Undergraduate antimicrobial stewardship training for pharmacy students: Creating a foundation for containment of antimicrobial resistance in South Africa

To the Editor: The inappropriate and excessive use of antimicrobial agents has cultivated the development and progression of antimicrobial resistance worldwide, which has been recognised as a threat to global health and safety.[1] In response to this alarming growth in antimicrobial resistance, antimicrobial stewardship initiatives, which aim to improve the judicious use of antimicrobial agents, have gained global support.[2] The Antimicrobial Resistance Strategy Framework in South Africa (SA) recognises the education of healthcare professionals as a strategy for containment of antimicrobial resistance in SA.[3

Magnetic resonance enterography compared with ultrasonography in newly diagnosed and relapsing Crohn's disease patients: the METRIC diagnostic accuracy study

Magnetic resonance enterography and enteric ultrasonography are used to image Crohn's disease patients. Their diagnostic accuracy for presence, extent and activity of enteric Crohn's disease was compared. To compare diagnostic accuracy, observer variability, acceptability, diagnostic impact and cost-effectiveness of magnetic resonance enterography and ultrasonography in newly diagnosed or relapsing Crohn's disease. Prospective multicentre cohort study. Eight NHS hospitals. Consecutive participants aged ≥ 16 years, newly diagnosed with Crohn's disease or with established Crohn's disease and suspected relapse. Magnetic resonance enterography and ultrasonography. The primary outcome was per-participant sensitivity difference between magnetic resonance enterography and ultrasonography for small bowel Crohn's disease extent. Secondary outcomes included sensitivity and specificity for small bowel Crohn's disease and colonic Crohn's disease extent, and sensitivity and specificity for small bowel Crohn's disease and colonic Crohn's disease presence; identification of active disease; interobserver variation; participant acceptability; diagnostic impact; and cost-effectiveness. Out of the 518 participants assessed, 335 entered the trial, with 51 excluded, giving a final cohort of 284 (133 and 151 in new diagnosis and suspected relapse cohorts, respectively). Across the whole cohort, for small bowel Crohn's disease extent, magnetic resonance enterography sensitivity [80%, 95% confidence interval (CI) 72% to 86%] was significantly greater than ultrasonography sensitivity (70%, 95% CI 62% to 78%), with a 10% difference (95% CI 1% to 18%;  = 0.027). For small bowel Crohn's disease extent, magnetic resonance enterography specificity (95%, 95% CI 85% to 98%) was significantly greater than ultrasonography specificity (81%, 95% CI 64% to 91%), with a 14% difference (95% CI 1% to 27%). For small bowel Crohn's disease presence, magnetic resonance enterography sensitivity (97%, 95% CI 91% to 99%) was significantly greater than ultrasonography sensitivity (92%, 95% CI 84% to 96%), with a 5% difference (95% CI 1% to 9%). For small bowel Crohn's disease presence, magnetic resonance enterography specificity was 96% (95% CI 86% to 99%) and ultrasonography specificity was 84% (95% CI 65% to 94%), with a 12% difference (95% CI 0% to 25%). Test sensitivities for small bowel Crohn's disease presence and extent were similar in the two cohorts. For colonic Crohn's disease presence in newly diagnosed participants, ultrasonography sensitivity (67%, 95% CI 49% to 81%) was significantly greater than magnetic resonance enterography sensitivity (47%, 95% CI 31% to 64%), with a 20% difference (95% CI 1% to 39%). For active small bowel Crohn's disease, magnetic resonance enterography sensitivity (96%, 95% CI 92% to 99%) was significantly greater than ultrasonography sensitivity (90%, 95% CI 82% to 95%), with a 6% difference (95% CI 2% to 11%). There was some disagreement between readers for both tests. A total of 88% of participants rated magnetic resonance enterography as very or fairly acceptable, which is significantly lower than the percentage (99%) of participants who did so for ultrasonography. Therapeutic decisions based on magnetic resonance enterography alone and ultrasonography alone agreed with the final decision in 122 out of 158 (77%) cases and 124 out of 158 (78%) cases, respectively. There were no differences in costs or quality-adjusted life-years between tests. Magnetic resonance enterography and ultrasonography scans were interpreted by practitioners blinded to clinical data (but not participant cohort), which does not reflect use in clinical practice. Magnetic resonance enterography has higher accuracy for detecting the presence, extent and activity of small bowel Crohn's disease than ultrasonography does. Both tests have variable interobserver agreement and are broadly acceptable to participants, although ultrasonography produces less participant burden. Diagnostic impact and cost-effectiveness are similar. Recommendations for future work include investigation of the comparative utility of magnetic resonance enterography and ultrasonography for treatment response assessment and investigation of non-specific abdominal symptoms to confirm or refute Crohn's disease. Current Controlled Trials ISRCTN03982913. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 23, No. 42. See the NIHR Journals Library website for further project information

A simplified (modified) Duke Activity Status Index (M-DASI) to characterise functional capacity: A secondary analysis of the Measurement of Exercise Tolerance before Surgery (METS) study

Background Accurate assessment of functional capacity, a predictor of postoperative morbidity and mortality, is essential to improving surgical planning and outcomes. We assessed if all 12 items of the Duke Activity Status Index (DASI) were equally important in reflecting exercise capacity. Methods In this secondary cross-sectional analysis of the international, multicentre Measurement of Exercise Tolerance before Surgery (METS) study, we assessed cardiopulmonary exercise testing and DASI data from 1455 participants. Multivariable regression analyses were used to revise the DASI model in predicting an anaerobic threshold (AT) >11 ml kg −1 min −1 and peak oxygen consumption (VO 2 peak) >16 ml kg −1 min −1, cut-points that represent a reduced risk of postoperative complications. Results Five questions were identified to have dominance in predicting AT>11 ml kg −1 min −1 and VO 2 peak>16 ml.kg −1min −1. These items were included in the M-DASI-5Q and retained utility in predicting AT>11 ml.kg −1.min −1 (area under the receiver-operating-characteristic [AUROC]-AT: M-DASI-5Q=0.67 vs original 12-question DASI=0.66) and VO 2 peak (AUROC-VO2 peak: M-DASI-5Q 0.73 vs original 12-question DASI 0.71). Conversely, in a sensitivity analysis we removed one potentially sensitive question related to the ability to have sexual relations, and the ability of the remaining four questions (M-DASI-4Q) to predict an adequate functional threshold remained no worse than the original 12-question DASI model. Adding a dynamic component to the M-DASI-4Q by assessing the chronotropic response to exercise improved its ability to discriminate between those with VO 2 peak>16 ml.kg −1.min −1 and VO 2 peak<16 ml.kg −1.min −1. Conclusions The M-DASI provides a simple screening tool for further preoperative evaluation, including with cardiopulmonary exercise testing, to guide perioperative management

Pulmonary Function and Blood DNA Methylation A Multiancestry Epigenome-Wide Association Meta-analysis

Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication. Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function. Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV1, FVC, and FEV1/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics. Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery rate,,0.025) in relation to FEV1, FVC, or FEV1/FVC, including 1,240 novel and 73 also related to chronic obstructive pulmonary disease (1,787 cases). We found 294 CpGs unique to European or African ancestry and 395 CpGs unique to never or ever smokers. The majority of significant CpGs correlated with nearby gene expression in blood. Findings were enriched in key regulatory elements for gene function, including accessible chromatin elements, in both blood and lung. Sixty-nine implicated genes are targets of investigational or approved drugs. One example novel gene highlighted by integrative epigenomic and druggable target analysis is TNFRSF4. Mendelian randomization and colocalization analyses suggest that epigenome-wide association study signals capture causal regulatory genomic loci. Conclusions: We identified numerous novel loci differentially methylated in relation to pulmonary function; few were detected in large genome-wide association studies. Integrative analyses highlight functional relevance and potential therapeutic targets. This comprehensive discovery of potentially modifiable, novel lung function loci expands knowledge gained from genetic studies, providing insights into lung pathogenesis

Assessment of the impact of irrigation with low-quality mine water on virgin and rehabilitated soils in the Upper Olifants Basin

Low-quality mine water from collieries may be used in large quantities to irrigate agricultural crops on virgin (unmined) and rehabilitated soils in South Africa. Such a use could enhance crop production and allow environmentally sustainable mine water disposal. In this study, the volume and qualities of the runoff from two centre pivots irrigated with moderately saline mine water, as well as their soil water salinities, were monitored and used to determine water and salt balances, using the modified ACRU agrohydrological model, ACRU2000, and its salinity module, ACRUSalinity. At both sites, much of the water evaporated, while a significant part of the salt input either recipitated or remained with the water in the soil horizons. A higher percentage of drainage water (and salinity) were retained as ground water storage and a lower percentage of runoff occurred in the rehabilitated sandy loam soil, while a higher percentage of salts accompanied runoff in the virgin clayey soils. Simulated salt saturation values indicate that many crops could be successfully irrigated at 100% yield potential at either site. Electrical resistivity surveys were carried out at both sites. A general decrease in resistivities with depth in both the virgin and rehabilitated soils reflected the decreasing influence of the mine water used for irrigation with depth and the precipitation of salts in the soils close to the ground surface. The occurrence of a thicker, low- resistivity, near-surface layer near the exit of each pivot area indicates that the water and salt content of the subsurface increased in the direction that the surface and near-surface irrigation water flowed

Comparative assessment of widespread irrigation with low quality mine-water in undisturbed and rehabilitated mine-lands in the upper Olifants using the ACRU2000 model

The ACRU agrohydrological model, in the form of ACRU2000 and its salinity module, ACRUSalinity, was employed in catchment-scale assessment of widespread irrigation with low quality mine-water in undisturbed (un-mined) and rehabilitated soils in the Upper Olifants basin of South Africa. The study area comprised a small catchment of 4.7 km2 located in a coal-mine environment, known as the Tweefontein Pan catchment. The catchment drained to a surface reservoir (Tweefontein Reservoir) of maximum capacity and surface area 4 000 Mℓ and 1.5 km2, respectively. The catchment was instrumented to measure hydrodynamic responses and simulated as a hydrological system. Consideration was given to runoff, groundwater storage, evapotranspiration, baseflow, interception, irrigation water supply and rainfall, thereby accounting for all the dominant hydrological components of the system. Three scenarios were simulated using the available records for 5 years (1999 to 2004). The first was a baseline scenario representing the prevailing condition in the study area and the other 2 scenarios represented widespread irrigation with the mine-water on undisturbed and rehabilitated soils. In simulating the widespread irrigation on rehabilitated soils, a distinction was made between a rehabilitated irrigated area before and after the re-establishment of the equilibrium water table. Comparison of the results from the simulated scenarios indicated that a greater undisturbed area (max of 160 ha) than rehabilitated area (max of 120 ha) could be irrigated with mine-water from the Tweefontein Reservoir. Irrigation on rehabilitated soils depleted the water in the reservoir more rapidly than irrigation on undisturbed soils, due to lower runoff and higher ingress to groundwater in rehabilitated areas.Keywords: mine-water, widespread irrigation, mined land irrigation, Upper Olifants, catchment scale, hydrological assessment, ACRU200

Assessment of the impact of irrigation with low-quality mine water on virgin and rehabilitated soils in the upper Olifants basin

Low-quality mine water from collieries may be used in large quantities to irrigate agricultural crops on virgin (unmined) and rehabilitated soils in South Africa. Such a use could enhance crop production and allow environmentally sustainable mine water disposal. In this study, the volume and qualities of the runoff from two centre pivots irrigated with moderately saline mine water, as well as their soil water salinities, were monitored and used to determine water and salt balances, using the modified ACRU agrohydrological model, ACRU2000, and its salinity module, ACRUSalinity. At both sites, much of the water evaporated, while a significant part of the salt input either precipitated or remained with the water in the soil horizons. A higher percentage of drainage water (and salinity) were retained as ground water storage and a lower percentage of runoff occurred in the rehabilitated sandy loam soil, while a higher percentage of salts accompanied runoff in the virgin clayey soils. Simulated salt saturation values indicate that many crops could be successfully irrigated at 100% yield potential at either site. Electrical resistivity surveys were carried out at both sites. A general decrease in resistivities with depth in both the virgin and rehabilitated soils reflected the decreasing influence of the mine water used for irrigation with depth and the precipitation of salts in the soils close to the ground surface. The occurrence of a thicker, low-resistivity, near-surface layer near the exit of each pivot area indicates that the water and salt content of the subsurface increased in the direction that the surface and near-surface irrigation water flowed

Comparative assessment of widespread irrigation with low quality mine-water in undisturbed and rehabilitated mine-lands in the upper Olifants using the ACRU2000 model

The ACRU agrohydrological model, in the form of ACRU2000 and its salinity module, ACRUSalinity, was employed in catchment-scale assessment of widespread irrigation with low quality mine-water in undisturbed (un-mined) and rehabilitated soils in the Upper Olifants basin of South Africa. The study area comprised a small catchment of 4.7 km2 located in a coal-mine environment, known as the Tweefontein Pan catchment. The catchment drained to a surface reservoir (Tweefontein Reservoir) of maximum capacity and surface area 4 000 Mℓ and 1.5 km2, respectively. The catchment was instrumented to measure hydrodynamic responses and simulated as a hydrological system. Consideration was given to runoff, groundwater storage, evapotranspiration, baseflow, interception, irrigation water supply and rainfall, thereby accounting for all the dominant hydrological components of the system. Three scenarios were simulated using the available records for 5 years (1999 to 2004). The first was a baseline scenario representing the prevailing condition in the study area and the other 2 scenarios represented widespread irrigation with the mine-water on undisturbed and rehabilitated soils. In simulating the widespread irrigation on rehabilitated soils, a distinction was made between a rehabilitated irrigated area before and after the re-establishment of the equilibrium water table. Comparison of the results from the simulated scenarios indicated that a greater undisturbed area (max of 160 ha) than rehabilitated area (max of 120 ha) could be irrigated with mine-water from the Tweefontein Reservoir. Irrigation on rehabilitated soils depleted the water in the reservoir more rapidly than irrigation on undisturbed soils, due to lower runoff and higher ingress to groundwater in rehabilitated areas