Reproductive outcomes in women and men using complementary and alternative medicine treatment and not receiving artificial reproductive technology: a systematic review

Funder: Medical Research Council (GB)Funder: British Heart Foundation; doi: http://dx.doi.org/10.13039/501100000274Funder: Homerton College, University of Cambridge; doi: http://dx.doi.org/10.13039/501100008420Funder: University of CambridgeAbstract: Purpose: Infertility is a global problem, but only a minority of couples access assisted reproductive technologies due to financial and sociocultural barriers. Complementary and alternative medicine are seen as another option. We aimed to determine the impact of complementary and alternative medicine on conception, miscarriage and live birth rates in couples not receiving assisted reproductive technology treatments. Methods: The electronic databases EMBASE, PubMed, Web of Science and the Allied and Complementary Medicine Database were systematically searched before March 24th 2020. Reference lists of eligible studies were searched for relevant studies. Eligible studies included trials and observational studies that assessed a complementary or alternative medicine and conception, miscarriage or live births in men or women not undergoing fertility treatment. Data were extracted by two independent reviewers using a pre-designed data collection form. The study protocol was published in the PROSPERO database (CRD42018086980). Results: Twenty randomized controlled trials were identified, including 2748 individuals. Most studies did not demonstrate any effect of a complementary or alternative medicine on pregnancy, live birth or miscarriage rates. Limited evidence was found for a positive effect of herbal therapies taken by women on conception rates. There was substantial diversity in quality across the studies. Conclusion: There is limited evidence of the effectiveness of complementary and alternative medicine on improving the chances of conception and live births, or increasing miscarriage risk. Owing to the generally sub-optimal quality and heterogeneous nature of the evidence, rigorous studies are needed to determine the impact of complementary and alternative medicine on fertility

Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies.

OBJECTIVE: To evaluate the extent to which circulating biomarker and supplements of vitamin D are associated with mortality from cardiovascular, cancer, or other conditions, under various circumstances. DESIGN: Systematic review and meta-analysis of observational studies and randomised controlled trials. DATA SOURCES: Medline, Embase, Cochrane Library, and reference lists of relevant studies to August 2013; correspondance with investigators. STUDY SELECTION: Observational cohort studies and randomised controlled trials in adults, which reported associations between vitamin D (measured as circulating 25-hydroxyvitamin D concentration or vitamin D supplement given singly) and cause specific mortality outcomes. DATA EXTRACTION: Data were extracted by two independent investigators, and a consensus was reached with involvement of a third. Study specific relative risks from 73 cohort studies (849,412 participants) and 22 randomised controlled trials (vitamin D given alone versus placebo or no treatment; 30,716 participants) were meta-analysed using random effects models and were grouped by study and population characteristics. RESULTS: In the primary prevention observational studies, comparing bottom versus top thirds of baseline circulating 25-hydroxyvitamin D distribution, pooled relative risks were 1.35 (95% confidence interval 1.13 to 1.61) for death from cardiovascular disease, 1.14 (1.01 to 1.29) for death from cancer, 1.30 (1.07 to 1.59) for non-vascular, non-cancer death, and 1.35 (1.22 to 1.49) for all cause mortality. Subgroup analyses in the observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements. In randomised controlled trials, relative risks for all cause mortality were 0.89 (0.80 to 0.99) for vitamin D3 supplementation and 1.04 (0.97 to 1.11) for vitamin D2 supplementation. The effects observed for vitamin D3 supplementation remained unchanged when grouped by various characteristics. However, for vitamin D2 supplementation, increased risks of mortality were observed in studies with lower intervention doses and shorter average intervention periods. CONCLUSIONS: Evidence from observational studies indicates inverse associations of circulating 25-hydroxyvitamin D with risks of death due to cardiovascular disease, cancer, and other causes. Supplementation with vitamin D3 significantly reduces overall mortality among older adults; however, before any widespread supplementation, further investigations will be required to establish the optimal dose and duration and whether vitamin D3 and D2 have different effects on mortality risk

Case-ascertainment of acute myocardial infarction hospitalizations in cancer patients: a cohort study using English linked electronic health data.

AIMS: To assess the recording and accuracy of acute myocardial infarction (AMI) hospital admissions between two electronic health record databases within an English cancer population over time and understand the factors that affect case-ascertainment. METHODS AND RESULTS: We identified 112 502 hospital admissions for AMI in England 2010-2017 from the Myocardial Ischaemia National Audit Project (MINAP) disease registry and hospital episode statistics (HES) for 95 509 patients with a previous cancer diagnosis up to 15 years prior to admission. Cancer diagnoses were identified from the National Cancer Registration Dataset (NCRD). We calculated the percentage of AMI admissions captured by each source and examined patient characteristics associated with source of ascertainment. Survival analysis assessed whether differences in survival between case-ascertainment sources could be explained by patient characteristics. A total of 57 265 (50.9%) AMI admissions in patients with a prior diagnosis of cancer were captured in both MINAP and HES. Patients captured in both sources were younger, more likely to have ST-segment elevation myocardial infarction and had better prognosis, with lower mortality rates up to 9 years after AMI admission compared with patients captured in only one source. The percentage of admissions captured in both data sources improved over time. Cancer characteristics (site, stage, and grade) had little effect on how AMI was captured. CONCLUSION: MINAP and HES define different populations of patients with AMI. However, cancer characteristics do not substantially impact on case-ascertainment. These findings support a strategy of using multiple linked data sources for observational cardio-oncological research into AMI

Better Palliative Care for people with a Dementia: Summary of InterdisciplinaryWorkshop Highlighting Current Gaps and Recommendations for Future Research

Background: Dementia is the most common neurological disorder worldwide and is a life-limiting condition, but very often is not recognised as such. People with dementia, and their carers, have been shown to have palliative care needs equal in extent to those of cancer patients. However, many people with advanced dementia are not routinely being assessed to determine their palliative care needs, and it is not clear why this is so. Main body: An interdisciplinary workshop on "Palliative Care in Neurodegeneration, with a focus on Dementia", was held in Cork, Ireland, in May 2016. The key aim of this workshop was to discuss the evidence base for palliative care for people with dementia, to identify 'gaps' for clinical research, and to make recommendations for interdisciplinary research practice. To lead the discussion throughout the day a multidisciplinary panel of expert speakers were brought together, including both researchers and clinicians from across Ireland and the UK. Targeted invitations were sent to attendees ensuring all key stakeholders were present to contribute to discussions. In total, 49 experts representing 17 different academic and practice settings, attended. Key topics for discussion were pre-selected based on previously identified research priorities (e.g. James Lind Alliance) and stakeholder input. Key discussion topics included: i. Advance Care Planning for people with Dementia; ii. Personhood in End-of-life Dementia care; iii. Topics in the care of advanced dementia at home. These topics were used as a starting point, and the ethos of the workshop was that the attendees could stimulate discussion and debate in any relevant area, not just the key topics, summarised under iv. Other priorities. Conclusions: The care experienced by people with dementia and their families has the potential to be improved; palliative care frameworks may have much to offer in this endeavour. However, a solid evidence base is required to translate palliative care into practice in the context of dementia. This paper presents suggested research priorities as a starting point to build this evidence base. An interdisciplinary approach to research and priority setting is essential to develop actionable knowledge in this area

The use of teledermatology for the diagnosis of skin cancer in adults

Background: Early accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell carcinoma (SCC) are high risk skin cancers which have the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised with potential to infiltrate and damage surrounding tissue. Anxiety around missing early curable cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Teledermatology provides a way for generalist clinicians to access the opinion of a specialist dermatologist for skin lesions that they consider to be suspicious without referring the patients concerned through the normal referral pathway. Teledermatology consultations can be ‘store-and-forward’ with electronic digital images of a lesion sent to a dermatologist for review at a later time, or can be live and interactive consultations using video conferencing to connect the patient, referrer and dermatologist in real time. Objectives: To determine the diagnostic accuracy of teledermatology for the detection of any skin cancer (melanoma, BCC or cSCC) in adults, and to compare its accuracy with that of in-person diagnosis. Search methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; EMBASE; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles. Selection criteria: Studies evaluating skin cancer diagnosis for teledermatology alone, or in comparison with face-to-face diagnosis by a specialist clinician, compared with a reference standard of histological confirmation or clinical follow-up and expert opinion. Studies evaluating the referral accuracy of teledermatology compared with a reference standard of face-to-face diagnosis by a specialist clinician were also included. Data collection and analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition of any skin cancer was missing. Data permitting, we estimated summary sensitivities and specificities using the bivariate hierarchical model. Due to scarcity of data, no covariate investigations were undertaken for this review. For illustrative purposes, estimates of sensitivity and specificity were plotted on coupled forest plots for diagnostic threshold and target condition under consideration. Main results: Twenty-two studies were included reporting diagnostic accuracy data for 4057 lesions and 879 malignant cases (16 studies) and referral accuracy data for reported data for 1449 lesions and 270 ‘positive’ cases as determined by the reference standard face-to-face decision (six studies). Methodological quality was variable with poor reporting hindering assessment. The overall risk of bias was rated as high or unclear for participant selection, reference standard and participant flow and timing in at least half of all studies; the majority were considered at low risk of bias for the index test. The applicability of study findings were of high or unclear concern for the majority of studies in all domains assessed due to the recruitment of study participants from secondary care settings or specialist clinics rather than from the primary or community-based settings in which teledermatology is more likely to be used and due to the acquisition of lesion images by dermatologists or in specialist imaging units rather than by primary care clinicians. Seven studies provided data for the primary target condition of any skin cancer (1588 lesions and 638 malignancies). For the correct diagnosis of lesions as malignant using photographic images, summary sensitivity was 94.9% (95% CI 90.1 to 97.4%) and summary specificity 84.3% (95% CI 48.5 to 96.8%) (from four studies). Individual study estimates using dermoscopic images or a combination of photographic and dermoscopic images generally suggested similarly high sensitivities with highly variable specificities. Limited comparative data suggested similar diagnostic accuracy between teledermatology assessment and in-person diagnosis by a dermatologist; however, data were too scarce to draw firm conclusions. For the detection of invasive melanoma or atypical intraepidermal melanocytic variants both sensitivities and specificities were more variable. Sensitivities ranged from 59% (95% CI 42% to 74%) to 100% (95% CI 54% to 100%) and specificities from 30% (95% CI 22% to 40%) to 100% (95% CI 93% to 100%), with reported diagnostic thresholds including the correct diagnosis of melanoma, classification of lesions as ‘atypical’ or ‘typical as well as the decision to refer or to excise a lesion. Referral accuracy data comparing teledermatology against a face-to-face reference standard suggested good agreement for lesions considered to require some positive action by face to face assessment (sensitivities of over 90%). For lesions considered of less concern when assessed face-to-face (e.g. for those not recommended for excision or referral), agreement was more variable with teledermatology specificities ranging from 57% (95% CI 39 to 73%) to 100% (95% CI 86% to 100%), suggesting that remote assessment is more likely recommend excision, referral or follow-up compared to in-person decisions. Authors' conclusions: Studies were generally small and heterogeneous and methodological quality was difficult to judge due to poor reporting. Bearing in mind concerns regarding the applicability of study participants and of lesion image acquisition in specialist settings, our results suggest that teledermatology can correctly identify the majority of malignant lesions. Using a more widely defined threshold to identify ‘possibly’ malignant cases or lesions that should be considered for excision is likely to appropriately triage those lesions requiring face-to-face assessment by a specialist. Despite the increasing use of teledermatology on an international level, the evidence base to support its ability to accurately diagnose lesions and to triage lesions from primary to secondary care is lacking and further prospective and pragmatic evaluation is needed

Smartphone applications for triaging adults with skin lesions that are suspicious for melanoma

Background: Melanoma accounts for a small proportion of all skin cancer cases but is responsible for the majority of skin cancer-related deaths. Early detection and treatment can improve survival. Smartphone applications are readily accessible and potentially offer an instant risk assessment of the likelihood of malignancy, so that the right people seek further medical attention from a clinician for more detailed assessment of the lesion. There is, however, a risk that melanomas will be missed and treatment delayed if the application reassures the user that their lesion is low risk. Objectives: To determine the diagnostic accuracy of smartphone applications to rule out cutaneous invasive melanoma and intraepidermal melanocytic variants in adults with concerns about suspicious skin lesions. Search methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles. Selection criteria: Studies of any design evaluating smartphone applications intended for use by individuals in a community setting who have lesions that might be suspicious for melanoma or intraepidermal melanocytic variants compared with a reference standard of histological confirmation or clinical follow-up and expert opinion. Data collection and analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Due to scarcity of data and poor quality of studies, no meta-analysis was undertaken for this review. For illustrative purposes, estimates of sensitivity and specificity were plotted on coupled forest plots for each application under consideration. Main results: This review reports on two cohorts of lesions published in two studies. Both studies were at high risk of bias from selective participant recruitment, and high rates of non-evaluable images. Concerns about applicability of findings were high due to inclusion only of lesions already selected for excision in a dermatology clinic setting, and image acquisition by clinicians rather than by smartphone app users. Data for five mobile phone applications were reported for 332 suspicious skin lesions with 86 melanomas across the two studies. Across the four artificial intelligence-based applications which classified lesion images (photographs) as melanomas (one application) or as high risk or ‘problematic’ lesions (three applications) using a pre-programmed algorithm, sensitivities ranged from 7% (95% CI: 2%, 16%) to 73% (95% CI: 52%, 88%) and specificities from 37% (95% CI: 29% to 46%) to 94% (95% CI: 87%, 97%). The single application using store-and-forward review of lesion images by a dermatologist had a sensitivity of 98% (95% CI: 90%, 100%) and specificity 30% (95% CI: 22%, 40%). The number of test failures (lesion images analysed by the applications but classed as ‘not evaluable’ and excluded by the study authors) ranged from 3 to 31 (or 2% to 18% of lesions analysed). The store-and-forward application had one of the highest rates of test failure (15%). At least one melanoma was classed as ‘not evaluable’ in three of the four application evaluations. Authors' conclusions: Smartphone applications using artificial intelligence-based analysis have not yet demonstrated sufficient promise in terms of accuracy, and are associated with a high likelihood of missing melanomas. Applications based on store-and-forward images could have a potential role in the timely presentation of people with potentially malignant lesions by facilitating active self-management health practices and early engagement of those with suspicious skin lesions; however, they may incur a significant increase in resource and workload. Given the paucity of evidence and low methodological quality, no implications for practice can be drawn. Nevertheless, this is a rapidly advancing field and new and better applications with robust reporting of studies could change these conclusions substantially

An atlas of genetic scores to predict multi-omic traits

The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics. Here we examine a large cohort (the INTERVAL study; n = 50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n = 3,175; Olink, n = 4,822), plasma metabolomics (Metabolon HD4, n = 8,153), serum metabolomics (Nightingale, n = 37,359) and whole-blood Illumina RNA sequencing (n = 4,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores

Search for supersymmetry in events with b-quark jets and missing transverse energy in pp collisions at 7 TeV

Results are presented from a search for physics beyond the standard model based on events with large missing transverse energy, at least three jets, and at least one, two, or three b-quark jets. The study is performed using a sample of proton-proton collision data collected at sqrt(s) = 7 TeV with the CMS detector at the LHC in 2011. The integrated luminosity of the sample is 4.98 inverse femtobarns. The observed number of events is found to be consistent with the standard model expectation, which is evaluated using control samples in the data. The results are used to constrain cross sections for the production of supersymmetric particles decaying to b-quark-enriched final states in the context of simplified model spectra.Comment: Submitted to Physical Review

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London