Improving conventional prognosticators in diffuse large B cell lymphoma using marker ratios

Risk stratification for diffuse large B-cell lymphoma (DLBCL) is required as patients with disease may not be cured despite initial R-CHOP treatment. We investigated gene ratio tests to predict survival outcome of DLBCL patients based on the relationship between immune-effector and inhibitory (checkpoint) genes from nanoString™ nCounter in 158 paraffin-embedded DLBCL tissues. We assessed the predictive value of several possible gene ratios using a tree-based survival statistical model, and investigated the predictive value of those gene ratios in an independent R-CHOP treated cohorts of 233 patients. We showed that an immune ratio composed of CD4∗CD8∗:(CD163/CD68)∗PD-L1 was able to stratify overall survival better than single or combination of immune markers, distinguishing groups with disparate 4-year survivals (92% versus 47%). The immune ratio was independent of and added to the revised international prognostic index (R-IPI) and cell-of-origin (COO) and has potential implications for selection of patients for checkpoint-blockade within clinical trials

Women’s knowledge and attitudes to the menopause: a comparison of women over 40 who were in the perimenopause, post menopause and those not in the peri or post menopause

Objectives: To evaluate women’s knowledge and attitudes towards the menopause by comparing three groups of women: perimenopause, post menopause and those women not in either the peri or post menopause (other). // Methods: A 35 question online survey was advertised on social media to evaluate women’s attitudes and knowledge of the menopause. Three groups of women were compared: perimenopause, post menopause and those women not in either the peri or post menopause (other). // Results: Most women were completely uninformed or only had some knowledge of the menopause before the age of 40. Most women thought that the menopause should be taught at school, but over 80% had received no menopause education at school themselves. The most popular sources of menopause information were independent websites and friends. Perimenopausal women were significantly more likely than postmenopausal women to use online resources for menopause information. The perimenopausal and postmenopausal groups had more positive attitudes towards the menopause than the other group. 57.5% of postmenopausal women found the menopause difficult or very difficult. Most women were happy about no longer menstruating, although some expressed sadness regarding fertility loss. // Conclusions: Most women had limited knowledge and negative attitudes towards the menopause, leaving them unprepared to cope with the physical and psychological changes associated with this stage of life. Improved menopause education is required to improve quality of life during the menopausal transition and a most positive narrative of life postmenopause

Menopause knowledge and education in women under 40: Results from an online survey

BACKGROUND: All women experience the menopause, yet education around the topic is limited. Studies conducted in women aged over 40 show that women have limited knowledge about the menopause. OBJECTIVES: This study aims to understand what women under 40 know about the menopause, how they have acquired this knowledge and where they think menopause education should be taught. This data will help to determine how to effectively deliver menopause education. DESIGN: A survey was designed that asked women under 40 what they know of, and their attitudes to, the menopause, using Qualtrics XM software. METHODS: The survey was advertised for 5 weeks on social media. Six questions related to menopause education were analysed. Responses between age groups under 20, 21-30 and over 30 were compared using a chi-square test. A thematic-style analysis was also conducted on a free-text question where answers referred to education. RESULTS: A total of 738 women's responses were included in the analysis; over 80% had no knowledge or just some knowledge of the menopause. Women over 30 used official websites (p = 0.017) and scientific literature (p = 0.047) significantly more than other age groups to learn about the menopause, while women under 20 were more likely to learn from family members (p = 0.002). These women felt education should start in schools. CONCLUSION: Many women under 40 have limited education of the menopause. Women under 20 are more passive in their approach to learning about the menopause compared with those over 30, who are more proactive. Menopause education strategies must start at school and extend beyond schools adopting a multifaceted approach; it is recommended that the workplace, social media and public health campaigns are used to deliver menopause education moving forward

Empirical algorithm to estimate the average cosine of underwater light field at 490 nm

The average cosine of the underwater light field μ(λ), where λ is the wavelength, is an apparent optical property (AOP) that describes the angular distribution of radiance at a given point in water. Here, we present a simple algorithm to determine the average cosine at 490 nm, μ(490), which was developed using the measured optical parameters from the eastern Arabian Sea and coastal waters off Goa. The algorithm is validated using measured optical parameters. This algorithm, based on a single optical parameter, performed better compared with other empirical algorithms in determining the average cosine of underwater light field. The absorption coefficient at 490 nm, derived as an application of μ(490), compared well with the synthetic optical data and optical data measured from other regions

Variation in antral follicle counts at different times in the menstrual cycle: does it matter?

Antral follicle count (AFC) variation was examined across the menstural cycle and its effect on clinical management assessed. In 79 women, AFC was documented in early (iAFC) and late follicular phase (sAFC). Absolute agreement between iAFC and sAFC and agreement for classification into categories of risk of extremes of ovarian response were examined. Ovarian stimulation protocols designed with iAFC and sAFC, and the predictive value of iAFC and sAFC for extremes of ovarian response, were compared in women undergoing ovarian stimulation. Significant differences were found between iAFC and sAFC (16 [IQR 9-24] versus 13 [IQR 7- 21]; P = 0.001), with moderate agreement for the classification into at risk of extremes of response (k = 0.525). Agreement for protocol selection based on either AFC (k = 0.750) and starting gonadotrophin dose was good (concordance correlation coefficient 0.970 [95% CI 0.951 to 0.982]). Predictive value for iAFC and sAFC was maintained for poor ovarian response and risk of ovarian hyperstimulation syndrome (OR 0.634 [0.427 to 0.920], 0.467 [0.233 to 0.935]) and (OR 1.049 [0.974 to 1.131], 1.140 [1.011 to 1.285]). Across the cycle, AFC varies but does not significantly affect ovarian stimulation protocol design and prediction of extreme ovarian response

Clinical Practice Guidelines on the Diagnosis and Management of Polycystic Ovary Syndrome: A Systematic Review and Quality Assessment Study

CONTEXT: Clinical practice guidelines (CPGs) are key instruments to implement the practice of evidence-based medicine. We aimed to evaluate the methodological quality and variations in CPGs recommendations on the diagnosis and management of polycystic ovary syndrome (PCOS). EVIDENCE ACQUISITION: We searched MEDLINE, EMBASE, and CENTRAL until December 2020 for all evidence-based CPGs and consensus statements on PCOS. We extracted data in duplicate to map clinical recommendations across prespecified disease domains and assessed CPGs methodological quality of using the Appraisal of Guidelines, Research & Evaluation II tool. EVIDENCE SYNTHESIS: We included 13 PCOS CPGs published between 2007 and 2018. CPGs recommendations were mostly focused on screening for and managing metabolic disease (12/13, 92%), followed by cardiovascular risk assessment (10/13, 77%). Mental health (8/13, 62%) and diagnosis in adolescents (7/13, 54%) were the least reported domains. Most CPGs had a high quality for scope and purpose description (12/13, 92%) while stakeholder's involvement and applicability of recommendations to clinical practice were appropriate in only 2 CPGs (2/13, 15%). We identified inconsistency in recommendations on PCOS diagnosis in adolescents, optimal lifestyle interventions, hirsutism and acne treatments, interventions to reduce the risk of ovarian hyperstimulation syndrome, the frequency and screening criteria for metabolic and cardiovascular disease, and optimal screening tools for mental health illness in women with PCOS. CONCLUSION: Current CPGs on the diagnosis and management of PCOS vary in their scope and methodological quality, which may hinder evidence translation into clinical practice. We identified disease domains with existing evidence gap to guide future research and guideline updates

An online survey of perimenopausal women to determine their attitudes and knowledge of the menopause

INTRODUCTION: Women are not usually taught about the menopause formally, and many general practitioners have relatively little training. The aim of this study was to explore perimenopausal women's attitudes and knowledge of the menopause. METHOD: An online survey was designed to evaluate attitudes and knowledge of the menopause in women older than 40 years. The survey was generated with Qualtrics XM® and promoted via social media. In all, 3150 women started the survey. In this study, data from 947 perimenopausal women were analysed. RESULTS: Regarding women's attitudes to the menopause, 38.8% were accepting of it but more than 30% were dreading it. The women had experienced a number of menopause symptoms including mood swings (68.9%), brain fog (68.3%), and fatigue (66.8%). More than 90% of women had never been taught about the menopause at school, and more than 60% did not feel informed at all about the menopause. School was thought to be the best place for menopause education to start (83.6%). In all, 68.2% of women had only looked for information about the menopause as their symptoms started and they had talked to friends and used a variety of websites to look for information. When asked for their free-text views on the menopause, thematic analysis produced four themes: the overarching knowledge gap, the onset and impact of symptoms, perimenopause: the hidden phenomenon, and managing symptoms: differing schools of thought. CONCLUSION: Lack of education for women and their general practitioners is causing perimenopausal women to go through this important stage in their lives with a lack of knowledge and appropriate medical care. It is essential that women are taught about the menopause, from school onwards and that we offer health professionals appropriate training starting from the medical school curriculum

Risk-Reducing Salpingo-Oophorectomy and the Use of Hormone Replacement Therapy Below the Age of Natural Menopause: Scientific Impact Paper No. 66

This paper deals with the use of hormone replacement therapy (HRT) after the removal of fallopian tubes and ovaries to prevent ovarian cancer in premenopausal high risk women. Some women have an alteration in their genetic code, which makes them more likely to develop ovarian cancer. Two well-known genes which can carry an alteration are the BRCA1 and BRCA2 genes. Examples of other genes associated with an increased risk of ovarian cancer include RAD51C, RAD51D, BRIP1, PALB2 and Lynch syndrome genes. Women with a strong family history of ovarian cancer and/or breast cancer, may also be at increased risk of developing ovarian cancer. Women at increased risk can choose to have an operation to remove the fallopian tubes and ovaries, which is the most effective way to prevent ovarian cancer. This is done after a woman has completed her family. However, removal of ovaries causes early menopause and leads to hot flushes, sweats, mood changes and bone thinning. It can also cause memory problems and increases the risk of heart disease. It may reduce libido or impair sexual function. Guidance on how to care for women following preventative surgery who are experiencing early menopause is needed. HRT is usually advisable for women up to 51 years of age (average age of menopause for women in the UK) who are undergoing early menopause and have not had breast cancer, to minimise the health risks linked to early menopause. For women with a womb, HRT should include estrogen coupled with progestogen to protect against thickening of the lining of the womb (called endometrial hyperplasia). For women without a womb, only estrogen is given. Research suggests that, unlike in older women, HRT for women in early menopause does not increase breast cancer risk, including in those who are BRCA1 and BRCA2 carriers and have preventative surgery. For women with a history of receptor-negative breast cancer, the gynaecologist will liaise with an oncology doctor on a case-by-case basis to help to decide if HRT is safe to use. Women with a history of estrogen receptor-positive breast cancer are not normally offered HRT. A range of other therapies can be used if a woman is unable to take HRT. These include behavioural therapy and non-hormonal medicines. However, these are less effective than HRT. Regular exercise, healthy lifestyle and avoiding symptom triggers are also advised. Whether to undergo surgery to reduce risk or not and its timing can be a complex decision-making process. Women need to be carefully counselled on the pros and cons of both preventative surgery and HRT use so they can make informed decisions and choices

Newer cardiac troponin I assays have similar performance to troponin T in patients with end-stage renal disease

Background: Troponin T is present in the blood of a majority of patients with end-stage renal disease (ESRD) undergoing regular dialysis and presence of troponin T is a predictor of adverse outcome in these patients. With several new formulations of troponin I assays available, this study was performed to see whether these newer assays were able to detect troponin I in these patients more effectively than the older assays. Methods: One hundred and forty-three patients undergoing regular haemodialysis or peritoneal dialysis had plasma collected and troponin T and troponin I measured by a variety of assays. Results: The newer troponin I assays (Abbott Architect, Bayer Centaur and Beckman Accu-TnI) were able to detect troponin I (>75% of samples) as effectively as the Roche assay was able to detect troponin T, while other troponin I assays had a much lower rate of detection of troponin - DPC Immulite 2000 16% and Abbott AxSYM 35%. However, the troponin T assay had more samples detected at concentrations corresponding to an assay CV of 10% (59% of samples) than did the newer troponin I assays (highest on the Bayer Centaur at 37%). Conclusions: Newer assays demonstrate that troponin I is present in a similar number of samples as is troponin T, in the blood of patients with dialysis-dependent renal failure, and these newer troponin I assays identify patients at risk of experiencing a cardiac event

Multifaceted intervention to reduce haemodialysis catheter related bloodstream infections: REDUCCTION stepped wedge, cluster randomised trial.

OBJECTIVE: To identify whether multifaceted interventions, or care bundles, reduce catheter related bloodstream infections (CRBSIs) from central venous catheters used for haemodialysis. DESIGN: Stepped wedge, cluster randomised design. SETTING: 37 renal services across Australia. PARTICIPANTS: All adults (age ≥18 years) under the care of a renal service who required insertion of a new haemodialysis catheter. INTERVENTIONS: After a baseline observational phase, a service-wide, multifaceted intervention bundle that included elements of catheter care (insertion, maintenance, and removal) was implemented at one of three randomly assigned time points (12 at the first time point, 12 at the second, and 13 at the third) between 20 December 2016 and 31 March 2020. MAIN OUTCOMES MEASURE: The primary endpoint was the rate of CRBSI in the baseline phase compared with intervention phase at the renal service level using the intention-to-treat principle. RESULTS: 1.14 million haemodialysis catheter days of use were monitored across 6364 patients. Patient characteristics were similar across baseline and intervention phases. 315 CRBSIs occurred (158 in the baseline phase and 157 in the intervention phase), with a rate of 0.21 per 1000 days of catheter use in the baseline phase and 0.29 per 1000 days in the intervention phase, giving an incidence rate ratio of 1.37 (95% confidence interval 0.85 to 2.21; P=0.20). This translates to one in 10 patients who undergo dialysis for a year with a catheter experiencing an episode of CRBSI. CONCLUSIONS: Among patients who require a haemodialysis catheter, the implementation of a multifaceted intervention did not reduce the rate of CRBSI. Multifaceted interventions to prevent CRBSI might not be effective in clinical practice settings. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12616000830493