Impact of cervical screening on cervical cancer mortality: estimation using stage-specific results from a nested case-control study

Cancer Research UK (A16892 to P.S.)

Responsiveness and minimal clinically important difference for pain and disability instruments in low back pain patients

BACKGROUND: The choice of an evaluative instrument has been hampered by the lack of head-to-head comparisons of responsiveness and the minimal clinically important difference (MCID) in subpopulations of low back pain (LBP). The objective of this study was to concurrently compare responsiveness and MCID for commonly used pain scales and functional instruments in four subpopulations of LBP patients. METHODS: The Danish versions of the Oswestry Disability Index (ODI), the 23-item Roland Morris Disability Questionnaire (RMQ), the physical function and bodily pain subscales of the SF36, the Low Back Pain Rating Scale (LBPRS) and a numerical rating scale for pain (0–10) were completed by 191 patients from the primary and secondary sectors of the Danish health care system. Clinical change was estimated using a 7-point transition question and a numeric rating scale for importance. Responsiveness was operationalised using standardardised response mean (SRM), area under the receiver operating characteristic curve (ROC), and cut-point analysis. Subpopulation analyses were carried out on primary and secondary sector patients with LBP only or leg pain +/- LBP. RESULTS: RMQ was the most responsive instrument in primary and secondary sector patients with LBP only (SRM = 0.5–1.4; ROC = 0.75–0.94) whereas ODI and RMQ showed almost similar responsiveness in primary and secondary sector patients with leg pain (ODI: SRM = 0.4–0.9; ROC = 0.76–0.89; RMQ: SRM = 0.3–0.9; ROC = 0.72–0.88). In improved patients, the RMQ was more responsive in primary and secondary sector patients and LBP only patients (SRM = 1.3–1.7) while the RMQ and ODI were equally responsive in leg pain patients (SRM = 1.3 and 1.2 respectively). All pain measures demonstrated almost equal responsiveness. The MCID increased with increasing baseline score in primary sector and LBP only patients but was only marginally affected by patient entry point and pain location. The MCID of the percentage change score remained constant for the ODI (51%) and RMQ (38%) specifically and differed in the subpopulations. CONCLUSION: RMQ is suitable for measuring change in LBP only patients and both ODI and RMQ are suitable for leg pain patients irrespectively of patient entry point. The MCID is baseline score dependent but only in certain subpopulations. Relative change measured using the ODI and RMQ was not affected by baseline score when patients quantified an important improvement

A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications.

RNA sequencing (RNA-seq) is a genomic approach for the detection and quantitative analysis of messenger RNA molecules in a biological sample and is useful for studying cellular responses. RNA-seq has fueled much discovery and innovation in medicine over recent years. For practical reasons, the technique is usually conducted on samples comprising thousands to millions of cells. However, this has hindered direct assessment of the fundamental unit of biology-the cell. Since the first single-cell RNA-sequencing (scRNA-seq) study was published in 2009, many more have been conducted, mostly by specialist laboratories with unique skills in wet-lab single-cell genomics, bioinformatics, and computation. However, with the increasing commercial availability of scRNA-seq platforms, and the rapid ongoing maturation of bioinformatics approaches, a point has been reached where any biomedical researcher or clinician can use scRNA-seq to make exciting discoveries. In this review, we present a practical guide to help researchers design their first scRNA-seq studies, including introductory information on experimental hardware, protocol choice, quality control, data analysis and biological interpretation

Synthesis and Enzymatic Deprotection of Fully Protected 2 '-5 ' Oligoadenylates (2-5A): Towards a Prodrug Strategy for Short 2-5A

Fully protected pA2'p5'A2'p5'A trimers 1a and 1b have been prepared as prodrug candidates for a short 2'-5' oligoadenylate, 2-5A, and its 3'-O-Me analog, respectively. The kinetics of hog liver carboxyesterase (HLE)-triggered deprotection in HEPES buffer (pH 7.5) at 37 degrees has been studied. The deprotection of 1a turned out to be very slow, and 2-5A never appeared in a fully deprotected form. By contrast, a considerable proportion of 1b was converted to the desired 2-5A trimer, although partial removal of the 3'-O-[(acetyloxy)methyl] group prior to exposure of the adjacent phosphodiester linkage resulted in 2',5'?3',5' phosphate migration and release of adenosine as side reactions