Direct Nanopore Sequencing of Human Cytomegalovirus Genomes from High-Viral-Load Clinical Samples.

Nanopore sequencing is becoming increasingly commonplace in clinical settings, particularly for diagnostic assessments and outbreak investigations, due to its portability, low cost, and ability to operate in near real-time. Although high sequencing error rates initially hampered the wider implementation of this technology, improvements have been made continually with each iteration of the sequencing hardware and base-calling software. Here, we assess the feasibility of using nanopore sequencing to determine the complete genomes of human cytomegalovirus (HCMV) in high-viral-load clinical samples without viral DNA enrichment, PCR amplification, or prior knowledge of the sequences. We utilised a hybrid bioinformatic approach that involved assembling the reads de novo, improving the consensus sequence by aligning reads to the best-matching genome from a collated set of published sequences, and polishing the improved consensus sequence. The final genomes from a urine sample and a lung sample, the former with an HCMV to human DNA load approximately 50 times greater than the latter, achieved 99.97 and 99.93% identity, respectively, to the benchmark genomes obtained independently by Illumina sequencing. Thus, we demonstrated that nanopore sequencing is capable of determining HCMV genomes directly from high-viral-load clinical samples with a high accuracy.

Genetic epidemiology of SARS-CoV-2 transmission in renal dialysis units - A high risk community-hospital interface.

OBJECTIVES: Patients requiring haemodialysis are at increased risk of serious illness with SARS-CoV-2 infection. To improve the understanding of transmission risks in six Scottish renal dialysis units, we utilised the rapid whole-genome sequencing data generated by the COG-UK consortium. METHODS: We combined geographical, temporal and genomic sequence data from the community and hospital to estimate the probability of infection originating from within the dialysis unit, the hospital or the community using Bayesian statistical modelling and compared these results to the details of epidemiological investigations. RESULTS: Of 671 patients, 60 (8.9%) became infected with SARS-CoV-2, of whom 16 (27%) died. Within-unit and community transmission were both evident and an instance of transmission from the wider hospital setting was also demonstrated. CONCLUSIONS: Near-real-time SARS-CoV-2 sequencing data can facilitate tailored infection prevention and control measures, which can be targeted at reducing risk in these settings.

An outbreak of hepatitis A virus associated with a multi-national inner-city nursery in Glasgow, Scotland.

This report describes an outbreak of hepatitis A virus linked to a nursery which affected a total of 10 individuals. Active case finding, using oral fluid testing, helped identify asymptomatic cases. Nucleotide sequencing showed that all cases were caused by the same virus, which was most similar to HAV strains circulating Zimbabwe. Interestingly, an asymptomatic child had recently returned from visiting family in that country. Standard infection control procedures and vaccination of contacts successfully contained the outbreak. Only one patient developed hepatitis A despite having been vaccinated a week before symptoms began. This hepatitis A outbreak scenario may become more common as the numbers of international travellers and immigrants increase in the UK. It highlights the importance of recommending HAV vaccination to foreign nationals and their families who are travelling to countries endemic for hepatitis A.

Conceptualizing the use of public involvement in health policy decision-making.

The concept of public involvement use is not well-defined in the literature. Previous research studies have provided brief accounts of how public involvement may influence health policy, but have not detailed the internal dynamics and process through which it is actually used in the policy process. The study objective is to examine and clarify the concept and process of public involvement use in health policy decision-making. Using qualitative concept analysis methods, we reviewed the literature on the use of public involvement and conducted semi-structured interviews with key informants who have theoretical and/or practical insights on public involvement and its use in policy decision-making. Our findings are organized around interrelated questions that animate how the concept of use is understood, interpreted, and operationalized. In asking, "How is 'use' perceived in relation to health policy decision-making?" meanings are constructed for the concept by identifying differences and drawing connections between "use" and related terms. In asking "How would one know if public involvement was used in health policy decision-making?" our findings weigh in on the act of listening as a precursor to use, the ways in which use is mediated, and responses to the input obtained from public involvement processes as signals of use. These findings are a first step toward improving conceptual clarity about what public involvement use means, how it is understood and interpreted by relevant actors in the public involvement and public policy fields, and how it might be operationalized. We expect our findings to be particularly useful for public involvement practitioners who are often confronted with questions from public involvement participants regarding how their input will be used in health policy decision-making.

A survey of physicians show a one-third reduction in harmful outcomes to be a clinically important difference for statin therapy.

OBJECTIVE: To establish a minimal clinically important difference (MCID) for outcomes of statin therapy with physicians using a cross-sectional design. The MCID was defined as the smallest benefit of statin therapy that would result in physicians recommending it to their patients after considering potential harm and cost. STUDY DESIGN AND SETTING: A self-administered questionnaire was sent to family practitioners, internal medicine specialists, and cardiologists practicing in Hamilton. They provided an MCID of statin therapy using clinical scenarios based on 5-year risk of vascular outcomes, namely coronary death, nonfatal myocardial infarction, stroke, and coronary revascularization. RESULTS: Two hundred nine physicians participated, of which 638 were initially approached. Physicians would recommend statin therapy if it would at least reduce the relative risk of vascular events by about one-third. For patient scenarios involving a 30%, 13%, and 5% baseline risk of developing a vascular event in 5 years, physicians would recommend treatment if it would reduce the baseline risk by 31.4% (standard deviation [SD], 19.8), 34.6% (SD, 18.0), and 46.2% (SD, 24.6), respectively. CONCLUSION: Physicians were consistent in their choice of MCID for statin therapy across vascular events. They required a larger benefit of statin therapy for patients at a lower baseline risk (5%) of developing a vascular event before they would recommend treatment.

A multidisciplinary bone metastases clinic at Toronto Sunnybrook Regional Cancer Centre - A review of the experience from 1999 to 2005.

Our objective in this study was to review the experience of a one-stop multidisciplinary bone metastases clinic (BMC) that offers a coordinated multidisciplinary approach to the care of cancer patients with bone metastases in a tertiary cancer centre. Patients with symptomatic bone metastases were referred to BMC and assessed by a team of specialists in various disciplines - interventional radiology, orthopedic surgery, palliative medicine, and radiation oncology. At initial consultation, patient demographics, reasons for referral, and case disposition were recorded. From January 1999 to February 2005, a total of 272 patients with bone metastases were referred to the BMC. The median age was 65 years (range 28-95) and median KPS score at consultation was 60 (range 30-90). The majority of patients came from home (74%), while others came from a nursing home or the hospital (9%). Almost a third (28%) of patients had 2 or more reasons of referral, yielding a total of 354 reasons. The most common reason for referral was bone pain (42%), bone metastases (21%), high risk for pathological fracture (12%), and pathological fracture (10%). Of the 272 patients who received consultation, 40% received palliative radiotherapy, 19% received interventional surgery, 7% were referred to other support services such as palliative care, physiotherapy, and 7% had further investigation or imaging. A multidisciplinary clinic is useful for co-coordinating the management of bone metastatic disease in symptomatic patients.

What should be the optimal cut points for mild, moderate, and severe pain?

PURPOSE: Grouping patients' rating of pain intensity from 0 to 10 into categories of mild, moderate, and severe pain is useful for informing treatment decisions, interpreting study outcomes, as well as aiding policy or clinical practice guidelines development. In 1995, Serlin and colleagues developed a technique to establish the cut points for mild, moderate, and severe pain by grading pain intensity with functional interference. Since then, a number of studies attempted to confirm these findings in similar or different populations but had different results. Such inconsistencies in the literature prompt for more research to establish the definition of mild, moderate and severe pain. Thus, the purpose of the current study was to identify optimal cut points (CP) of the three pain severity categories for worst, average, and current pain. PATIENTS AND METHODS: The study population (n = 199) was patients with symptomatic bone metastases referred to a palliative radiotherapy clinic. Using the Brief Pain Inventory (BPI), patients reported their worst, average, and current pain intensity, as well as the degree of functional interference due to pain. All possible combinations for the CPs, between 2 and 8, were created and related to the set of 7 interference items from the BPI using the multivariate analysis of variance (MANOVA). The criteria used to determine the optimal set of cut points for mild, moderate and severe pain was a MANOVA among pain severity categories that yielded the largest F ratio for the between-category effect on the 7 interference items as indicated by Pillai's trace, Wilk's lambda, and Hotelling's trace F statistics. RESULTS: Results confirmed a non-linear relationship between cancer pain severity and functional interference. The optimal CP for worst and average pain was CP4, 6 (mild = 1-4, moderate = 5-6, and severe = 7-10), confirming Serlin and colleagues's findings. CONCLUSION: These findings are pivotal in further understanding the meaning of pain intensity levels and the assessment of pain in patients with metastatic cancer. However, further research in alternative methods of defining the optimal CP and clinically important change should be considered.