Trends in gabapentinoid prescribing in patients with osteoarthritis: a United Kingdom national cohort study in primary care

Summary Objective To investigate trends in gabapentinoid prescribing in patients with osteoarthritis (OA). Methods Patients aged 40 years and over with a new OA diagnosis recorded between 1995 and 2015 were identified in the Clinical Practice Research Datalink and followed to first prescription of gabapentin or pregabalin, or other censoring event. We estimated the crude and age-standardised annual incidence rates of gabapentinoid prescribing, stratified by patient age, sex, geographical region, and time since OA diagnosis, and the proportion of prescriptions attributable to OA, or to other conditions representing licensed and unlicensed indications for a gabapentinoid prescription. Results Of 383,680 newly diagnosed OA cases, 35,031 were prescribed at least one gabapentinoid. Irrespective of indication, the annual age-standardised incidence rate of first gabapentinoid prescriptions rose from 1.6 (95% CI: 1.3, 2.0) per 1,000 person-years in 2000, to 27.6 (26.7, 28.4) in 2015, a trend seen across all ages and not explained by length of follow-up. Rates were higher among women, younger patients, and in Northern Ireland, Scotland and the North of England. Approximately 9% of first prescriptions could be attributed to OA, a further 13% to comorbid licensed or unlicensed indications. Conclusion Gabapentinoid prescribing in patients with OA increased dramatically between 1995 and 2015. In most cases, diagnostic codes for licensed or unlicensed indications were absent. Gabapentinoid prescribing may be attributable to OA in a significant proportion but evidence for their effectiveness in OA is lacking. Further research to investigate clinical decision making around prescribing these expensive and potentially harmful medicines is recommended

Remote Reactor Ranging via Antineutrino Oscillations

Antineutrinos from nuclear reactors can be used for monitoring in the mid- to far-field as part of a non-proliferation toolkit. Antineutrinos are an unshieldable signal and carry information about the reactor core and the distance they travel. Using gadolinium-doped water Cherenkov detectors for this purpose has been previously proposed alongside rate-only analyses. As antineutrinos carry information about their distance of travel in their energy spectrum, the analyses can be extended to a spectral analysis to gain more knowledge about the detected core. Two complementary analyses are used to evaluate the distance between a proposed gadolinium-doped water-based liquid scintillator detector and a detected nuclear reactor. Example cases are shown for a detector in Boulby Mine, near the Boulby Underground Laboratory in the UK, and six reactor sites in the UK and France. The analyses both show strong potential to range reactors, but are limited by the detector design.Comment: 12 pages, 9 figure

Lack of correlation of stem cell markers in breast cancer stem cells

BACKGROUND: Various markers are used to identify the unique sub-population of breast cancer cells with stem cell properties. Whether these markers are expressed in all breast cancers, identify the same population of cells, or equate to therapeutic response is controversial. METHODS: We investigated the expression of multiple cancer stem cell markers in human breast cancer samples and cell lines in vitro and in vivo, comparing across and within samples and relating expression with growth and therapeutic response to doxorubicin, docetaxol and radiotherapy. RESULTS: CD24, CD44, ALDH and SOX2 expression, the ability to form mammospheres and side-population cells are variably present in human cancers and cell lines. Each marker identifies a unique rather than common population of cancer cells. In vivo, cells expressing these markers are not specifically localized to the presumptive stem cell niche at the tumour/stroma interface. Repeated therapy does not consistently enrich cells expressing these markers, although ER-negative cells accumulate. CONCLUSIONS: Commonly employed methods identify different cancer cell sub-populations with no consistent therapeutic implications, rather than a single population of cells. The relationships of breast cancer stem cells to clinical parameters will require identification of specific markers or panels for the individual cancer

Sequence Variability of P2-Like Prophage Genomes Carrying the Cytolethal Distending Toxin V Operon in Escherichia coli O157

Cytolethal distending toxins (CDT) are potent cytotoxins of several Gram-negative pathogenic bacteria, including Escherichia coli, in which five types (CDT-I to CDT-V) have been identified so far. CDT-V is frequently associated with Shiga-toxigenic E. coli (STEC), enterohemorrhagic E. coli (EHEC) O157 strains, and strains not fitting any established pathotypes. In this study, we were the first to sequence and annotate a 31.2-kb-long, noninducible P2-like prophage carrying the cdt-V operon from an stx- and eae-negative E. coli O157:H43 strain of bovine origin. The cdt-V operon is integrated in the place of the tin and old phage immunity genes (termed the TO region) of the prophage, and the prophage itself is integrated into the bacterial chromosome between the housekeeping genes cpxP and fieF. The presence of P2-like genes (n = 20) was investigated in a further five CDT-V-positive bovine E. coli O157 strains of various serotypes, three EHEC O157:NM strains, four strains expressing other variants of CDT, and eight CDT-negative strains. All but one CDT-V-positive atypical O157 strain uniformly carried all the investigated genomic regions of P2-like phages, while the EHEC O157 strains missed three regions and the CDT-V-negative strains carried only a few P2-like sequences. Our results suggest that P2-like phages play a role in the dissemination of cdt-V between E. coli O157 strains and that after integration into the bacterial chromosome, they adapted to the respective hosts and became temperate

A short report examining the introduction of routine use of patient reported outcome measures in a mixed oncology population

Aims: People living with treatable but not curable cancer often experience a range of symptoms related to their cancer and its treatment. During the COVID-19 pandemic, face-to-face consultations were reduced and so remote monitoring of these needs was necessary. University Hospitals Sussex implemented the routine use of electronic remote patient-reported outcome measures (PROMs) in a mixed oncology population, focusing on those with treatable but not curable cancers. Materials and methods: Over a 9-month period, patients were invited to register with My Clinical Outcomes (MCO) – a secure online platform for the collection of electronic PROMs. They were prompted by e-mail to complete assessments (EORTC QLQ-C30, EQ-5D-3L and EQ-5D VAS) routinely every 2 weeks. The team monitored patient scores and changes in these prompted clinical interventions. Results: In total, 324 patients completed at least one assessment. The median number of assessments completed by each patient was eight. The most represented tumour groups were secondary breast (28%), prostate (25%) and other (32%). Median scores for the assessments did not deteriorate in a clinically or numerically significant way for patients living with non-curable conditions for the majority of patients monitored. Conclusion: Routine collection of electronic remote PROMs is an effective and useful strategy to provide real-time clinical feedback to teams. With integration into existing systems, online platforms (such as MCO) could provide efficient and patient-centred information for those providing care for people with cancer

Comprehensive geriatric assessment in men aged 70 years or older with localised prostate cancer undergoing radical radiotherapy

Aims Treatment decisions for men aged 70 years or over with localised prostate cancer need to take into account the risk of death from competing causes and fitness for the proposed treatment. Objective assessments such as those included in a comprehensive geriatric assessment (CGA) might help to inform the decision-making process. The aim of this study was to describe the CGA scores of a cohort of older men with prostate cancer, evaluate potential screening tools in this population and assess whether any CGA component predicts significant acute radiotherapy toxicity. Materials and methods This was a prospective cohort study undertaking pretreatment CGA, Vulnerable Elders Survey (VES-13) and G8 assessment in patients aged 70 years and over with localised prostate cancer planned to undergo radical external beam radiotherapy. Results In total, 178 participants were recruited over a 3 year period and underwent a CGA. Fifty-five (30.1%) participants were defined as having health needs identified by their CGA. Both VES-13 and G8 screening tools showed a statistically significant association with CGA needs (P < 0.001 and X2 = 15.02, P < 0.001, respectively), but their sensitivity was disappointing. There was no association between a CGA (or its components) and significant acute radiotherapy toxicity. Conclusions Many older men with localised prostate cancer are vulnerable according to a CGA. The screening tools evaluated were not sufficiently sensitive to identify this group. CGA outcome does not predict for significant acute radiotherapy toxicity

Groundwater contamination by trichloroethene (TCE) in a residential area of Perth: Distribution, mobility, and implications for management

Substantial TCE and ammonia contamination was detected in groundwater beneath a residential area in Perth. Investigation has successfully determined broad aspects of the extent of the TCE plume and its impact. The plume extends approximately 900 m in groundwater downgradient of an industrial area. The contamination is about 300 m wide and 6 - 8 m thick. A peak concentration of 2000 ugL{-1} TCE was measured. The mobility of the plume and the residence time for the contamination in the sand aquifer are estimated based on the groundwater velocities and retardation factors. Biological or chemical transformation of TCE cannot be excluded, although no transformation products have been found in a small portion of the plume. Currently no remediation of the contaminated site is planned. An approach for managing the contamination is presented and important issues for future remediation options for TCE contaminated sites in Perth are discussed