Potential Drug-Drug Interactions in Psychiatric Ward of a Tertiary Care Hospital: Prevalence, Levels and Association with Risk Factors

Purpose: To identify the prevalence of potential drug-drug interactions (pDDIs) in a psychiatric ward, their levels and association with risk factors.Methods: This study was conducted in the psychiatric ward of Ayub Teaching Hospital, Abbottabad, Pakistan. Medical records of 415 patients were retrospectively reviewed for pDDIs using Micromedex Drug-Reax software. Logistic regression was applied to determine association of pDDIs with age, gender, hospital stay and number of drugs.Results: In our study, we identified total number of 825 pDDIs of 126 types, with median number of 1 pDDIs per patient. Overall 64.8 % of the patients had at least one pDDI; 27.2 % at least one major pDDI; and 58.5 % patients at least one moderate pDDI. Among 825 identified pDDIs, most were of moderate (75.6 %) or major (20.8 %) severity, good (66.4 %) or fair (29 %) type of scientific evidence; and delayed onset (71 %). The most frequent major and moderate pDDIs included haloperidol + procyclidine (127 cases), haloperidol + olanzapine (49), haloperidol + promethazine (47), haloperidol + fluphenazine (41), diazepam + divalproex sodium (40), haloperidol + trihexyphenidyl (37), lorazepam + divalproex sodium (34), fluphenazine + procyclidine (33) and olanzapine + divalproex sodium (32). There was significant association of occurrence of pDDIs with hospital stay of 7 days or longer (p = 0.005) and taking 7 or more drugs (p < 0.001).                                                       Conclusion: A high prevalence of pDDIs in the psychiatric ward was recorded, a majority of which were of moderate severity. Patients with long hospital stay and increased number of drugs were more exposed to pDDIs.Keywords: Drug-drug interactions, Potential drug-drug interaction, Prescriptions screening, Drug-related problems, Clinical pharmacy

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Midterm follow-up of composite graft replacement of the aortic root (30-year experience)—remarkably safe, effective, and durableCentral MessagePerspective

Objectives: Contemporary operative choices for aortic root disease include aortic root replacement (ARR) and a variety of valve-sparing and aortic root-repair procedures. We evaluate ultra-long-term outcomes of ARR, focusing on survival, freedom from late reoperation, and adverse events. Methods: Prospectively kept records were used to accomplish long-term follow-up of patients who underwent ARR (4-pronged Yale survival assessment paradigm). Results: Between 1990 and 2020, 564 patients underwent ARR (mean 56 years, 84% male). A modified Cabrol procedure (Dacron coronary graft) was employed in 9.0% (51/564) and concomitant coronary artery bypass grafting in 9.4% (53/564). There were 12.8% (72/564) urgent/emergent and 7.4% (42/564) redo procedures. Operative mortality occurred in 12 patients (2.1%) overall, or 1.4% (8/554) of nondissection and 1.3% (6/468) of elective first-time operations. Six of the 12 deaths presented with acute type A dissection, urgent operation, or reoperative states. Operative mortality dropped to 0.6% during the past 10 years. In total, 11 patients developed endocarditis. Stroke occurred in 11 of 564 patients (2.0%), 4 of whom had presented with type A dissection. Late events included bleeding in 2.8% (16/564), thromboembolism in 1.4% (8/564), and reoperation of the root in 5 of 564 (0.9%) at 15 years and more distal aortic segments in 16/564 (2.8%). Survival was no different from age/sex-matched controls. Conclusions: This ultra-long-term experience finds ARR to be extraordinarily safe, effective, and durable, with minimal long-term bleeding, thromboembolism, or graft failure. This experience provides a standard of durability for ARR against which ultra-long-term outcomes with alternate procedures (valve-sparing, Ross, other) may be compared