Mathematical Models for Predicting the Epidemiologic and Economic Impact of Vaccination against Human Papillomavirus Infection and Disease

Infection with human papillomavirus (HPV) is the primary causeof cervical cancer, other anogenital cancers, genital warts,and recurrent respiratory papillomatosis. Clinical studies havedemonstrated that a prophylactic HPV vaccine can prevent infection,genital warts, and the precancerous lesions that lead to cervicalcancer. Given the absence of data on the long-term effectivenessof HPV vaccination, a number of mathematical models have beendeveloped to provide insight to policy makers by projectingthe long-term epidemiologic and economic consequences of vaccinationand evaluate alternative vaccination policies. This paper reviewsthe state of these models. Three types of HPV mathematical modelshave been reported in the literature: cohort, population dynamic,and hybrid. All have demonstrated that vaccination can significantlyreduce the incidence of cervical cancer in the long term. However,only the cohort and hybrid models have evaluated the cost-effectivenessof vaccination strategies for preventing cervical cancer. Thesemodels have generally shown that vaccinating females can becost-effective. None has accounted for the potential benefitsof vaccinating the population to reduce the burden of recurrentrespiratory papillomatosis and cancers of the vagina, vulva,anus, penis, and head/neck. Given that only the population dynamicmodel can account for both the direct and indirect (i.e., herdimmunity effects) benefits of vaccination in the population,future research should focus on further development of dynamicmodels by expanding the range of epidemiologic outcomes trackedand including the ability to assess the cost-effectiveness ofalternative vaccination policies. cost-benefit analysis • economics • papillomavirus, human • vaccines     

Placenta increta; conservative management -- a successful outcome. Case report and literature review.

Placenta increta, a rare complication of pregnancy, is associated with significant postpartum hemorrhage often requiring emergency hysterectomy. We report a case of conservative management, with a combination of parenteral methotrexate, serial ultrasound and Doppler assessment, followed by interval manual removal of placenta.     

Pharmacokinetics of Artesunate Alone and in Combination with Sulfadoxine/Pyrimethamine in Healthy Sudanese Volunteers

Artesunate (AS) in combination with sulfadoxine/pyrimethamine (SP) is the first-line therapy for management of uncomplicated Plasmodium falciparum malaria in Sudan. The objective of this study was to assess the potential impact of SP on the pharmacokinetics of AS and its active metabolite, dihydroartemisinin (DHA), in healthy adults. A single-dose, randomized, open-label, crossover study design with a washout period of three weeks was performed with 16 volunteers. After oral administration of AS alone or in combination with SP, T_max values of AS and DHA were significantly prolonged in the combination group (P < 0.05). However, there was no significant effect on the other pharmacokinetic parameters (P > 0.05). The t_1/2 values of AS and DHA were significantly higher in females than in males (P < 0.05). The present findings suggest that co-administration of SP with AS has no clinically relevant impact on the pharmacokinetics of AS or DHA in healthy persons.     

Phase Variation Mediates Reductions in Expression of Surface Proteins during Persistent Meningococcal Carriage

Asymptomatic and persistent colonization of the upper respiratory tract by Neisseria meningitidis occurs despite elicitation of adaptive immune responses against surface antigens. A putative mechanism for facilitating host persistence of this bacterial commensal and pathogen is alterations in expression of surface antigens by simple sequence repeat (SSR)-mediated phase variation. We investigated how often phase variation occurs during persistent carriage by analyzing the SSRs of eight loci in multiple isolates from 21 carriers representative of 1 to 6 months carriage. Alterations in repeat number were detected by a GeneScan analysis and occurred at 0.06 mutations/gene/month of carriage. The expression states were determined by Western blotting and two genes, fetA and nadA, exhibited trends toward low expression states. A critical finding from our unique examination of combinatorial expression states, “phasotypes,” was for significant reductions in expression of multiple phase-variable surface proteins during persistent carriage of some strains. The immune responses in these carriers were examined by measuring variant-specific PorA IgG antibodies, capsular group Y IgG antibodies and serum bactericidal activity in concomitant serum samples. Persistent carriage was associated with high levels of specific IgG antibodies and serum bactericidal activity while recent strain acquisition correlated with a significant induction of antibodies. We conclude that phase-variable genes are driven into lower expression states during long-term persistent meningococcal carriage, in part due to continuous exposure to antibody-mediated selection, suggesting localized hypermutation has evolved to facilitate host persistence.     

Osimertinib,Surgery, and Radiation Therapy in Treating Patients with Stage IIIB or IV Non-Small Cell Lung Cancer with EGFR Mutations (NORTHSTAR)

Annals of Surgical Oncology -     

Use of the exercise maximal ST segment/heart rate slope in assessing the results of coronary angioplasty.

A new exercise test was used to assess the effects of coronary angioplasty in 22 patients. Twenty five angioplasty procedures were performed and the exercise maximal ST segment/heart rate slope was measured before and after operation on 23 occasions; in two patients treated for unstable angina the slope was measured only after the two procedures. Successful angioplasty (23 of the 25 procedures) resulted in a significant reduction of the maximal ST/HR slope, usually falling by the equivalent of single vessel disease according to previously published criteria. When angioplasty produced little angiographic change (two of the 25 procedures) the maximal ST/HR slope was not significantly altered. A second, and successful, angioplasty for these two patients led to a significant reduction of the maximal ST/HR slope. Twelve patients were restudied by coronary angiography and exercise testing approximately six months after angioplasty. Of these, six had experienced recurrent chest pain, and the exercise test successfully identified the three who had restenoses and the three who did not. Thus the maximal ST/HR slope was useful as a non-invasive and accurate method for following the progress of individual patients after coronary angioplasty.