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Routine HIV drug resistance genotyping identified an integrase sequence harbouring T97A, E138K, G140S and Q148H, with high predicted resistance to all integrase strand transfer inhibitors (INSTIs).

To assess the impact of these substitutions alone and together on phenotypic INSTI susceptibility.

We constructed recombinant NL4.3 viruses harbouring all mutation combinations in the autologous integrase sequence. Viruses were grown in GFP-reporter CD4+ T-cells in the presence of 0.01-1000 nM raltegravir, elvitegravir, dolutegravir, bictegravir, and cabotegravir. Infection was measured by imaging cytometry.

Q148H-containing viruses lacking G140S failed to propagate or mutated in vitro, consistent with fitness costs. Statistically significant reductions in INSTI susceptibility were observed for several mutation combinations, as follows. T97A or G140S alone conferred 3.6- to 5.6-fold decreased susceptibility to raltegravir and elvitegravir. Two-mutation combinations conferred low-to-moderate resistance to rality to all INSTIs when all four mutations are present.

300-fold decreased susceptibility to all INSTIs when all four mutations are present.

There is uncertainty about whether and how to perform screening for atrial fibrillation (AF). SRT2104 To estimate the incidence of previously undetected AF that would be captured using a continuous 14-day ECG monitor and the associated risk of stroke.

We analysed data from a cohort of patients >65 years old with hypertension and a pacemaker, but without known AF. For each participant, we simulated 1000 ECG monitors by randomly selecting 14-day windows in the 6 months following enrolment and calculated the average AF burden (total time in AF). We used Cox proportional hazards models adjusted for CHA2DS2-VASc score to estimate the risk of subsequent ischaemic stroke or systemic embolism (SSE) associated with burdens of AF > and <6 min. Among 2470 participants, the median CHA2DS2-VASc score was 4.0, and 44 patients experienced SSE after 6 months following enrolment. The proportion of participants with an AF burden >6 min was 3.10% (95% CI 2.53-3.72). This was consistent across strata of age and CHA2DS2-VASc scores. Over a mean follow-up of 2.4 years, the rate of SSE among patients with <6 min of AF was 0.70%/year, compared to 2.18%/year (adjusted HR 3.02; 95% CI 1.39-6.56) in those with >6 min of AF.

Approximately 3% of individuals aged >65 years with hypertension may have more than 6 min of AF detected by a 14-day ECG monitor. This is associated with a stroke risk of over 2% per year. Whether oral anticoagulation will reduce stroke in these patients is unknown.

65 years with hypertension may have more than 6 min of AF detected by a 14-day ECG monitor. This is associated with a stroke risk of over 2% per year. Whether oral anticoagulation will reduce stroke in these patients is unknown.Non-Hispanic Black (NHB) and Hispanic patients with acute myeloid leukemia (AML) have higher mortality rates than non-Hispanic White (NHW) patients despite more favorable genetics and younger age. A discrete survival analysis was performed on 822 adult patients with AML from 6 urban cancer centers and revealed inferior survival among NHB (hazard ratio [HR] = 1.59; 95% confidence interval [CI] 1.15, 2.22) and Hispanic (HR = 1.25; 95% CI 0.88, 1.79) patients compared with NHW patients. A multilevel analysis of disparities was then conducted to investigate the contribution of neighborhood measures of structural racism on racial/ethnic differences in survival. Census tract disadvantage and affluence scores were individually calculated. Mediation analysis of hazard of leukemia death between groups was examined across 6 composite variables structural racism (census tract disadvantage, affluence, and segregation), tumor biology (European Leukemia Network risk and secondary leukemia), health care access (insurance and clinical trial enrollment), comorbidities, treatment patterns (induction intensity and transplant utilization), and intensive care unit (ICU) admission during induction chemotherapy. Strikingly, census tract measures accounted for nearly all of the NHB-NHW and Hispanic-NHW disparity in leukemia death. Treatment patterns, including induction intensity and allogeneic transplant, and treatment complications, as assessed by ICU admission during induction chemotherapy, were additional mediators of survival disparities in AML. This is the first study to formally test mediators for observed disparities in AML survival and highlights the need to investigate the mechanisms by which structural racism interacts with known prognostic and treatment factors to influence leukemia outcomes.

The European Association of Cardiovascular Imaging Scientific Initiatives Committee conducted a global survey to evaluate the impact of the 2019 coronavirus disease (COVID-19) pandemic on the mental well-being of cardiac imaging specialists.

In a prospective international survey performed between 23 July 2021 and 31 August 2021, we assessed the mental well-being of cardiac imaging specialists ∼18 months into the COVID-19 pandemic. One-hundred-and-twenty-five cardiac imaging specialists from 34 countries responded to the survey. More than half described feeling anxious during the pandemic, 34% felt melancholic, 27% felt fearful, and 23% respondents felt lonely. A quarter of respondents had increased their alcohol intake and more than half reported difficulties in sleeping. Two-thirds of respondents described worsening features of burnout during the past 18 months, 44% considered quitting their job. One in twenty respondents had experienced suicidal ideation during the pandemic. Despite these important issues, the majority of participants (57%) reported having no access to any formal mental health support at work.

The survey has highlighted important issues regarding the mental well-being of cardiac imaging specialists during the COVID-19 pandemic. This is a major issue in our sub-specialty, which requires urgent action and prioritization so that we can improve the mental health of cardiovascular imaging specialists.

The survey has highlighted important issues regarding the mental well-being of cardiac imaging specialists during the COVID-19 pandemic. This is a major issue in our sub-specialty, which requires urgent action and prioritization so that we can improve the mental health of cardiovascular imaging specialists.

Atrial fibrillation (AF) increases the risk of dementia, and catheter ablation of AF may be associated with a lower risk of dementia. We investigated the association of a rhythm-control strategy for AF with the risk of dementia, compared with a rate-control strategy.

This population-based cohort study included 41,135 patients with AF on anticoagulation who were newly treated with rhythm-control (anti-arrhythmic drugs or ablation) or rate-control strategies between 1 January 2005 and 31 December 2015 from the Korean National Health Insurance Service database. The primary outcome was all-cause dementia, which was compared using propensity score overlap weighting.

In the study population (46.7% female; median age 68years), a total of 4,039 patients were diagnosed with dementia during a median follow-up of 51.7months. Rhythm control, compared with rate control, was associated with decreased dementia risk (weighted incidence rate 21.2 versus 25.2 per 1,000 person-years; subdistribution hazard ratio [sHR] 0.86, 95% confidence interval [CI] 0.80-0.93). The associations between rhythm control and decreased dementia risk were consistently observed even after censoring for incident stroke (sHR 0.89, 95% CI 0.82-0.97) and were more pronounced in relatively younger patients and those with lower CHA2DS2-VASc scores. Among dementia subtypes, rhythm control was associated with a lower risk of Alzheimer's disease (sHR 0.86, 95% CI 0.79-0.95).

Among anticoagulated patients with AF, rhythm control was associated with a lower risk of dementia, compared with rate control. Initiating rhythm control in AF patients with fewer stroke risk factors might help prevent subsequent dementia.

Among anticoagulated patients with AF, rhythm control was associated with a lower risk of dementia, compared with rate control. Initiating rhythm control in AF patients with fewer stroke risk factors might help prevent subsequent dementia.

delirium is common in older emergency department (ED) patients, but vastly under-recognised, in part due to lack of standardised screening processes. Understanding local context and barriers to delirium screening are integral for successful implementation of a delirium screening protocol.

we sought to identify barriers and facilitators to delirium screening by nurses in older ED patients.

we conducted 15 semi-structured, face-to-face interviews based on the Theoretical Domains Framework with bedside nurses, nurse educators and managers at two academic EDs in 2017. Two research assistants independently coded transcripts. Relevant domains and themes were identified.

a total of 717 utterances were coded into 14 domains. Three dominant themes emerged (i) lack of clinical prioritisation because of competing demands, lack of time and heavy workload; (ii) discordance between perceived capabilities and knowledge and (iii) hospital culture.

this qualitative study explored nursing barriers and facilitators to delirium screening in older ED patients. We found that delirium was recognised as an important clinical problem; however, it was not clinically prioritised; there was a false self-perception of knowledge and ability to recognise delirium and hospital culture was a strong influencer of behaviour. Successful adoption of a delirium screening protocol will only be realised if these issues are addressed.

this qualitative study explored nursing barriers and facilitators to delirium screening in older ED patients. We found that delirium was recognised as an important clinical problem; however, it was not clinically prioritised; there was a false self-perception of knowledge and ability to recognise delirium and hospital culture was a strong influencer of behaviour. Successful adoption of a delirium screening protocol will only be realised if these issues are addressed.

Chronic pain is a risk factor contributing to mobility impairment and falls in older adults. Little is known about the patterns of circumstances of falls among older adults with chronicpain.

To examine the relationship between chronic pain and circumstances of falls including location, activities at the time of falls and self-reported causes of falls in older adults.

Prospective cohort study.

Communities in/around Boston, Massachusetts.

The MOBILIZE Boston Study enrolled 765 adults aged ≥70years.

Pain severity, fall occurrence and fall circumstances were recorded using monthly calendar postcards and fall follow-up interviews during a 4-year follow-up period. Generalised estimating equation models were performed to examine the relation between monthly pain ratings and circumstances of the first fall in the subsequent month.

Compared to fallers without chronic pain, fallers with moderate-to-severe pain had around twice the likelihood of reporting indoor falls (aOR = 1.93, 95%CI 1.32-2.83), falls in living or dining rooms (aOR = 2.

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