Desperately Seeking Dissonance: Identifying the Disconfirming Case in Qualitative Evidence Synthesis

Actively seeking the disconfirming or deviant case is properly regarded as a hallmark of trustworthiness in primary qualitative research. The need to subject emergent theory to such testing is no less important within qualitative systematic reviews. There is, as yet, little available guidance on how to implement such strategies. Few researchers have described the practicalities of seeking the disconfirming case. We survey the methodological literature to gain a better understanding of how systematic reviews of qualitative research handle the disconfirming case. We reflect on our own experience from three recent qualitative evidence syntheses. We describe how reviewers might actively manufacture opportunities to identify discrepant or refutational findings. We conclude by outlining possible methods by which a team might integrate active seeking of a disconfirming case within the overall review process

High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis

Aims: High-sensitivity cardiac troponin I (cTnI) assays hold promise in detecting the transition from hypertrophy to heart failure in aortic stenosis. We sought to investigate the mechanism for troponin release in patients with aortic stenosis and whether plasma cTnI concentrations are associated with long-term outcome. Methods and results: Plasma cTnI concentrations were measured in two patient cohorts using a high-sensitivity assay. First, in the Mechanism Cohort, 122 patients with aortic stenosis (median age 71, 67% male, aortic valve area 1.0 ± 0.4 cm2) underwent cardiovascular magnetic resonance and echocardiography to assess left ventricular (LV) myocardial mass, function, and fibrosis. The indexed LV mass and measures of replacement fibrosis (late gadolinium enhancement) were associated with cTnI concentrations independent of age, sex, coronary artery disease, aortic stenosis severity, and diastolic function. In the separate Outcome Cohort, 131 patients originally recruited into the Scottish Aortic Stenosis and Lipid Lowering Trial, Impact of REgression (SALTIRE) study, had long-term follow-up for the occurrence of aortic valve replacement (AVR) and cardiovascular deaths. Over a median follow-up of 10.6 years (1178 patient-years), 24 patients died from a cardiovascular cause and 60 patients had an AVR. Plasma cTnI concentrations were associated with AVR or cardiovascular death HR 1.77 (95% CI, 1.22 to 2.55) independent of age, sex, systolic ejection fraction, and aortic stenosis severity. Conclusions: In patients with aortic stenosis, plasma cTnI concentration is associated with advanced hypertrophy and replacement myocardial fibrosis as well as AVR or cardiovascular death

An occupational therapy intervention for residents with stroke related disabilities in UK care homes (OTCH): cluster randomised controlled trial

Objective To evaluate the clinical efficacy of an established programme of occupational therapy in maintaining functional activity and reducing further health risks from inactivity in care home residents living with stroke sequelae. Design Pragmatic, parallel group, cluster randomised controlled trial. Setting 228 care homes (>10 beds each), both with and without the provision of nursing care, local to 11 trial administrative centres across the United Kingdom. Participants 1042 care home residents with a history of stroke or transient ischaemic attack, including those with language and cognitive impairments, not receiving end of life care. 114 homes (n=568 residents, 64% from homes providing nursing care) were allocated to the intervention arm and 114 homes (n=474 residents, 65% from homes providing nursing care) to standard care (control arm). Participating care homes were randomised between May 2010 and March 2012. Intervention Targeted three month programme of occupational therapy, delivered by qualified occupational therapists and assistants, involving patient centred goal setting, education of care home staff, and adaptations to the environment. Main outcome measures Primary outcome at the participant level: scores on the Barthel index of activities of daily living at three months post-randomisation. Secondary outcome measures at the participant level: Barthel index scores at six and 12 months post-randomisation, and scores on the Rivermead mobility index, geriatric depression scale-15, and EuroQol EQ-5D-3L questionnaire, at all time points. Results 64% of the participants were women and 93% were white, with a mean age of 82.9 years. Baseline characteristics were similar between groups for all measures, personal characteristics, and diagnostic tests. Overall, 2538 occupational therapy visits were made to 498 participants in the intervention arm (mean 5.1 visits per participant). No adverse events attributable to the intervention were recorded. 162 (11%) died before the primary outcome time point, and 313 (30%) died over the 12 months of the trial. The primary outcome measure did not differ significantly between the treatment arms. The adjusted mean difference in Barthel index score at three months was 0.19 points higher in the intervention arm (95% confidence interval −0.33 to 0.70, P=0.48). Secondary outcome measures also showed no significant differences at all time points. Conclusions This large phase III study provided no evidence of benefit for the provision of a routine occupational therapy service, including staff training, for care home residents living with stroke related disabilities. The established three month individualised course of occupational therapy targeting stroke related disabilities did not have an impact on measures of functional activity, mobility, mood, or health related quality of life, at all observational time points. Providing and targeting ameliorative care in this clinically complex population requires alternative strategies

The study protocol for a pseudo-randomised pre-post designed controlled intervention trial to study the effects of a 7-week cooking program on self-efficacy and biomarkers of health: the ECU lifestyle and biomarkers get connected study (ECULABJMOF) including the Jamie’s Ministry of Food WA participant experience

Background: Australia, like other nations, has experienced a shift in dietary patterns away from home cooking of nutritious foods, towards a reliance on pre-prepared convenience meals. These are typically energy-dense, nutrient-poor and contribute to the rising prevalence of obesity and chronic disease burden. The aims of this study were to evaluate whether a community-based cooking program instigated a change to participants’ skills, attitudes, knowledge, enjoyment and satisfaction of cooking and cooking confidence (self-efficacy). Methods: The pseudo-random, pre-post study design consisted of an intervention and a control group. Participant recruitment and group allocation was based on their program start dates. Intervention participants were surveyed three times (baseline, 7 weeks and 6 months) and the control group were surveyed at baseline and 5 weeks. All participants were registered via an online website and were 18 years or over. Upon consent, participants were offered four levels of commitment, defined by different assessments. The minimum participation level included an online survey and levels 2, 3 and 4 involved attendance at a clinic with increasing functional, anthropometric and biomarker measurements. Primary endpoints were participants’ cooking confidence as a proxy for self-efficacy. Secondary endpoints were dietary intake, physical activity levels, body composition, anthropometry, blood, urine and faecal biomarkers of systemic, physical and mental health. Discussion: The community cooking program provided participants with information and advice on food sourcing, preparation and nutrition to improve home cooking skills. The study was designed to explore whether food literacy programs are efficacious in improving participant physical health and well-being in order to combat the rise in obesity and diet-related disease. It will support future use of public health cooking program initiatives aimed at improving food literacy, self-efficacy and physical and mental health. The extensive data collected will inform future research into the relationship between diet, the gut-microbiota and human health

The type III secretion system effector SeoC of salmonella enterica subsp. salamae and S. enterica subsp. arizonae ADP-Ribosylates Src and inhibits opsonophagocytosis

Salmonella species utilize type III secretion systems (T3SSs) to translocate effectors into the cytosol of mammalian host cells, subverting cell signaling and facilitating the onset of gastroenteritis. In this study, we compared a draft genome assembly of Salmonella enterica subsp. salamae strain 3588/07 against the genomes of S. enterica subsp. enterica serovar Typhimurium strain LT2 and Salmonella bongori strain 12419. S. enterica subsp. salamae encodes the Salmonella pathogenicity island 1 (SPI-1), SPI-2, and the locus of enterocyte effacement (LEE) T3SSs. Though several key S Typhimurium effector genes are missing (e.g., avrA, sopB, and sseL), S. enterica subsp. salamae invades HeLa cells and contains homologues of S. bongori sboK and sboC, which we named seoC SboC and SeoC are homologues of EspJ from enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively), which inhibit Src kinase-dependent phagocytosis by ADP-ribosylation. By screening 73 clinical and environmental Salmonella isolates, we identified EspJ homologues in S. bongori, S. enterica subsp. salamae, and Salmonella enterica subsp. arizonae The β-lactamase TEM-1 reporter system showed that SeoC is translocated by the SPI-1 T3SS. All the Salmonella SeoC/SboC homologues ADP-ribosylate Src E310 in vitro Ectopic expression of SeoC/SboC inhibited phagocytosis of IgG-opsonized beads into Cos-7 cells stably expressing green fluorescent protein (GFP)-FcγRIIa. Concurrently, S. enterica subsp. salamae infection of J774.A1 macrophages inhibited phagocytosis of beads, in a seoC-dependent manner. These results show that S. bongori, S. enterica subsp. salamae, and S. enterica subsp. arizonae share features of the infection strategy of extracellular pathogens EPEC and EHEC and shed light on the complexities of the T3SS effector repertoires of Enterobacteriaceae

Accelerometer-measured physical activity and sedentary time among children and their parents in the UK before and after COVID-19 lockdowns:a natural experiment

BACKGROUND: Restrictions due to the coronavirus disease 2019 (COVID-19) pandemic reduced physical activity provision for both children and their parents. Recent studies have reported decreases in physical activity levels during lockdown restrictions, but these were largely reliant on self-report methods, with data collected via unrepresentative self-report surveys. The post-pandemic impacts on children’s activity levels remain unknown. A key question is how active children become once lockdown restrictions are lifted. METHODS: Active-6 is a repeated cross-sectional natural experiment. Accelerometer data from 1296 children aged 10–11 and their parents were collected in 50 schools in the Greater Bristol area, UK in March 2017-May 2018 (pre-COVID-19 comparator group), and compared to 393 children aged 10–11 and parents in 23 of the same schools, collected in May-December 2021. Mean minutes of accelerometer-measured moderate-to-vigorous physical activity (MVPA) were derived for weekdays and weekend and compared pre- and post-lockdown via linear multilevel models. RESULTS: After adjusting for seasonality, accelerometer wear time and child/parent demographics, children’s mean weekday and weekend MVPA were 7.7 min (95% CI: 3.5 to 11.9) and 6.9 min (95% CI: 0.9 to 12.9) lower in 2021 than in 2018, respectively, while sedentary time was higher by 25.4 min (95% CI: 15.8 to 35.0) and 14.0 min (95% CI: 1.5 to 26.5). There was no evidence that differences varied by child gender or household education. There was no significant difference in parents’ MVPA or sedentary time, either on weekdays or weekends. CONCLUSIONS: Children’s MVPA was lower by 7–8 min/day in 2021 once restrictions were lifted than before the pandemic for all groups, on both weekdays and weekends. Previous research has shown that there is an undesirable age-related decline in children’s physical activity. The 8-min difference reported here would be broadly comparable to the decline that would have previously been expected to occur over a three-year period. Parents’ physical activity was similar to pre-pandemic levels. Our results suggest that despite easing of restrictions, children’s activity levels have not returned to pre-pandemic levels. There is an urgent need to understand why these changes have occurred and how long they are maintained. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12966-022-01290-4

Syntheses, protonation constants and antimicrobial activity of 2-substituted N-alkylimidazole derivatives

A series of N-alkylimidazole-2-carboxylic acid, N-alkylimidazole-2-carboxaldehyde and N-alkylimidazole-2-methanol derivatives [alkyl = benzyl, methyl, ethyl, propyl, butyl, heptyl, octyl and decyl] have been synthesized and the protonation constants determined. The antimicrobial properties of the compounds were tested against Gram-negative (Escherichi coli), Gram-positive (Staphylococcus aureus and Bacillus subtilis subsp. spizizenii) bacterial strains and yeast (C. albicans). Both the disk diffusion and broth microdilution methods for testing the antimicrobial activity showed that N-alkylation of imidazole with longer alkyl chains and the substitution with low pKa group at 2-position resulted in enhanced antimicrobial activity. Particularly, the N-alkylimidazole-2-carboxylic acids exhibited the best antimicrobial activity due to the low pKa of the carboxylic acid moiety. Generally, all the N-alkylimidazole derivatives were most active against the Gram-positive bacteria [S. aureus (MIC = 5–160 µg mL–1) and B. subtilis subsp. spizizenii (5–20 µg mL–1)], with the latter more susceptible. All the compounds showed poor antimicrobial activity against both Gram-negative (E. coli, MIC = 0.15 to >2500 µg mL–1) bacteria and all the compounds were inactive against the yeast (Candida albicans)