Effect of Dexmedetomidine on Incidence of Hypertension Following Repair of Coarctation of the Aorta.

OBJECTIVE: Recent literature suggests a potential role for dexmedetomidine in reducing the incidence and severity of hypertension following repair of coarctation of the aorta (CoA). The primary aim of this study was to assess the association between dexmedetomidine use and the incidence of hypertension following repair of CoA in pediatric patients. METHODS: This was a single-center, retrospective cohort study in patients younger than 19 years who underwent surgical repair of CoA between January 1, 2016, and September 30, 2021. Patients were divided into 2 groups: dexmedetomidine initiation within the first 3 hours after surgery or no dexmedetomidine. The primary outcome was incidence of hypertension within the first 4 to 24 hours after repair. Secondary outcomes included the incidence of hypotension and bradycardia. RESULTS: A total of 80 patients were included, 25 (31.25%) received dexmedetomidine. Median age at the time of procedure was 26 days (IQR, 13-241) in the dexmedetomidine group and 14 days (IQR, 8-53) in the no dexmedetomidine group (p = 0.014). The primary outcome of hypertension was met in 7 patients (28%) in the dexmedetomidine group and 12 patients (21.8%) in the no dexmedetomidine group, p = 0.547. The only variable found to be associated with the incidence of hypertension was age greater than 30 days at the time of procedure. More patients who received dexmedetomidine experienced bradycardia. There was no difference in the incidence of hypotension. CONCLUSIONS: There was no association between the use of dexmedetomidine and the incidence of -hypertension following repair of CoA in pediatric patients.

Current Practices and Safety of Medication Use During Pediatric Rapid Sequence Intubation.

OBJECTIVES: This study aimed to characterize medication-related practices during and immediately -following rapid sequence intubation (RSI) in pediatric care units across the United States and to evaluate adverse drug events. METHODS: This was a multicenter, observational study of medication practices surrounding intubation in pediatric and neonatal intensive care unit (NICU) and emergency department patients across the United States. RESULTS: A total of 172 patients from 13 geographically diverse institutions were included. Overall, 24%, 69%, and 50% received preinduction, induction, and neuromuscular blockade, respectively. Induction and neuromuscular blocking agent (NMBA) use was low in NICU patients (52% and 23%, respectively), whereas nearly all patients intubated outside of the NICU received both (98% and 95%, respectively). NICU patients who received RSI medications were older and weighed more. Despite infrequent use of atropine (21%), only 3 patients developed bradycardia after RSI. Of the 119 patients who received an induction agent, fentanyl (67%) and midazolam (34%) were administered most frequently. Hypotension and hypertension occurred in 23% and 24% of patients, respectively, but were not associated with a single induction agent. Etomidate use was low and not associated with development of adrenal insufficiency. Rocuronium was the most used NMBA (78%). Succinylcholine use was low (11%) and administered despite hyperkalemia in 2 patients. Postintubation sedation and analgesia were not used or inadequate based on timing of initiation in many patients who received a non-depolarizing NMBA. CONCLUSIONS: Medication practices surrounding pediatric RSI vary across the United States and may be influenced by patient location, age, and weight.

Enoxaparin Reduces Catheter-associated Venous Thrombosis After Infant Cardiac Surgery.

BACKGROUND: Central venous catheter (CVC) related venous thrombosis (VT) after pediatric cardiac surgery increases morbidity and mortality. Although VT prevention using low-dose anticoagulation therapy has proven ineffective, anticoagulation therapy using high-dose enoxaparin to achieve a therapeutic anti-Xa level has not been studied. We hypothesized that high-dose enoxaparin would reduce VT after pediatric cardiac surgery. METHODS: Enoxaparin was administered to infants aged less than 150 days when postoperative CVC duration was anticipated to extend beyond 5 days. The primary outcome was the rate of VT, reexploration for bleeding, and postoperative red blood cell transfusions per 1000 CVC days. RESULTS: From 2012 to 2019, 157 infants were treated with enoxaparin. Infants were divided into two groups: (1) subtherapeutic (n = 51), in which therapeutic anti-Xa level (0.5 to 1.0 IU/mL) was not achieved; and (2) therapeutic (n = 106), in which therapeutic anti-Xa level was achieved. Baseline demographics demonstrated a lower age at operation in the therapeutic group. The subtherapeutic group had a higher VT rate per 1000 CVC days (8.2) compared with the therapeutic group (2.6; P = .005). Reexploration for bleeding was similar between groups. The number of postoperative red blood cell transfusions per 1000 CVC days was significantly greater in the subtherapeutic group (109.4 vs 81.6; P = .008). Multivariate analysis demonstrated that higher median anti-Xa levels reduced the risk of VT (odds ratio 0.02; 95% confidence interval, 0.001 to 0.63; P = .02). CONCLUSIONS: These data suggest that enoxaparin treatment resulting in a therapeutic anti-Xa level reduces postoperative CVC-associated VT without increasing bleeding complications.

The Rochester Relapse Risk Scale: Developing a Standardized Approach to Predicting Substance Relapse in Liver Transplant Candidates.

OBJECTIVES: Substance abuse is a risk factor for nonadherence and graft failure after orthotopic liver transplant. This study aimed to evaluate the ability of an internally developed tool, the Rochester Relapse Risk Scale, to predict substance relapse in liver transplant candidates. MATERIALS AND METHODS: This single-center, retrospective, observational study included adult patients evaluated for orthotopic liver transplant using the Rochester Relapse Risk Scale. Primary outcome was rate of substance relapse, as measured by the risk scale, which stratified patients into relapse risk levels based on the number of factors present. RESULTS: In total, 303 patients (71.6% men, 90.4% White, median age of 55 years [interquartile range, 49-60 y]) were included. Median follow-up time was 212 days (interquartile range, 73-661 d). Seventy-four patients (24.4%) relapsed at 127 days (interquartile range, 55-461 d) after evaluation, with 60.8% who relapsed within 6 months. Relapse rates correlated with assigned risk level, with 8.3% relapsing at low, 19.0% at low-moderate, 25.3% at moderate, 33.8% at moderate-high, and 40.0% at high risk. High-risk cohorts had significantly shorter median time to relapse versus low-risk cohorts (104 vs 154 days; P = .001). CONCLUSIONS: Assignment of relapse risk level according to the Rochester Relapse Risk Scale aligned with rates of relapse. Additional studies are needed to refine the tool, assess inter-rater reliability, and confirm findings in prospective, multicenter studies.

Escalation in Therapy Based on Intravenous Magnesium Sulfate Dosing in Pediatric Patients With Asthma Exacerbations.

OBJECTIVE: Our objective was to compare doses of intravenous magnesium sulfate and their association with escalations in therapy in children and adolescents presenting to the emergency department with an asthma exacerbation. METHODS: This was a retrospective cohort study among children who received both magnesium sulfate and standard of care therapy for asthma exacerbations. A classification and regression tree (CART) analysis was performed to identify a breakpoint in dose in which a difference in the primary outcome was present. The primary endpoint was need for escalation in therapy within 24 hours of initial magnesium sulfate dose, defined as need for invasive or non-invasive mechanical ventilation or need for adjunctive therapy, that is, epinephrine, terbutaline, aminophylline, theophylline, ketamine, heliox, or additional doses of magnesium sulfate. RESULTS: A total of 210 patients were included in the study. A CART analysis identified that a breakpoint of 27 mg/kg of magnesium was associated with a difference in the primary outcome of escalation in therapy in patients <40 kg. A subgroup analysis of patients <40 kg (n = 149) found patients who received magnesium doses >27 mg/kg had a higher incidence of the primary outcome of escalation in therapy, 15 patients (18.3%) versus 3 patients (4.5%) in the ≤27-mg/kg/dose group (p = 0.011). CONCLUSIONS: Our results demonstrate larger doses of magnesium sulfate are associated with an increased need for invasive or non-invasive mechanical ventilation or need for adjunctive therapy(ies). Our findings are limited by confounding factors that may have influenced this outcome in our population.

Stability of Extemporaneously Prepared Sodium Benzoate Oral Suspension.

The stability of extemporaneously prepared sodium benzoate oral suspension in cherry syrup and Ora-Sweet was studied. Oral solutions of 250-mg/mL sodium benzoate were prepared in either cherry syrup or Ora-Sweet. To a beaker, 50 grams of Sodium Benzoate Powder USP was dissolved and filtered, the solution was divided equally into two parts, and each aliquot was added into two separate calibrated 100-mL amber vials. In the first vial, cherry syrup was added to make a final volume of 100 mL. In the second vial, Ora-Sweet was added to give a final volume of 100 mL. This process was repeated to prepare three solutions of each kind and all were stored at room temperature. A 250-µL sample was withdrawn immediately after preparation and again at 7, 14, 28, 60, and 90 days for each sample. At each time point, further dilution was made to an expected concentration of 0.25 mg/mL with sample diluent, and the samples were assayed in triplicate by stability-indicating high-performance liquid chromatography. Stability was defined as the retention of at least 90% of the initial concentration. At least 92% of the initial concentration of sodium benzoate in cherry syrup and at least 96% of the sodium benzoate in Ora-Sweet remained throughout the 90-day study period. There were no detectable changes in color and no visible microbial growth in any sample. Extemporaneously compounded suspensions of sodium benzoate in cherry syrup or Ora-Sweet were stable for at least 90 days when stored in a 4-oz amber plastic bottle at room temperature in reduced lighting.

Stability of extemporaneously prepared cinacalcet oral suspensions.

PURPOSE: The stability of extemporaneously prepared cinacalcet suspensions over 90 days was evaluated. METHODS: Cinacalcet 5-mg/mL suspension was prepared by triturating 30-mg cinacalcet tablets. Twelve 30-mL batches were prepared with a 1:1 mixture of Ora-Plus and either Ora-Sweet or Ora-Sweet SF (sugar free). Three suspensions of each kind were stored at both room temperature and refrigerated conditions. A 1-mL sample was taken from each bottle at 0, 7, 18, 32, 64, and 90 days. Each sample was assayed using high-performance liquid chromatography (HPLC). A new HPLC method for evaluating drug peaks of pure cinacalcet was developed. Stability was defined as retention of at least 90% of the initial drug concentration. RESULTS: The HPLC method established in this study serves as a novel assay for evaluating cinacalcet oral suspensions. For all suspensions tested at individual conditions, the concentration remained above 90% of the initial concentration for 90 days of storage with the exception of Ora-Plus and Ora-Sweet SF suspensions stored under refrigeration, which were stable for 64 days. Usual sedimentation of the suspensions occurred over time but resolved with agitation; there was no other change in visual appearance of the suspensions over the course of the 90-day study. The color and odor of the suspensions throughout the study remained unchanged with respect to the initial time point. CONCLUSION: Extemporaneously compounded cinacalcet 5-mg/mL oral suspensions prepared with a 1:1 mixture of Ora-Plus and either Ora-Sweet or Ora-Sweet SF and stored in 2-oz amber polypropylene plastic bottles were stable for at least 64 days at room temperature and under refrigeration.

Methadone and Corrected QT Prolongation in Pain and Palliative Care Patients: A Case-Control Study.

BACKGROUND: Methadone (ME) is commonly used in pain and palliative care (PPC) patients with refractory pain or intolerable opioid adverse effects (AEs). A unique ME AE is its corrected QT (QTc) interval prolongation risk, but most evidence exists in methadone maintenance therapy patients. OBJECTIVE: Our goal was to identify QTc interval prolongation risk factors in PPC patients receiving ME and other medications known to prolong the QTc interval and develop a risk stratification tool. DESIGN: We performed a case-control study of adult inpatients receiving ME for pain management. Settings/Subjects: Adult inpatients receiving ME with a QTc >470 msec (males) and >480 msec (females) were matched 1:2 according to age, history of QTc prolongation, and gender with ME patients who did not have a prolonged QTc interval. QTc prolongation risk factors were collected for both groups. Covariates were analyzed using conditional logistic regression. Classification and regression tree analysis was used to identify the ME dose associated with QTc prolongation. RESULTS: Predictors of QTc prolongation included congestive heart failure (CHF) (OR: 11.9; 95% CI: 3.7-38.2; p < 0.00), peptic ulcer disease (PUD) (odds ratio [OR]: 8.3; 95% confidence interval [95% CI]: 2.4-28.9; p < 0.00), hypokalemia (OR: 6.5; 95% CI: 1.5-28.2; p < 0.01), rheumatologic diseases (OR: 4.7; 95% CI: 1.6-13.9; p < 0.00), taking medications with a known torsades de pointes (TdP) risk (OR: 4.4; 95% CI: 1.8-10.7; p < 0.01), malignancy (OR: 3.3; 95% CI: 1.2-9.3; p < 0.03), hypocalcemia (OR: 2.1; 95% CI: 0.9-4.8; p < 0.07), and ME doses >45 mg per day (OR: 1.9; 95% CI: 0.8-4.8; p < 0.16). Mild liver disease was protective against QTc prolongation (OR: 0.05; 95% CI: 0.0-0.46; p < 0.01). CONCLUSIONS: Predictors of QTc prolongation in our multivariate conditional logistic regression model included CHF, PUD, hypokalemia, rheumatologic disorders, use of medications with a known TdP risk, malignancy, hypocalcemia, and ME doses >45 mg per day.

Education in pediatrics in US colleges and schools of pharmacy.

OBJECTIVE: To determine the extent to which pediatrics is taught at US doctor of pharmacy (PharmD) programs and to characterize what is being taught and how. METHODS: A 40-question online survey instrument was sent to accredited and candidate-status US PharmD programs. RESULTS: Of 86 participating programs (67.2% response rate), 81 (94.2%) indicated that pediatric topics were included in their required classroom curricula (mean, 21.9 contact hours). A pediatric elective course was offered by 61.0% of programs (mean, 25.9 contact hours). Advanced pharmacy practice experiences (APPEs) in pediatrics were offered by 97.4% of programs, with an average of 27 students per program completing this practice experience annually. CONCLUSIONS: Almost all responding programs incorporated pediatrics in their required curricula. Pediatric elective courses provided an adequate mean number of contact hours, but 39.0% of programs did not offer an elective course. One-fifth of students completed a pediatric APPE prior to graduation. Continued expansion of pediatric-focused classroom and experiential curricula across US PharmD programs is recommended.

Stability of diluted adenosine solutions in polyvinyl chloride infusion bags.

PURPOSE: The stability of diluted adenosine solutions in polyvinyl chloride infusion bags was studied. METHODS: Adenosine 50-, 100-, and 220-µg/mL solutions were prepared in 50-mL polyvinyl chloride (PVC) infusion bags containing 0.9% sodium chloride injection or 5% dextrose injection and stored at room temperature (23-25 °C) or under refrigeration (2-8 °C). Each sample of every combination of concentration, diluent, and storage temperature was prepared in triplicate, yielding 36 samples. The samples were assayed using a stability-indicating, reverse-phase high-performance liquid chromatographic method immediately after preparation (time zero) and at 24 hours, 48 hours, 7 days, and 14 days. pH was measured at time zero, 48 hours, 7 days, and 14 days. Time zero concentrations were calculated from the equation produced from a calibration curve of standards ranging from 10 to 500 µg/mL. Samples were also visually inspected against a light background for clarity, color, and the presence of crystalline particulate matter. Stability was defined as retaining at least 90% of the initial adenosine concentration. RESULTS: After 14 days, all samples retained greater than 98% of the initial adenosine concentration, with no evidence of adsorption, visible precipitation, or considerable change in pH, suggesting minimal to no loss of product due to degradation or adsorption. CONCLUSION: Adenosine 50-, 100-, and 220-µg/mL solutions in 50-mL PVC infusion bags containing 0.9% sodium chloride injection or 5% dextrose injection stored at room temperature and refrigerated conditions were stable for at least 14 days.

Respiratory Syncytial Virus Prophylaxis in Special Populations: Is it Something Worth Considering in Cystic Fibrosis and Immunosuppression?

Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of infant hospitalization in the United States. Prophylaxis with palivizumab is effective in reducing RSV hospitalizations in premature infants and in infants or children with chronic lung disease or congenital heart disease. Patients with CF or those who are immunocompromised may be at increased risk for RSV infection-related complications; hence, prophylaxis may prove beneficial to these populations. The extent of palivizumab use in the CF and immunocompromised populations is variable. Palivizumab appears to be safe and may be effective in infants and young children with CF and immunocompromise. However, well-designed, randomized, controlled trials published in peer-reviewed journals are lacking, and its routine use can therefore not be recommended at this time. If used in patients with CF or those who are immunocompromised, RSV prophylaxis should be restricted to peak outbreak months in order to optimize the cost benefit of palivizumab.

Monocarboxylate Transporter Inhibition with Osmotic Diuresis Increases γ-Hydroxybutyrate Renal Elimination in Humans: A Proof-of-Concept Study.

BACKGROUND AND OBJECTIVE: The purpose of the current study was to demonstrate proof-of-concept that monocarboxylate transporter (MCT) inhibition with L-lactate combined with osmotic diuresis increases renal clearance of γ-hydroxybutyrate (GHB) in human subjects. GHB is a substrate for human and rodent MCTs, which are responsible for GHB renal reabsorption, and this therapy increases GHB renal clearance in rats. METHODS: Ten healthy volunteers were administered GHB orally as sodium oxybate 50 mg/kg (4.5 gm maximum dose) on two different study days. On study day 1, GHB was administered alone. On study day 2, treatment of L-lactate 0.125 mmol/kg and mannitol 200 mg/kg followed by L-lactate 0.75 mmol/kg/hr was administered intravenously 30 minutes after GHB ingestion. Blood and urine were collected for 6 hours, analyzed for GHB, and pharmacokinetic and statistical analyses performed. RESULTS: L-lactate/mannitol administration significantly increased GHB renal clearance compared to GHB alone, 439 vs. 615 mL/hr (P=0.001), and increased the percentage of GHB dose excreted in the urine, 2.2 vs. 3.3% (P=0.021). Total clearance was unchanged. CONCLUSIONS: MCT inhibition with L-lactate combined with osmotic diuresis increases GHB renal elimination in humans. No effect on total clearance was observed in this study due to the negligible contribution of renal clearance to total clearance at this low GHB dose. Considering the nonlinear renal elimination of GHB, further research in overdose cases is warranted to assess the efficacy of this treatment strategy for increasing renal and total clearance at high GHB doses.

Treatment of hypervolemic or euvolemic hyponatremia associated with heart failure, cirrhosis, or the syndrome of inappropriate antidiuretic hormone with tolvaptan: a clinical review.

BACKGROUND: Tolvaptan is an oral nonpeptide selective vasopressin V(2)-receptor antagonist indicated for the treatment of clinically relevant hypervolemic or euvolemic hyponatremia associated with heart failure, cirrhosis, or syndrome of inappropriate antidiuretic hormone. OBJECTIVE: The objective of this article was to review the pharmacology, efficacy, and tolerability of tolvaptan in the treatment of hypervolemic or euvolemic hyponatremia, heart failure, and autosomal dominant polycystic kidney disease (ADPKD). METHODS: Articles were identified using MEDLINE (1966-February 28, 2010) and EMBASE (1947-February 28, 2010). Abstracts and proceedings from the annual meetings (2007-2009) of the American Heart Association, the European Society of Cardiology, and the American Society of Nephrology were searched to identify additional relevant publications. Searches were conducted using the terms tolvaptan, vasopressin antagonist, heart failure, polycystic kidney disease, hyponatremia, drug interaction, pharmacokinetics, and pharmacology. The reference lists of the identified publications were reviewed for additional references. All clinical trials that assessed the use of tolvaptan in the management of hypervolemic/euvolemic hyponatremia or heart failure in humans were included, regardless of study design. RESULTS: A total of 9 trials were identified. For the treatment of hyponatremia, tolvaptan was associated with significantly increased serum sodium concentrations compared with placebo on treatment days 4 (3.62 [2.68] vs 0.25 [2.08] mmol/L, respectively; P < 0.001) and 30 (6.22 [4.10] vs 1.66 [3.59] mmol/L; P < 0.001). In the clinical trials in patients with heart failure, tolvaptan at doses of 30, 60, and 90 mg/d was associated with mean weight changes of -1.80, -2.10, and -2.05 kg, respectively, versus -0.60 kg with placebo (P = 0.002, P = 0.002, and P = 0.009). Trials of tolvaptan in humans with ADPKD are ongoing. Overall, mortality rates were not significantly altered with tolvaptan compared with placebo (25.9% vs 26.3%). The most commonly reported adverse events associated with tolvaptan in clinical trials were dry mouth (4.2%-23.0%), thirst (7.7%-40.3%), and polyuria (0.6%-31.7%), all consistent with the mechanism of action of the drug. CONCLUSION: Based on findings from clinical trials to date, tolvaptan is effective for the correction of hyponatremia but has not been associated with significant improvements in mortality in patients with heart failure compared with placebo, and its utility in the treatment of ADPKD in humans remains to be determined.

Stability of extemporaneously prepared rufinamide oral suspensions.

BACKGROUND: Rufinamide is an oral antiepileptic drug indicated for adjunctive therapy in treating generalized seizures associated with Lennox-Gastaut syndrome. Currently, rufinamide is available as 200-mg and 400-mg tablets. A liquid dosage form does not exist at the present time. Lack of a suspension formulation may present an administration problem for many children and adults who are unable to swallow tablets. The availability of a liquid dosage form will provide an easy and accurate way to measure and administer the medication. OBJECTIVE: To determine the stability of both sugar-containing and sugar-free rufinamide suspensions over a 90-day period. METHODS: A suspension of rufinamide 40 mg/mL was prepared by grinding twelve 400-mg tablets of rufinamide tablets in a glass mortar. Sixty milliliters of Ora-Plus and 60 mL of either Ora-Sweet or Ora-Sweet SF (sugar free) were mixed and added to the powder to make a final volume of 120 mL. Three identical samples of each formulation were prepared and placed in 60-mL amber plastic bottles and were stored at room temperature. A 1-mL sample was withdrawn from each of the 6 bottles with a micropipette immediately after preparation and at 7, 14, 28, 56, and 90 days. After further dilution to an expected concentration of 0.4 mg/mL, the samples were assayed using high-performance liquid chromatography. Stability was defined as the retention of at least 90% of the initial concentration. RESULTS: At least 90% of the initial rufinamide concentration remained throughout the 90-day study period in both preparations. There were no detectable changes in color, odor, taste, and pH and no visible microbial growth. CONCLUSIONS: Extemporaneously compounded suspensions of rufinamide 40 mg/mL in a 1:1 mixture of Ora-Plus and Ora-Sweet or Ora-Sweet SF were stable for at least 90 days when stored in 59-mL amber polypropylene plastic bottles at room temperature.

Stability of extemporaneously prepared moxifloxacin oral suspensions.

PURPOSE: The stability of extemporaneously prepared moxifloxacin oral suspensions was studied. METHODS: An oral suspension of moxifloxacin 20 mg/mL was prepared by thoroughly grinding three 400-mg tablets of moxifloxacin in a glass mortar. Thirty milliliters of Ora-Plus and 30 mL of either Ora-Sweet or Ora-Sweet SF were mixed and added to the powder to make a final volume of 60 mL. Three identical samples of each formulation were prepared and placed in 2-oz amber plastic bottles with child-resistant caps and were stored at room temperature (23-25 degrees C). A 1-mL sample was withdrawn from each of the six bottles with a micropipette immediately after preparation and at 7, 14, 28, 60, and 90 days. After further dilution to an expected concentration of 8 microg/ mL with sample diluent, the samples were assayed in duplicate by stability-indicating high-performance liquid chromatography. Stability was defined as the retention of at least 90% of the initial concentration. RESULTS: At least 99% of the initial moxifloxacin remained throughout the 90-day study period in both preparations. There were no detectable changes in color, odor, taste, and pH and no visible microbial growth in any sample. CONCLUSION: Extemporaneously compounded suspensions of moxifloxacin 20 mg/mL in a 1:1 mixture of Ora-Plus and Ora-Sweet or Ora-Sweet SF were stable for at least 90 days when stored in 2-oz amber plastic bottles at room temperature.

Human papillomavirus disease and vaccines.

PURPOSE: Human papillomavirus (HPV) disease and vaccines and several controversial issues associated with vaccine administration are reviewed. SUMMARY: HPV infection is the most common sexually transmitted disease in the United States. It is estimated that 20 million individuals are currently infected with HPV, with 6.2 million new infections occurring each year. Although most HPV infections are benign and are often cleared without clinical sequelae, persistent infections are associated with the development of cervical cancer in women and genital warts in both women and men. The identification of the most common disease-causing HPV types has led to the development of a quadrivalent vaccine and a bivalent vaccine. The prophylactic administration of the quadrivalent vaccine has resulted in a 96% efficacy in preventing persistent infection associated with HPV types 6, 11, 16, and 18. Similar to the quadrivalent vaccine, the bivalent vaccine is highly efficacious (96%) in preventing persistent infection against vaccine-specific HPV types (HPV-16 and HPV-18) among women who were HPV seronegative at the time of vaccination. However, many controversial issues still remain regarding routine administration and widespread acceptance. These include appropriate age at time of vaccination, parental concerns, vaccination of men or women age 26 years or older, inadequate long-term efficacy and safety data, and potential for nonvaccine-related strains to emerge as prominent oncogenic serotypes. CONCLUSION: HPV vaccines provide a high level of protection for seronegative women against persistent infection and precancerous cervical lesions associated with vaccine-specific HPV types. However, many controversial issues still remain regarding the vaccines' routine administration and widespread acceptance.