Measurement of the major ignored burden of multiple myeloma, pernicious anaemia and of other haematological conditions on partners and family members: A cross-sectional study.

BACKGROUND: Having a haematological condition can adversely affect the quality of life (QoL) of family members/partners of patients. It is important to measure this often ignored burden in order to implement appropriate supportive interventions. OBJECTIVE: To measure current impact of haematological conditions on the QoL of family members/partners of patients, using the Family Reported Outcome Measure-16 (FROM-16). METHODS: A cross-sectional study, recruited online through patient support groups, involved UK family members/partners of people with haematological conditions completing the FROM-16. RESULTS: 183 family members/partners (mean age = 60.5 years, SD = 13.2; females = 62.8%) of patients (mean age = 64.1, SD = 12.8; females = 46.4%) with 12 haematological conditions completed the FROM-16. The FROM-16 mean total score was 14.0 (SD = 7.2), meaning 'a moderate effect on QoL'. The mean FROM-16 scores of family members of people with multiple myeloma (mean = 15.8, SD = 6.3, n = 99) and other haematological malignancies (mean = 13.9, SD = 7.8, n = 29) were higher than of people with pernicious anaemia (mean = 10.7, SD = 7.5, n = 47) and other non-malignant conditions (mean = 11, SD = 7.4, n = 56, p < .01). Over one third (36.1%, n = 183) of family members experienced a 'very large effect' (FROM-16 score>16) on their quality of life. CONCLUSIONS: Haematological conditions, in particular those of malignant type, impact the QoL of family members/partners of patients. Healthcare professionals can now, using FROM-16, identify those most affected and should consider how to provide appropriate holistic support within routine practice.

British Association of Dermatologists National Clinical Audit on the Management of Hidradenitis Suppurativa in the UK.

BACKGROUND: The first UK guidelines for the management of hidradenitis suppurativa (HS) were published by the British Association of Dermatologists (BAD) in 2018. The guidelines contained a set of audit criteria. AIM: To evaluate current HS management against the audit standards in the BAD guidelines. METHODS: BAD members were invited to complete audit questionnaires between January and May 2020 for five consecutive patients with HS per department. RESULTS: In total, 88 centres participated, providing data for 406 patients. Disease staging using the Hurley system and disease severity using a validated tool during follow-ups was documented in 75% and 56% of cases, respectively, while quality of life and pain were documented in 49% and 50% of cases, respectively. Screening for cardiovascular disease risk factors was as follows: smoking 75%, body mass index 27% and others such as lipids and diabetes 57%. Screening for depression and anxiety was performed in 40% and 25% of cases, respectively. Support for smokers or obese patients was documented in 35% and 23% of cases. In total, 182 patients were on adalimumab, of whom 68% had documentation of baseline disease severity, and 76% were reported as having inadequate response or contraindications to systemic treatments; 44% of patients continued on adalimumab despite having < 25% improvement in lesion count. CONCLUSION: UK dermatologists performed well against several audit standards, including documenting disease staging at baseline and smoking status. However, improvements are needed, particularly with regard to screening and management of comorbidities that could reduce the long-term complications associated with HS. A re-audit is required to evaluate changes in practice in the future.

Arsenic Concentrations in Ground and Surface Waters across Arizona Including Native Lands.

Parts of the Southwestern United States report arsenic levels in water resources that are above the United States Environmental Protection Agency's current drinking water limits. Prolonged exposure to arsenic through food and drinking water can contribute to significant health problems including cancer, developmental effects, cardiovascular disease, neurotoxicity, and diabetes. In order to understand exposure risks, water sampling and testing has been conducted throughout Arizona. This information is available to the public through often non-overlapping databases that are difficult to access and in impracticable formats. The current study utilized a systemic compilation of online databases to compile a spreadsheet containing over 33,000 water samples. The reported arsenic concentrations from these databases were collected from 1990-2017. Using ArcGIS software, these data were converted into a map shapefile and overlaid onto a map of Arizona. This visual representation shows that arsenic levels in surface and ground water exceed the United States Environmental Protection Agency's drinking water limits for many sites in several counties in Arizona, and there is an underrepresentation of sampling in several tribal jurisdictions. This information is useful for water managers and private well owners throughout the State for determining safe drinking water sources and limiting exposure to arsenic.

Rationale for Early Diagnosis of Mild Cognitive Impairment (MCI) Supported by Emerging Digital Technologies.

Disease-modifying pharmacotherapies for Alzheimer's Disease (AD) are currently in late-stage clinical development; once approved, new healthcare infrastructures and services, including primary healthcare, will be necessary to accommodate a huge demand for early and large-scale detection of AD. The increasing global accessibility of digital consumer electronics has opened up new prospects for early diagnosis and management of mild cognitive impairment (MCI) with particular regard to AD. This new wave of innovation has spurred research in both academia and industry, aimed at developing and validating a new "digital generation" of tools for the assessment of the cognitive performance. In light of this paradigm shift, an international working group (the Global Advisory Group on Future MCI Care Pathways) convened to elaborate on how digital tools may be optimally integrated in screening-diagnostic pathways of AD The working group developed consensus perspectives on new algorithms for large-scale screening, detection, and diagnosis of individuals with MCI within primary medical care delivery. In addition, the expert panel addressed operational aspects concerning the implementation of unsupervised at-home testing of cognitive performance. The ultimate intent of the working group's consensus perspectives is to provide guidance to developers of cognitive tests and tools to facilitate the transition toward globally accessible cognitive screening aimed at the early detection, diagnosis, and management of MCI due to AD.

Early Detection of Mild Cognitive Impairment (MCI) in Primary Care.

Mild cognitive impairment (MCI) is significantly misdiagnosed in the primary care setting due to multi-dimensional frictions and barriers associated with evaluating individuals' cognitive performance. To move toward large-scale cognitive screening, a global panel of clinicians and cognitive neuroscientists convened to elaborate on current challenges that hamper widespread cognitive performance assessment. This report summarizes a conceptual framework and provides guidance to clinical researchers and test developers and suppliers to inform ongoing refinement of cognitive evaluation. This perspective builds upon a previous article in this series, which outlined the rationale for and potentially against efforts to promote widespread detection of MCI. This working group acknowledges that cognitive screening by default is not recommended and proposes large-scale evaluation of individuals with a concern or interest in their cognitive performance. Such a strategy can increase the likelihood to timely and effective identification and management of MCI. The rising global incidence of AD demands innovation that will help alleviate the burden to healthcare systems when coupled with the potentially near-term approval of disease-modifying therapies. Additionally, we argue that adequate infrastructure, equipment, and resources urgently should be integrated in the primary care setting to optimize the patient journey and accommodate widespread cognitive evaluation.

Early Detection of Mild Cognitive Impairment (MCI) in an At-Home Setting.

Emerging digital tools have the potential to enable a new generation of qualitative and quantitative assessment of cognitive performance. Moreover, the ubiquity of consumer electronics, such as smartphones and tablets, can be harnessed to support large-scale self-assessed cognitive screening with benefit to healthcare systems and consumers. A wide variety of apps, wearables, and new digital technologies are either available or in development for the detection of mild cognitive impairment (MCI), a risk factor for dementia. Two categories of novel methodologies may be considered: passive technologies (which monitor a user's behavior without active user input) and interactive assessments (which require active user input). Such examinations can be self-administered, supervised by a caregiver, or conducted by an informant at home or outside of a clinical setting. These direct-to-consumer tools have the potential to sidestep barriers associated with cognitive evaluation in primary care, thus improving access to cognitive assessments. Although direct-to-consumer cognitive assessment is associated with its own barriers, including test validation, user experience, and technological concerns, it is conceivable that these issues can be addressed so that a large-scale, self-assessed cognitive evaluation that would represent an initial cognitive screen may be feasible in the future.

Systematic review of the impact of breast-conserving surgery on cancer outcomes of multiple ipsilateral breast cancers.

BACKGROUND: The clinical effectiveness of treating ipsilateral multifocal (MF) and multicentric (MC) breast cancers using breast-conserving surgery (BCS) compared with the standard of mastectomy is uncertain. Inconsistencies relate to definitions, incidence, staging and intertumoral heterogeneity. The primary aim of this systematic review was to compare clinical outcomes after BCS versus mastectomy for MF and MC cancers, collectively defined as multiple ipsilateral breast cancers (MIBC). METHODS: Comprehensive electronic searches were undertaken to identify complete papers published in English between May 1988 and July 2015, primarily comparing clinical outcomes of BCS and mastectomy for MIBC. All study designs were included, and studies were appraised critically using the Newcastle-Ottawa Scale. The characteristics and results of identified studies were summarized. RESULTS: Twenty-four retrospective studies were included in the review: 17 comparative studies and seven case series. They included 3537 women with MIBC undergoing BCS; breast cancers were defined as MF in 2677 women, MC in 292, and reported as MIBC in 568. Six studies evaluated MIBC treated by BCS or mastectomy, with locoregional recurrence (LRR) rates of 2-23 per cent after BCS at median follow-up of 59·5 (i.q.r. 56-81) months. BCS and mastectomy showed apparently equivalent rates of LRR (risk ratio 0·94, 95 per cent c.i. 0·65 to 1·36). Thirteen studies compared BCS in women with MIBC versus those with unifocal cancers, reporting LRR rates of 2-40 per cent after BCS at a median follow-up of 64 (i.q.r. 57-73) months. One high-quality study reported 10-year actuarial LRR rates of 5·5 per cent for BCS in 300 women versus 6·5 per cent for mastectomy among 887 women. CONCLUSION: The available studies were mainly of moderate quality, historical and underpowered, with limited follow-up and biased case selection favouring BCS rather than mastectomy for low-risk patients. The evidence was inconclusive, weakening support for the St Gallen consensus and supporting a future randomized trial.

Levels of wound calprotectin and other inflammatory biomarkers aid in deciding which patients with a diabetic foot ulcer need antibiotic therapy (INDUCE study).

AIMS: Deciding if a diabetic foot ulcer is infected in a community setting is challenging without validated point-of-care tests. Four inflammatory biomarkers were investigated to develop a composite algorithm for mildly infected diabetic foot ulcers: venous white cell count, C-reactive protein (CRP) and procalcitonin, and a novel wound exudate calprotectin assay. Calprotectin is a marker of neutrophilic inflammation. METHODS: In a prospective study, people with uninfected or mildly infected diabetic foot ulcers who had not received oral antibiotics in the preceding 2 weeks were recruited from community podiatry clinics for measurement of inflammatory biomarkers. Antibiotic prescribing decisions were based on clinicians' baseline assessments and participants were reviewed 1 week later; ulcer infection was defined by clinicians' overall impression from their two assessments. RESULTS: Some 363 potential participants were screened, of whom 67 were recruited, 29 with mildly infected diabetic foot ulcers and 38 with no infection. One participant withdrew early in each group. Ulcer area was 1.32 cm2 [interquartile range (IQR) 0.32-3.61 cm2 ] in infected ulcers and 0.22 cm2 (IQR 0.09-1.46 cm2 ) in uninfected ulcers. Baseline CRP for mild infection was 9.00 mg/ml and 6.00 mg/ml for uninfected ulcers; most procalcitonin levels were undetectable. Median calprotectin level in infected diabetic foot ulcers was 1437 ng/ml and 879 ng/ml in uninfected diabetic foot ulcers. Area under the receiver operating characteristic curve for a composite algorithm incorporating calprotectin, CRP, white cell count and ulcer area was 0.68 (95% confidence intervals 0.52-0.82), sensitivity 0.64, specificity 0.81. CONCLUSIONS: A composite algorithm including CRP, calprotectin, white cell count and ulcer area may help to distinguish uninfected from mildly infected diabetic foot ulcers. Venous procalcitonin is unhelpful for mild diabetic foot ulcer infection.

The chemokine, CXCL16, and its receptor, CXCR6, are constitutively expressed in human annulus fibrosus and expression of CXCL16 is up-regulated by exposure to IL-1ß in vitro.

Chemokines are an important group of soluble molecules with specialized functions in inflammation. The roles of many specialized chemokines and their receptors remain poorly understood in the human intervertebral disc. We investigated CXCL16 and its receptor, CXCR6, to determine their immunolocalization in disc tissue and their presence following exposure of cultured human annulus fibrosus cells to proinflammatory cytokines. CXCL16 is a marker for inflammation; it also can induce hypoxia-inducible factor 1α (HIF-1α), which is a phenotypic marker of heathy nucleus pulposus tissue. We found CXCL16 and CXCR6 immunostaining in many cells of the annulus portion of the disc. Molecular studies showed that annulus fibrosus cells exposed to IL-1ß, but not TNF-α, exhibited significant up-regulation of CXCL16 expression vs. control cells. There was no significant difference in the percentage of annulus cells that exhibited immunolocalization of CXCL16 in grade I/II, grade III or grade IV/V specimens. The presence of CXCL16 and its receptor, CXCR6, in the annulus in vivo suggests the need for future research concerning the role of this chemokine in proinflammatory functions, HIF-1α expression and disc vascularization.

Management of agricultural soils for greenhouse gas mitigation: Learning from a case study in NE Spain.

A portfolio of agricultural practices is now available that can contribute to reaching European mitigation targets. Among them, the management of agricultural soils has a large potential for reducing GHG emissions or sequestering carbon. Many of the practices are based on well tested agronomic and technical know-how, with proven benefits for farmers and the environment. A suite of practices has to be used since none of the practices can provide a unique solution. However, there are limitations in the process of policy development: (a) agricultural activities are based on biological processes and thus, these practices are location specific and climate, soils and crops determine their agronomic potential; (b) since agriculture sustains rural communities, the costs and potential for implementation have also to be regionally evaluated and (c) the aggregated regional potential of the combination of practices has to be defined in order to inform abatement targets. We believe that, when implementing mitigation practices, three questions are important: Are they cost-effective for farmers? Do they reduce GHG emissions? What policies favour their implementation? This study addressed these questions in three sequential steps. First, mapping the use of representative soil management practices in the European regions to provide a spatial context to upscale the local results. Second, using a Marginal Abatement Cost Curve (MACC) in a Mediterranean case study (NE Spain) for ranking soil management practices in terms of their cost-effectiveness. Finally, using a wedge approach of the practices as a complementary tool to link science to mitigation policy. A set of soil management practices was found to be financially attractive for Mediterranean farmers, which in turn could achieve significant abatements (e.g., 1.34 MtCO2e in the case study region). The quantitative analysis was completed by a discussion of potential farming and policy choices to shape realistic mitigation policy at European regional level.

Interventions for hidradenitis suppurativa: a Cochrane systematic review incorporating GRADE assessment of evidence quality.

More than 50 interventions have been used to treat hidradenitis suppurativa (HS), and so therapy decisions can be challenging. Our objective was to summarize and appraise randomized controlled trial (RCT) evidence for HS interventions in adults. Searches were conducted in Medline, Embase, CENTRAL, LILACS, five trials registers and abstracts from eight dermatology conferences until 13 August 2015. Two review authors independently assessed study eligibility, extracted data and assessed methodological quality. Primary outcomes were quality of life and adverse effects of the interventions. Twelve trials, from 1983 to 2015, investigating 15 different interventions met our inclusion criteria. The median trial duration was 16 weeks and the median number of participants was 27. Adalimumab 40 mg weekly improved the Dermatology Life Quality Index (DLQI) by 4·0 points, which equates to the minimal clinically important difference for the scale, compared with placebo (95% confidence interval -6·5 to -1·5 points). Evidence quality was reduced to 'moderate' because the results are based on only a single study. Adalimumab 40 mg every other week was ineffective in a meta-analysis of two studies comprising 124 participants. Infliximab 5 mg kg(-1) improved the DLQI score by 8·4 points after 8 weeks in a moderate-quality study completed by 33 of 38 participants. Etanercept 50 mg twice weekly was ineffective. Inclusion of a gentamicin sponge prior to primary closure did not improve outcomes. Other interventions, including topical and oral antibiotics, were investigated by relatively small studies, preventing treatment recommendations due to imprecision. More, larger RCTs are required to investigate most HS interventions, particularly oral treatments and surgical therapy. Moderate-quality evidence suggests that adalimumab given weekly and infliximab are effective, whereas adalimumab every other week is ineffective.

An assessment of adherence to basic ecological principles by payments for ecosystem service projects.

Programs and projects employing payments for ecosystem service (PES) interventions achieve their objectives by linking buyers and sellers of ecosystem services. Although PES projects are popular conservation and development interventions, little is known about their adherence to basic ecological principles. We conducted a quantitative assessment of the degree to which a global set of PES projects adhered to four ecological principles that are basic scientific considerations for any project focused on ecosystem management: collection of baseline data, identification of threats to an ecosystem service, monitoring, and attention to ecosystem dynamics or the formation of an adaptive management plan. We evaluated 118 PES projects in three markets-biodiversity, carbon, and water-compiled using websites of major conservation organizations; ecology, economic, and climate-change databases; and three scholarly databases (ISI Web of Knowledge, Web of Science, and Google Scholar). To assess adherence to ecological principles, we constructed two scientific indices (one additive [ASI] and one multiplicative [MSI]) based on our four ecological criteria and analyzed index scores by relevant project characteristics (e.g., sector, buyer, seller). Carbon-sector projects had higher ASI values (P < 0.05) than water-sector projects and marginally higher ASI scores (P < 0.1) than biodiversity-sector projects, demonstrating their greater adherence to ecological principles. Projects financed by public-private partnerships had significantly higher ASI values than projects financed by governments (P < 0.05) and marginally higher ASI values than those funded by private entities (P < 0.1). We did not detect differences in adherence to ecological principles based on the inclusion of cobenefits, the spatial extent of a project, or the size of a project's budget. These findings suggest, at this critical phase in the rapid growth of PES projects, that fundamental ecological principles should be considered more carefully in PES project design and implementation in an effort to ensure PES project viability and sustainability.

Increased IL-17 expression in degenerated human discs and increased production in cultured annulus cells exposed to IL-1ß and TNF-α.

IL-17 is expressed in a number of tissues including the intervertebral disc, where it exerts strong inflammatory properties. We evaluated IL-17 using immunolocalization in herniated and non-herniated human discs, IL-17 gene expression, and the production of IL-17 by annulus cells cultured in three dimensions in the presence of IL-1ß or TNF-α. There was no difference in the percentage of IL-17 positive cells in annulus or nucleus in herniated vs. non-herniated disc specimens. Molecular studies confirmed expression of IL-17 in disc tissue, with significantly increased expression in more degenerated discs; there was no difference in expression between herniated vs. non-herniated discs. Exposure to IL-1ß or TNF-α resulted in significantly greater production of IL-17. Our findings expand understanding of IL-17 production by disc cells and reveal the importance of non-canonical IL-17 production in the disc. Significantly greater expression of IL-17 in more degenerated discs adds to our understanding of the changes in disc cell function with advancing stages of disc degeneration.

Segmental cherry angiomas associated with extragenital lichen sclerosus: a report of two cases.

Cherry angiomas (Campbell de Morgan spots) are common acquired red skin papules composed of dilated capillary loops, usually of unknown aetiology. Extragenital lichen sclerosus (LS) presents as porcelain-white scaly atrophic lesions with or without genital involvement. We report two cases of segmental multiple cherry angiomas in association with extragenital LS. Two unrelated women, aged 46 and 66 years, presented with extragenital LS affecting their axillae and lower abdomen. During the examination, both patients were noted to have several hundred red skin papules in a segmental distribution, affecting the left thigh and flank of one woman, and the right abdomen and back of the other. Clinically and histologically, the papules were consistent with cherry angiomas. The striking segmental distribution of multiple cherry angiomas may be due to genetic mosaicism; however, segmental Fabry disease was excluded by sequence analysis of the α-galactosidase A gene. Any causal link between cherry angiomas and LS remains uncertain.

Human adipose-derived mesenchymal stem cells: serial passaging, doubling time and cell senescence.

Adult adipose-derived mesenchymal stem cells (AD-MSC) are very interesting to our research group because they are easy to harvest, they are abundant in humans, and they have potential clinical applications in autologous cell therapy for disc degeneration. We examined these cells through sequential serial passages to assess osteogenic and chondrogenic capabilities, mean doubling time and cell senescence. Osteogenic and chondrogenic potencies were maintained through 13 passages. Mean passage doubling time increased significantly with increasing passage number. When donor age was evaluated, passages 1-4 from older donors had significantly longer doubling times compared to cells from younger donors. Passages 5-11 showed similar findings when analyzed by donor age. The mean percent senescence increased significantly with cell passaging, rising from 0% at passage 1 to 3.4% at passage 13. These novel data suggest that caution should be exercised when using AD-MSC with long passage times.

Environmental influences on Adelie penguin breeding schedules, endocrinology, and chick survival.

To understand how the social and physical environment influences behaviour, reproduction and survival, studies of underlying hormonal processes are crucial; in particular, interactions between stress and reproductive responses may have critical influences on breeding schedules. Several authors have examined the timing of breeding in relation to environmental stimuli, while others have independently described endocrine profiles. However, few studies have simultaneously measured endocrine profiles, breeding behaviour, and offspring survival across seasons. We measured sex and stress hormone concentrations (oestrogens, testosterone, and corticosterone), timing of breeding, and chick survival, in Adelie penguins (Pygoscelis adeliae) at two colonies in two different years. Clutch initiation at Cape Bird South (CBS; year 1, ~14,000 pairs) occurred later than at Cape Crozier East (CCE; year 2, ~ 25,000 pairs); however, breeding was more synchronous at CBS. This pattern was probably generated by the persistence of extensive sea ice at CBS (year 1). Higher corticosterone metabolite and lower sex hormone concentrations at CBS correlated with later breeding and lower chick survival compared to at CCE - again, a likely consequence of sea ice conditions. Within colonies, sub-colony size (S, 50-100; M, 200-300; L, 500-600; XL, >1000 pairs) did not influence the onset or synchrony of breeding, chick survival, or hormone concentrations. We showed that the endocrine profiles of breeding Adelie penguins can differ markedly between years and/or colonies, and that combining measures of endocrinology, behaviour, and offspring survival can reveal the mechanisms and consequences that different environmental conditions can have on breeding ecology.