‘Scrutinised, judged and sabotaged’: A qualitative video diary study of first-time breastfeeding mothers

Objective To explore how support impacted on mothers’ breastfeeding experiences in the first few weeks following birth. Design A qualitative approach explored real-time experiences of breastfeeding captured by five first-time mothers in the South of England on camcorder as video diaries. A multi-dimensional approach involving thematic analysis ensured both the audio and visual elements of the data were analysed. Findings Mothers felt ‘under surveillance’ by the biomedical approach to support from the healthcare team. At best mothers felt reassured that they were ‘on the right track’. When mothers felt their breastfeeding was constantly being examined, criticised and threatened they felt ‘scrutinised, judged and sabotaged’. When they found it difficult to access healthcare support, or they avoided it altogether to circumvent further scrutiny, they felt ‘abandoned and alone’. Key conclusions Collecting audio-visual data in real-time adds fresh insights into how support impacts mothers’ experiences of breastfeeding. The biomedical approach to support for breastfeeding is not effective. Scrutinising, judging and/or sabotaging mothers’ attempts to breastfeed can have long-lasting effects on maternal emotional wellbeing. Implications for practice Breastfeeding support might be improved by adopting a more social model of care. Future research needs to explore how relationship-based support can be provided by the health service

Molecular testing for Lynch syndrome in people with colorectal cancer: systematic reviews and economic evaluation

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Inherited mutations in deoxyribonucleic acid (DNA) mismatch repair (MMR) genes lead to an increased risk of colorectal cancer (CRC), gynaecological cancers and other cancers, known as Lynch syndrome (LS). Risk-reducing interventions can be offered to individuals with known LS-causing mutations. The mutations can be identified by comprehensive testing of the MMR genes, but this would be prohibitively expensive in the general population. Tumour-based tests - microsatellite instability (MSI) and MMR immunohistochemistry (IHC) - are used in CRC patients to identify individuals at high risk of LS for genetic testing. MLH1 (MutL homologue 1) promoter methylation and BRAF V600E testing can be conducted on tumour material to rule out certain sporadic cancers. OBJECTIVES: To investigate whether testing for LS in CRC patients using MSI or IHC (with or without MLH1 promoter methylation testing and BRAF V600E testing) is clinically effective (in terms of identifying Lynch syndrome and improving outcomes for patients) and represents a cost-effective use of NHS resources. REVIEW METHODS: Systematic reviews were conducted of the published literature on diagnostic test accuracy studies of MSI and/or IHC testing for LS, end-to-end studies of screening for LS in CRC patients and economic evaluations of screening for LS in CRC patients. A model-based economic evaluation was conducted to extrapolate long-term outcomes from the results of the diagnostic test accuracy review. The model was extended from a model previously developed by the authors. RESULTS: Ten studies were identified that evaluated the diagnostic test accuracy of MSI and/or IHC testing for identifying LS in CRC patients. For MSI testing, sensitivity ranged from 66.7% to 100.0% and specificity ranged from 61.1% to 92.5%. For IHC, sensitivity ranged from 80.8% to 100.0% and specificity ranged from 80.5% to 91.9%. When tumours showing low levels of MSI were treated as a positive result, the sensitivity of MSI testing increased but specificity fell. No end-to-end studies of screening for LS in CRC patients were identified. Nine economic evaluations of screening for LS in CRC were identified. None of the included studies fully matched the decision problem and hence a new economic evaluation was required. The base-case results in the economic evaluation suggest that screening for LS in CRC patients using IHC, BRAF V600E and MLH1 promoter methylation testing would be cost-effective at a threshold of £20,000 per quality-adjusted life-year (QALY). The incremental cost-effectiveness ratio for this strategy was £11,008 per QALY compared with no screening. Screening without tumour tests is not predicted to be cost-effective. LIMITATIONS: Most of the diagnostic test accuracy studies identified were rated as having a risk of bias or were conducted in unrepresentative samples. There was no direct evidence that screening improves long-term outcomes. No probabilistic sensitivity analysis was conducted. CONCLUSIONS: Systematic review evidence suggests that MSI- and IHC-based testing can be used to identify LS in CRC patients, although there was heterogeneity in the methods used in the studies identified and the results of the studies. There was no high-quality empirical evidence that screening improves long-term outcomes and so an evidence linkage approach using modelling was necessary. Key determinants of whether or not screening is cost-effective are the accuracy of tumour-based tests, CRC risk without surveillance, the number of relatives identified for cascade testing, colonoscopic surveillance effectiveness and the acceptance of genetic testing. Future work should investigate screening for more causes of hereditary CRC and screening for LS in endometrial cancer patients. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016033879. FUNDING: The National Institute for Health Research Health Technology Assessment programme.Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Researc

A systematic review and economic evaluation of diagnostic strategies for Lynch syndrome

Background Lynch syndrome (LS) is an inherited autosomal dominant disorder characterised by an increased risk of colorectal cancer (CRC) and other cancers, and caused by mutations in the deoxyribonucleic acid (DNA) mismatch repair genes. Objective To evaluate the accuracy and cost-effectiveness of strategies to identify LS in newly diagnosed early-onset CRC patients (aged < 50 years). Cascade testing of relatives is employed in all strategies for individuals in whom LS is identified. Data sources and methods Systematic reviews were conducted of the test accuracy of microsatellite instability (MSI) testing or immunohistochemistry (IHC) in individuals with CRC at risk of LS, and of economic evidence relating to diagnostic strategies for LS. Reviews were carried out in April 2012 (test accuracy); and in February 2012, repeated in February 2013 (economic evaluations). Databases searched included MEDLINE (1946 to April week 3, 2012), EMBASE (1980 to week 17, 2012) and Web of Science (inception to 30 April 2012), and risk of bias for test accuracy was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) quality appraisal tool. A de novo economic model of diagnostic strategies for LS was developed. Results Inconsistencies in study designs precluded pooling of diagnostic test accuracy results from a previous systematic review and nine subsequent primary studies. These were of mixed quality, with significant methodological concerns identified for most. IHC and MSI can both play a part in diagnosing LS but neither is gold standard. No UK studies evaluated the cost-effectiveness of diagnosing and managing LS, although studies from other countries generally found some strategies to be cost-effective compared with no testing. The de novo model demonstrated that all strategies were cost-effective compared with no testing at a threshold of £20,000 per quality-adjusted life-year (QALY), with the most cost-effective strategy utilising MSI and BRAF testing [incremental cost-effectiveness ratio (ICER) = £5491 per QALY]. The maximum health benefit to the population of interest would be obtained using universal germline testing, but this would not be a cost-effective use of NHS resources compared with the next best strategy. When the age limit was raised from 50 to 60 and 70 years, the ICERs compared with no testing increased but remained below £20,000 per QALY (except for universal germline testing with an age limit of 70 years). The total net health benefit increased with the age limit as more individuals with LS were identified. Uncertainty was evaluated through univariate sensitivity analyses, which suggested that the parameters substantially affecting cost-effectiveness: were the risk of CRC for individuals with LS; the average number of relatives identified per index patient; the effectiveness of colonoscopy in preventing metachronous CRC; the cost of colonoscopy; the duration of the psychological impact of genetic testing on health-related quality of life (HRQoL); and the impact of prophylactic hysterectomy and bilateral salpingo-oophorectomy on HRQoL (this had the potential to make all testing strategies more expensive and less effective than no testing). Limitations The absence of high-quality data for the impact of prophylactic gynaecological surgery and the psychological impact of genetic testing on HRQoL is an acknowledged limitation. Conclusions Results suggest that reflex testing for LS in newly diagnosed CRC patients aged < 50 years is cost-effective. Such testing may also be cost-effective in newly diagnosed CRC patients aged < 60 or < 70 years. Results are subject to uncertainty due to a number of parameters, for some of which good estimates were not identified. We recommend future research to estimate the cost-effectiveness of testing for LS in individuals with newly diagnosed endometrial or ovarian cancer, and the inclusion of aspirin chemoprevention. Further research is required to accurately estimate the impact of interventions on HRQoL

An experimental study on the impact of two dimensional materials in waste disposal sites: What are the implications for engineered landfills?

It is generally accepted that landfilled municipal solid waste develops a heterogeneous and anisotropic structure during placement, degradation and settlement. Flow and transport processes, in traditional and alternative landfills, are strongly influenced by the type of structure developed. The presence of pref- erential flow has gained research interest, given its impact on landfill processes. This paper describes an experimental investigation carried out on a specimen of degraded municipal solid waste. Preferential flow was detected and caused by the specimen layered structure composed of two dimensional particles derived from less easily degradable materials such as plastics, textiles and paper which made up more than 50% of the specimen dry mass. The results suggest that two dimensional particles play a role in promoting preferential flow because they modify flow paths and increase the tortuosity. A high content of less easily degradable two dimensional materials suggests incompatibility with better management practices, seeking a more even distribution of fluids to enhance degradation and faster stabilisation rates within engineered landfills. Consequently, there is a need to re-think the types and quantities of materials that are restricted under current landfill [email protected]

Population-level salt intake in the WHO European Region in 2022 : a systematic review

Objective: The WHO recommends that adults consume less than 5 g of salt per day to reduce the risk of CVD. This study aims to examine the average population daily salt intake in the fifty-three Member States of the WHO European Region. Design: A systematic review was conducted to examine the most up-to-date salt intake data for adults published between 2000 and 2022. Data were obtained from peer-reviewed and grey literature, WHO surveys and studies, as well as from national and global experts. Setting: The fifty-three Member States of the WHO European Region. Participants: People aged 12 years or more. Results: We identified fifty studies published between 2010 and 2021. Most countries in the WHO European Region (n 52, 98 %) reported salt intake above WHO recommended maximum levels. In almost all countries (n 52, 98 %), men consume more salt than women, ranging between 5·39 and 18·51 g for men and 4·27 and 16·14 g for women. Generally, Western and Northern European countries have the lowest average salt intake, whilst Eastern European and Central Asian countries have the highest average. Forty-two percentage of the fifty-three countries (n 22) measured salt intake using 24 h urinary collection, considered the gold standard method. Conclusions: This study found that salt intakes in the WHO European Region are significantly above WHO recommended levels. Most Member States of the Region have conducted some form of population salt intake. However, methodologies to estimate salt intake are highly disparate and underestimations are very likely

Telling the world we're in love

Gift of Dr. Mary Jane Esplen.Piano vocal ukulele banjulele banjo [instrumentation]Why can't I say [first line]I told the breeze [first line of chorus]G major [key]Not fast [tempo]Popular song [form/genre]Couple embracing ; Chas W. [Lawap] (photograph) [illustration]Barbelle [graphic artist]Publisher's advertisement on back cover [note

Activation and inhibition of rat neuronal nicotinic receptors by ABT-418

1. ABT-418 appeared to function as a relatively broad spectrum activator of neuronal nicotinic receptors, expressed in Xenopus oocytes, with little cross reactivity to the mammalian muscle receptor subtype. However, the relative potencies of ABT-418 at the various subtypes differed from those acetylcholine (ACh). For example, ACh was most potent at α3β2 (EC(50)≈30 μM) and least potent at α2β2 (EC(50)≈500 μM). ABT-418 was most potent at α4β2 and α2β2 (EC(50)≈6 μM and 11 μM, respectively) and least potent at α3β4 (EC(50)≈188 μM). 2. In addition to activating neuronal receptors, ABT-418 exhibited complex properties, including the inhibition of ACh responses. 3. The current responses elicited by relatively high concentrations of ABT-418 on the α4β2 receptor subtype were protracted beyond the application interval. The coapplication of ABT-418 with either of the use-dependent inhibitors bis(1,2,2,6,6-tetramethyl-4-pipendimyl)sebacate (BTMPS) or tetramethyl-pipenidine (TMP) eliminated the late protracted phase of the currents with only small effects on the initial activation phase. When the reversible inhibitor TMP was washed from the bath, the previously inhibited late current reappeared, suggesting that the observed mixed agonist-antagonist effects of ABT-418 and (±)-epibatidine on α(4)β(2) were due to a concentration-dependent noncompetitive inhibition, an effect similar to that obtained for (−)-nicotine. 4. The inhibition of α4β2 receptors by ABT-418 was voltage-dependent. When high concentrations of ABT-418 were applied under depolarizing conditions, additional late currents could be observed under conditions which suggested that a build up of ABT-418 in an unstirred layer over the surface of the oocyte was occurring. This may have been due to the dissociation of the drug from channel blocking sites on the receptors themselves, or alternatively, from the plasma membrane of the cells