polyps of known diameter. Polyp diameter was estimated ...during endoscopy by two observers independently. The phantom was then scanned using a 64-detector-row machine and diameter estimated by a further two observers independently, using 2D and 3D visualisation methods. All measurements were obtained twice. Bland-Altman statistics were used to assess agreement between observers’ estimates and the reference diameter. The mean difference between observers’ measurements and the reference diameter was smallest for estimates made using 3D CT (−0.09 mm and −0.03 mm) and greatest for endoscopy (−1.10 mm and −1.19 mm), with 2D CT intermediate. However, 95% limits of agreement were largest for 3D CT estimates (−4.38 mm to 4.20 mm). Estimates by 2D CT consistently overestimated polyp diameter, whereas endoscopy consistently underestimated diameter. In contrast, measurements by 3D CT were a combination of over- and under-estimates, with a tendency for disagreement to increase with the size of the polyp. The effect of observer experience was small and repeatability was best for 2D CT. Measurement error was encountered with all three modalities tested. Estimates made by 2D CT were believed to offer the best compromise overall.
Objective To evaluate the performance of the QFractureScores for predicting the 10 year risk of osteoporotic and hip fractures in an independent UK cohort of patients from general practice ...records.Design Prospective cohort study.Setting 364 UK general practices contributing to The Health Improvement Network (THIN) database.Participants 2.2 million adults registered with a general practice between 27 June 1994 and 30 June 2008, aged 30-85 (13 million person years), with 25 208 osteoporotic fractures and 12 188 hip fractures.Main outcome measures First (incident) diagnosis of osteoporotic fracture (vertebra, distal radius, or hip) and incident hip fracture recorded in general practice records.Results Results from this independent and external validation of QFractureScores indicated good performance data for both osteoporotic and hip fracture end points. Discrimination and calibration statistics were comparable to those reported in the internal validation of QFractureScores. The hip fracture score had better performance data for both women and men. It explained 63% of the variation in women and 60% of the variation in men, with areas under the receiver operating characteristic curve of 0.89 and 0.86, respectively. The risk score for osteoporotic fracture explained 49% of the variation in women and 38% of the variation in men, with corresponding areas under the receiver operating characteristic curve of 0.82 and 0.74. QFractureScores were well calibrated, with predicted risks closely matching those across all 10ths of risk and for all age groups.Conclusion QFractureScores are useful tools for predicting the 10 year risk of osteoporotic and hip fractures in patients in the United Kingdom.
Summary Objective To compare the safety and efficacy of acetaminophen extended-release (APAP ER) with rofecoxib for the management of pain associated with knee osteoarthritis (OA). Methods Four ...hundred and three adult patients with moderate pain secondary to knee OA were randomized to receive APAP ER 1300 mg three times daily, rofecoxib 12.5 mg once daily, or rofecoxib 25 mg once daily. Primary end point was change from baseline at week 4 in the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale score using a visual analog scale. This 4-week study was conducted at 23 US research sites from October 1999 to October 2000. Results APAP ER was noninferior to rofecoxib 12.5 mg because the upper 95% confidence limit (CL) for the least squares mean (LSM) change from baseline (35.27 mm at week 4) did not exceed the prespecified noninferiority limit of 50 mm. The upper CL (57.39 mm) exceeded the noninferiority limit for APAP ER compared with rofecoxib 25 mg at week 4. There were no significant differences among groups in the overall incidence of adverse events. Conclusion APAP ER 3900 mg daily was noninferior to rofecoxib 12.5 mg daily, but noninferiority was not established to rofecoxib 25 mg daily. APAP ER was well tolerated and no safety issues were identified. Based on the results of this study, APAP ER 3900 mg daily is an alternative to nonsteroidal anti-inflammatory drugs (NSAIDs), such as rofecoxib, in treating pain associated with knee OA.
Introduction and hypothesis
Vaginal prolapse mesh may effectively restore vaginal anatomy. The aim of this study was to investigate how the in vivo mesh position correlates to clinical outcomes.
...Methods
Seventy-one women operated on using Uphold mesh for apical pelvic organ prolapse (POP-Q, C ≥ stage II) were examined 5 years after surgery by introital-perineal 2D ultrasound in a midsagittal plane at rest and Valsalva. The horizontal line and pubis symphysis were considered the reference for all measures. Ultrasound measures were statistically compared to clinical outcomes: POP-Q, Pelvic Floor Distress Inventory (PFDI-20) and subscales Pelvic Organ Distress Inventory (PODI-6), and Urinary Distress Inventory (UDI-6) and the VAS scale for pain.
Results
Original mesh length was preserved by 86% and correlated to improved pain as estimated by VAS scale (
r
0.321). Valsalva was associated with a lowering of the superior and inferior mesh margins by 7.3 and 6.1 mm, respectively (
p
< 0.001) but a reduction of total mesh length by only 1 mm (30.2 ± 5.2 to 29.2 ± 4.7 mm,
p
< 0.001). Mobility of the anterior vaginal wall (bladder neck and midurethra) at Valsalva was parallel to downward movement of the mesh inferior margin (
r
0.346 and 0.314) but inversely correlated to total UDI-6 (
r
− 0.254 and − 0.263). Mobility of the midurethra was inversely correlated to bladder emptying (PFDI-20 Question 19,
r
− 0.245).
Conclusions
Five years after surgery, preserved original length of the mesh with apical support was correlated to improved anatomical and patient-reported outcomes. Mesh support to the vaginal apex was associated with improved bladder emptying and total urinary distress outcomes but not stress urinary incontinence.
In patients with a particular disease or health condition, stratified medicine seeks to identify those who will have the most clinical benefit or least harm from a specific treatment. In this ...article, the fourth in the PROGRESS series, the authors discuss why prognosis research should form a cornerstone of stratified medicine, especially in regard to the identification of factors that predict individual treatment response
An audit was carried out of 51 oncology patients referred to a clinical psychology service to identify the characteristics of patients selected for referral and to assess change following ...psychological intervention. A survey was conducted of an unselected sample of oncology patients representative of the workload of the oncology department from which the referrals came, to determine the prevalence of comparable psychosocial problems among patients who were not referred for help and to assess whether doctors were aware of the problems patients reported. Data were collected using the Hospital Anxiety and Depression (HAD) and Mental Adjustment to Cancer (MAC) scales and a problem checklist devised for this study. Referred patients were significantly more anxious and depressed (P < 0.001) and showed poorer adjustment on MAC scales than the surveyed sample, but 30% of the latter group warranted assessment for anxiety and 23% for depression. The number of psychosocial problems of their severity. Intervention was clinically significant mood disorder irrespective of the specific problems of their severity. Intervention was associated with a significant improvement in distress and problems for referred patients by the time of discharge. Psychosocial problems were often undetected by staff even in referred patients. The checklist is a feasible screening method for potentially remediable problems which are cumulatively a significant contributor to cancer patients' distress.
The c-erbB-2 gene is overexpressed in about 20% of human breast cancers. Four hundred and eighty-three cases previously examined by immunohistochemical staining for c-erbB-2 expression were analysed ...to assess the risk associated with the elevated protein expression. Oncoprotein expression was correlated with increasing tumour grade but not with oestrogen receptor status, nodal involvement, tumour size or age. There was an increased risk of relapse and death associated with c-erbB-2 expression irrespective of nodal involvement. This marker thus appears to be a significant prognostic factor in the early as well as the late stages of breast cancer.
To describe the perioperative morbidity associated with transvaginal mesh repair of pelvic organ prolapse.
During a 6-month time period, 25 centers registered all surgical procedures using a ...commercially available mesh. The frequency and type of perioperative complications, during surgery and the associated hospital stay, were documented using a standardized protocol.
During the inclusion period, 248 women underwent transvaginal mesh surgery: anterior repair in 106 patients (43%), posterior repair in 71 (29%), combined anterior and posterior repair in 20 (8%), and total repair in 51 (21%). Mean age was 67.8 years (+/-10.3 standard deviation) and median parity was 2 (range 0-6). Surgery for prolapse recurrence was performed in 56% of the patients (n=140), and 91% (n=225) had undergone at least one previous pelvic floor surgical procedure. Serious complications occurred in 4.4% of patients (n=11) and were dominated by visceral injury (10 of 11 cases). One case of bleeding in excess of 1,000 mL occurred. Minor complications occurred in 14.5% of patients (n=36), and the majority were urinary tract infections, urinary retention, and postoperative fever. A multivariable risk analysis showed that concurrent pelvic floor surgery was associated with an increased risk for minor complications, odds ratio 2.8 (95% confidence interval 1.1-6.9). There were no other predictors of outcomes when assessing the association with age, parity, weight, previous pelvic floor surgery, previous hysterectomy, or concurrent hysterectomy.
Perioperative serious complications are uncommon after transvaginal mesh procedures although particular care should be taken to detect visceral injury at the time of surgery.
III.
Certain major histocompatibility complex class I (MHC-I) alleles (e.g., HLA-B*27) are enriched among human immunodeficiency virus type 1 (HIV-1)-infected individuals who suppress viremia without ...treatment (termed "elite controllers" ECs). Likewise, Mamu-B*08 expression also predisposes rhesus macaques to control simian immunodeficiency virus (SIV) replication. Given the similarities between Mamu-B*08 and HLA-B*27, SIV-infected Mamu-B*08(+) animals provide a model to investigate HLA-B*27-mediated elite control. We have recently shown that vaccination with three immunodominant Mamu-B*08-restricted epitopes (Vif RL8, Vif RL9, and Nef RL10) increased the incidence of elite control in Mamu-B*08(+) macaques after challenge with the pathogenic SIVmac239 clone. Furthermore, a correlate analysis revealed that CD8(+) T cells targeting Nef RL10 was correlated with improved outcome. Interestingly, this epitope is conserved between SIV and HIV-1 and exhibits a delayed and atypical escape pattern. These features led us to postulate that a monotypic vaccine-induced Nef RL10-specific CD8(+) T-cell response would facilitate the development of elite control in Mamu-B*08(+) animals following repeated intrarectal challenges with SIVmac239. To test this, we vaccinated Mamu-B*08(+) animals with nef inserts in which Nef RL10 was either left intact (group 1) or disrupted by mutations (group 2). Although monkeys in both groups mounted Nef-specific cellular responses, only those in group 1 developed Nef RL10-specific CD8(+) T cells. These vaccine-induced effector memory CD8(+) T cells did not prevent infection. Escape variants emerged rapidly in the group 1 vaccinees, and ultimately, the numbers of ECs were similar in groups 1 and 2. High-frequency vaccine-induced CD8(+) T cells focused on a single conserved epitope and therefore did not prevent infection or increase the incidence of elite control in Mamu-B*08(+) macaques.
Since elite control of chronic-phase viremia is a classic example of an effective immune response against HIV/SIV, elucidating the basis of this phenomenon may provide useful insights into how to elicit such responses by vaccination. We have previously established that vaccine-induced CD8(+) T-cell responses against three immunodominant epitopes can increase the incidence of elite control in SIV-infected Mamu-B*08(+) rhesus macaques—a model of HLA-B*27-mediated elite control. Here, we investigated whether a monotypic vaccine-induced CD8(+) T-cell response targeting the conserved "late-escaping" Nef RL10 epitope can increase the incidence of elite control in Mamu-B*08(+) monkeys. Surprisingly, vaccine-induced Nef RL10-specific CD8(+) T cells selected for variants within days after infection and, ultimately, did not facilitate the development of elite control. Elite control is, therefore, likely to involve CD8(+) T-cell responses against more than one epitope. Together, these results underscore the complexity and multidimensional nature of virologic control of lentivirus infection.
PDF
