Do Antibiotics Prevent Infectious Complications in Critically Injured Patients With Blunt Nonoperative Midfacial Trauma?

BACKGROUND: While recent literature suggests antibiotics are not needed in patients with nonoperative facial fractures involving sinuses, the existing studies do not focus on critically injured patients who are known to be at higher risk for sinusitis and ventilator-associated pneumonia, which could be exacerbated by facial fractures. PURPOSE: The purpose of this study was to determine if antibiotics reduce the rate of infectious complications in critically injured patients who have blunt midfacial trauma treated nonoperatively. STUDY DESIGN, SETTING, SAMPLE: The authors conducted a retrospective cohort study consisting of patients admitted to the trauma intensive care unit who sustained blunt midfacial injuries managed nonoperatively at an urban Level 1 trauma center from August 13th, 2012, to July 30th, 2020. Adults who were critically injured on admission and sustained a midfacial fracture involving a sinus were included in the study. Patients who underwent operative repair of any facial fracture were excluded. PREDICTOR VARIABLE: The predictor variable was the use of antibiotics. MAIN OUTCOME VARIABLE: The primary outcome variable was the development of infectious complications, such as sinusitis, soft tissue infection, or any type of pneumonia, including ventilator-associated pneumonia (VAP). ANALYSES: The data were analyzed using Wilcoxon rank sum tests, Fisher exact tests, and multivariable logistic regression as appropriate for analysis type with significance level set at <0.05. RESULTS: The study included 307 patients, with a mean age of 40.6 years. Men accounted for 85.0% of the study population. Antibiotics were administered to 229 (74.6%) of the study population. Complications developed in 13.6% of the patients, which included sinusitis (0.3%), VAP (7.5%), and other types of pneumonia (5.9%). Clostridioides difficile colitis developed in 2 patients (0.6%). Antibiotics were not associated with a decrease in infectious complications in either the unadjusted analysis (13.1% in antibiotic group, 15.4% in no antibiotic group, RR = 0.85 [95% confidence interval = 0.5 to 1.6], P = .7) or the adjusted analysis (odds ratio 0.74 [0.34 to 1.62]). CONCLUSIONS AND RELEVANCE: Even in this critically injured patient population thought to be at elevated risk for infectious complications from their midfacial fractures, the rates of infectious complications in those who received antibiotics and those who did not were no different. These results suggest that consideration of more judicious use of antibiotics is warranted in critically ill patients with nonoperative midface fractures.

Cinacalcet hydrochloride is an effective treatment for secondary hyperparathyroidism in patients with CKD not receiving dialysis.

BACKGROUND: Secondary hyperparathyroidism develops early in patients with chronic kidney disease (CKD). Clinical guidelines from the National Kidney Foundation-Kidney/Disease Outcomes Quality Initiative emphasize the need to control parathyroid hormone (PTH), calcium, and phosphorus levels in patients with CKD not receiving dialysis to reduce poor outcomes. This phase 2 study evaluated the effects of the oral calcimimetic cinacalcet hydrochloride in patients with CKD not on dialysis therapy. METHODS: A randomized, double-blind, placebo-controlled, 18-week study enrolled adults with an estimated glomerular filtration rate of 15 to 50 mL/min/1.73 m2 (0.25 to 0.83 mL/s/1.73 m2) and an intact PTH (iPTH) level greater than 130 pg/mL (ng/L). Cinacalcet (or placebo) was titrated from 30 to 180 mg once daily to obtain a 30% or greater reduction in iPTH levels from baseline. RESULTS: Baseline mean iPTH levels were 243 pg/mL (ng/L) in the cinacalcet group (n = 27) and 236 pg/mL (ng/L) in the control group (n = 27). At baseline, 28% of subjects were being administered vitamin D sterols and 43% were being administered phosphate binders or calcium supplements. The addition of cinacalcet significantly decreased iPTH concentrations compared with controls during the efficacy-assessment phase: 56% versus 19% of subjects achieved a 30% or greater reduction in iPTH levels (P = 0.006), and mean iPTH levels decreased by 32% in the cinacalcet group, but increased by 6% in the control group (P < 0.001). Mean serum calcium and phosphorus levels remained within normal range throughout the study. Cinacalcet generally was well tolerated; the most frequent adverse events were gastrointestinal. CONCLUSION: This preliminary study provides evidence that cinacalcet is efficacious for the treatment of secondary hyperparathyroidism in subjects with CKD not receiving dialysis.

Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study.

Management of secondary hyperparathyroidism is challenging with traditional therapy. The calcimimetic cinacalcet HCl acts on the calcium-sensing receptor to increase its sensitivity to calcium, thereby reducing parathyroid hormone (PTH) secretion. This phase 3, multicenter, randomized, placebo-controlled, double-blind study evaluated the efficacy and safety of cinacalcet in hemodialysis (HD) and peritoneal dialysis (PD) patients with PTH > or =300 pg/ml despite traditional therapy. A total of 395 patients received once-daily oral cinacalcet (260 HD, 34 PD) or placebo (89 HD, 12 PD) titrated from 30 to 180 mg to achieve a target intact PTH (iPTH) level of < or =250 pg/ml. During a 10-wk efficacy assessment phase, cinacalcet was more effective than control for PTH reduction outcomes, including proportion of patients with mean iPTH levels < or =300 pg/ml (46 versus 9%), proportion of patients with > or =30% reduction in iPTH from baseline (65 versus 13%), and proportion of patients with > or =20, > or =40, or > or =50% reduction from baseline. Cinacalcet had comparable efficacy in HD and PD patients; 50% of PD patients achieved a mean iPTH < or =300 pg/ml. Cinacalcet also significantly reduced serum calcium, phosphorus, and Ca x P levels compared with control treatment. The most common side effects, nausea and vomiting, were usually mild to moderate in severity and transient. Once-daily oral cinacalcet was effective in rapidly and safely reducing PTH, Ca x P, calcium, and phosphorus levels in patients who received HD or PD. Cinacalcet offers a new therapeutic option for controlling secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.

Achieving NKF-K/DOQI bone metabolism and disease treatment goals with cinacalcet HCl.

BACKGROUND: The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF-K/DOQItrade mark) has established guidelines for treatment of secondary hyperparathyroidism (HPT). The ability of cinacalcet HCl (Sensipartrade mark) treatment to improve achievement of target levels of parathyroid hormone (PTH), calcium, phosphorus, and calcium-phosphorus product (Ca x P) was investigated in subjects on dialysis with secondary HPT. METHODS: Data were combined from three placebo-controlled, double-blind, 26-week studies with similar design that randomized 1136 subjects on dialysis to receive traditional therapy plus cinacalcet or placebo. Oral cinacalcet was titrated from 30 to 180 mg/day. Achievement of K/DOQI goals was determined for each treatment group overall and for subgroups defined by baseline intact PTH (iPTH) and Ca x P levels. RESULTS: Cinacalcet-treated subjects were more likely to achieve a mean iPTH

Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4.

BACKGROUND: Calcitriol lowers parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD) stages 3 and 4, but its use is limited by a low therapeutic index and concerns regarding hypercalcemia and acceleration of kidney disease. We evaluated doxercalciferol (1alpha-hydroxyvitamin D2) as an alternative therapy in a randomized, double-blinded, placebo-controlled, multicenter trial. METHODS: Fifty-five adults with stage 3 or 4 CKD and an intact PTH (iPTH) level greater than 85 pg/mL (ng/L) completed 8 baseline weeks, followed by 24 weeks of oral therapy with doxercalciferol or placebo. Pretreatment demographics and biochemical features did not differ between groups. Dosages were increased gradually if iPTH level was not decreased by 30% or greater and serum calcium and phosphorus levels were stable. Regular monitoring included plasma iPTH, serum calcium and phosphorus, urinary calcium, bone-specific serum markers, and serum lalpha,25-dihydroxyvitamin D levels. Glomerular filtration rate (GFR) was measured before and after treatment. RESULTS: Mean plasma iPTH level decreased by 46% from baseline after 24 weeks of doxercalciferol treatment (P <0.001), but was unchanged with placebo. After 6 weeks, iPTH level reductions with doxercalciferol treatment exceeded those with placebo at all subsequent intervals (P <0.001). No clinically significant differences in mean serum calcium or phosphorus or urinary calcium levels or incidence of hypercalcemia, hyperphosphatemia, or hypercalciuria were noted between groups. Serum C- and N-telopeptide and bone-specific alkaline phosphatase levels decreased with doxercalciferol treatment relative to both baseline and placebo (P <0.01). Adverse-event rates and changes in GFR did not differ between groups. CONCLUSION: Doxercalciferol is safe and effective in controlling secondary hyperparathyroidism of patients with CKD stages 3 and 4.

An update on vitamin D as related to nephrology practice: 2003.

In this article, an up-to-date consideration of vitamin D therapeutics in nephrology is reviewed. The condition of vitamin D insufficiency is defined as the level of serum 25(OH)vitamin D at which vitamin D2 or D3 supplementation leads to a reduction of levels of parathyroid hormone (PTH). The risks of such vitamin D insufficiency in the normal population and likely risks in individuals with chronic kidney disease (CKD) stages 3 and 4 are reviewed. The potential for its safe treatment and prevention using moderate supplements of vitamin D2 or vitamin D3 are outlined. The role of altered "vitamin D nutrition" in leading to the observed greater incidence of secondary hyperparathyroidism in African Americans with ESRD compared to other racial groups is considered. The actions of active vitamin D sterols to augment intestinal absorption of both calcium and phosphorus, the effect to reduce levels of PTH, and to be a factor contributing to the rising incidence of low bone turnover (adynamic bone) are discussed. Growing evidence for contributions of elevated levels of serum calcium, serum phosphorus, and the calcium x phosphorus product as factors contributing to vascular and cardiac calcification in ESRD patients are cited. Questions are raised about whether the current practice of vitamin D usage in ESRD patients might be a contributing factor to such vascular abnormalities. The economic factors that likely affect the usage of intravenous vitamin D sterols in the United States are reviewed. It is recommended that potential adverse vascular effects of vitamin D sterols related to the increments of serum Ca and P be carefully evaluated.

Use of active vitamin D sterols in patients with chronic kidney disease, stages 3 and 4.

This paper reviews randomized controlled trials and other reported data on the use of the active vitamin D sterols, such as calcitriol, alfacalcidol, and doxercalciferol, in the management of secondary hyperparathyroidism in patients with mild-to-moderate renal insufficiency (stage 3 or 4 chronic kidney disease). Data on potential benefits, including improved histologic abnormalities of bone from secondary hyperparathyroidism, increased bone mineral density, and a reduction of elevated parathyroid hormone levels, are documented. Consideration is given to the risks of such therapy, which include the production of hypercalcemia, more rapid progression of renal insufficiency, the induction of adynamic bone "disease," and accelerated vascular and soft tissue calcification. The low therapeutic index, or "benefit/risk ratio" of calcitriol and alfacalcidol, the sterols currently licensed for such treatment, is recognized. It is recommended that phosphate-restricted diets, phosphate-binding agents, and oral calcium supplements be given adequate trials before starting calcitriol or alfacalcidol. If PTH levels cannot be controlled by these measures, initial doses of these sterols and the proper surveillance during treatment are given. It is emphasized that the risks of hypercalcemia are likely to increase as the degree of kidney failure worsens. Further research using the "less calcemic" vitamin D sterols is clearly needed.

The calcimimetic AMG 073 reduces parathyroid hormone and calcium x phosphorus in secondary hyperparathyroidism.

BACKGROUND: A need exists for a therapy that lowers parathyroid hormone (PTH) without increasing calcium x phosphorus in patients with secondary hyperparathyroidism. The calcimimetic AMG 073 increases the sensitivity of the parathyroid calcium-sensing receptor to extracellular calcium, thereby reducing PTH secretion. Consequently, AMG 073 may provide a novel therapy for secondary hyperparathyroidism. METHODS: Seventy-eight hemodialysis patients with secondary hyperparathyroidism were enrolled into this 18-week, double-blind, randomized, placebo-controlled, dose titration study. Daily oral AMG 073 doses were administered to determine the effect on PTH, serum calcium, phosphorus, and calcium x phosphorus. RESULTS: The mean baseline PTH was similar in patients administered AMG 073 or placebo (632 +/- 280.1 pg/mL vs. 637 +/- 455.9 pg/mL, respectively). PTH decreased by 26.0% in the AMG 073-treated group, compared with an increase of 22.0% in the placebo group (P < 0.001). A greater proportion in the AMG 073 group (38%) had a decrease in PTH >or=30%, compared with the placebo group (8%) (P = 0.001). Decreases in PTH were independent of baseline vitamin D usage. Patients receiving AMG 073 had an 11.9% decrease in calcium x phosphorus compared with a 10.9% increase in the placebo group (P < 0.001). Use of vitamin D sterols, as well as both calcium and noncalcium-containing phosphate binders. were similar between treatment groups. Administration of AMG 073 was safe and well tolerated in this 18-week study. CONCLUSIONS: The calcimimetic AMG 073 decreases both PTH and calcium x phosphorus levels in hemodialysis patients with secondary hyperparathyroidism.

The calcimimetic agents: perspectives for treatment.

Recognition of the role of the extracellular calcium sensing receptor (CaR) in mineral metabolism has greatly improved our understanding of calcium homeostasis. The biology of the low affinity, G-protein-coupled CaR and the effects of its activation in various tissues are reviewed. Physiological roles include regulation of parathyroid hormone (PTH) secretion by small changes in ionized calcium (Ca++), and control of urinary calcium excretion with small changes in blood Ca++. The CaR also affects the renal handling of sodium, magnesium, and water. Mutations affecting the CaR that make it either less or more sensitive to Ca++ cause various clinical disorders. Disorders, such as primary and secondary hyperparathyroidism, may exhibit acquired abnormalities of the CaR. Calcimimetic drugs, which amplify the sensitivity of the CaR to Ca++, can suppress PTH levels with a resultant fall in blood Ca++. Experiences with R-568 in patients with secondary and primary hyperparathyroidism and parathyroid carcinoma are summarized. In humans with hyperparathyroidism, these agents produce a dose-dependent fall in PTH and blood Ca++, with larger doses causing more sustained effects. The second generation calcimimetic, AMG 073, with a better pharmacokinetic profile appears to be an effective and safe treatment for secondary hyperparathyroidism, producing suppression of PTH levels with a simultaneous reduction in serum phosphorus levels and the calcium X phosphorus product. The advantage of controlling PTH secretion without the complications related to hypercalcemia, hyperphosphatemia, and increased calcium X phosphorus product is very promising. Treatment trials have been relatively short-term except for one patient treated with R-568 for more than 600 days for parathyroid carcinoma; nonetheless the drug had no major side effects and appeared to be safe. Further long-term controlled studies are underway to further confirm the effectiveness and safety of these compounds.

The Calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism.

Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH) in many patients with secondary hyperparathyroidism due to end-stage renal disease, but hypercalcemia, hyperphosphatemia, or both often develop during treatment. As such, alternative therapeutic approaches to managing excess PTH secretion are needed. Calcimimetic agents directly inhibit PTH secretion by activating the calcium-sensing receptor in the parathyroid glands, but clinical experience with them is limited. Fifty-two hemodialysis patients with secondary hyperparathyroidism were given single orally administered doses of the calcimimetic agent AMG 073 ranging from 5 to 100 mg, or placebo. Plasma PTH levels decreased 2 h after 25-, 50-, 75-, or 100-mg doses, falling by a maximum of 43 +/- 29%, 40 +/- 36%, 54 +/- 28%, or 55 +/- 39%, respectively. Plasma PTH levels decreased in all patients given doses of > or =25 mg but did not change in those who received placebo. In patients treated with daily doses of 25 or 50 mg of AMG 073 for 8 d, plasma PTH levels declined for the first 3 to 4 d and remained below baseline values after 8 d of treatment. Serum calcium concentrations also decreased by 5 to 10% from pretreatment levels in patients given 50 mg of AMG 073 for 8 d, but values were unchanged in those who received lower doses. Serum phosphorus levels and values for the calcium-phosphorus ion product both decreased after treatment with AMG 073. Thus, 8 d of treatment with AMG 073 effectively lowers plasma PTH levels and improves several disturbances in mineral metabolism that have been associated with soft tissue and vascular calcification and with adverse cardiovascular outcomes in patients with end-stage renal disease.