Baseline characteristics including blood and urine metal levels in the Trial to Assess Chelation Therapy 2 (TACT2).

BACKGROUND: The reduction in cardiovascular disease (CVD) events with edetate disodium (EDTA) in the Trial to Assess Chelation Therapy (TACT) suggested that chelation of toxic metals might provide novel opportunities to reduce CVD in patients with diabetes. Lead and cadmium are vasculotoxic metals chelated by EDTA. We present baseline characteristics for participants in TACT2, a randomized, double-masked, placebo-controlled trial designed as a replication of the TACT trial limited to patients with diabetes. METHODS: TACT2 enrolled 1,000 participants with diabetes and prior myocardial infarction, age 50 years or older between September 2016 and December 2020. Among 959 participants with at least one infusion, 933 had blood and/or urine metals measured at the Centers for Diseases Control and Prevention using the same methodology as in the National Health and Nutrition Examination Survey (NHANES). We compared metal levels in TACT2 to a contemporaneous subset of NHANES participants with CVD, diabetes and other inclusion criteria similar to TACT2's participants. RESULTS: At baseline, the median (interquartile range, IQR) age was 67 (60, 72) years, 27% were women, 78% reported white race, mean (SD) BMI was 32.7 (6.6) kg/m2, 4% reported type 1 diabetes, 46.8% were treated with insulin, 22.3% with GLP1-receptor agonists or SGLT-2 inhibitors, 90.2% with aspirin, warfarin or P2Y12 inhibitors, and 86.5% with statins. Blood lead was detectable in all participants; median (IQR) was 9.19 (6.30, 13.9) µg/L. Blood and urine cadmium were detectable in 97% and median (IQR) levels were 0.28 (0.18, 0.43) µg/L and 0.30 (0.18, 0.51) µg/g creatinine, respectively. Metal levels were largely similar to those in the contemporaneous NHANES subset. CONCLUSIONS: TACT2 participants were characterized by high use of medication to treat CVD and diabetes and similar baseline metal levels as in the general US population. TACT2 will determine whether chelation therapy reduces the occurrence of subsequent CVD events in this high-risk population. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov. Identifier: NCT02733185. https://clinicaltrials.gov/study/NCT02733185.

The NIDDK Diabetic Foot Consortium.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diabetic Foot Consortium (DFC) was established in September 2018 by the NIDDK to build an organization to facilitate the highest quality of clinical research on diabetic foot ulcers (DFUs) that will answer clinically significant questions to improve DFU healing and prevent amputations. The initial focus of the DFC is to develop and validate biomarkers for DFUs that can be used in clinical care and research. The DFC consists of a data coordinating center (DCC) for operational oversight and statistical analysis, clinical sites for participant recruitment and evaluation, and biomarker analysis units (BAUs). The DFC is currently studying biomarkers to predict wound healing and recurrence and is collecting biosamples for future studies through a biorepository. The DFC plans to address the challenges of recruitment and eligibility criteria for DFU clinical trials by taking an approach of "No DFU Patient Goes Unstudied." In this platform approach, clinical history, DFU outcome, wound imaging, and biologic measurements from a large number of patients will be captured and the in-depth longitudinal data set will be analyzed to develop a computational-based DFU risk factor profile to facilitate scientifically sound clinical trial design. The DFC will expand its platform to include studies of the role of social determinants of health, such as food insecurity, housing instability, limited health literacy, and poor social support. The DFC is starting partnerships with the broad group of stakeholders in the wound care community.

Pain Catastrophizing Influences Preoperative and Postoperative Patient-Reported Outcomes in Adolescent Idiopathic Scoliosis.

BACKGROUND: Patients with adolescent idiopathic scoliosis (AIS) often report chronic back pain; however, there is inadequate research on psychological factors associated with pain in this patient population. Pain catastrophizing, a psychological factor that describes a pattern of negative thoughts and feelings about pain, has been associated with poorer responses to medical treatment for pain. The purpose of this study was to report the prevalence of pain catastrophizing in the AIS population and assess its relationship with preoperative and postoperative self-reported outcomes. METHODS: In this prospective cohort study of consecutive patients undergoing posterior spinal fusion (PSF) for AIS, patients experiencing clinically relevant pain catastrophizing, defined as a Pain Catastrophizing Scale for Children (PCS) score in the 75th percentile or higher, were compared with patients with normal PCS scores. Preoperative and 2-year postoperative Scoliosis Research Society Society Questionnaire-30 (SRS-30) scores were correlated with the preoperative PCS score. RESULTS: One hundred and eighty-nine patients underwent PSF for AIS, and 20 (10.6%) were considered to be experiencing pain catastrophizing. Despite comparable demographic and radiographic variables, pain catastrophizing was associated with significantly lower preoperative scores than were found in the normal-PCS group in all SRS-30 domains, including pain (2.98 versus 3.95; p < 0.001), appearance (2.98 versus 3.48; p < 0.001), activity (3.51 versus 4.06; p < 0.001), mental health (3.12 versus 4.01; p < 0.001), and total score (3.18 versus 3.84; p < 0.001), except satisfaction (3.72 versus 3.69; p > 0.999). At 2 years, the pain catastrophizing group experienced significant improvement from their preoperative scores in most SRS-30 domains, including a large clinically relevant improvement in pain (from 2.98 preoperatively to 3.84 postoperatively; p < 0.001) and the total score (from 3.18 to 3.85; p < 0.001), but continued to have lower scores than the normal-PCS group for pain (3.84 versus 4.22; p = 0.028) and the total score (3.85 versus 4.15; p = 0.038). Receiver operating characteristic (ROC) curve analysis indicated that an SRS-30 pain score of <3.5 has good sensitivity for predicting pain catastrophizing (PCS ≥75th percentile). CONCLUSIONS: In this cohort, patients with AIS who exhibited pain catastrophizing experienced significant improvement in self-reported health 2 years after PSF. However, they did not have the same levels of self-reported health as the normal-PCS group. Pain catastrophizing may be identifiable by lower preoperative SRS-30 pain scores. LEVEL OF EVIDENCE: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

The trial to assess chelation therapy 2 (TACT2): Rationale and design.

BACKGROUND: Intravenous edetate disodium-based infusions reduced cardiovascular events in a prior clinical trial. The Trial to Assess Chelation Therapy 2 (TACT2) will replicate the initial study design. METHODS: TACT2 is an NIH-sponsored, randomized, 2x2 factorial, double masked, placebo-controlled, multicenter clinical trial testing 40 weekly infusions of a multi-component edetate disodium (disodium ethylenediamine tetra-acetic acid, or Na2EDTA)-based chelation solution and twice daily oral, high-dose multivitamin and mineral supplements in patients with diabetes and a prior myocardial infarction (MI). TACT2 completed enrollment of 1000 subjects in December 2020, and infusions in December 2021. Subjects are followed for 2.5 to 5 years. The primary endpoint is time to first occurrence of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The trial has >;85% power to detect a 30% relative reduction in the primary endpoint. TACT2 also includes a Trace Metals and Biorepository Core Lab, to test whether benefits of treatment, if present, are due to chelation of lead and cadmium from patients. Design features of TACT2 were chosen to replicate selected features of the first TACT, which demonstrated a significant reduction in cardiovascular outcomes in the EDTA chelation arm compared with placebo among patients with a prior MI, with the largest effect in patients with diabetes. RESULTS: Results are expected in 2024. CONCLUSION: TACT2 may provide definitive evidence of the benefit of edetate disodiumbased chelation on cardiovascular outcomes, as well as the clinical importance of longitudinal changes in toxic metal levels of participants.

National Institutes of Health Research Plan on Rehabilitation: NIH Medical Rehabilitation Coordinating Committee.

One in five Americans experiences disability that affects their daily function because of impairments in mobility, cognitive function, sensory impairment, or communication impairment. The need for rehabilitation strategies to optimize function and reduce disability is a clear priority for research to address this public health challenge. The National Institutes of Health (NIH) recently published a Research Plan on Rehabilitation that provides a set of priorities to guide the field over the next 5 years. The plan was developed with input from multiple Institutes and Centers within the NIH, the National Advisory Board for Medical Rehabilitation Research, and the public. This article provides an overview of the need for this research plan, an outline of its development, and a listing of six priority areas for research. The NIH is committed to working with all stakeholder communities engaged in rehabilitation research to track progress made on these priorities and to work to advance the science of medical rehabilitation.This article is being published almost simultaneously in the following six journals: American Journal of Occupational Therapy, American Journal of Physical Medicine and Rehabilitation, Archives of Physical Medicine and Rehabilitation, Neurorehabilitation and Neural Repair, Physical Therapy, and Rehabilitation Psychology. Citation information is as follows: NIH Medical Rehabilitation Coordinating Committee. Am J Phys Med Rehabil. 2017;97(4):404-407.

Functional Outcomes of Thoracolumbar Junction Spine Fractures.

INTRODUCTION: Few studies have evaluated the functional outcomes of traumatic thoracic and lumbar vertebral body fractures. This study evaluated the functional and clinical outcomes of patients, who sustained a fracture to the thoracolumbar area of the spine (T10 to L2 region), with ≥ 25° kyphosis versus those with less kyphotic curvature. METHODS: The trauma registry records of two level 1 trauma centers using ICD-9 codes for fracture to the thoracolumbar juncture (T10 to L2 region) were reviewed. Kyphosis angle was measured on the standing lateral thoracolumbar (T1 - L5) radiograph at initial trauma and at clinical follow-up. Functional outcome questionnaires, including the Oswestry Disability Questionnaire (ODQ), the Roland Morris Disability Questionnaire (RMDQ), and the Nottingham Health Profile (NHP), were evaluated at clinical follow-up. Work status and medication used after trauma also were recorded. RESULTS: A total of 38 patients met the inclusive criteria. Seventeen patients (45%) had ≥ 25° kyphosis and 21 patients (55%) had < 25° kyphosis at follow-up. These two groups were similar based on sex and age. Based on the ODQ Score, the RMDQ Score, and the NHP, no statistically significant differences were detected between the two groups in regards to energy, pain, mobility, emotional reaction, social isolation, and sleep. CONCLUSIONS: Patients who sustained a fracture to the thoracolumbar area of the spine with ≥ 25° kyphosis do not report worse clinical outcomes. When using the kyphosis angle as an indication for surgery, it should be used with caution and not exclusively.

Impact of glycemic control strategies on the progression of diabetic peripheral neuropathy in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Cohort.

OBJECTIVE: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial demonstrated similar long-term clinical effectiveness of insulin-sensitizing (IS) versus insulin-providing (IP) treatments for type 2 diabetes on cardiovascular outcomes in a cohort with documented coronary artery disease. We evaluated the effects of randomized glycemic control strategy (IS vs. IP) on the prevalence and incidence of diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS: DPN (defined as Michigan Neuropathy Screening Instrument [MNSI] clinical examination score>2) was assessed at baseline and yearly for 4 years. DPN prevalence and incidence were compared by intention-to-treat modeling by logistic generalized estimating equation models for prevalence and Kaplan-Meier estimates and Cox regression models for incidence rates. RESULTS: Results are reported for 2,159 BARI 2D participants (70% males) with valid baseline and at least one follow-up MNSI score (mean age 62±9 years, mean HbA1c 7.7±1.6%, diabetes duration 10±9 years). There were no differences in the prevalence of DPN between the IS and the IP groups throughout the 4 years of follow-up. In 1,075 BARI 2D participants with no DPN at baseline, the 4-year cumulative incidence rate of DPN was significantly lower in the IS (66%) than in the IP (72%) strategy group (P=0.02), which remained significant after adjusting for the in-trial HbA1c (P=0.04). In subgroup analyses, IS strategy had a greater benefit in men (hazard ratio 0.75 [99% CI 0.58-0.99], P<0.01). CONCLUSIONS: Among patients with type 2 diabetes followed for up to 4 years during BARI 2D, a glycemic control therapy with IS significantly reduced the incidence of DPN compared with IP therapy and may add further benefit for men.

Effect of initial postoperative visit radiographs on treatment plans.

BACKGROUND: It is a common practice among orthopaedic surgeons to make radiographs at the first outpatient postoperative visit after surgical repair of acute fractures. There is not much literature that investigates the benefits and necessity of such a practice. We hypothesized that the practice of routine postoperative radiographs is unnecessary and increases cost to the patients and the health-care system, increases radiation exposure, and provides no change in patient management. METHODS: A retrospective review of patients sustaining acute fractures requiring operative fixation was done with the goal of determining how often a radiograph made at the first postoperative visit in the surgeon's office resulted in a change in patient management. RESULTS: Fifteen (7.5%) of 200 fractures in 171 patients had a clinical indication for a radiograph because of an abnormal physical examination finding or history of additional trauma. Three (1.5%) of these fractures had a deviation from standard postoperative care; this deviation was a change in postoperative care on the basis of the patient history and physical examination rather than radiographs. One fracture (0.5%) had a radiographic change from the immediate postoperative radiograph to the clinic radiograph, yet did not have a change in treatment. The estimated average radiation exposure per radiograph was 0.164 mSv, and the average charge to the patient per radiograph was $335.13. CONCLUSIONS: The majority of radiographs made at the first postoperative visit in the surgeon's office after acute fracture fixation did not result in a change in patient management and added substantial cost to the health-care system.

Resting heart rate and metabolic syndrome in patients with diabetes and coronary artery disease in bypass angioplasty revascularization investigation 2 diabetes (BARI 2D) trial.

The relation between the metabolic syndrome (MetS) and resting heart rate (rHR) in patients with diabetes and coronary artery disease is unknown. The authors examined the cross-sectional association at baseline between components of the MetS and rHR and between rHR and left ventricular ejection fraction in the population from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) randomized clinical trial. The mean rHR in the MetS group was significantly higher than in those without (68.4+/-12.3 vs 65.6+/-11.8 beats per min, P=.0017). The rHR was higher (P<.001 for trend) with increasing number of components for MetS. Linear regression analyses demonstrated that as compared to individuals without MetS, rHR was significantly higher in participants with MetS (regression coefficient, 2.9; P=.0015). In patients with type 2 diabetes and coronary artery disease, the presence of higher rHR is associated with increasing number of criteria of MetS and the presence of ventricular dysfunction.

Knot security, loop security, and elongation of braided polyblend sutures used for arthroscopic knots.

In the study described here, we evaluated load to failure and cyclic loading elongation of different braided polyblend sutures under different sliding knot configurations. Four braided polyblend sutures (FiberWire, Herculine, Orthocord, Ultrabraid) were tied with 5 sliding arthroscopic knots (Static surgeon, Weston, Roeder, Nicky, Tennessee slider) with a series of 3 reversing half-hitches on alternating posts (RHAPs). Each knot was tied around a 30-mm circumference post to ensure a consistent loop circumference. Loop security was measured as load to failure (load at 3-mm cross-head displacement or suture breakage) and loop elongation at a frequency of 1 Hz from 6 N to 30 N for 1000 cycles. Twenty knots were tied for each possible combination of knots and sutures, 10 for load to failure and 10 for cyclic loading test. For any given knot type, tying with Ultrabraid suture material resulted in maximum performance in the maximum load-to-failure test. Conversely, tying with Orthocord resulted in a significantly lower maximum load to failure, with the exception of the Surgeon knot. The Weston knot with 3 RHAPs using Ultrabraid provided the highest load to failure(mean, 346 N; SD, 24 N). All knots elongated less than 0.45 mm at the 1000th cycle and experienced higher suture slippage at initial cyclic loading (50th cycles). At higher cycles, FiberWire and Orthocord demonstrated less than half of the suture slippage of Herculine and Ultrabraid (5x10(-5) vs 11x10(-5) mm/cycle). Different braided polyblend sutures provide different knot and loop security for a given type of sliding knot. All knots in this study appear to be durable with respect to resistance to loosening under cyclic loading conditions. The Weston knot with 3 RHAPs using Ultrabraid provided the best loop and knot security. Our study results help further our understanding of the biomechanics of knot and loop security differences for different braided polyblend sutures.

Relation of severe coronary artery narrowing to insulin or thiazolidinedione use in patients with type 2 diabetes mellitus (from the Bypass Angioplasty Revascularization Investigation 2 Diabetes Study).

Patients with diabetes continue to die of coronary artery disease (CAD) at rates 2 to 4 times higher than patients without diabetes, despite advances in treatment of cardiovascular disease. The role of glycemic control therapies, independent of their glucose-lowering effects, on cardiovascular disease is a recurring question. We examined the association of glycemic control therapies with extent of CAD as measured by coronary angiogram obtained at baseline in 1,803 subjects in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial who had type 2 diabetes mellitus, documented moderate to severe CAD, and no previous cardiac revascularization procedures. The association between glycemic control therapy use recorded at baseline and percent coronary artery stenosis and myocardial jeopardy index was analyzed by multiple regression models. Insulin use at study entry was associated with 23% fewer highly stenotic lesions (> or =70%) (p <0.001) and a significantly lower myocardial jeopardy index compared with subjects not on insulin, despite a worse cardiac risk factor profile, more unstable angina, and increased inflammatory markers in insulin users. Subjects taking thiazolidinediones (TZDs) for > or =6 months had 17% fewer highly stenotic lesions (p = 0.02) and significantly lower C-reactive protein, fibrinogen, and plasminogen activator inhibitor-1 levels compared with those not taking TZDs. In conclusion, this cross-sectional study of patients with type 2 diabetes mellitus and CAD showed that treatment with insulin or TZDs was associated with fewer highly stenotic lesions, independent of disease duration, glycemic control, and other risk factors.

A randomized trial of therapies for type 2 diabetes and coronary artery disease.

BACKGROUND: Optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established. METHODS: We randomly assigned 2368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy. Primary end points were the rate of death and a composite of death, myocardial infarction, or stroke (major cardiovascular events). Randomization was stratified according to the choice of percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) as the more appropriate intervention. RESULTS: At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulin-provision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7% in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no significant difference in primary end points between the revascularization group and the medical-therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Adverse events and serious adverse events were generally similar among the groups, although severe hypoglycemia was more frequent in the insulin-provision group (9.2%) than in the insulin-sensitization group (5.9%, P=0.003). CONCLUSIONS: Overall, there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision. (ClinicalTrials.gov number, NCT00006305.)

Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort.

We evaluated the associations between glycemic therapies and prevalence of diabetic peripheral neuropathy (DPN) at baseline among participants in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial on medical and revascularization therapies for coronary artery disease (CAD) and on insulin-sensitizing vs. insulin-providing treatments for diabetes. A total of 2,368 patients with type 2 diabetes and CAD was evaluated. DPN was defined as clinical examination score >2 using the Michigan Neuropathy Screening Instrument (MNSI). DPN odds ratios across different groups of glycemic therapy were evaluated by multiple logistic regression adjusted for multiple covariates including age, sex, hemoglobin A1c (HbA1c), and diabetes duration. Fifty-one percent of BARI 2D subjects with valid baseline characteristics and MNSI scores had DPN. After adjusting for all variables, use of insulin was significantly associated with DPN (OR = 1.57, 95% CI: 1.15-2.13). Patients on sulfonylurea (SU) or combination of SU/metformin (Met)/thiazolidinediones (TZD) had marginally higher rates of DPN than the Met/TZD group. This cross-sectional study in a cohort of patients with type 2 diabetes and CAD showed association of insulin use with higher DPN prevalence, independent of disease duration, glycemic control, and other characteristics. The causality between a glycemic control strategy and DPN cannot be evaluated in this cross-sectional study, but continued assessment of DPN and randomized therapies in BARI 2D trial may provide further explanations on the development of DPN.

Optimal design features for surveying low-income populations.

Improving Medicaid program effectiveness for underserved populations is hampered by low survey response rates. This study determined how to maximize Medicaid consumer satisfaction survey response rates to the Consumer Assessment of Health Plans Study (CAHPS) survey. In a public immunization clinic, 8 focus groups and 15 extended interviews were used to assess consumer-preferred survey design features and incentives. To test hypotheses, we conducted the following trial. Out of 10,733 total participants in a Kansas Medicaid managed care plan, 3,685 eligible for CAHPS were unduplicated by household. After randomization of the 968 households with valid addresses to one of three groups, a controlled trial was conducted to assess response rates to CAHPS survey formats and incentives. Response rates were 35% for a standard mailing, 44% for a user-friendly low-literacy mailing, and 64% for a user-friendly low-literacy mailing with a $10 contingent incentive. Both experimental arms significantly improved response compared with the control; the response rate of the mailing group with the incentive was higher than the response rate of the group receiving that mailing without any incentive (p<0.0001). Using consumer-based preferences significantly increased response rates to this Medicaid satisfaction survey. Raising CAHPS response rates may increase validity of Medicaid consumer satisfaction information.

Regulation of meiotic prophase arrest in mouse oocytes by GPR3, a constitutive activator of the Gs G protein.

The arrest of meiotic prophase in mouse oocytes within antral follicles requires the G protein G(s) and an orphan member of the G protein-coupled receptor family, GPR3. To determine whether GPR3 activates G(s), the localization of Galpha(s) in follicle-enclosed oocytes from Gpr3(+/+) and Gpr3(-/-) mice was compared by using immunofluorescence and Galpha(s)GFP. GPR3 decreased the ratio of Galpha(s) in the oocyte plasma membrane versus the cytoplasm and also decreased the amount of Galpha(s) in the oocyte. Both of these properties indicate that GPR3 activates G(s). The follicle cells around the oocyte are also necessary to keep the oocyte in prophase, suggesting that they might activate GPR3. However, GPR3-dependent G(s) activity was similar in follicle-enclosed and follicle-free oocytes. Thus, the maintenance of prophase arrest depends on the constitutive activity of GPR3 in the oocyte, and the follicle cell signal acts by a means other than increasing GPR3 activity.

Complexity of medication use in the Veterans Affairs healthcare system: Part I: Outpatient use in relation to age and number of prescribers.

CONTEXT: Multiple medication use is associated with an increased incidence of adverse drug-drug interactions (DDIs), medication errors, noncompliance, hospitalization, and healthcare costs. Drugs acting systemically or gastrointestinally ("SG" drugs) are of particular concern because of their potential to interact. A better understanding is needed of the relationship between multiple medication use, particularly of SG drugs, and age, number of prescribers, and common drug regimens. OBJECTIVE: to determine the levels of multiple SG medication use in relation to age, number of prescribers, and common drug regimens in an outpatient population served by U.S. Veterans Integrated Service Network 15 (VISN 15). DESIGN, SETTING, AND PARTICIPANTS: cross-sectional analysis of the subset of 5,003 currently active patients from a stratified random sample of 7,000 potentially active outpatients (1,000 each from 7 sites comprising VISN 15) selected from the prescription database on a single day. MAIN OUTCOME MEASURES: number of SG drugs/patient; number and frequency of SG drug entities and regimens. RESULTS: Most patients (97%) were dispensed at least one SG drug: 80% received > or =2 SG drugs, of which 42% received 2-4 SG drugs, 24%, 5-7 SG drugs, and 14%, > or =8 SG drugs. 394 different SG drugs were dispensed, only 88 of which occurred in 1% or more of patients. A significant increase (p < 0.0001) in level of multiple medication use occurred with increasing age and number of prescribers. Proportions of patients receiving 8 or more SG drugs approximately doubled with each additional prescriber, up to 4 or more prescribers. No drug regimen containing 2 or more drugs occurred in 1% or more of patients; 71% of patients were receiving a unique drug regimen (based on specific SG drugs without regard to dose or administration schedule). CONCLUSIONS: The uniqueness of SG drug regimens suggests no single prescriber could have extensive clinical experience with even a small fraction of the drug regimens patients receive. These findings suggest that potential DDIs cannot be predicted based on occurrence of common drug regimens in a general patient population. A follow-up study (reported separately) investigated whether common drug regimens can be identified by selecting for a specific drug treatment (e.g., an antidepressant). The improved ability to predict DDIs is particularly relevant for psychiatric patients, who are at increased risk for DDIs because of greater frequency of multiple medication use. In addition, DDIs may present in this population in ways that mimic worsening of primary symptoms, which may lead to increased doses of the medication that is actually responsible for the problem, causing still more toxicity.

Complexity of medication use in the Veterans Affairs healthcare system: Part II. Antidepressant use among younger and older outpatients.

CONTEXT: A previous study, described in Part I of this report, found that 71% of a sample of 5,003 general outpatients in the Veterans Affairs healthcare system were receiving a unique drug regimen (i.e., total specific drug entities regardless of dose, formulation, or administration schedule). The simplest regimens contained only one drug, while the most complex regimens exceeded 20 different drugs. The purpose of the present study was to determine if patients receiving a specific therapeutic class of medications (e.g., antidepressants) have more homogeneous drug regimens. OBJECTIVE: to examine the extent and complexity of multiple medication use in younger and older adult outpatients receiving antidepressants compared with those not receiving antidepressants. The study focused on drugs that act systemically or gastrointestinally and hence have the potential to interact. DESIGN, SETTING, AND PARTICIPANTS: Two subsets of stratified random samples of outpatients selected from prescription databases of U.S. Veterans Integrated Service Network 15. The first group involved 1,991 patients deemed to be on antidepressants (AD patients): 891 aged < 60 years and 1,100 aged > or = 60 years. The second group involved 3,732 patients who had received no antidepressants within the previous 365 days but who had a supply of at least one other current prescription (NoAD patients): 1,195 aged < 60 years and 2,535 aged > or = 60 years; 2 missing age information. MAIN OUTCOME MEASURES: number of drugs, frequency of drug regimens, level of multiple medication use including and excluding antidepressants. RESULTS: Younger AD patients received 3 more drugs than younger NoAD patients. 23.6% of younger AD patients, versus 5.9% of younger NoAD patients, received > or = 8 drugs. Older AD patients received 2 more drugs than older NoAD patients. 37.6% of older AD patients, versus 12.8% of older NoAD patients, received > or = 8 drugs. In both the AD and NoAD groups, 62%-96% of patients of all ages were receiving unique drug regimens. Each drug regimen containing 2 or more drugs occurred in fewer than 1% of patients. CONCLUSIONS: AD patients were receiving more complex drug regimens and had a higher frequency of unique drug regimens than NoAD patients, even when the results were adjusted for age group and number of prescribers. The high prevalence of unique drug combinations in all patient groups in this study indicates that clinicians in this system have only limited experience with the total effects of all of the medications their patients are receiving and thus cannot rely on experience to guard against adverse multi-drug interactions. This fact is a particular concern with psychiatric medications because adverse DDIs involving these medications can mimic psychiatric symptoms and may therefore be more difficult to detect.