Comparison of Xpert® HPV and Hybrid Capture® 2 DNA Test™ for detection of high-risk HPV infection in cervical atypical squamous cells of undetermined significance.

This study compares Xpert® HPV and Hybrid Capture® 2 High-Risk HPV DNA Test™ (hc2) for the detection of high-risk HPV infection in cervical smears. Papanicolaou smears with atypical squamous cells of undetermined significance (ASC-US) constituted the study specimens. Of the 168 ASC-US samples, 134 (79.8%) were from Saudi patients. The hc2 test was positive in 33 (19.6%) of the total patients, 20% among Saudi patients, and 17.6% among non-Saudi patients. Xpert® HPV produced positive results in 30 (17.8%) of the samples. The overall concordance rate between the two tests was 98.2%, and the positive concordance rate was 91%. There were three samples tested positive by hc2 that tested negative by Xpert® HPV. HPV 16, HPV 18/45 and HPV other types were the most common types. Both tests have a reasonable positive concordance rate, although hc2 detected more cases than Xpert® HPV. Xpert® HPV provides a viable alternative to the hc2 test with similar detection results for samples with ASC-US.

Epidemiology and detection of acinetobacter using conventional culture and in-house developed PCR based methods.

Active surveillance cultures for multidrug-resistant (MDR) gram-negative bacteria is one strategy to control outbreaks. The objectives of the study are to evaluate the prevalence of Acinetobacter colonization and to compare conventional culture and in-house developed PCR based method. Swabs were collected from patients transferred from another organization or were admitted to the intensive care units. Swabs were cultured by conventional method and were tested using in-house LightCycler® 2.0 real-time PCR method. Of 449 tested samples, the majority came from cardiac step down unit (188, 42%), male medical floor (80; 18%), and coronary care unit (66; 13.4%). Of the total specimens, 14 (3%) were positive by PCR and 12 (2.6%) were positive by routine cultures. The positivity rates among wounds, respiratory, perineal, and nasal samples were 3.2%, 9.7%, 4.6% and 0.8% respectively. Two positive samples by PCR were negative by routine culture. The overall concordance rate was 99.5% and the positive concordance rate was 85.7%. The current study revealed a low prevalence of MDR Acinetobacter among the studied population. The LightCycler® 2.0 PCR produced comparable positive results to routine cultures.

Single-dose fentanyl sublingual spray for breakthrough cancer pain.

Breakthrough cancer pain (BTCP) is defined as a transient exacerbation of pain that arises in patients with otherwise controlled persistent pain. BTCP typically has a rapid onset and relatively short duration, but it causes a significant amount of physical and psychological distress for patients. Several rapid-onset fentanyl formulations have been introduced in the USA to replace traditional oral opioids for the treatment of BTCP: a transmucosal lozenge, a sublingual orally disintegrating tablet, a buccal tablet, a buccal soluble film, a pectin nasal spray and, the newest formulation to enter the market, a sublingual spray. This article reviews the six rapid-onset formulations of fentanyl approved in the USA for the management of BTCP with emphasis on describing the published literature on fentanyl sublingual spray. The different fentanyl formulations vary in pharmacokinetic properties and ease of use, but all have a rapid onset and a relatively short duration of analgesia. Fentanyl sublingual spray has demonstrated absorption within 5 minutes of administration, with fentanyl plasma concentrations increasing over the first 30 minutes and remaining elevated for 60-90 minutes in pharmacokinetic studies in healthy subjects. Fentanyl sublingual spray shows linear dose proportionality, and changes in the temperature or acidity of the oral cavity do not alter its pharmacokinetic properties. In patients with BTCP, statistically significant pain relief is measurable at 5 minutes after administration of fentanyl sublingual spray, when compared with placebo, with significant pain relief lasting at least 60 minutes after administration. Adverse events are typical of opioid treatment and are considered mild to moderate in intensity. In summary, fentanyl sublingual spray provides rapid onset of analgesia and is a tolerable and effective treatment for BTCP.

Safety and tolerability of OROS® hydromorphone ER in adults with chronic noncancer and cancer pain: pooled analysis of 13 studies.

OBJECTIVE: This analysis was designed to assess the pooled safety and tolerability of once-daily hydromorphone extended release (ER) (OROS® hydromorphone ER) in opioid-naïve and opioid-tolerant patients with chronic cancer or noncancer pain. DESIGN: Safety results were pooled from 13 controlled and uncontrolled clinical studies, with varying approaches to dosing and titration, pain etiology, and duration of exposure. PATIENTS AND INTERVENTIONS: Of the 3,075 patients in the pooled population, 2,335 (76 percent) received at least one dose of OROS hydromorphone ER, with a duration of dosing of up to 1.5 years; 420 patients were treated for at least 6 months and 141 for longer than 1 year. MAIN OUTCOME MEASURES: The primary outcome measure was the occurrence of adverse events (AEs). Descriptive statistics were used to analyze the incidence of AEs in the overall population as well as according to baseline characteristics. RESULTS: Overall AE incidence with OROS hydromorphone ER treatment was 80.5 percent (1,880/2,335 patients). The most common treatment-related AEs were constipation (28.9 percent, 674 patients) and nausea (22.7 percent, 529 patients), and most cases were mild to moderate in severity. The incidence of overall AEs did not undergo a notable change over time. Opioid-related AEs were higher in patients ≥65 years of age, female patients, and opioid-naïve patients. Serious adverse events (SAEs) were reported by 10.2 percent (239) of patients. A total of 64 deaths occurred, none of which were considered related to OROS hydromorphone ER treatment. CONCLUSIONS: OROS hydromorphone was generally well tolerated in short- and long-term studies and demonstrated a consistent AE profile over time.

Fentanyl pectin nasal spray for breakthrough cancer pain.

Optimal management of breakthrough cancer pain (BTCP) requires analgesics with a rapid onset of action, consistent efficacy, improved patient acceptability and tolerability and ease of use. Fentanyl pectin nasal spray (FPNS) incorporates a proprietary pectin-based gelling agent to enhance absorption and produce a faster onset of action and consistent plasma concentration. FPNS is indicated for the treatment of breakthrough pain in cancer patients who are tolerant to opioid therapy for their underlying persistent cancer pain. FPNS has been evaluated in clinical studies in patients with BTCP and shown to be effective, safe and well tolerated. In addition, FPNS has demonstrated high levels of patient satisfaction, convenience and ease of use. FPNS therefore represents an important addition to the treatment options for BTCP.

Efficacy and tolerability of cyclobenzaprine extended release for acute muscle spasm: a pooled analysis.

OBJECTIVE: To assess the efficacy and tolerability of once-daily cyclobenzaprine extended release (CER) 15 and 30 mg in relieving acute muscle spasm. METHODS: This is a pooled analysis of 2 randomized, double-blind, placebo-controlled, parallel-group studies of identical design. Adults with local muscle spasm associated with neck/low back pain were randomized to treatment with once-daily CER 15 (n = 127) or 30 mg (n = 126), cyclobenzaprine immediate release (CIR) 10 mg 3 times daily (n = 123), or placebo (n = 128) for 14 days. Primary outcome measures were the patient's rating of medication helpfulness and physician's clinical global assessment of response to therapy at day 4. RESULTS: Of 504 patients, 330 (65.5%) completed the studies. Significantly greater improvements in patient's rating of medication helpfulness were reported with CER 15 and 30 mg versus placebo at day 4 (P < 0.025). No differences were reported between groups in physician's clinical global assessment. Significantly greater improvements (P < 0.025) were noted in patient-rated secondary measures versus placebo: relief from local pain at days 4 (CER 30 mg) and 8 (CER 15 and 30 mg), global impression of change at days 4 and 8 (CER 30 mg), and restriction of movement at day 4 (CER 30 mg). Improvements with CER 15 and 30 mg on most efficacy measures were similar to CIR. There was less reported daytime drowsiness with CER 15 and 30 mg than with CIR (P < 0.05). Most adverse events (AEs) were mild in intensity. The most common AEs for all groups were dry mouth, constipation, dizziness, headache, and somnolence. The rate of somnolence reported as an AE was lower (P < 0.05) with CER 15 (0.8%) and 30 mg (1.6%) than with CIR (7.3%). CONCLUSION: Once-daily CER was effective in relieving acute muscle spasm based on patient's rating of medication helpfulness at day 4 and was generally well tolerated with a low rate of reported somnolence.

Fentanyl buccal tablet: rapid relief from breakthrough pain.

Breakthrough pain--a transient increase in pain occurring over a baseline of controlled persistent pain--represents an important clinical challenge in the management of cancer and other chronic pain conditions. The fentanyl buccal tablet is a new sugar-free, easily-administered formulation that uses an effervescent drug delivery system to enhance the rate and extent of fentanyl absorption across the buccal mucosa. Clinical trials indicate that the rapid systemic exposure provided by fentanyl buccal tablets translates into clinically significant improvements in pain intensity. Pain relief is observed within 10-15 min of administration. Fentanyl buccal tablets are generally well tolerated, with the most commonly observed adverse events being typical opioid side effects. Fentanyl buccal tablets represent a convenient and effective treatment for the control of breakthrough pain.

Calcium carbonate gallstones in children.

BACKGROUND: In the United States, cholesterol stones account for 70% to 95% of adult gallstones and black pigment stones for most of the remainder. Calcium carbonate stones are exceptionally rare. A previous analysis of a small number of pediatric gallstones from the north of England showed a remarkably high prevalence of calcium carbonate stones. The aims of this study were to analyze a much larger series of pediatric gallstones from our region and to compare their chemical composition with a series of adult gallstones from the same geographic area. METHODS: A consecutive series of gallbladder stones from 63 children and 50 adults from the north of England were analyzed in detail using Fourier transform infrared microspectroscopy. Demographic and clinical data were collected on all patients. The relative proportions of each major stone component were assessed: cholesterol, protein and calcium salts of bilirubin, fatty acids, calcium carbonate, and hydroxyapatite. RESULTS: Thirty-nine (78%) adults had typical cholesterol stones, 7 (14%) had black pigment bilirubinate stones, and only 2 (4%) had calcium carbonate stones. In contrast, 30 (48%) children had black pigment stones, 13 (21%) had cholesterol stones, 15 (24%) had calcium carbonate stones, 3 (5%) had protein dominant stones, and 2 (3%) had brown pigment stones. In children, cholesterol stones were more likely in overweight adolescent girls with a family history of gallstones, whereas black pigment stones were equally common in boys and girls and associated with hemolysis, parenteral nutrition, and neonatal abdominal surgery. Calcium carbonate stones were more common in boys, and almost half had undergone neonatal abdominal surgery and/or required neonatal intensive care. CONCLUSION: The composition of pediatric gallstones differs significantly from that found in adults. In particular, one quarter of the children in this series had calcium carbonate stones, previously considered rare. Geographic differences are not the major reason for the high prevalence of calcium carbonate gallstones in children.

Impact of breakthrough pain on quality of life in patients with chronic, noncancer pain: patient perceptions and effect of treatment with oral transmucosal fentanyl citrate (OTFC, ACTIQ).

OBJECTIVE: To characterize breakthrough pain (BTP), its qualitative impact on quality of life (QoL), and the effects of BTP treatment on QoL. DESIGN: Multicenter patient-reported survey. SETTING: Five pain treatment centers. PATIENTS: Fifty-six adults with chronic noncancer pain using oral transmucosal fentanyl citrate (OTFC, ACTIQ). RESULTS: Forty-three patients qualified for in-depth analysis. BTP had a mean intensity of 9.0 (range 5-10) on an 11-point numerical scale (0 = no pain to 10 = worst possible pain), had a mean duration of 83 minutes, and had an adverse effect on multiple QoL domains. The largest negative QoL impacts were on "general activity level" and "ability to work." OTFC had a positive impact on both controlling BTP and improving QoL. CONCLUSIONS: BTP appears to be a clinically important condition in this population and is associated with an adverse impact on QoL. Understanding those QoL domains most affected by BTP and those potentially improved with treatment should help in developing quantitative QoL assessment tools and other outcome measures for BTP management studies.

Gallbladder mucin production and calcium carbonate gallstones in children.

In contrast to adults, calcium carbonate gallstones are relatively common in children. Their pathogenesis is poorly understood. Cystic duct obstruction promotes calcium carbonate formation in bile and increases gallbladder mucin production. We tested the hypothesis that mucin producing epithelial cells would be increased in gallbladders of children with calcium carbonate gallstones. Archival gallbladder specimens from 20 consecutive children who had undergone elective cholecystectomy for cholelithiasis were examined. In each case, gallstone composition was determined by Fourier transform infrared microspectroscopy. Gallbladder specimens from six children who had undergone cholecystectomy for conditions other than cholelithiasis during the same period were used as controls. Multiple sections were examined in a blinded fashion and scored semiquantitatively for mucin production using two stains (alcian blue and periodic acid-Schiff). Increased mucin staining was observed in 50% or more epithelial cells in five gallbladder specimens from seven children with calcium carbonate stones, compared to 5 of 13 with other stone types (P = 0.17) and none of the control gallbladders (P = 0.02). Gallbladders containing calcium carbonate stones were significantly more likely than those containing other stone types or controls to contain epithelial cells with the greatest mucin content (P = 0.03). Gallbladders containing calcium carbonate stones were also more likely to show the ulcer-associated cell lineage. These results demonstrate an increase in mucin producing epithelial cells in gallbladders from children containing calcium carbonate stones. This supports the hypothesis that cystic duct obstruction leading to increased gallbladder mucin production may play a role in the development of calcium carbonate gallstones in children.

Maternal and fetal outcomes of spontaneous preterm premature rupture of membranes.

The authors retrospectively evaluated maternal and fetal outcomes of 73 consecutive singleton pregnancies complicated by preterm premature rupture of amniotic membranes. When preterm labor occurred and fetuses were at a viable gestational age, pregnant patients were managed aggressively with tocolytic therapy, antenatal corticosteroid injections, and antenatal fetal testing. The mean gestational age at the onset of membrane rupture and delivery was 22.1 weeks and 23.8 weeks, respectively. The latency from membrane rupture to delivery ranged from 0 to 83 days with a mean of 8.6 days. Among the 73 pregnant patients, there were 22 (30.1%) stillbirths and 13 (17.8%) neonatal deaths, resulting in a perinatal death rate of 47.9%. The perinatal survival rate based on gestational age at the onset of fetal membrane rupture was 12.1% at less than 23 weeks of gestation, 60% at 23 weeks, and 100% at 24 to 26 weeks. Maternal morbidity was minimal with puerperal endomyometritis in 5 (6.8%) cases, one of which became septic; however, there was no long-term sequela. Eight (15.7%) liveborn infants had pulmonary hypoplasia, 5 (62.5%) of which resulted in neonatal death. In 33 (45.2%) patients, amniotic membranes ruptured before 23 weeks of gestation. At previable gestational age, the risk of neonatal pulmonary hypoplasia appears to be primarily dependent on gestational age at the onset of premature rupture of membrane rather than gestational age at delivery. Pregnancy outcomes remain dismal when the fetal membrane ruptures before 23 weeks of gestation.

Gallstone composition: are children different?

During a 5-year period (1997-2002) 20 consecutive children (11 boys; median age, 8 years; range, 0.3-13.9 years) underwent cholecystectomy for cholelithiasis at a regional pediatric surgical center. Multiple stones were present in 16 patients (80%). All stones were collected prospectively. Composition studies were performed after grinding an aliquot of stone and examining a layer of crushed powder by Fourier transform infrared microspectroscopy. The relative proportions of each major stone component were assessed: cholesterol, protein and calcium salts of bilirubin, fatty acids, carbonate, and hydroxyapatite. Of the 20 children, 10 had black pigment stones, 2 had cholesterol stones, 1 had brown pigment stones, and 7 had calcium carbonate stones; the latter are exceptionally rare in adults. The composition of pediatric gallstones in this series differs from that found in adults.

Uterine rupture with the use of PGE2 vaginal inserts for labor induction in women with previous cesarean sections.

OBJECTIVE: To analyze the rate of uterine rupture in women with previous cesarean sections undergoing a trial of labor in which a prostaglandin E2 (PGE2) vaginal insert was used. STUDY DESIGN: The study was based on a computerized search and review of pharmacy records, medical records and the pertinent literature. Pharmacy records were correlated with the medical records of all women undergoing a trial of labor after cesarean section over a 33-month period. RESULTS: Between January 1998 and September 2000, 13,544 patients delivered. Of these cases, 790 were vaginal trials of labor after previous cesarean section. A PGE2 vaginal insert was used in 58 of the patients. A total of 6 of these 58 patients (10.3%) experienced uterine rupture. This compares to a rupture rate of 1.1% (8/732) in deliveries not using PGE2 vaginal inserts. CONCLUSION: The risk of uterine rupture was significantly increased in patients undergoing a trial of labor after previous cesarean section when a PGE2 vaginal insert was used. Physicians need to be aware that using a PGE2 vaginal inserts for cervical ripening and/or induction of labor in women with a previous cesarean section might increase the risk of uterine rupture above the standard risk for vaginal birth after cesarean (VBAC) candidates. We recommend that all VBAC patients using a PGE2 vaginal insert be closely monitored for evidence of uterine rupture.