Dying of lung cancer or cardiac failure: prospective qualitative interview study of patients and their carers in the community

OBJECTIVE: To compare the illness trajectories, needs, and service use of patients with cancer and those with advanced non-malignant disease. DESIGN: Qualitative interviews every three months for up to one year with patients, their carers, and key professional carers. Two multidisciplinary focus groups. SETTING: Community based. PARTICIPANTS: 20 patients with inoperable lung cancer and 20 patients with advanced cardiac failure and their main informal and professional carers. MAIN OUTCOME MEASURES: Perspectives of patients and carers about their needs and available services. RESULTS: 219 qualitative interviews were carried out. Patients with cardiac failure had a different illness trajectory from the more linear and predictable course of patients with lung cancer. Patients with cardiac failure also had less information about and poorer understanding of their condition and prognosis and were less involved in decision making. The prime concern of patients with lung cancer and their carers was facing death. Frustration, progressive losses, social isolation, and the stress of balancing and monitoring a complex medication regimen dominated the lives of patients with cardiac failure. More health and social services including financial benefits were available to those with lung cancer, although they were not always used effectively. Cardiac patients received less health, social, and palliative care services, and care was often poorly coordinated. CONCLUSIONS: Care for people with advanced progressive illnesses is currently prioritised by diagnosis rather than need. End of life care for patients with advanced cardiac failure and other non-malignant diseases should be proactive and designed to meet their specific needs

Ancient Antimicrobial Peptides Kill Antibiotic-Resistant Pathogens: Australian Mammals Provide New Options

Background: To overcome the increasing resistance of pathogens to existing antibiotics the 10× 20 Initiative declared the urgent need for a global commitment to develop 10 new antimicrobial drugs by the year 2020. Naturally occurring animal antibiotics are an obvious place to start. The recently sequenced genomes of mammals that are divergent from human and mouse, including the tammar wallaby and the platypus, provide an opportunity to discover novel antimicrobials. Marsupials and monotremes are ideal potential sources of new antimicrobials because they give birth to underdeveloped immunologically naïve young that develop outside the sterile confines of a uterus in harsh pathogen-laden environments. While their adaptive immune system develops innate immune factors produced either by the mother or by the young must play a key role in protecting the immune-compromised young. In this study we focus on the cathelicidins, a key family of antimicrobial peptide genes. Principal Finding: We identified 14 cathelicidin genes in the tammar wallaby genome and 8 in the platypus genome. The tammar genes were expressed in the mammary gland during early lactation before the adaptive immune system of the young develops, as well as in the skin of the pouch young. Both platypus and tammar peptides were effective in killing a broad range of bacterial pathogens. One potent peptide, expressed in the early stages of tammar lactation, effectively killed multidrug-resistant clinical isolates of Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Conclusions and Significance: Marsupial and monotreme young are protected by antimicrobial peptides that are potent, broad spectrum and salt resistant. The genomes of our distant relatives may hold the key for the development of novel drugs to combat multidrug-resistant pathogens

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Evaluating the suitability of current mitochondrial DNA interpretation guidelines for multigenerational whole mitochondrial genome comparisons

Sanger sequencing of the mitochondrial DNA (mtDNA) control region was previously the only method available for forensic casework involving degraded samples from skeletal remains. The introduction of Next Generation Sequencing (NGS) has transformed genetic data generation and human identification using mtDNA. Whole mitochondrial genome (mtGenome) analysis is now being introduced into forensic laboratories around the world to analyze historical remains. Research into large pedigrees using the mtGenome is critical to evaluate currently available interpretation guidelines for mtDNA analysis, which were developed for comparisons using the control region. This study included mtGenomes from 225 individuals from the last four generations of the Norfolk Island (NI) genetic isolate pedigree consisting of 49 distinct maternal lineages. The data from these individuals were arranged into 2339 maternally related pairs separated by up to 18 meioses. Our results show that 97.3% of maternally related pairs were concordant at all nucleotide positions, resulting in the correct interpretation of “Cannot Exclude”; 2.7% of pairs produced an “Inconclusive” result, and there were no instances of false exclusion. While these results indicate that existing guidelines are suitable for multigenerational whole mtGenome analysis, we recommend caution be taken when classifying heteroplasmic changes as differences for human identification. Our data showed the classification of heteroplasmic changes as differences increases the prevalence of inconclusive identification by 6%, with false exclusions observed in 0.34% of pairs examined. Further studies of multigenerational pedigrees, however, are needed to validate mtGenome interpretation guidelines for historical case work to more fully utilize emerging advancements.</p

The use of off-farm habitats by foraging bumblebees in agricultural landscapes: Implications for conservation management

Recent studies have focused on ways to enhance floral availability on arable farmland, but little attention has been paid to the importance of off-farm habitats in providing forage for pollinators within farmed landscapes. We conducted a comparative study to assess bumblebees and flower abundance on farmed and off-farm habitats in two low-intensity systems in the UK, the Somerset Levels and the Outer Hebrides. In both farming systems, both on- and off-farm habitats contributed to the mosaic of bumblebee forage. In the Somerset Levels, track edges and road verges were particularly important sources of forage for long-tongued bumblebees. Cattle-grazed pasture in Somerset and winter-grazed pasture in the Outer Hebrides were also notable sources of bumblebee forage. Non-agricultural habitats need to be integrated into local land management plans to ensure the provision of forage for bumblebees throughout the breeding season

Restoration and management of machair grassland for the conservation of bumblebees

Machair is a grassland habitat that supports nationally rare species including the bumblebee species Bombus distinguendus and Bombus muscorum. Changes in land management practices have resulted in a loss of floral diversity in some areas, reducing the availability of bumblebee foraging resources. In order to determine the most effective way of increasing forage plant availability on degraded machair, a restoration trial was established in western Scotland and comprised four seed mixes and a fallow treatment. Treatments were monitored over 3 years in order to compare the relative abundance of bumblebees and their forage plants. Two mixes contained wildflower species; one mix is currently used to create bird and bee foraging habitat on nature reserves and the fourth is a commercially available grass mix. There was little variation in inflorescence and bumblebee abundance between treatments early on but marked differences emerged later in the season in all 3 years. By the end of the monitoring period, the wildflower treatments contained between four and eighteen times more inflorescences than other treatment types. Similar trends were observed in bumblebee abundances. Some of the rarest bumblebee species exist primarily in areas that have largely escaped agricultural intensification. In these areas it is important that habitat management is specifically targeted and translated into appropriate agri-environment schemes. We suggest that the most effective method for restoring bumblebee forage plants on machair is to sow wildflower-rich seed mixes and this should be combined with late cutting and winter grazing practices to maintain sward diversity over time