Assessment of attribution algorithms for resolving CIN3-related HPV genotype prevalence in mixed-genotype biopsy specimens using laser capture microdissection as the reference standard.

To make accurate determinations regarding potential and actual impact of HPV vaccine programs, precise estimates of genotype-specific contributions to disease are required for pre- and post-vaccine populations. Definitive determination of lesion-specific genotypes, particularly where multiple genotypes are detected in a sample, can be technically demanding and resource intensive; therefore, most prevalence studies use mathematical algorithms to adjust for multiple genotype detections. There are currently several algorithms, which can produce genotype estimates within a wide range of variability. The use of these for cervical cytology samples has recently been assessed for accuracy against a definitive reference standard, but none have yet been assessed for multiple-genotype-containing whole biopsy specimens. Using laser capture microdissection (LCM) on biopsy samples, lesion-specific genotype prevalence data were generated for a cohort of 516 young Australian women (aged 18-32 years) with cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ. Using whole tissue section genotype data from the same cohort, including 71 (13.7%) with multiple genotypes, lesion-associated genotype prevalence was estimated using four different attribution algorithms. The proportion of lesions attributable to HPV16 and HPV18 by LCM were 58.4% and 5%, respectively; hierarchical, proportional, single type/minimum and any type/maximum attribution estimates were comparable across genotypes. For analyses utilising whole tissue biopsy cervical specimens, attribution estimates are appropriate for estimating the proportional contribution of individual genotypes to lesions in a population.

Incorporating the American Pharmacists Association's Delivering Medication Therapy Management services certificate program into an accelerated pharmacy curriculum.

BACKGROUND AND PURPOSE: To describe the incorporation of the American Pharmacists Association (APhA) Delivering Medication Therapy Management (MTM) Services program into a PharmD curriculum and to describe student perceptions of the program. EDUCATIONAL ACTIVITY AND SETTING: The program was delivered over 12 months to students on two campuses via two didactic courses in the second professional year and during the first two advanced pharmacy practice experiences in the third professional year of an accelerated school of pharmacy program. FINDINGS: Student perceptions were assessed by review of responses to the APhA MTM program evaluation survey. DISCUSSION AND SUMMARY: Incorporation of the APhA MTM program into an accelerated PharmD program required careful planning and coordination amongst faculty and course coordinators. Students perceived that the program was valuable, met their educational needs, and incorporated effective learning experiences and cases. These perceptions were reinforced by the high percentage of students who completed the program.

Host immunity to Plasmodium falciparum and the assessment of emerging artemisinin resistance in a multinational cohort.

Artemisinin-resistant falciparum malaria, defined by a slow-clearance phenotype and the presence of kelch13 mutants, has emerged in the Greater Mekong Subregion. Naturally acquired immunity to malaria clears parasites independent of antimalarial drugs. We hypothesized that between- and within-population variations in host immunity influence parasite clearance after artemisinin treatment and the interpretation of emerging artemisinin resistance. Antibodies specific to 12 Plasmodium falciparum sporozoite and blood-stage antigens were determined in 959 patients (from 11 sites in Southeast Asia) participating in a multinational cohort study assessing parasite clearance half-life (PCt1/2) after artesunate treatment and kelch13 mutations. Linear mixed-effects modeling of pooled individual patient data assessed the association between antibody responses and PCt1/2.P. falciparum antibodies were lowest in areas where the prevalence of kelch13 mutations and slow PCt1/2 were highest [Spearman ρ = -0.90 (95% confidence interval, -0.97, -0.65), and Spearman ρ = -0.94 (95% confidence interval, -0.98, -0.77), respectively]. P. falciparum antibodies were associated with faster PCt1/2 (mean difference in PCt1/2 according to seropositivity, -0.16 to -0.65 h, depending on antigen); antibodies have a greater effect on the clearance of kelch13 mutant compared with wild-type parasites (mean difference in PCt1/2 according to seropositivity, -0.22 to -0.61 h faster in kelch13 mutants compared with wild-type parasites). Naturally acquired immunity accelerates the clearance of artemisinin-resistant parasites in patients with falciparum malaria and may confound the current working definition of artemisinin resistance. Immunity may also play an important role in the emergence and transmission potential of artemisinin-resistant parasites.

Assessment of herd immunity and cross-protection after a human papillomavirus vaccination programme in Australia: a repeat cross-sectional study.

BACKGROUND: After the introduction of a quadrivalent human papillomavirus (HPV) vaccination programme in Australia in April, 2007, we measured the prevalence of vaccine-targeted and closely related HPV types with the aim of assessing direct protection, cross-protection, and herd immunity. METHODS: In this repeat cross-sectional study, we recruited women aged 18-24 years who attended Pap screening between October, 2005, and July, 2007, in three major metropolitan areas of Australia to form our prevaccine-implementation sample. For our postvaccine-implementation sample, we recruited women aged 18-24 years who attended Pap screening in the same three metropolitan areas from August, 2010, to November, 2012. We compared the crude prevalence of HPV genotypes in cervical specimens between the prevaccine and the postvaccine implementation groups, with vaccination status validated against the National HPV Vaccination Program Register. We estimated adjusted prevalence ratios using log linear regression. We estimated vaccine effectiveness both for vaccine-targeted HPV types (16, 18, 6, and 11) and non-vaccine but related HPV types (31, 33, and 45). FINDINGS: 202 women were recruited into the prevaccine-implementation group, and 1058 were recruited into the postvaccine-implementation group. Crude prevalence of vaccine-targeted HPV genotypes was significantly lower in the postvaccine-implementation sample than in the prevaccine-implementation sample (58 [29%] of 202 vs 69 [7%] of 1058; p<0·0001). Compared with the prevaccine-implementation sample, adjusted prevalence ratios for vaccine-targeted HPV genotypes were 0·07 (95% CI 0·04-0·14; p<0·0001) in fully vaccinated women and 0·65 (0·43-0·96; p=0·03) in unvaccinated women, which suggests herd immunity. No significant declines were noted for non-vaccine-targeted HPV genotypes. However, within the postvaccine-implementation sample, adjusted vaccine effectiveness against vaccine-targeted HPV types for fully vaccinated women compared with unvaccinated women was 86% (95% CI 71-93), and was 58% (26-76) against non-vaccine-targeted but related genotypes (HPV 31, 33, and 45). INTERPRETATION: 6 years after the initiation of the Australian HPV vaccination programme, we have detected a substantial fall in vaccine-targeted HPV genotypes in vaccinated women; a lower prevalence of vaccine-targeted types in unvaccinated women, suggesting herd immunity; and a possible indication of cross-protection against HPV types related to the vaccine-targeted types in vaccinated women. FUNDING: Australian National Health and Medical Research Council and Cancer Council Victoria.

Post-PharmD industry fellowship opportunities and proposed guidelines for uniformity.

The focus of this paper is to examine the surge in the development of post-PharmD industry fellowships (ie, pharmacy fellowship programs sponsored by the biopharmaceutical or pharmaceutical industry). These post-PharmD training programs do not fit the currently accepted definition of a pharmacy fellowship; therefore, the authors propose a new and distinct definition to encompass these fellowships. The authors provide program examples to showcase the establishment of the post-PharmD industry fellowship institutional centers. Finally, the authors provide recommendations to create uniformity in the programs of this relatively new category of post-PharmD training.

Impact of cesarean section on neonatal mortality rates among very preterm infants in the United States, 2000-2003.

OBJECTIVE: The objective of this analysis was to compare the neonatal mortality rates for infants delivered through primary cesarean section versus vaginal delivery, taking into consideration a number of potentially risk-modifying conditions. METHODS: US linked birth and infant death certificate files for 2000-2003 were used. Demographic, medical, and labor and delivery complications were abstracted from the files with infant information. The primary outcome examined was neonatal death (death at 0-27 days of age). Because of concern regarding misclassification of gestational age, a procedure was used to trim away births for which the birth weight for a specific gestational age was incongruous. Adjusted odds ratios were calculated for the risk of neonatal death relative to the mode of delivery (primary cesarean section versus vaginal delivery), using logistic regression analysis. RESULTS: There were data for 13,733 neonatal deaths and 106,809 survivors available from the trimmed data set for analysis for the 4-year period. More than 80% of pregnancies with delivery between 22 and 31 weeks of gestation experienced >or=1 risk factor. Adjusted odds ratios demonstrated significantly reduced risk of neonatal death for infants delivered through cesarean section at 22 to 25 weeks of gestation (adjusted odds ratios of 0.58, 0.52, 0.72, and 0.81 for 22, 23, 24, and 25 weeks, respectively). CONCLUSION: Cesarean section does seem to provide survival advantages for the most immature infants delivered at 22 to 25 weeks of gestation, independent of maternal risk factors for cesarean section.

Decreased incidence of bronchopulmonary dysplasia after early management changes, including surfactant and nasal continuous positive airway pressure treatment at delivery, lowered oxygen saturation goals, and early amino acid administration: a historical cohort study.

OBJECTIVE: The goal was to investigate the clinical impact of 3 early management practice changes for infants of < or = 1000 g. METHODS: We performed an historical cohort study of appropriately sized, preterm infants without congenital anomalies who were born between January 2001 and June 2002 (pre-early management practice change group; n = 87) and between July 2004 and December 2005 (post-early management practice change group; n = 76). RESULTS: Only 1 (1%) of 87 infants in the pre-early management practice change group received continuous positive airway pressure treatment in the first 24 hours of life, compared with 61 (80%) of 76 infants in the post-early management practice change group. The proportions of infants who required any synchronized intermittent mandatory ventilation during their hospital stays were 98.8% and 59.5%, respectively. The mean durations of synchronized intermittent mandatory ventilation were 35 days and 15 days, respectively. The combined incidence rates of moderate and severe bronchopulmonary dysplasia at corrected gestational age of 36 weeks were 43% and 24%, respectively. The use of vasopressor support for hypotension in the first 24 hours of life decreased from 39.1% (before early management practice changes) to 19.7% (after practice changes), the cumulative days of oxygen therapy decreased from 77 +/- 52 days to 56 +/- 47 days, and the proportions of infants discharged with home oxygen therapy decreased from 25.7% to 10.1%; the incidence of patent ductus arteriosus requiring surgical ligation increased from 1% to 10%. There were no differences in rates of death, intraventricular hemorrhage, periventricular leukomalacia, pneumothorax, necrotizing enterocolitis, or retinopathy of prematurity. CONCLUSIONS: Successful early management of extremely preterm infants with surfactant treatment followed by continuous positive airway pressure treatment at delivery, lowered oxygen saturation goals, and early amino acid supplementation is possible and is associated with reductions in the incidence and severity of bronchopulmonary dysplasia.

3 steps to profitable managed care contracts.

An effective managed care contract negotiation strategy should be founded on: Internal analysis that compares performance of your current managed care contracts in terms of volume versus discount rates and volume versus profit. External analysis that compares your current contracts with those of competitors and assesses prevailing market rates, contract language and provisions, and premium trends Payment performance analysis that identifies payment promptness and accuracy and associated penalty dollars for each payer.

Enforcing prompt-payment regulations: the Texas approach.

To ensure that insurance carriers pay providers in a timely manner, Texas has adopted strict payment regulations. Enforcement of the regulations has led to restitution payments for many providers. However, issues such as clean claims, underpayment, discrepancies in payment dates, and self-funded claims continue to present challenges.

Trends and characteristics of induced labour in the United States, 1989-98.

Induction of labour is one of the fastest growing medical procedures in the United States. In 1998, 19.2% of all US births were a product of induced labour, more than twice the 9.0% in 1989. Induction of labour has been efficacious in the management of post-term pregnancy and in expediting delivery when the mother or infant is sufficiently ill to make continuation of the pregnancy hazardous. However, the recent rapid increase in induction, and particularly the doubling of the induction rate for preterm pregnancies (from 6.7% in 1989 to 13.4% in 1998), has generated concern among some clinicians. The present study uses vital statistics natality data to examine the epidemiology of induced labour in the US. Multivariable analysis is used to examine the probability of having an induced delivery in relation to a wide variety of socio-demographic and medical characteristics, and also in relation to relative indications and contraindications for induced labour as outlined by the American College of Obstetricians and Gynecologists (ACOG). Induction rates were higher for women who were non-Hispanic white, college educated, born in the US, primaparae and those with intensive prenatal care utilisation. Induction rates were also higher for women with various medical conditions including hypertension, eclampsia and renal disease. For non-Hispanic white women with singleton births, 59% of the increase in the preterm birth rate from 1989 to 1998 can be accounted for by the increase in preterm inductions. The adjusted odds ratio for neonatal mortality among preterm births with induced labour was 1.20 [95% confidence interval 1.11, 1.31]. The rapid increase in induction rates, particularly among preterm births, marks a shift in the obstetric management of pregnancy. More detailed studies are needed to examine physician decision-making protocols, particularly for preterm induction, and to assess the impact of these practice changes on patient outcomes.