Dengue Vaccines Regulatory Pathways: A Report on Two Meetings with Regulators of Developing Countries

Richard Mahoney and colleagues summarize two recent meetings convened by the Pediatric Dengue Vaccine Initiative and the Developing Countries' Vaccine Regulators Network on regulatory issues that need to be addressed before licensing dengue vaccines

Population Dynamics of Aedes aegypti and Dengue as Influenced by Weather and Human Behavior in San Juan, Puerto Rico

Previous studies on the influence of weather on Aedes aegypti dynamics in Puerto Rico suggested that rainfall was a significant driver of immature mosquito populations and dengue incidence, but mostly in the drier areas of the island. We conducted a longitudinal study of Ae. aegypti in two neighborhoods of the metropolitan area of San Juan city, Puerto Rico where rainfall is more uniformly distributed throughout the year. We assessed the impacts of rainfall, temperature, and human activities on the temporal dynamics of adult Ae. aegypti and oviposition. Changes in adult mosquitoes were monitored with BG-Sentinel traps and oviposition activity with CDC enhanced ovitraps. Pupal surveys were conducted during the drier and wetter parts of the year in both neighborhoods to determine the contribution of humans and rains to mosquito production. Mosquito dynamics in each neighborhood was compared with dengue incidence in their respective municipalities during the study. Our results showed that: 1. Most pupae were produced in containers managed by people, which explains the prevalence of adult mosquitoes at times when rainfall was scant; 2. Water meters were documented for the first time as productive habitats for Ae. aegypti; 3. Even though Puerto Rico has a reliable supply of tap water and an active tire recycling program, water storage containers and discarded tires were important mosquito producers; 4. Peaks in mosquito density preceded maximum dengue incidence; and 5. Ae. aegypti dynamics were driven by weather and human activity and oviposition was significantly correlated with dengue incidence

Malignant mesothelioma

Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10–20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis

A role for pharmacists in community-based post-discharge warfarin management: protocol for the 'the role of community pharmacy in post hospital management of patients initiated on warfarin' study

<p>Abstract</p> <p>Background</p> <p>Shorter periods of hospitalisation and increasing warfarin use have placed stress on community-based healthcare services to care for patients taking warfarin after hospital discharge, a high-risk period for these patients. A previous randomised controlled trial demonstrated that a post-discharge service of 4 home visits and point-of-care (POC) International Normalised Ratio (INR) testing by a trained pharmacist improved patients' outcomes. The current study aims to modify this previously trialled service model to implement and then evaluate a sustainable program to enable the smooth transition of patients taking warfarin from the hospital to community setting.</p> <p>Methods/Design</p> <p>The service will be trialled in 8 sites across 3 Australian states using a prospective, controlled cohort study design. Patients discharged from hospital taking warfarin will receive 2 or 3 home visits by a trained 'home medicines review (HMR)-accredited' pharmacist in their 8 to 10 days after hospital discharge. Visits will involve a HMR, comprehensive warfarin education, and POC INR monitoring in collaboration with patients' general practitioners (GPs) and community pharmacists. Patient outcomes will be compared to those in a control, or 'usual care', group. The primary outcome measure will be the proportion of patients experiencing a major bleeding event in the 90 days after discharge. Secondary outcome measures will include combined major bleeding and thromboembolic events, death, cessation of warfarin therapy, INR control at 8 days post-discharge and unplanned hospital readmissions from any cause. Stakeholder satisfaction will be assessed using structured postal questionnaire mailed to patients, GPs, community pharmacists and accredited pharmacists at the completion of their study involvement.</p> <p>Discussion</p> <p>This study design incorporates several aspects of prior interventions that have been demonstrated to improve warfarin management, including POC INR testing, warfarin education and home visits by trained pharmacists. It faces several potential challenges, including the tight timeframe for patient follow-up in the post-discharge period. Its strengths lie in a strong multidisciplinary team and the utilisation of existing healthcare frameworks. It is hoped that this study will provide the evidence to support the national roll-out of the program as a new Australian professional community pharmacy service.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trials Registry Number <a href="http://www.anzctr.org.au/trial_view.aspx?ID=82959">12608000334303</a>.</p

Behavioral interactions between Sitophilus zeamais and Tribolium castaneum: the first colonizer matters

There is lack of knowledge on the interactions between kernel aging and the simultaneous infestation by insects, both internal and external feeders. In the present paper, we report results obtained in arena-olfactometer assays in which we studied possible preference and behavioral relationships between the primary colonizer Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae) and the secondary colonizer Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae). For this purpose, three experiments were conducted. The experiment I examined the response of S. zeamais adults at the fresh or stored kernels damaged by T. castaneum adults, compared to the control and the response of T. castaneum adults at the fresh or stored kernels damaged by S. zeamais adults, compared to the control. The experiment II examined the response of S. zeamais adults at the intact fresh or stored kernels conditioned at different conditioning intervals (1, 7, and 14 days) with kernels damaged by T. castaneum, compared to the control and the response of T. castaneum adults at the intact fresh or stored kernels conditioned at different conditioning intervals (1, 7 and 14 days) with kernels damaged by S. zeamais, compared to the control. The experiment III examined the response of S. zeamais adults at kernels contaminated at different contamination intervals by larvae or adults of T. castaneum, and the response of T. castaneum adults at kernels contaminated by larvae or adults of S. zeamais. In experiment I, significantly more S. zeamais adults were found in traps containing fresh or stored kernels damaged by T. castaneum than in the controls. Significantly more T. castaneum adults were found in traps containing fresh or stored kernels damaged by S. zeamais than in the controls. In experiment II, at 7 days of conditioning, significantly more adults of S. zeamais were captured in the traps used as control than in the traps containing either fresh conditioned kernels or stored conditioned kernels. At 1 and 14 days of conditioning, significantly more adults of T. castaneum were captured in the traps that contained stored conditioned kernels damaged by S. zeamais than in the controls. In experiment III, at 1, 7, and 14 days of contamination, significantly more adults of S. zeamais were captured in traps with kernels contaminated by larvae of T. castaneum or in the traps with kernels contaminated by adult females of T. castaneum than in the controls. Significantly more S. zeamais adults were found in traps containing kernels contaminated by T. castaneum adult males than in control kernels at the 7 and 14 days of contamination. At 1 day of contamination, significantly more adults of T. castaneum were captured in traps with kernels contaminated by larvae of S. zeamais than in the controls. The results of the present study suggest that kernels which were previously infested by S. zeamais were more prone to be selected by T. castaneum adults and kernels that were previously infested by T. castaneum were more prone to be selected by S. zeamais. Thus, the first colonizer can serve as the primary colonizer of stored grains, even if this first colonizer cannot infest sound kernels. The kernel age was also a crucial issue for the attraction of S. zeamais and T. castaneum. Stored kernels exhibited a stronger influence on the attraction of T. castaneum than for S. zeamais