Chronic Medication Use and Factors Associated With Polypharmacy Among Outpatient Pediatric Patients.

OBJECTIVE: This study aimed to determine the prevalence and predictors of chronic polypharmacy among pediatric patients in an outpatient setting. METHODS: We conducted a review of medications dispensed to patients from an outpatient pediatric facility during a 12-month period. Patients who received chronic medications (≥30 days' supply), which contained at least 1 active pharmaceutical ingredient were included in the study. Descriptive analysis was used to determine prevalence of polypharmacy while predictive factors for polypharmacy were evaluated using logistic regression. RESULTS: Our study included 3920 patients (median age, 9.9 years; IQR, 9.4) and 16,401 medications. The median number of chronic medications used among our study cohort was 2.0 (IQR, 1) with polypharmacy identified in 309 (7.9%) patients. Predictors for polypharmacy were age and the use of certain therapeutic class of medications. Patients 12 to <19 years old (OR, 6.95; 95% CI, 4.1-10.1) were more likely to require ≥5 concurrent medications compared with patients younger than 2 years of age. Use of calcium supplements (OR, 21.2; 95% CI, 11.3-39.6), Vitamin D analogues (OR, 14.3; 95% CI, 8.0-25.8), and systemic glucocorticoids (OR, 18.8; 95% CI, 10.7-33.2) were also highly associated with polypharmacy. CONCLUSIONS: Adolescents and children with chronic medical conditions who require prolonged systemic glucocorticoids, calcium, and Vitamin D supplements are at higher risk of incurring long-term polypharmacy. This subgroup of pediatric patients may be more vulnerable to the occurrence of negative outcomes resulting from the use of multiple chronic medications.

Prunin suppresses viral IRES activity and is a potential candidate for treating enterovirus A71 infection.

Human enterovirus A71 (HEVA71) causes hand, foot, and mouth disease (HFMD) in young children and is considered a major neurotropic pathogen but lacks effective antivirals. To identify potential therapeutic agents against HFMD, we screened a 502-compound flavonoid library for compounds targeting the HEVA71 internal ribosome entry site (IRES) that facilitates translation of the HEVA71 genome and is vital for the production of HEVA71 viral particles. We validated hits using cell viability and viral plaque assays and found that prunin was the most potent inhibitor of HEVA71. Downstream assays affirmed that prunin disrupted viral protein and RNA synthesis and acted as a narrow-spectrum antiviral against enteroviruses A and B, but not enterovirus C, rhinovirus A, herpes simplex 1, or chikungunya virus. Continuous HEVA71 passaging with prunin yielded HEVA71-resistant mutants with five mutations that mapped to the viral IRES. Knockdown studies showed that the mutations allowed HEVA71 to overcome treatment-induced suppression by differentially regulating recruitment of the IRES trans-acting factors Sam68 and hnRNPK without affecting the hnRNPA1-IRES interaction required for IRES translation. Furthermore, prunin effectively reduced HEVA71-associated clinical symptoms and mortality in HEVA71-infected BALB/c mice and suppressed hepatitis C virus at higher concentrations, suggesting a similar mechanism of prunin-mediated IRES inhibition for both viruses. These studies establish prunin as a candidate for further development as a HEVA71 therapeutic agent.

How useful are perioperative biochemical parameters in predicting the duration of calcium and/or vitamin D supplementation after total thyroidectomy?

BACKGROUND: Oral calcium and calcitriol are often prescribed after total thyroidectomy to avoid biochemical and/or symptomatic hypocalcemia. We aimed to identify independent perioperative factors that correlated with the duration of calcium and/or calcitriol supplementation after total thyroidectomy. METHODS: Of 271 eligible patients, 48 (17.7 %) required calcium and/or calcitriol supplements on discharge. Patients were gradually weaned from the supplementation by one surgeon according to a biweekly algorithm based on serum calcium (Ca). Duration of supplementation was calculated from the date of operation to the date of ceasing all supplementation without biochemical hypocalcemia (i.e., serum adjusted Ca ≥ 8.44 mg/dL). The Cox regression analysis was performed to identify independent perioperative factors for duration of supplementation. The best cut-off value for these independent factors was determined by the receiver characteristic curve. RESULTS: In the multivariate analysis, parathyroid hormone (PTH) at skin closure (PTH-SC) (RR 1.742, 95 % CI 1.080-2.810) and on postoperative day 1 adjusted Ca (Ca-D1) (RR 77.526, 95 % CI 3.600-1669.57) were the only two independent determinants for shorter duration before ceasing all supplementation. The best cut-off values in predicting supplementation ≥ 6 months for PTH-SC and Ca-D1 were 7.08 pg/mL (sensitivity = 100 %, specificity = 60.5 %, PPV = 40.0 % and NPV = 100 %) and 7.88 mg/dL (sensitivity = 90.0 %, specificity = 55.3 %, PPV = 34.6 % and NPV = 95.5 %), respectively. CONCLUSIONS: Both PTH-SC and Ca-D1 were independently associated with the duration of supplementation after total thyroidectomy. Almost all patients with PTH-SC ≥ 7.08 pg/mL or Ca-D1 ≥ 7.88 mg/dL did not require supplementation ≥ 6 months whereas about one third of patients with PTH-SC <7.08 pg/mL or Ca-D1 <7.88 mg/dL required supplementation ≥ 6 months.

Do low preoperative vitamin D levels reduce the accuracy of quick parathyroid hormone in predicting postthyroidectomy hypocalcemia?

BACKGROUND: Although some studies have suggested that low preoperative 25-hydroxyvitamin D (25-OHD) levels may increase the risk of hypocalcemia and decrease the accuracy of single quick parathyroid hormone in predicting hypocalcemia after total thyroidectomy, the literature remains scarce and inconsistent. Our study aimed to address these issues. METHODS: Of the 281 consecutive patients who underwent a total/completion total thyroidectomy, 244 (86.8%) did not require any oral calcium and/or calcitriol supplements (group 1), while 37 (13.2%) did (group 2) at hospital discharge. 25-OHD level was checked 1 day before surgery, and postoperative quick parathyroid hormone (PTH) was checked at skin closure (PTH-SC). Postoperative serum calcium was checked regularly. Hypocalcemia was defined by the presence of symptoms or adjusted calcium of <1.90 mmol/L. Significant factors for hypocalcemia were determined by univariate and multivariate analyses. The accuracy of PTH-SC in predicting hypocalcemia was measured by area under a receiver operating characteristic curve (AUC), and the AUC of PTH-SC was compared between patients with preoperative 25-OHD <15 and ≥15 ng/mL via bootstrapping. RESULTS: Preoperative 25-OHD level was not significantly different between groups 1 and 2 (13.1 vs. 12.5 ng/mL, p = 0.175). After adjusting for other significant factors, PTH-SC (odds ratio 2.49, 95% confidence interval 1.52-4.07, p < 0.001) and parathyroid autotransplantation (odds ratio 3.23, 95% confidence interval 1.22-8.60, p = 0.019) were the two independent factors for hypocalcemia. The AUC of PTH-SC was similar between those with 25-OHD <15 and ≥15 ng/mL (0.880 vs. 0.850, p = 0.61) CONCLUSIONS: Low 25-OHD was not a significant factor for hypocalcemia and did not lower the accuracy of quick PTH in predicting postthyroidectomy hypocalcemia.

Comparative effectiveness of pain management interventions for hip fracture: a systematic review.

BACKGROUND: Pain management is integral to the management of hip fracture. PURPOSE: To review the benefits and harms of pharmacologic and nonpharmacologic interventions for managing pain after hip fracture. DATA SOURCES: 25 electronic databases (January 1990 to December 2010), gray literature, trial registries, and reference lists, with no language restrictions. STUDY SELECTION: Multiple reviewers independently and in duplicate screened 9357 citations to identify randomized, controlled trials (RCTs); nonrandomized, controlled trials (non-RCTs); and cohort studies of pain management techniques in older adults after acute hip fracture. DATA EXTRACTION: Independent, duplicate data extraction and quality assessment were conducted, with discrepancies resolved by consensus or a third reviewer. Data extracted included study characteristics, inclusion and exclusion criteria, participant characteristics, interventions, and outcomes. DATA SYNTHESIS: 83 unique studies (64 RCTs, 5 non-RCTs, and 14 cohort studies) were included that addressed nerve blockade (n = 32), spinal anesthesia (n = 30), systemic analgesia (n = 3), traction (n = 11), multimodal pain management (n = 2), neurostimulation (n = 2), rehabilitation (n = 1), and complementary and alternative medicine (n = 2). Overall, moderate evidence suggests that nerve blockades are effective for relieving acute pain and reducing delirium. Low-level evidence suggests that preoperative traction does not reduce acute pain. Evidence was insufficient on the benefits and harms of most interventions, including spinal anesthesia, systemic analgesia, multimodal pain management, acupressure, relaxation therapy, transcutaneous electrical neurostimulation, and physical therapy regimens, in managing acute pain. LIMITATIONS: No studies evaluated outcomes of chronic pain or exclusively examined participants from nursing homes or with cognitive impairment. Systemic analgesics (narcotics, nonsteroidal anti-inflammatory drugs) were understudied during the search period. CONCLUSION: Nerve blockade seems to be effective in reducing acute pain after hip fracture. Sparse data preclude firm conclusions about the relative benefits or harms of many other pain management interventions for patients with hip fracture. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.