Socioeconomic indicators of health inequalities and female mortality: a nested cohort study within the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

Evidence is mounting that area-level socioeconomic indicators are important tools for predicting health outcomes. However, few studies have examined these alongside individual-level education. This nested cohort study within the control arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) assesses the association of mutually adjusted individual (education) and area-level (Index of Multiple Deprivation-IMD 2007) socioeconomic status indicators and all-cause female mortality

Type and Timing of Rehabilitation Following Acute and Subacute Spinal Cord Injury: A Systematic Review

Objectives: The objective of this study was to conduct a systematic review of the literature to address the following clinical questions: In adult patients with acute and subacute complete or incomplete traumatic SCI, (1) does the time interval between injury and commencing rehabilitation affect outcome?; (2) what is the comparative effectiveness of different rehabilitation strategies, including different intensities and durations of treatment?; (3) are there patient or injury characteristics that affect the efficacy of rehabilitation?; and (4) what is the cost-effectiveness of various rehabilitation strategies? Methods: A systematic search was conducted for literature published through March 31, 2015 that evaluated rehabilitation strategies in adults with acute or subacute traumatic SCI at any level. Studies were critically appraised individually and the overall strength of evidence was evaluated using methods proposed by the GRADE (Grades of Recommendation Assessment, Development and Evaluation) working group. Results: The search strategy yielded 384 articles, 19 of which met our inclusion criteria. Based on our results, there was no difference between body weight–supported treadmill training and conventional rehabilitation with respect to improvements in Functional Independence Measure (FIM) Locomotor score, Lower Extremity Motor Scores, the distance walked in 6 minutes or gait velocity over 15.2 m. Functional electrical therapy resulted in slightly better FIM Motor, FIM Self-Care, and Spinal Cord Independence Measure Self-Care subscores compared with conventional occupational therapy. Comparisons using the Toronto Rehabilitation Institute Hand Function Test demonstrated no differences between groups in 7 of 9 domains. There were no clinically important differences in Maximal Lean Test, Maximal Sidewards Reach Test, T-shirt Test, or the Canadian Occupational Performance Measure between unsupported sitting training and standard in-patient rehabilitation. Conclusion: The current evidence base for rehabilitation following acute and subacute spinal cord injury is limited. Methodological challenges have contributed to this and further research is still needed. © 2017, © The Author(s) 2017

Improved early detection of ovarian cancer using longitudinal multimarker models

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Background: Ovarian cancer has a poor survival rate due to late diagnosis and improved methods are needed for its early detection. Our primary objective was to identify and incorporate additional biomarkers into longitudinal models to improve on the performance of CA125 as a first-line screening test for ovarian cancer. Methods: This case–control study nested within UKCTOCS used 490 serial serum samples from 49 women later diagnosed with ovarian cancer and 31 control women who were cancer-free. Proteomics-based biomarker discovery was carried out using pooled samples and selected candidates, including those from the literature, assayed in all serial samples. Multimarker longitudinal models were derived and tested against CA125 for early detection of ovarian cancer. Results: The best performing models, incorporating CA125, HE4, CHI3L1, PEBP4 and/or AGR2, provided 85.7% sensitivity at 95.4% specificity up to 1 year before diagnosis, significantly improving on CA125 alone. For Type II cases (mostly high-grade serous), models achieved 95.5% sensitivity at 95.4% specificity. Predictive values were elevated earlier than CA125, showing the potential of models to improve lead time. Conclusions: We have identified candidate biomarkers and tested longitudinal multimarker models that significantly improve on CA125 for early detection of ovarian cancer. These models now warrant independent validation.Peer reviewe

The graded redefined assessment of strength sensibility and prehension: reliability and validity.

Abstract With the advent of new interventions targeted at both acute and chronic spinal cord injury (SCI), it is critical that techniques and protocols are developed that reliably evaluate changes in upper limb impairment/function. The Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP) protocol, which includes five subtests, is a quantitative clinical upper limb impairment measure designed for use in acute and chronic cervical SCI. The objectives of this study were to: (1) establish the inter-rater and test-retest reliability, and (2) establish the construct and concurrent validity with the International Standards of Neurological Classification of Spinal Cord Injury (ISNCSCI), Spinal Cord Independence Measure II (SCIM), and the Capabilities of Upper Extremity Questionnaire (CUE). The study protocol included repeated administration of the GRASSP to a cross-section of individuals with tetraplegia who were neurologically stable (n=72). ISNCSCI, CUE, and SCIM assessments were also administered. Two assessors examined the individuals over a 7-day period. Reliability was tested with intra-class correlation coefficients; construct validity was established with agreement/discordance analysis between the GRASSP and ISNCSCI sensory and motor items; and concurrent validity was tested with Spearman correlation coefficients. Inter-rater and test-retest reliability for all subtests within the GRASSP were above the hypothesized value of 0.80 (0.84-0.96 and 0.86-0.98, respectively). The GRASSP is about 50% more sensitive (construct validity) than the ISNCSCI when defining sensory and motor integrity of the upper limb; the subtests showed concurrence with the SCIM, SCIM self-care subscale, and CUE. The strongest concurrence to impairment was with self-perception of function (CUE) (0.57-0.83, p\u3c0.0001). The GRASSP was found to demonstrate reliability, construct validity, and concurrent validity for use as a standardized upper limb impairment measure for individuals with tetraplegia

Change-point of multiple biomarkers in women with ovarian cancer

To date several algorithms for longitudinal analysis of ovarian cancer biomarkers have been proposed in the literature. An issue of specific interest is to determine whether the baseline level of a biomarker changes significantly at some time instant (change-point) prior to the clinical diagnosis of cancer. Such change-points in the serum biomarker Cancer Antigen 125 (CA125) time series data have been used in ovarian cancer screening, resulting in earlier detection with a sensitivity of 85% in the most recent trial, the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS, number ISRCTN22488978; NCT00058032). Here we propose to apply a hierarchical Bayesian change-point model to jointly study the features of time series from multiple biomarkers. For this model we have analytically derived the conditional probability distribution of every unknown parameter, thus enabling the design of efficient Markov Chain Monte Carlo methods for their estimation. We have applied these methods to the estimation of change-points in time series data of multiple biomarkers, including CA125 and others, using data from a nested case-control study of women diagnosed with ovarian cancer in UKCTOCS. In this way we assess whether any of these additional biomarkers can play a role in change-point detection and, therefore, aid in the diagnosis of the disease in patients for whom the CA125 time series does not display a change-point. We have also investigated whether the change-points for different biomarkers occur at similar times for the same patient. The main conclusion of our study is that the combined analysis of a group of specific biomarkers may possibly improve the detection of change-points in time series data (compared to the analysis of CA125 alone) which, in turn, are relevant for the early diagnosis of ovarian cancer

Socioeconomic Status and Ovarian Cancer Stage at Diagnosis: A Study Nested Within UKCTOCS

BACKGROUND: Tubo-ovarian cancer (OC) continues to be the most lethal of all gynaecological cancers. Over half of women are diagnosed with late stage (III/IV) disease, which has a five-year survival rate of 11%. Socioeconomic status (SES) has been shown to have an impact on outcomes of several cancer types, including OC. This study aims to investigate any potential association between SES and stage at diagnosis of OC. METHODS: Women from the non-screening arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) with a confirmed diagnosis of OC prior to 01 January 2015 and an English index of multiple deprivation (IMD) score were eligible for the study. The association between IMD and OC stage (FIGO) was analysed using an ordinal logistic regression model adjusted for age at diagnosis and BMI. RESULTS: Four-hundred and fifty seven women were eligible for inclusion in the primary analysis. The odds of being diagnosed with the higher dichotomization of stage (I vs. II/III/IV; I/II vs. III/IV; I/II/III vs. IV) was 1.29 (p = 0.017; 95% CI: 1.048-1.592) per unit SD (standard deviation) increase in IMD. This translates to a 29% increase in odds of being diagnosed at the higher stage per each unit SD increase in IMD. CONCLUSION: Increased deprivation is consistently associated with a higher probability of being diagnosed with later stage OC

Validity of self-reported hysterectomy: a prospective cohort study within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

To evaluate the validity of self-reported hysterectomy against the gold standard of uterine visualisation using pelvic ultrasound

Serial endometrial thickness and risk of non-endometrial hormone-dependent cancers in postmenopausal women in UKCTOCS

Objective: Estrogen is a well‐established risk factor for various cancers. It causes endometrial proliferation, which is assessed routinely as endometrial thickness (ET) using transvaginal ultrasound (TVS). Only one previous study, restricted to endometrial and breast cancer, has considered ET and the risk of non‐endometrial cancer. The aim of this study was to explore the association between baseline and serial ET measurements and nine non‐endometrial hormone‐sensitive cancers, in postmenopausal women, using contemporary statistical methodology that attempts to minimize the biases typical of endogenous serial data. Methods: This was a cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). In the ultrasound arm of UKCTOCS, 50639 postmenopausal women, aged 50–74, underwent annual TVS examination, of whom 38 105 had a valid ET measurement, no prior hysterectomy and complete covariate data, and were included in this study. All women were followed up through linkage to national cancer registries. The effect of ET on the risk of six estrogen‐dependent cancers (breast, ovarian, colorectal, bladder, lung and pancreatic) was assessed using joint models for longitudinal biomarker and time‐to‐event data, and Cox models were used to assess the association between baseline ET measurement and these six cancers in addition to liver cancer, gastric cancer and non‐Hodgkin's lymphoma (NHL). All models were adjusted for current hormone‐replacement therapy (HRT) use, body mass index, age at last menstrual period, parity and oral contraceptive pill use. Results: The 38 105 included women had a combined total of 267 567 (median, 8; interquartile range, 5–9) valid ET measurements. During a combined total of 407 838 (median, 10.9) years of follow‐up, 1398 breast, 351 endometrial, 381 lung, 495 colorectal, 222 ovarian, 94 pancreatic, 79 bladder, 62 gastric, 38 liver cancers and 52 NHLs were registered. Using joint models, a doubling of ET increased significantly the risk of breast (hazard ratio (HR), 1.21; 95% CI, 1.09–1.36; P  = 0.001), ovarian (HR, 1.39; 95% CI, 1.06–1.82; P  = 0.018) and lung (HR, 1.25; 95% CI, 1.02–1.54; P  = 0.036) cancers. There were no statistically significant associations between ET and the remaining six cancers. Conclusion: Postmenopausal women with high/increasing ET on TVS are at increased risk of breast, ovarian and lung cancer. It is important that clinicians are aware of these risks, as TVS is a common investigatio

Is there a role for postoperative physiotherapy in degenerative cervical myelopathy? A systematic review.

OBJECTIVE: To review peer-reviewed literature relating to postoperative physiotherapy for degenerative cervical myelopathy (DCM), to determine efficacy in improving clinical outcome and recovery. DATA SOURCES: MEDLINE, EMBASE, CENTRAL, PEDro, ISRCTN registry, WHO ICTRP and Clinicaltrials.gov . References and citations of relevant articles were searched. METHODS: A systematic search was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42016039511) from the origins of the databases till 15 February 2018. Included were all studies investigating physiotherapy as an intervention after surgical treatment of DCM to determine effect on clinical outcome and recovery. Study quality was determined using the Grades of Recommendation, Assessment, Development and Evaluation guidelines. RESULTS: In all, 300 records were identified through tailored systematic searches, after removing duplicates. After screening, only one investigated postoperative rehabilitation using physiotherapy for DCM; however, this was retrospective with no controls. This study suggested that rehabilitation including physiotherapy improved postoperative recovery. There are currently two registered trials investigating the use of postoperative physiotherapy for DCM. CONCLUSIONS: The literature provides insufficient evidence to make any evidence-based recommendations regarding postoperative physiotherapy use in DCM.his report is an independent research supported by a Clinician Scientist Award by the National Institute for Health Research (grant no. CS-2015-15-023)