Impaired Cardiac and Skeletal Muscle Energetics Following Anthracycline Therapy for Breast Cancer

Acknowledgments The fellow (Dr Gamble) recruited participants, scheduled, coordinated, and performed all clinical imaging investigations, patients skeletal muscle biopsies and venesection, conducted mitochondrial copy number analysis of muscle biopsies under supervision, analyzed all data, performed statistical analyses under supervision, and drafted this article. H. Khan and A. Rudd helped with the investigations and reviewed and contributed to this article. S. Baliga provided the healthy volunteer skeletal muscle biopsies. Dr Ross designed and developed the protocol for cardiac and skeletal muscle spectroscopy. L. Cheyne supervised muscle biopsy analyses. Drs Unger and Linke performed the skeletal muscle transmission electron microscopy and immunofluorescence confocal microscopy investigations. Dr Horgan is the study statistician. Drs Urquhart, Masannat, Elsberger, Fuller, Mustafa, and Sharma identified and recruited participants and reviewed and contributed to this article. Drs Hannah, Sharma, and Saunders contributed to the design of the study. D. Dawson (PI) designed the study, obtained funding (together with Drs Sharma and Masannat) and regulatory approvals, supervised the unfolding of the study, its analyses and revised the article drafts. Sources of Funding Tenovus Scotland G18.01, D. Dawson and Dr Sharma, Friends of Anchor 2019, Grampian National Health Service-Endowments (Drs Sharma and Masannat), British Health Foundation PG/18/35/33786 to D. Dawson funded DG salary and BHF FS/RTF/20/30009 to D. Dawson funded AR salary.Peer reviewedPublisher PD

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Cardiovascular disease behavioural risk factors in rural interventions: cross-sectional study

Abstract This study aims to (1) assess the distribution of variables within the population and the prevalence of cardiovascular disease (CVD) behavioural risk factors in patients, (2) identify target risk factor(s) for behaviour modification intervention, and (3) develop an analytical model to define cluster(s) of risk factors which could help make any generic intervention more targeted to the local patient population. Study patients with at least one CVD behavioural risk factor living in a rural region of the Scottish Highlands. The study used the STROBE methodology for cross-sectional studies. Demographic and clinical data of patients (n = 2025) in NHS Highlands hospital were collected at the point of admission for PCI between 04.01.2016 and 31.12.2019. Collected data distributions were analysed by CVD behavioural risk factors for prevalence, associations, and direction of associations. Cluster definition was measured by assignment of a unit score each for the overall level of prevalence and significance of associations, and general logistics modelling for direction and significance of the risk. The mean (SD) age was 69.47(± 10.93) years [95% CI (68.99–69.94)]. The key risk factors were hyperlipidaemia, hypertension, and elevated body mass index (BMI). Approximately 40% of the population have multiple risk factor counts of two. Analytical measures revealed a population risk factor cluster with elevated BMI [77.5% (1570/2025)] that is mostly either hyperlipidaemic [9.43%, co-eff. (17), P = 0.007] or hypertensive [22.72%, co-eff. (17), P = 0.99] as key risk factor clusters. Carefully modelled analyses revealed clustered risk associated with elevated BMI. This information would support a strategy for targeting risk factor clusters in novel interventions to improve implementation efficiency. Exposure to and outcome of an elevated BMI is linked more to the population’s socio-economic outcomes rather than to regional rurality or urbanity

Cardiovascular Disease Behavioural Risk Factors in Rural Interventions: Cross-Sectional Study.

Abstract Aims:This study aims to 1) assess the prevalence of cardiovascular disease (CVD) behavioural risk factors in patients who have undergone percutaneous coronary intervention (PCI) 2) identify target risk factor(s) for behaviour modification intervention, and 3) develop an analytical model to define cluster(s) of risk factors which could help make any generic intervention more targeted to the local patient population.Subject and Methods:Study patients with at least one CVD behavioural risk factors living in a rural region. The study used STROBE methodology for cross-sectional studies. Demographic and clinical data of patients (n=2025) were collected at the point of admission for PCI between 04.01.2016 to 31.12.2019. Collected data distributions were analysed by CVD behavioural risk factors for prevalence, associations, and direction of associations. Cluster definition was measured by assignment of a unit score each for overall level of prevalence and significance of associations, and general logistics modelling for direction and significance of risk.Results:The mean (SD) age was 69.47(±10.93) years [95% CI (68.99 - 69.94)]. The key risk factors were hyperlipidaemia, hypertension, and elevated body mass index (BMI). Approximately 40% of the population have multiple risk factor counts of two. Analytical measures revealed a population risk factor cluster with elevated BMI [77.5% (1570/2025)] that is mostly either hyperlipidaemic [9.43%, co-eff. (17), P=.007] or hypertensive [22.72%, co-eff. (17), P=.99] as key risk factor clusters.Conclusion:Carefully modelled analyses revealed clustered behavioural risk associated with elevated BMI. This information would support a strategy for applying targeted clusters in novel interventions to improve implementation efficiency.Conclusion: Risk factors, cardiovascular disease, obesity, and percutaneous coronary intervention.</jats:p

Diagnostic accuracy of Xpert MTB/RIF Ultra and culture assays to detect Mycobacterium Tuberculosis using OMNIgene-sputum processed stool among adult TB presumptive patients in Uganda.

BackgroundStool is a potential sample for diagnosing Mycobacterium tuberculosis (Mtb) in patients with difficulty in expectorating. However, high mycobacterial culture contamination rates and Xpert MTB/RIF Ultra test error rates on stool samples have limited its use. OMNIgene SPUTUM (OM-S) is a sample transport reagent with characteristics of sputum decontamination while maintaining viable Mtb. We evaluated the impact of OM-S on Mtb diagnostic yield from stool using smear microscopy, Xpert MTB/RIF Ultra, and culture among presumptive TB patients.MethodsPaired stool and expectorated sputum samples were collected from consecutive Ugandan adults undergoing diagnostic evaluation for pulmonary TB between June 2018 and June 2019. Stool was divided into 2 portions: one was homogenized in OM-S (OM-S stool) and the other in PBS (PBS stool) as control. Both sputum and processed stool were tested for Mtb using concentrated smear fluorescence microscopy (CFM), Xpert MTB/RIF Ultra (Xpert) and Mycobacteria Growth Indicator Tube (MGIT) culture. Sensitivity, specificity, and predictive values for each test were calculated against sputum MGIT culture as the reference standard.ResultsOf the 200 participants, 120 (60%) were male, 73 (37%) were HIV positive (median CD4 120 cells/uL (IQR 43-297)) and 128 (64%) had confirmed pulmonary TB by sputum MGIT culture. Seven (4%) OM-S stool Xpert samples reported errors while 47 (25%) and 103 (61%) were contaminated on OM-S stool MGIT and PBS stool MGIT, respectively. OM-S stool MGIT was able to accurately diagnose 56 of the contaminated PBS stool MGIT samples compared to only 5 of the contaminated OM-S stool MGIT samples diagnosed by PBS stool MGIT. Sensitivity (95% Confidence Interval, CI) 89% (83-94) for OM-S stool Xpert was higher compared to that of OM-S stool MGIT 60% (51-69) and PBS stool MGIT 42% (32-52). Specificity (95%CI) 91% (82-97) was also higher for OM-S stool Xpert compared to OM-S stool MGIT 64% (51-75) and PBS stool MGIT 26% (16-38).ConclusionStool processed with OM-S showed potential to improve Mtb diagnostic yield and reduce rates of indeterminate results when tested on Xpert and MGIT culture. The method may thus be of value in Mtb detection among patients with difficulty to expectorate

Diagnostic accuracy of Xpert MTB/RIF Ultra and culture assays to detect <i>Mycobacterium Tuberculosis</i> using OMNIgene-sputum processed stool among adult TB presumptive patients in Uganda

Background Stool is a potential sample for diagnosing Mycobacterium tuberculosis (Mtb) in patients with difficulty in expectorating. However, high mycobacterial culture contamination rates and Xpert MTB/RIF Ultra test error rates on stool samples have limited its use. OMNIgene SPUTUM (OM-S) is a sample transport reagent with characteristics of sputum decontamination while maintaining viable Mtb. We evaluated the impact of OM-S on Mtb diagnostic yield from stool using smear microscopy, Xpert MTB/RIF Ultra, and culture among presumptive TB patients. Methods Paired stool and expectorated sputum samples were collected from consecutive Ugandan adults undergoing diagnostic evaluation for pulmonary TB between June 2018 and June 2019. Stool was divided into 2 portions: one was homogenized in OM-S (OM-S stool) and the other in PBS (PBS stool) as control. Both sputum and processed stool were tested for Mtb using concentrated smear fluorescence microscopy (CFM), Xpert MTB/RIF Ultra (Xpert) and Mycobacteria Growth Indicator Tube (MGIT) culture. Sensitivity, specificity, and predictive values for each test were calculated against sputum MGIT culture as the reference standard. Results Of the 200 participants, 120 (60%) were male, 73 (37%) were HIV positive (median CD4 120 cells/uL (IQR 43–297)) and 128 (64%) had confirmed pulmonary TB by sputum MGIT culture. Seven (4%) OM-S stool Xpert samples reported errors while 47 (25%) and 103 (61%) were contaminated on OM-S stool MGIT and PBS stool MGIT, respectively. OM-S stool MGIT was able to accurately diagnose 56 of the contaminated PBS stool MGIT samples compared to only 5 of the contaminated OM-S stool MGIT samples diagnosed by PBS stool MGIT. Sensitivity (95% Confidence Interval, CI) 89% (83–94) for OM-S stool Xpert was higher compared to that of OM-S stool MGIT 60% (51–69) and PBS stool MGIT 42% (32–52). Specificity (95%CI) 91% (82–97) was also higher for OM-S stool Xpert compared to OM-S stool MGIT 64% (51–75) and PBS stool MGIT 26% (16–38). Conclusion Stool processed with OM-S showed potential to improve Mtb diagnostic yield and reduce rates of indeterminate results when tested on Xpert and MGIT culture. The method may thus be of value in Mtb detection among patients with difficulty to expectorate

Diagnostic accuracy of Xpert MTB/RIF Ultra and culture assays to detect Mycobacterium Tuberculosis using OMNIgene-sputum processed stool among adult TB presumptive patients in Uganda

BackgroundStool is a potential sample for diagnosing Mycobacterium tuberculosis (Mtb) in patients with difficulty in expectorating. However, high mycobacterial culture contamination rates and Xpert MTB/RIF Ultra test error rates on stool samples have limited its use. OMNIgene SPUTUM (OM-S) is a sample transport reagent with characteristics of sputum decontamination while maintaining viable Mtb. We evaluated the impact of OM-S on Mtb diagnostic yield from stool using smear microscopy, Xpert MTB/RIF Ultra, and culture among presumptive TB patients.MethodsPaired stool and expectorated sputum samples were collected from consecutive Ugandan adults undergoing diagnostic evaluation for pulmonary TB between June 2018 and June 2019. Stool was divided into 2 portions: one was homogenized in OM-S (OM-S stool) and the other in PBS (PBS stool) as control. Both sputum and processed stool were tested for Mtb using concentrated smear fluorescence microscopy (CFM), Xpert MTB/RIF Ultra (Xpert) and Mycobacteria Growth Indicator Tube (MGIT) culture. Sensitivity, specificity, and predictive values for each test were calculated against sputum MGIT culture as the reference standard.ResultsOf the 200 participants, 120 (60%) were male, 73 (37%) were HIV positive (median CD4 120 cells/uL (IQR 43-297)) and 128 (64%) had confirmed pulmonary TB by sputum MGIT culture. Seven (4%) OM-S stool Xpert samples reported errors while 47 (25%) and 103 (61%) were contaminated on OM-S stool MGIT and PBS stool MGIT, respectively. OM-S stool MGIT was able to accurately diagnose 56 of the contaminated PBS stool MGIT samples compared to only 5 of the contaminated OM-S stool MGIT samples diagnosed by PBS stool MGIT. Sensitivity (95% Confidence Interval, CI) 89% (83-94) for OM-S stool Xpert was higher compared to that of OM-S stool MGIT 60% (51-69) and PBS stool MGIT 42% (32-52). Specificity (95%CI) 91% (82-97) was also higher for OM-S stool Xpert compared to OM-S stool MGIT 64% (51-75) and PBS stool MGIT 26% (16-38).ConclusionStool processed with OM-S showed potential to improve Mtb diagnostic yield and reduce rates of indeterminate results when tested on Xpert and MGIT culture. The method may thus be of value in Mtb detection among patients with difficulty to expectorate

Study profile showing participants included and excluded from the study and total number and outcome of the OM-S stool samples per index test.

Legend:MGIT, Mycobacteria Growth Indicator Tube; OM-S, OMNIgene SPUTUM, Pos, Positive; Neg, Negative; Cont, Contaminated.</p