ABSTRACT
Previous research shows that manipulations (e.g. levels-of-processing) that facilitate true memory often increase susceptibility to false memory. An exception is the generation effect. Using the Deese/Roediger-McDermott (DRM) paradigm, Soraci et al. found that generating rather than reading list items led to an increase in true but not false memories. They argued that generation led to enhanced item-distinctiveness that drove down false memory production. In the current study, we investigated the effects of generative processing on valenced stimuli and after a delayed retention interval to examine factors that may lead to a generation effect that increases false memories. At the immediate test, false recognition rates for both negative and neutral valanced critical lures were similar across read and generate conditions. However, after a one-week delay, we saw a valence differentiation, with a generation effect for false recognition but only for negative stimuli. The roles of item-specific and relational processing during encoding and their interaction with long-term retention are discussed.
Subject(s)
Memory , Recognition, Psychology , Humans , Emotions , Reading , Repression, Psychology , Mental RecallABSTRACT
BACKGROUND: Significant improvements in mortality among patients with non-small cell lung cancer (NSCLC) in the USA over the past two decades have been reported based on Surveillance, Epidemiology, and End Results (SEER) data. The timing of these improvements led to suggestions that they result from the introduction of new treatments; however, few studies have directly investigated this. The aim of this study was to investigate the extent to which population level improvements in survival of advanced and/or metastatic NSCLC (admNSCLC) patients were associated with changes in treatment patterns. METHODS: We utilized a de-identified database to select three cohorts of patients with admNSCLC: (1) patients with non-oncogene (EGFR/ALK/ROS1/BRAF) positive tumors, (2) patients with ALK-positive (ALK+) tumors, and (3) patients with EGFR-positive (EGFR+) tumors. All patients were diagnosed with admNSCLC between 2012 and 2019. Multivariable Cox models adjusting for baseline characteristics and receipt of targeted and immunotherapy were utilized to explore the relationship between these variables and changes in the hazard of death by calendar year in each cohort. RESULTS: We included 28,154 admNSCLC patients with non-oncogene positive tumors, 598 with ALK+ tumors, and 2464 with EGFR+ tumors eligible for analysis. After adjustment for differences in baseline characteristics, the hazard of death in patients who had non-oncogene positive tumors diagnosed in 2015, 2016, 2017, 2018 ,and 2019 was observed to be 12%, 11%, 17%, 20%, and 21% lower respectively than that for those diagnosed in 2012. Upon additionally adjusting for receipt of first line or second line immunotherapy, the decrease in the hazard of death by calendar year was no longer observed, suggesting improvements in survival observed over time may be explained by the introduction of these treatments. Similarly, decreases in the hazard of death were only observed in patients with ALK+ tumors diagnosed between 2017 and 2019 relative to 2012 but were no longer observed following adjustment for the use of 1st and later generation ALK inhibitors. Among patients with EGFR+ tumors, the hazard of death did not improve significantly over time. CONCLUSION: Our findings expand on the SEER data and provide additional evidence suggesting improvements in survival of patients with advanced and metastatic NSCLC over the past decade could be explained by the change in treatment patterns over this period.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/therapy , Humans , Immunotherapy , Lung Neoplasms/therapy , Mutation , Protein-Tyrosine Kinases , Proto-Oncogene Proteins/geneticsABSTRACT
Assessing the risk of tick-borne disease in areas with high visitor numbers is important from a public health perspective. Evidence suggests that tick presence, density, infection prevalence and the density of infected ticks can vary between habitats within urban green space, suggesting that the risk of Lyme borreliosis transmission can also vary. This study assessed nymph density, Borrelia prevalence and the density of infected nymphs across a range of habitat types in nine parks in London which receive millions of visitors each year. Ixodes ricinus were found in only two of the nine locations sampled, and here they were found in all types of habitat surveyed. Established I. ricinus populations were identified in the two largest parks, both of which had resident free-roaming deer populations. Highest densities of nymphs (15.68 per 100 m2) and infected nymphs (1.22 per 100 m2) were associated with woodland and under canopy habitats in Richmond Park, but ticks infected with Borrelia were found across all habitat types surveyed. Nymphs infected with Borrelia (7.9%) were only reported from Richmond Park, where Borrelia burgdorferi sensu stricto and Borrelia afzelii were identified as the dominant genospecies. Areas with short grass appeared to be less suitable for ticks and maintaining short grass in high footfall areas could be a good strategy for reducing the risk of Lyme borreliosis transmission to humans in such settings. In areas where this would create conflict with existing practices which aim to improve and/or meet historic landscape, biodiversity and public access goals, promoting public health awareness of tick-borne disease risks could also be utilised.
Subject(s)
Borrelia burgdorferi Group , Borrelia burgdorferi , Deer , Ixodes , Lyme Disease , Animals , London/epidemiology , Lyme Disease/epidemiology , Nymph , United KingdomABSTRACT
AIM: To assess the comparative effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors, sulphonylureas (SUs) and dipeptidyl peptidase-4 (DPP-4) inhibitors on cardiometabolic risk factors in routine care. MATERIALS AND METHODS: Using primary care data on 10 631 new users of SUs, SGLT2 inhibitors or DPP-4 inhibitors added to metformin, obtained from the UK Clinical Practice Research Datalink, we created propensity-score matched cohorts and used linear mixed models to describe changes in glycated haemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), systolic blood pressure (BP) and body mass index (BMI) over 96 weeks. RESULTS: HbA1c levels fell substantially after treatment intensification for all drugs: mean change at week 12: SGLT2 inhibitors: -15.2 mmol/mol (95% confidence interval [CI] -16.9, -13.5); SUs: -14.3 mmol/mol (95% CI -15.5, -13.2); and DPP-4 inhibitors: -11.9 mmol/mol (95% CI -13.1, -10.6). Systolic BP fell for SGLT2 inhibitor users throughout follow-up, but not for DPP-4 inhibitor or SU users: mean change at week 12: SGLT2 inhibitors: -2.3 mmHg (95% CI -3.8, -0.8); SUs: -0.8 mmHg (95% CI -1.9, +0.4); and DPP-4 inhibitors: -0.9 mmHg (95% CI -2.1,+0.2). BMI decreased for SGLT2 inhibitor and DPP-4 inhibitor users, but not SU users: mean change at week 12: SGLT2 inhibitors: -0.7 kg/m2 (95% CI -0.9, -0.5); SUs: 0.0 kg/m2 (95% CI -0.3, +0.2); and DPP-4 inhibitors: -0.3 kg/m2 (95% CI -0.5, -0.1). eGFR fell at 12 weeks for SGLT2 inhibitor and DPP-4 inhibitor users. At 60 weeks, the fall in eGFR from baseline was similar for each drug class. CONCLUSIONS: In routine care, SGLT2 inhibitors had greater effects on cardiometabolic risk factors than SUs. Routine care data closely replicated the effects of diabetes drugs on physiological variables measured in clinical trials.
Subject(s)
Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Metformin , Sodium-Glucose Transporter 2 Inhibitors , Symporters , Cohort Studies , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases , Glucose , Humans , Hypoglycemic Agents/adverse effects , Metformin/adverse effects , Primary Health Care , Sodium , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , United Kingdom/epidemiologyABSTRACT
In this paper we, twin sisters, present a joint autoethnographic account of providing end of life care for our mum who had terminal cancer. Using the theoretical framing of performance from Goffman's theory of Dramaturgy, we present the findings from a joint autoethnography, focusing on two key themes: performing emotion work and performing what we conceptualise as 'dignity work'. This paper's contributions are twofold. First, conceptually, this paper offers an important contribution to literature concerned with the sociology of illness, by critically engaging with Goffman's notion of frontstage and backstage performance, applied to the context of home care provided by family carers. The second contribution of this paper is methodological; we promote the under-utilised approach of a joint autoethnography and argue for its usefulness in the context of end of life care. We contend that the process of writing this paper was emotionally challenging, yet arriving at the final paper, which serves as a legacy of our mum, was cathartic. We argue for the usefulness of written diaries as a backstage arena through which other informal carers can think through, and come to terms with, experiences of death and dying.
Subject(s)
Respect , Terminal Care , Caregivers , Death , Emotions , HumansABSTRACT
The perspective of domiciliary workers is needed to recruit a high-quality workforce and meet growing demand. An English ethnographic study yielded extensive insights. To structure analysis of the study data, we apply a method developed by political theorists Boltanski and Thévenot that identifies key variables in different values systems. This "orders of worth" framework is used to map out the distinctive features of the subjective world of home carers. The results can be drawn on to formulate recruitment and retention policies, to design reward strategies or to ensure that training and education opportunities engage effectively with the workforce.
Subject(s)
Attitude of Health Personnel , Dementia/nursing , Dementia/psychology , Home Care Services , Home Health Aides/psychology , Personnel Selection/methods , Adult , Female , Humans , Male , Middle AgedABSTRACT
Recent research has shown that memory illusions can successfully prime both children's and adults' performance on complex, insight-based problems (compound remote associates tasks or CRATs). The current research aimed to clarify the locus of these priming effects. Like before, Deese-Roediger-McDermott (DRM) lists were selected to prime subsequent CRATs such that the critical lures were also the solution words to a subset of the CRATs participants attempted to solve. Unique to the present research, recognition memory tests were used and participants were either primed during the list study phase, during the memory test phase, or both. Across two experiments, primed problems were solved more frequently and significantly faster than unprimed problems. Moreover, when participants were primed during the list study phase, subsequent solution times and rates were considerably superior to those produced by those participants who were simply primed at test. Together, these are the first results to show that false-memory priming during encoding facilitates problem-solving in both children and adults.
Subject(s)
Adaptation, Psychological/physiology , Memory/physiology , Repression, Psychology , Adolescent , Age Factors , Child , Female , Humans , Male , Young AdultABSTRACT
Following domestication, livestock breeds have experienced intense selection pressures for the development of desirable traits. This has resulted in a large diversity of breeds that display variation in many phenotypic traits, such as coat colour, muscle composition, early maturity, growth rate, body size, reproduction, and behaviour. To better understand the relationship between genomic composition and phenotypic diversity arising from breed development, the genomes of 13 traditional and commercial European pig breeds were scanned for signatures of diversifying selection using the Porcine60K SNP chip, applying a between-population (differentiation) approach. Signatures of diversifying selection between breeds were found in genomic regions associated with traits related to breed standard criteria, such as coat colour and ear morphology. Amino acid differences in the EDNRB gene appear to be associated with one of these signatures, and variation in the KITLG gene may be associated with another. Other selection signals were found in genomic regions including QTLs and genes associated with production traits such as reproduction, growth, and fat deposition. Some selection signatures were associated with regions showing evidence of introgression from Asian breeds. When the European breeds were compared with wild boar, genomic regions with high levels of differentiation harboured genes related to bone formation, growth, and fat deposition.
Subject(s)
Breeding , Sus scrofa , Animals , Genome , Genomics , Phenotype , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Selection, Genetic , Sus scrofa/genetics , SwineABSTRACT
INTRODUCTION: Lung cancer is one of the most prevalent cancers and the leading cause of cancer death. Advanced non-small cell lung cancer (aNSCLC) patients frequently harbor mutations that impact their survival outcomes. There are limited data regarding the prognostic and predictive significance of these mutations on survival outcomes in the real-world setting. METHODS: This observational retrospective study analyzed de-identified electronic medical records from the Flatiron Health Clinico-Genomic and FoundationCore® databases to identify patients with aNSCLC who initiated first-line immune checkpoint inhibitors (ICI; alone or in combination) or chemotherapy under routine care between 2016 and 2021. The primary objectives were to assess the prevalence of non-actionable mutations and to determine their association with overall survival (OS). Real-world progression-free survival (rwPFS) and real-world response (rwR) were investigated as secondary exploratory outcomes. RESULTS: Based on an assessment of 185 non-actionable mutations in 2999 patients, the most prevalent mutations were TP53 (70%), KRAS (42%), CDKN2A/B (31%), and STK11 (21%). STK11, KEAP1, and CDKN2A/B mutations were significantly associated with lower rwR, shorter rwPFS and OS. KRAS mutations were clinically associated with shorter rwPFS in CIT-treated patients. Subgroup analysis revealed that fast progressors were significantly more likely to harbor STK11, KEAP1, and CDKN2A/B mutations. Accordingly, long-term survivors (LTS) showed a significantly lower prevalence of these mutations. CONCLUSION: Our results provide evidence on the prognostic value of STK11, KEAP1, and CDKN2A/B mutations in patients with aNSCLC. Further research is required to better understand the implications of these findings on patient management and future trial design and treatment selection.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Mutation , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Lung Neoplasms/drug therapy , Retrospective Studies , Male , Female , Prognosis , Aged , Middle Aged , Protein Serine-Threonine Kinases/genetics , AMP-Activated Protein Kinase Kinases , Kelch-Like ECH-Associated Protein 1/genetics , Immune Checkpoint Inhibitors/therapeutic use , Cyclin-Dependent Kinase Inhibitor p16/genetics , Progression-Free Survival , Proto-Oncogene Proteins p21(ras)/genetics , Tumor Suppressor Protein p53/genetics , Aged, 80 and over , Adult , Survival RateABSTRACT
BACKGROUND: The application of DNA markers for the identification of biological samples from both human and non-human species is widespread and includes use in food authentication. In the food industry the financial incentive to substituting the true name of a food product with a higher value alternative is driving food fraud. This applies to British pork products where products derived from traditional pig breeds are of premium value. The objective of this study was to develop a genetic assay for regulatory authentication of traditional pig breed-labelled products in the porcine food industry in the United Kingdom. RESULTS: The dataset comprised of a comprehensive coverage of breed types present in Britain: 460 individuals from 7 traditional breeds, 5 commercial purebreds, 1 imported European breed and 1 imported Asian breed were genotyped using the PorcineSNP60 beadchip. Following breed-informative SNP selection, assignment power was calculated for increasing SNP panel size. A 96-plex assay created using the most informative SNPs revealed remarkably high genetic differentiation between the British pig breeds, with an average FST of 0.54 and Bayesian clustering analysis also indicated that they were distinct homogenous populations. The posterior probability of assignment of any individual of a presumed origin actually originating from that breed given an alternative breed origin was > 99.5% in 174 out of 182 contrasts, at a test value of log(LR) > 0. Validation of the 96-plex assay using independent test samples of known origin was successful; a subsequent survey of market samples revealed a high level of breed label conformity. CONCLUSION: The newly created 96-plex assay using selected markers from the PorcineSNP60 beadchip enables powerful assignment of samples to traditional breed origin and can effectively identify mislabelling, providing a highly effective tool for DNA analysis in food forensics.
Subject(s)
Breeding , Food Analysis/methods , Animals , DNA/analysis , Genetic Markers , Genetic Variation , Meat/analysis , Phylogeny , Polymorphism, Single Nucleotide , Sus scrofa/classification , Sus scrofa/genetics , United KingdomABSTRACT
OBJECTIVES: COVID-19 has resulted in the greatest disruption to National Health Service (NHS) care in its over 70-year history. Building on our previous work, we assessed the ongoing impact of pandemic-related disruption on provision of emergency and elective hospital-based care across Scotland over the first year of the pandemic. DESIGN: We undertook interrupted time-series analyses to evaluate the impact of ongoing pandemic-related disruption on hospital NHS care provision at national level and across demographics and clinical specialties spanning the period 29 March 2020-28 March 2021. SETTING: Scotland, UK. PARTICIPANTS: Patients receiving hospital care from NHS Scotland. MAIN OUTCOME MEASURES: We used the percentage change of accident and emergency attendances, and emergency and planned hospital admissions during the pandemic compared to the average admission rate for equivalent weeks in 2018-2019. RESULTS: As restrictions were gradually lifted in Scotland after the first lockdown, hospital-based admissions increased approaching pre-pandemic levels. Subsequent tightening of restrictions in September 2020 were associated with a change in slope of relative weekly admissions rate: -1.98% (-2.38, -1.58) in accident and emergency attendance, -1.36% (-1.68, -1.04) in emergency admissions and -2.31% (-2.95, -1.66) in planned admissions. A similar pattern was seen across sex, socioeconomic status and most age groups, except children (0-14 years) where accident and emergency attendance, and emergency admissions were persistently low over the study period. CONCLUSIONS: We found substantial disruption to urgent and planned inpatient healthcare provision in hospitals across NHS Scotland. There is the need for urgent policy responses to address continuing unmet health needs and to ensure resilience in the context of future pandemics.
Subject(s)
COVID-19 , Patient Admission , Child , Humans , Infant, Newborn , Infant , Child, Preschool , Adolescent , Pandemics , State Medicine , COVID-19/epidemiology , Communicable Disease Control , Hospitals , Scotland/epidemiology , Emergency Service, HospitalABSTRACT
Genomic technologies for livestock and companion animal species have revolutionized the study of animal domestication, allowing an increasingly detailed description of the genetic changes accompanying domestication and breed development. This review describes important recent results derived from the application of population and quantitative genetic approaches to the study of genetic changes in the major domesticated species. These include findings of regions of the genome that show between-breed differentiation, evidence of selective sweeps within individual genomes and signatures of demographic events. Particular attention is focused on the study of the genetics of behavioural traits and the implications for domestication. Despite the operation of severe bottlenecks, high levels of inbreeding and intensive selection during the history of domestication, most domestic animal species are genetically diverse. Possible explanations for this phenomenon are discussed. The major insights from the surveyed studies are highlighted and directions for future study are suggested.
Subject(s)
Animals, Domestic/genetics , Behavior, Animal , Genetic Variation , Genetics, Population , Genomics/methods , Phenotype , Selection, Genetic , Animals , Genotype , Population DynamicsABSTRACT
Meals have long been considered relevant units of feeding behavior. Large data sets of feeding behavior of cattle, pigs, chickens, ducks, turkeys, dolphins, and rats were analyzed with the aims of 1) describing the temporal structure of feeding behavior and 2) developing appropriate methods for estimating meal criteria. Longer (between-meal) intervals were never distributed as the negative exponential assumed by traditional methods, such as log-survivorship analysis, but as a skewed Gaussian, which can be (almost) normalized by log-transformation of interval lengths. Log-transformation can also normalize frequency distributions of within-meal intervals. Meal criteria, i.e., the longest interval considered to occur within meals, can be estimated after fitting models consisting of Gaussian functions alone or of one Weibull and one or more Gaussian functions to the distribution of log-transformed interval lengths. Nonuniform data sets may require disaggregation before this can be achieved. Observations from all species were in conflict with assumptions of random behavior that underlie traditional methods for criteria estimation. Instead, the observed structure of feeding behavior is consistent with 1) a decrease in satiety associated with an increase in the probability of animals starting a meal with time since the last meal and 2) an increase in satiation associated with an increase in the probability of animals ending a meal with the amount of food already consumed. The novel methodology proposed here will avoid biased conclusions from analyses of feeding behavior associated with previous methods and, as demonstrated, can be applied across a range of species to address questions relevant to the control of food intake.
Subject(s)
Cattle/physiology , Feeding Behavior/physiology , Models, Biological , Models, Statistical , Animals , Birds/physiology , Dolphins/physiology , Female , Rats , Swine/physiology , Time FactorsABSTRACT
BACKGROUND: Genetic markers can be used to identify and verify the origin of individuals. Motivation for the inference of ancestry ranges from conservation genetics to forensic analysis. High density assays featuring Single Nucleotide Polymorphism (SNP) markers can be exploited to create a reduced panel containing the most informative markers for these purposes. The objectives of this study were to evaluate methods of marker selection and determine the minimum number of markers from the BovineSNP50 BeadChip required to verify the origin of individuals in European cattle breeds. Delta, Wright's FST, Weir & Cockerham's FST and PCA methods for population differentiation were compared. The level of informativeness of each SNP was estimated from the breed specific allele frequencies. Individual assignment analysis was performed using the ranked informative markers. Stringency levels were applied by log-likelihood ratio to assess the confidence of the assignment test. RESULTS: A 95% assignment success rate for the 384 individually genotyped animals was achieved with <80, <100, <140 and <200 SNP markers (with increasing stringency threshold levels) across all the examined methods for marker selection. No further gain in power of assignment was achieved by sampling in excess of 200 SNP markers. The marker selection method that required the lowest number of SNP markers to verify the animal's breed origin was Wright's FST (60 to 140 SNPs depending on the chosen degree of confidence). Certain breeds required fewer markers (<100) to achieve 100% assignment success. In contrast, closely related breeds require more markers (~200) to achieve>95% assignment success. The power of assignment success, and therefore the number of SNP markers required, is dependent on the levels of genetic heterogeneity and pool of samples considered. CONCLUSIONS: While all SNP selection methods produced marker panels capable of breed identification, the power of assignment varied markedly among analysis methods. Thus, with effective exploration of available high density genetic markers, a diagnostic panel of highly informative markers can be produced.
Subject(s)
Animal Identification Systems/methods , Cattle/genetics , Genetic Markers , Polymorphism, Single Nucleotide , Animals , Gene Frequency , GenotypeABSTRACT
The effects of embedding standard Deese/Roediger-McDermott (DRM) lists into stories whose context biased interpretation either toward or away from the overall themes of the DRM lists on both true and false recognition were investigated with 7- and 11-year-olds. These biased story contexts were compared with the same children's susceptibility to false memory illusions using the standard DRM list presentation paradigm. The results showed the usual age effects for true and false memories in the standard DRM list paradigm, where 11-year-olds exhibited higher rates of both true and false recognition compared with the 7-year-olds. Importantly, when DRM lists were embedded in stories, these age effects disappeared for true recognition. For false recognition, although developmental differences were attenuated, older children were still more susceptible to false memory illusions than younger children. These findings are discussed in terms of current theories of children's false memories as well as the role of themes and elaboration in children's memory development.
Subject(s)
Illusions , Memory , Child , Child Development , Female , Humans , Male , Narration , Repression, PsychologyABSTRACT
Importance: Quantitative assessment of bias from unmeasured confounding and missing data can help evaluate uncertainty in findings from indirect comparisons using real-world data (RWD). Objective: To compare the effectiveness of alectinib vs ceritinib in terms of overall survival (OS) in patients with ALK-positive, crizotinib-refractory, non-small cell lung cancer (NSCLC) and to assess the sensitivity of these findings to unmeasured confounding and missing data assumptions. Design, Setting, and Participants: This comparative effectiveness research study compared patients from 2 phase 2 alectinib trials and real-world patients. Patients were monitored from June 2013 to March 2020. Comparisons of interest were between alectinib trial data vs ceritinib RWD and alectinib RWD vs ceritinib RWD. RWD treatment groups were selected from nationally representative cancer data from US cancer clinics, the majority from community centers. Participants were ALK-positive patients aged 18 years or older with advanced NSCLC, prior exposure to crizotinib, and Eastern Cooperative Oncology Group Performance Status (PS) of 0 to 2. Data analysis was performed from October 2020 to March 2021. Exposures: Initiation of alectinib or ceritinib therapy. Main Outcomes and Measures: The main outcome was OS. Results: In total, there were 355 patients: 183 (85 men [46.4%]) in the alectinib trial, 91 (43 men [47.3%]) in the ceritinib RWD group, and 81 (38 men [46.9%]) in the alectinib RWD group. Patients in the alectinib trial were younger (mean [SD] age, 52.53 [11.18] vs 57.97 [11.71] years), more heavily pretreated (mean [SD] number of prior therapy lines, 1.95 [0.72] vs 1.47 [0.81]), and had more favorable baseline ECOG PS (ECOG PS of 0 or 1, 165 patients [90.2%] vs 37 patients [77.1%]) than those in the ceritinib RWD group. The alectinib RWD group (mean [SD] age, 58.69 [11.26] years) had more patients with favorable ECOG PS (ECOG PS of 0 or 1, 49 patients [92.4%] vs 37 patients [77.1%]) and more White patients (56 patients [72.7%] vs 53 patients [62.4%]) compared with the ceritinib group. Compared with ceritinib RWD, alectinib-exposed patients had significantly longer OS in alectinib trials (adjusted hazard ratio [HR], 0.59; 95% CI, 0.44-0.75; P < .001) and alectinib RWD (HR, 0.46; 95% CI, 0.29-0.63; P < .001) after adjustment for baseline confounders. For the worst-case HR estimate of 0.59, residual confounding by a hypothetical confounder associated with mortality and treatment by a risk ratio greater than 2.24 was required to reverse the findings. Conclusions were robust to plausible deviations from random missingness for missing ECOG PS and underrecorded comorbidities and central nervous system metastases in RWD. Conclusions and Relevance: Alectinib exposure was associated with longer OS compared with ceritinib in patients with ALK-positive NSCLC, and only substantial levels of bias examined reversed the findings. These findings suggest that quantitative bias analysis can be a useful tool to address uncertainty of findings for decision-makers considering RWD.
Subject(s)
Anaplastic Lymphoma Kinase/analysis , Carbazoles/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Piperidines/pharmacology , Pyrimidines/pharmacology , Sulfones/pharmacology , Anaplastic Lymphoma Kinase/blood , Anaplastic Lymphoma Kinase/drug effects , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Carbazoles/administration & dosage , Humans , Piperidines/administration & dosage , Proportional Hazards Models , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/pharmacology , Pyrimidines/administration & dosage , Sulfones/administration & dosage , Survival AnalysisABSTRACT
INTRODUCTION: For people with type 2 diabetes mellitus (T2DM) who require an antidiabetic drug as an add-on to metformin, there is controversy about whether newer drug classes such as dipeptidyl peptidase-4 inhibitors (DPP4i) or sodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce the risk of long-term complications compared with sulfonylureas (SU). There is widespread variation across National Health Service Clinical Commissioning Groups (CCGs) in drug choice for second-line treatment in part because National Institute for Health and Care Excellence guidelines do not specify a single preferred drug class, either overall or within specific patient subgroups. This study will evaluate the relative effectiveness of the three most common second-line treatments in the UK (SU, DPP4i and SGLT2i as add-ons to metformin) and help target treatments according to individual risk profiles. METHODS AND ANALYSIS: The study includes people with T2DM prescribed one of the second-line treatments-of-interest between 2014 and 2020 within the UK Clinical Practice Research Datalink linked with Hospital Episode Statistics and Office of National Statistics. We will use an instrumental variable (IV) method to estimate short-term and long-term relative effectiveness of second-line treatments according to individuals' risk profiles. This method minimises bias from unmeasured confounders by exploiting the natural variation in second-line prescribing across CCGs as an IV for the choice of prescribed treatment. The primary outcome to assess short-term effectiveness will be change in haemoglobin A1c (%) 12 months after treatment initiation. Outcome measures to assess longer-term effectiveness (maximum ~6 years) will include microvascular and macrovascular complications, all-cause mortality and hospital admissions during follow-up. ETHICS AND DISSEMINATION: This study was approved by the Independent Scientific Advisory Committee (20-064) and the London School of Hygiene & Tropical Medicine Research Ethics Committee (21395). Results, codelists and other analysis code will be made available to patients, clinicians, policy-makers and researchers.
Subject(s)
Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Metformin , Cohort Studies , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Humans , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Observational Studies as Topic , Precision Medicine , State MedicineABSTRACT
BACKGROUND: By creating a dichotomy between those who are 'out-of-control' 'binge drinkers' and those for whom alcohol contributes to friendship fun, academic and alcohol policy literature often fail to acknowledge the nuances in the diverse drinking practices of men. METHODS: This paper engages with findings from a multiple qualitative method research project (comprising of individual and friendship group interviews; diaries; and participant observation), conducted with 16 young men, aged 15-24: eight living in the middle-class area of Chorlton, and eight living in the working-class area of Wythenshawe, Manchester, United Kingdom. RESULTS: This paper provides fine-grained insights into the doings, complexities and contradictions of masculinity in the context of drinking. Young men are shown to tap into different co-existing versions of masculinity, one of which is based on the exclusion of femininity (i.e. they act as tough guys), while another version is more inclusive (i.e. it allows for displays of care). CONCLUSION: This paper shows a much more complex image of young men's drinking practices than has hitherto been conceptualised in the existing literature, and brings to the fore doings of alternative masculinities. This has important implications for alcohol policy interventions targeting men, in that the complexities and contradictions of masculinity in relation to drinking must be taken seriously.
Subject(s)
Alcohol Drinking , Masculinity , Adolescent , Adult , Alcohol Drinking/epidemiology , Friends , Humans , Male , Qualitative Research , United Kingdom , Young AdultABSTRACT
Homecare workers provide essential physical, social and emotional support to growing numbers of older people with dementia in the UK. Although it is acknowledged that the work can sometimes be demanding, some homecare workers regularly 'go the extra mile' for service users, working above and beyond the usual remit of the job. This form of voluntarism has been interpreted as an expression of an essentially caring nature, but also as the product of a work environment structured to tacitly endorse the provision of unpaid labour. This paper draws on a qualitative study of what constitutes 'good' homecare for older people with dementia. Using homecare workers' reflexive diaries (n = 11) and interviews with homecare workers (n = 14) and managers (n = 6), we explore manifestations of, and motivations for, homecare workers going the extra mile in their everyday work. We describe three modes of voluntary labour based on these accounts which we characterise as affective, performative and pragmatic. Our study highlights the complex relationships between job satisfaction, social benefit and commercial gain in the homecare work sector. Further research is needed to define the full range of affective and technical skills necessary to deliver good homecare, and to ensure that homecare work is appropriately credited.
Subject(s)
Dementia , Home Care Services , Home Health Aides , Aged , Aged, 80 and over , Humans , Qualitative ResearchABSTRACT
OBJECTIVE: To provide a description of the Imperial College Mortality Surveillance System and subsequent investigations by the Care Quality Commission (CQC) in National Health Service (NHS) hospitals receiving mortality alerts. BACKGROUND: The mortality surveillance system has generated monthly mortality alerts since 2007, on 122 individual diagnosis and surgical procedure groups, using routinely collected hospital administrative data for all English acute NHS hospital trusts. The CQC, the English national regulator, is notified of each alert. This study describes the findings of CQC investigations of alerting trusts. METHODS: We carried out (1) a descriptive analysis of alerts (2007-2016) and (2) an audit of CQC investigations in a subset of alerts (2011-2013). RESULTS: Between April 2007 and October 2016, 860 alerts were generated and 76% (654 alerts) were sent to trusts. Alert volumes varied over time (range: 40-101). Septicaemia (except in labour) was the most commonly alerting group (11.5% alerts sent). We reviewed CQC communications in a subset of 204 alerts from 96 trusts. The CQC investigated 75% (154/204) of alerts. In 90% of these pursued alerts, trusts returned evidence of local case note reviews (140/154). These reviews found areas of care that could be improved in 69% (106/154) of alerts. In 25% (38/154) trusts considered that identified failings in care could have impacted on patient outcomes. The CQC investigations resulted in full trust action plans in 77% (118/154) of all pursued alerts. CONCLUSION: The mortality surveillance system has generated a large number of alerts since 2007. Quality of care problems were found in 69% of alerts with CQC investigations, and one in four trusts reported that failings in care may have an impact on patient outcomes. Identifying whether mortality alerts are the most efficient means to highlight areas of substandard care will require further investigation.