A Structure-Based Approach for Mapping Adverse Drug Reactions to the Perturbation of Underlying Biological Pathways

Adverse drug reactions (ADR), also known as side-effects, are complex undesired physiologic phenomena observed secondary to the administration of pharmaceuticals. Several phenomena underlie the emergence of each ADR; however, a dominant factor is the drug's ability to modulate one or more biological pathways. Understanding the biological processes behind the occurrence of ADRs would lead to the development of safer and more effective drugs. At present, no method exists to discover these ADR-pathway associations. In this paper we introduce a computational framework for identifying a subset of these associations based on the assumption that drugs capable of modulating the same pathway may induce similar ADRs. Our model exploits multiple information resources. First, we utilize a publicly available dataset pairing drugs with their observed ADRs. Second, we identify putative protein targets for each drug using the protein structure database and in-silico virtual docking. Third, we label each protein target with its known involvement in one or more biological pathways. Finally, the relationships among these information sources are mined using multiple stages of logistic-regression while controlling for over-fitting and multiple-hypothesis testing. As proof-of-concept, we examined a dataset of 506 ADRs, 730 drugs, and 830 human protein targets. Our method yielded 185 ADR-pathway associations of which 45 were selected to undergo a manual literature review. We found 32 associations to be supported by the scientific literature

Obstructive Sleep Apnea in Elective Spine Surgery: National Prevalence and Inpatient Outcomes

Patients with OSA were, on average 2.6 years older than those without OSA (P < .001) and had a higher comorbidity burden. The prevalence of OSA increased between 2008 and 2012 from 3.5% to 6.8%; P < .001. OSA was associated with a 3-fold increase in major complications (P < .001) and was confirmed as an independent risk factor for major complications based on multivariate analysis (odds ratio [OR] = 2.82; 95% CI = 2.59-2.79; P < .001). Rates of deep venous thrombosis were doubled in patients with OSA. OSA was determined to be an independent predictor of pulmonary complications (OR = 2.69; 95% CI = 2.59-2.79; P < .001). OSA did not increase the risk of postoperative mortality.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The influence of foot position on stretching of the plantar fascia

Background: A recent study found nonweightbearing stretching exercises specific to the plantar fascia to be superior to the standard program of weightbearing Achilles tendon-stretching exercises in patients with chronic plantar fasciitis. The present study used a cadaver model to demonstrate the influence of foot and ankle position on stretching of the plantar fascia. Methods: Twelve fresh-frozen lower-leg specimens were tested in 15 different configurations representing various combinations of ankle and metatarsophalangeal (MTP) joint dorsiflexion, midtarsal transverse plane abduction and adduction, and forefoot varus and valgus. Measurements were recorded by a differential variable reluctance transducer (DVRT) implanted into the medial band of the plantar fascia, and primary measurement was a percent deformation of the plantar fascia (stretch) with respect to a reference position (90 degrees ankle dorsiflexion, 0 degrees midtarsal and forefoot orientation, and 0 degrees MTP dorsiflexion). Results: Ankle and MTP joint dorsiflexion produced a significant increase (14.91%) in stretch compared to the position of either ankle dorsiflexion alone (9.31 % increase, p \u3c 0.001) or MTP dorsiflexion alone (7.33% increase, p \u3c 0.01). There was no significant increase in stretch with positions of abduction or varus (2.49%, p = 0.27 and 0.55%, p = 0.79). Conclusion: This study provides a mechanical explanation for enhanced outcomes in recent clinical trials using plantar fascia tissue-specific stretching exercises and lends support to the use of ankle and MTP joint dorsiflexion when employing stretching protocols for nonoperative treatment in patients with chronic proximal plantar fasciitis. Copyright ©2007 by the American Orthopaedic Foot & Ankle Society, Inc

Risk factors for postoperative delirium in orthopaedic hip surgery patients: a database review.

BACKGROUND: Postoperative delirium is a common problem affecting admitted patients that decreases patient satisfaction and increases the cost and complexity of care. The purpose of this study was to use the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to compare rates and risk factors of postoperative delirium for total hip arthroplasty (THA) and hemiarthroplasty patients indicated for osteoarthritis or proximal femur fracture. METHODS: The 2021 NSQIP database was queried for patients using Current Procedural Terminology (CPT) codes for THA and hemiarthroplasty and ICD-10 codes for osteoarthritis or proximal femur fracture. Demographic, past medical history, preoperative labs, and functional status data were recorded. Procedural data were also collected. Finally, postoperative outcomes and complications were reviewed. RESULTS: Overall, 16% of patients had postoperative delirium. Delirium patients were older on average (82.4 years vs. 80.7 years, p &lt; 0.001), had a lower BMI (19.5 vs. 24.8, p &lt; 0.001), were more likely to have a history of dementia (54.6% vs. 13.6%, p &lt; 0.001), were less likely to have an independent functional status (p &lt; 0.001) or live alone (p &lt; 0.001), and were more likely to have sustained a recent fall (p &lt; 0.001). Delirium patients were more likely to be hyponatremic or hypernatremic (p = 0.002), anemic (p &lt; 0.001), and severely dehydrated (p &lt; 0.001), among other lab abnormalities. Delirium patients were also more likely to experience additional postoperative complications, including pneumonia, pulmonary embolism, urinary tract infection, stroke, cardiac arrest, sepsis, and unplanned reoperation and readmission after discharge (all p &lt; 0.05). CONCLUSIONS: In this study, factors associated with postoperative delirium in patients undergoing hemiarthroplasty and THA were identified, including older age, lower BMI, certain medical conditions, decreased functional status, certain lab abnormalities, and postoperative complications. These findings can be used by clinicians to better inform care and to determine when orthopaedic joint replacement patients may be at an increased risk for postoperative delirium