•SARS-CoV-2 viral loads peak from upper respiratory tract samples around symptom onset.•Viral loads from sputum samples may be higher than upper respiratory tract samples.•Viral loads appear to be ...similar between asymptomatic and symptomatic patients.•The prolonged virus detection in stool samples has unclear clinical significance.•Patients may not be infectious for the entire duration of virus detection.
To summarise the evidence on the detection pattern and viral load of SARS-CoV-2 over the course of an infection (including any asymptomatic or pre-symptomatic phase), and the duration of infectivity.
A systematic literature search was undertaken in PubMed, Europe PubMed Central and EMBASE from 30 December 2019 to 12 May 2020.
We identified 113 studies conducted in 17 countries. The evidence from upper respiratory tract samples suggests that the viral load of SARS-CoV-2 peaks around symptom onset or a few days thereafter, and becomes undetectable about two weeks after symptom onset; however, viral loads from sputum samples may be higher, peak later and persist for longer. There is evidence of prolonged virus detection in stool samples, with unclear clinical significance.
No study was found that definitively measured the duration of infectivity; however, patients may not be infectious for the entire duration of virus detection, as the presence of viral ribonucleic acid may not represent transmissible live virus.
There is a relatively consistent trajectory of SARS-CoV-2 viral load over the course of COVID-19 from respiratory tract samples, however the duration of infectivity remains uncertain.
The aim of this study was to estimate the contribution of deleterious mutations in the RAD51B, RAD51C, and RAD51D genes to invasive epithelial ovarian cancer (EOC) in the population and in a ...screening trial of individuals at high risk of ovarian cancer.
The coding sequence and splice site boundaries of the three RAD51 genes were sequenced and analyzed in germline DNA from a case-control study of 3,429 patients with invasive EOC and 2,772 controls as well as in 2,000 unaffected women who were BRCA1/BRCA2 negative from the United Kingdom Familial Ovarian Cancer Screening Study (UK_FOCSS) after quality-control analysis.
In the case-control study, we identified predicted deleterious mutations in 28 EOC cases (0.82%) compared with three controls (0.11%; P < .001). Mutations in EOC cases were more frequent in RAD51C (14 occurrences, 0.41%) and RAD51D (12 occurrences, 0.35%) than in RAD51B (two occurrences, 0.06%). RAD51C mutations were associated with an odds ratio of 5.2 (95% CI, 1.1 to 24; P = .035), and RAD51D mutations conferred an odds ratio of 12 (95% CI, 1.5 to 90; P = .019). We identified 13 RAD51 mutations (0.65%) in unaffected UK_FOCSS participants (RAD51C, n = 7; RAD51D, n = 5; and RAD51B, n = 1), which was a significantly greater rate than in controls (P < .001); furthermore, RAD51 mutation carriers were more likely than noncarriers to have a family history of ovarian cancer (P < .001).
These results confirm that RAD51C and RAD51D are moderate ovarian cancer susceptibility genes and suggest that they confer levels of risk of EOC that may warrant their use alongside BRCA1 and BRCA2 in routine clinical genetic testing.
Background
Multimorbidity prevalence is increasing globally. People with multimorbidity have higher health care costs, which can create a financial burden.
Objective
To synthesize qualitative ...research exploring experience of financial burden for people with multimorbidity.
Search strategy
Six databases were searched in May 2019. A grey literature search and backward and forward citation checking were also conducted.
Inclusion criteria
Studies were included if they used a qualitative design, conducted primary data collection, included references to financial burden and had at least one community‐dwelling adult participant with two or more chronic conditions.
Data extraction and synthesis
Screening and critical appraisal were conducted by two reviewers independently. One reviewer extracted data from the results section; this was checked by a second reviewer. GRADE‐CERQual was used to summarize the certainty of the evidence. Data were analysed using thematic synthesis.
Main results
Forty‐six studies from six continents were included. Four themes were generated: the high costs people with multimorbidity experience, the coping strategies they use to manage these costs, and the negative effect of both these on their well‐being. Health insurance and government supports determine the manageability and level of costs experienced.
Discussion
Financial burden has a negative effect on people with multimorbidity. Continuity of care and an awareness of the impact of financial burden of multimorbidity amongst policymakers and health care providers may partially address the issue.
Patient or public contribution
Results were presented to a panel of people with multimorbidity to check whether the language and themes ‘resonated’ with their experiences.
ObjectivesIndividuals with multimorbidity use more health services and take more medicines. This can lead to high out-of-pocket (OOP) healthcare expenditure. This study, therefore, aimed to assess ...the association between multimorbidity (two or more chronic conditions) and OOP healthcare expenditure in a nationally representative sample of adults aged 50 years or over.DesignCross-sectional analysis of data collected in 2016 from wave 4 of The Irish Longitudinal Study on Ageing.SettingIreland.ParticipantsCommunity-dwelling adults aged 50 years and over.MethodA generalised linear model with log-link and gamma distributed errors was fitted to assess the association between multimorbidity and OOP healthcare expenditure (including general practitioner, emergency department, outpatients, specialist consultations, hospital admissions, home care and prescription drugs).ResultsOverall, 3453 (58.5%) participants had multimorbidity. Among those with any OOP healthcare expenditure, individuals with multimorbidity spent more on average per annum (€806.8 for two conditions, €885.8 for three or more conditions), than individuals with no conditions (€580.3). Pharmacy-dispensed medicine expenditure was the largest component of expenditure. People with multimorbidity on average spent more of their equivalised household income on healthcare (7.1% for two conditions, 9.7% for three or more conditions), than people with no conditions (5.0%). A strong positive association was found between number of conditions and OOP healthcare expenditure (p<0.001) and between having private health insurance and OOP healthcare expenditure (p<0.001). A strong negative association was found between eligibility for free primary/hospital care and heavily subsidised medicines and OOP healthcare expenditure (p<0.001).ConclusionsThis study suggests that having multimorbidity in Ireland increases OOP healthcare expenditure, which is problematic for those with more conditions who have lower incomes. This highlights the need for this financial burden to be considered when designing healthcare/funding systems to address multimorbidity, so that access to essential healthcare can be maximised for those with greatest need.
Summary
The collection of nasopharyngeal swabs to test for the presence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an invasive technique with implications for patients and ...clinicians. Alternative clinical specimens from the upper respiratory tract may offer benefits in terms of collection, comfort and infection risk. The objective of this review was to synthesise the evidence for detection of SARS‐CoV‐2 ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT‐PCR) tested saliva or nasal specimens compared with RT‐PCR tested nasopharyngeal specimens. Searches were conducted in PubMed, Embase, Europe PMC and NHS evidence from December 2019 to 20 July 2020. Eighteen studies were identified; 12 for saliva, four for nasal and two included both specimen types. For saliva‐based studies, the proportion of saliva samples testing positive relative to all positive samples in each study ranged from 82.9% to 100%; detection in nasopharyngeal specimens ranged from 76.7% to 100%; positive agreement between specimens for overall detection ranged from 65.4% to 100%. For nasal‐based studies, the proportion of nasal swabs testing positive relative to all positive samples in each study ranged from 81.9% to 100%; detection in nasopharyngeal specimens ranged from 70% to 100%; positive agreement between specimens for overall detection ranged from 62.3% to 100%. The results indicate an inconsistency in the detection of SARS‐CoV‐2 RNA in the specimen types included, often with neither the index nor the reference of interest detecting all known cases. Depending on the test environment, these clinical specimens may offer a viable alternative to standard. However, at present the evidence is limited, of variable quality, and relatively inconsistent.
Self-management (SM) is defined as the provision of interventions to increase patients’ skills and confidence, empowering the individual to take an active part in their disease management. There is ...uncertainty regarding the optimal format and the short- and long-term benefits of chronic obstructive pulmonary disease (COPD) SM interventions in adults. Therefore, a high-quality overview of reviews was updated to examine their clinical effectiveness. Sixteen reviews were identified, interventions were broadly classified as education or action plans, complex interventions with an SM focus, pulmonary rehabilitation (PR), telehealth and outreach nursing. Systematic review and meta-analysis quality and the risk of bias of underlying primary studies were assessed. Strong evidence was found that PR is associated with significant improvements in health-related quality of life (HRQoL). Limited to moderate evidence for complex interventions (SM focus) with limited evidence for education, action plans, telehealth interventions and outreach nursing for HRQoL was found. There was strong evidence that education is associated with a significant reduction in COPD-related hospital admissions, moderate to strong evidence that telehealth interventions and moderate evidence that complex interventions (SM focus) are associated with reduced health care utilization. These findings from a large body of evidence suggesting that SM, through education or as a component of PR, confers significant health gains in people with COPD in terms of HRQoL. SM supported by telehealth confers significant reductions in healthcare utilization, including hospitalization and emergency department visits.
Intermittent pneumatic compression (IPC) is designed to aid wound healing and limb salvage for patients with critical limb ischaemia who are not candidates for revascularisation. We conducted a ...systematic review of the literature to identify and critically appraise the evidence supporting its use in this population. A search was conducted in Embase, MEDLINE and clinical trial registries up to the end of March 2013. No date or language restrictions were applied. Quality assessment was performed by two people independently. Quality was assessed using the Cochrane risk of bias tool and the NICE case-series assessment tool. Two controlled before-and-after (CBA) studies and six case series were identified. One retrospective CBA study involving compression of the calf reported improved limb salvage and wound healing (OR 7.00, 95% CI 1.82 to 26.89, p<0.01). One prospective CBA study involving sequential compression of the foot and calf reported statistically significant improvements in claudication distances and SF-36 quality of life scores. No difference in all-cause mortality was found. Complications included pain associated with compression, as well as skin abrasion and contact rash as a result of the cuff rubbing against the skin. All studies had a high risk of bias. In conclusion, the limited available results suggest that IPC may be associated with improved limb salvage, wound healing and pain management. However, in the absence of additional well-designed analytical studies examining the effect of IPC in critical limb ischaemia, this treatment remains unproven.
Abstract Objectives To evaluate the cost-effectiveness of a national atrial fibrillation screening program in Ireland involving annual opportunistic pulse palpation of all those older than 65 years ...during general practitioner consultations, with an electrocardiogram being performed if an irregular pulse is detected. Methods A probabilistic Markov model was used to simulate costs and clinical outcomes in a hypothetical cohort of men and women with and without screening over the course of 25 years, using a societal perspective. Results Screening was associated with an incremental cost-effectiveness ratio of €23,004/quality-adjusted life-year compared with routine care. Nevertheless, if the relative risk of stroke and systematic embolism in screen-detected patients is more than 12% lower than that in patients with atrial fibrillation identified through routine practice, then screening would not be considered cost-effective at a willingness-to-pay threshold of €45,000/quality-adjusted life-year. An analysis comparing alternative combinations of start age and screening interval found that less frequent screening with a later start age may be more cost-effective than an annual screening from age 65 years. Conclusions Annual opportunistic screening of men and women aged 65 years and older in primary care in Ireland is likely to be cost-effective using conventional willingness-to-pay thresholds, assuming that those detected through screening have a comparable stroke risk profile as those detected through routine practice. Raising the start age of screening or increasing the screening interval may improve the cost-effectiveness of a prospective screening program.
Understanding the regulatory landscape of the human genome is a central question in complex trait genetics. Most single-nucleotide polymorphisms (SNPs) associated with cancer risk lie in ...non-protein-coding regions, implicating regulatory DNA elements as functional targets of susceptibility variants. Here, we describe genome-wide annotation of regions of open chromatin and histone modification in fallopian tube and ovarian surface epithelial cells (FTSECs, OSECs), the debated cellular origins of high-grade serous ovarian cancers (HGSOCs) and in endometriosis epithelial cells (EECs), the likely precursor of clear cell ovarian carcinomas (CCOCs). The regulatory architecture of these cell types was compared with normal human mammary epithelial cells and LNCaP prostate cancer cells. We observed similar positional patterns of global enhancer signatures across the three different ovarian cancer precursor cell types, and evidence of tissue-specific regulatory signatures compared to non-gynecological cell types. We found significant enrichment for risk-associated SNPs intersecting regulatory biofeatures at 17 known HGSOC susceptibility loci in FTSECs (P = 3.8 × 10(-30)), OSECs (P = 2.4 × 10(-23)) and HMECs (P = 6.7 × 10(-15)) but not for EECs (P = 0.45) or LNCaP cells (P = 0.88). Hierarchical clustering of risk SNPs conditioned on the six different cell types indicates FTSECs and OSECs are highly related (96% of samples using multi-scale bootstrapping) suggesting both cell types may be precursors of HGSOC. These data represent the first description of regulatory catalogues of normal precursor cells for different ovarian cancer subtypes, and provide unique insights into the tissue specific regulatory variation with respect to the likely functional targets of germline genetic susceptibility variants for ovarian cancer.
Although no known asteroid poses a threat to Earth for at least the next century, the catalogue of near-Earth asteroids is incomplete for objects whose impacts would produce regional devastation
. ...Several approaches have been proposed to potentially prevent an asteroid impact with Earth by deflecting or disrupting an asteroid
. A test of kinetic impact technology was identified as the highest-priority space mission related to asteroid mitigation
. NASA's Double Asteroid Redirection Test (DART) mission is a full-scale test of kinetic impact technology. The mission's target asteroid was Dimorphos, the secondary member of the S-type binary near-Earth asteroid (65803) Didymos. This binary asteroid system was chosen to enable ground-based telescopes to quantify the asteroid deflection caused by the impact of the DART spacecraft
. Although past missions have utilized impactors to investigate the properties of small bodies
, those earlier missions were not intended to deflect their targets and did not achieve measurable deflections. Here we report the DART spacecraft's autonomous kinetic impact into Dimorphos and reconstruct the impact event, including the timeline leading to impact, the location and nature of the DART impact site, and the size and shape of Dimorphos. The successful impact of the DART spacecraft with Dimorphos and the resulting change in the orbit of Dimorphos
demonstrates that kinetic impactor technology is a viable technique to potentially defend Earth if necessary.
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