How to accelerate the supply of vaccines to all populations worldwide? Part I: Initial industry lessons learned and practical overarching proposals leveraging the COVID-19 situation.

The COVID-19 pandemic has shown itself to be an unprecedented challenge for vaccines which are widely recognized as the most important tool to exit this pandemic. We have witnessed vaccine scientists, developers, manufacturers, and stakeholders deliver several vaccines in just about a year. This is an unprecedented achievement in an environment that was not ready to manage such a global public health crisis. Indeed, the pandemic has highlighted some hurdles that need to be addressed in the system in order to streamline the regulatory processes and be in a situation where life-saving pharmaceutical solutions such as vaccines can be delivered quickly and equitably to people across the globe. More precisely, trade-offs had to be made between the need for regulatory flexibility in the requirements for manufacturing and controls to enable rapid availability of large volumes of vaccines vs the increased stringency and the lack of harmonization in the regulatory environment for vaccines globally. It is also characterized by a high heterogeneity in terms of review and approval processes, limiting equitable and timely access. We review and highlight the challenges relating to several topics, including process validation, comparability, stability, post-approval-changes, release testing, packaging, genetically modified organisms and variants. We see four areas for accelerating access to vaccines which provide solutions for the regulatory concerns, (1) science- and risk-based approaches, (2) global regulatory harmonization, (3) use of reliance, work-sharing, and recognition processes and (4) digitalization. These solutions are not new and have been previously highlighted. In recent months, we have seen some progress at the health authority level, but still much needs to be done. It is now time to reflect on the first lessons learnt from a devastating pandemic to ultimately ensure quick and wide access to medicines and vaccines for the citizens and patients.

How to accelerate the supply of vaccines to all populations worldwide? Part II: Initial industry lessons learned and detailed technical reflections leveraging the COVID-19 situation.

Vaccine discovery and vaccination against preventable diseases are one of most important achievements of the human race. While medical, scientific & technological advancements have kept in pace and found their way into treatment options for a vast majority of diseases, vaccines as a prevention tool in the public health realm are found languishing in the gap between such innovations and their easy availability/accessibility to vulnerable populations. This paradox has been best highlighted during the unprecedented crisis of the COVID-19 pandemic. As part of a two series publication on the vaccine industry's view on how to accelerate the availability of vaccines worldwide, this paper offers a deep dive into detailed proposals to enable this objective. These first-of-its-kind technical proposals gleaned from challenges and learnings from the COVID-19 pandemic are applicable to vaccines that are already on the market for routine pathogens as well as for production of new(er) vaccines for emerging pathogens with a public health threat potential. The technical proposals offer feasible and sustainable solutions in pivotal areas such as process validation, comparability, stability, post-approval changes, release testing, packaging, genetically modified organisms and variants, which are linked to manufacturing and quality control of vaccines. Ultimately these proposals aim to ease high regulatory complexity and heterogeneity surrounding the manufacturing & distribution of vaccines, by advocating the use of (1) Science and Risk based approaches, (2) global regulatory harmonization, (3) use of reliance, work-sharing, and recognition processes and (4) digitalization. Capitalizing & collaborating on such new-world advancements into the science of vaccines will eventually benefit the world by turning vaccines into vaccination, ensuring the health of everyone.

Human Consequences of Multiple Nuclear Detonations in New Delhi (India): Interdisciplinary Requirements in Triage Management.

The human casualties from simulated nuclear detonation scenarios in New Delhi, India are analyzed, with a focus on the distribution of casualties in urban environments and the theoretical application of a nuclear-specific triage system with significant innovation in interdisciplinary disaster management applicable generally to urban nuclear detonation medical response. Model estimates of nuclear war casualties employed ESRI's ArcGIS 9.3, blast and prompt radiation were calculated using the Defense Nuclear Agency's WE program, and fallout radiation was calculated using the Defense Threat Reduction Agency's (DTRA's) Hazard Prediction and Assessment Capability (HPAC) V404SP4, as well as custom GIS and database software applications. ESRI ArcGISTM programs were used to calculate affected populations from the Oak Ridge National Laboratory's LandScanTM 2007 Global Population Dataset for areas affected by thermal, blast and radiation data. Trauma, thermal burn, and radiation casualties were thus estimated on a geographic basis for New Delhi, India for single and multiple (six) 25 kt detonations and a single 1 mt (1000 kt) detonation. Major issues related to the emergency management of a nuclear incident are discussed with specific recommendations for improvement. The consequences for health management of thermal burn and radiation patients is the worst, as burn patients require enormous resources to treat, and there will be little to no familiarity with the treatment of radiation victims. Of particular importance is the interdisciplinary cooperation necessary for such a large-scale emergency response event, which would be exemplified by efforts such as the application of a Nuclear Global Health Workforce.

Emerging manufacturers engagements in the COVID -19 vaccine research, development and supply.

The World Health Organization declared the COVID-19 disease as a pandemic requiring a rapid response. Through online search, direct communication with network members and an internal survey, engagements of developing countries' vaccine manufacturers' network members in the research and development of COVID-19 vaccines and their capacities in the manufacturing, fill-finish and distribution of vaccines were assessed. Currently, 19 network members engaged in research and development of COVID-19 vaccines, using six principal technology platforms. In addition, an internal survey showed that the number of vaccines supplied collectively by 37 members, in 2018-19, was about 3.5 billion doses annually. Almost a third of network members having vaccines prequalified by the World Health Organization comply with international regulations and mechanisms to distribute vaccines across borders. The use of existing manufacturing, fill-finish and distribution capabilities can support an efficient roll-out of vaccines against COVID-19, while maintaining supply security of existing vaccines for on-going immunization programmes.

The Economic Impact of Hurricane Evacuations on a Coastal Georgia Hospital: A Case Study.

Coastal hospitals are often faced with the challenging decision to either evacuate or shelter-in-place in anticipation of a hurricane predicted to make landfall. The costs associated with hospital evacuation not only include transportation of patients to inland areas, but also the loss of revenue due to interruption of regular operations and the cost of potential damage to the hospital's infrastructure. Financial data provided by Memorial Health University Medical Center (MUMC, Savannah, Georgia) such as average inpatient and outpatient revenues, personnel wages, and transportation costs, were used to estimate the potential economic impact of hurricane evacuations on a coastal hospital. The results indicate that even prior to the arrival of tropical storm force winds, the hospital will incur an estimated total expenditure of approximately $9.5 million which includes evacuation expenses and loss of revenue due to disruption of regular services. In case the hurricane makes landfall, revenue losses will continue to accumulate until the hospital is able to resume regular operations. The cost of relocating patients back to MUMC after the hurricane event and the cost of any hurricane-related damage to the hospital infrastructure must also be taken into consideration. In conclusion, even though hospital evacuation for hurricanes may be unavoidable in certain circumstances, the financial burden placed upon the hospital may be mitigated to a certain extent by forward planning, infrastructure upgrades, and the rapid resumption of regular hospital function.

Evaluating a mobile application for improving clinical laboratory test ordering and diagnosis.

Objective: Mobile applications for improving diagnostic decision making often lack clinical evaluation. We evaluated if a mobile application improves generalist physicians' appropriate laboratory test ordering and diagnosis decisions and assessed if physicians perceive it as useful for learning. Methods: In an experimental, vignette study, physicians diagnosed 8 patient vignettes with normal prothrombin times (PT) and abnormal partial thromboplastin times (PTT). Physicians made test ordering and diagnosis decisions for 4 vignettes using each resource: a mobile app, PTT Advisor, developed by the Centers for Disease Control and Prevention (CDC)'s Clinical Laboratory Integration into Healthcare Collaborative (CLIHC); and usual clinical decision support. Then, physicians answered questions regarding their perceptions of the app's usefulness for diagnostic decision making and learning using a modified Kirkpatrick Training Evaluation Framework. Results: Data from 368 vignettes solved by 46 physicians at 7 US health care institutions show advantages for using PTT Advisor over usual clinical decision support on test ordering and diagnostic decision accuracy (82.6 vs 70.2% correct; P < .001), confidence in decisions (7.5 vs 6.3 out of 10; P < .001), and vignette completion time (3:02 vs 3:53 min.; P = .06). Physicians reported positive perceptions of the app's potential for improved clinical decision making, and recommended it be used to address broader diagnostic challenges. Conclusions: A mobile app, PTT Advisor, may contribute to better test ordering and diagnosis, serve as a learning tool for diagnostic evaluation of certain clinical disorders, and improve patient outcomes. Similar methods could be useful for evaluating apps aimed at improving testing and diagnosis for other conditions.

Different Combining Process Between Male and Female Patients to Reach Their Overall Satisfaction.

Patient satisfaction and how it is measured is an important field of study in healthcare. Consequently, there have been many patient satisfaction studies. However, there is a lack of studies that focused on how male and female patients perceive, or weigh, their overall satisfaction. Determining the weights of these attributes by gender is an important outcome to determine overall patient satisfaction and quality of care. Data were collected by applying the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey instrument to record regular patient experience at 70 United States hospitals. The data were collected between July 1, 2011 and June 30, 2012, and there are 43,938 cases in the data set. This study found that all five of the attributes (Nursing Care, Physician Care, Staff Care, Room, and Help) had an association with patient satisfaction. Among them, nursing Care had the largest influence on patient satisfaction of all of the five attributes. This study also showed a statistically significant interaction effect by gender for the interaction between Nursing care x Gender, Physician care x Gender, and Help x Gender. Female patients rated their relationship with their nurses as being more important to their overall satisfaction, while male patients rated their relationship with their doctor as being more important to overall satisfaction. Male patients also rated their relationship with help as being more important to overall satisfaction when compared with the results from female patients. Suggestions to healthcare managers are also discussed.

Diet and dermatology: the role of dietary intervention in skin disease.

For decades, it was thought that many common dermatological conditions had no relationship to diet. Studies from recent years, however, have made it clear that diet may influence outcome. In this review, the authors focus on conditions for which the role of diet has traditionally been an underappreciated aspect of therapy. In some cases, dietary interventions may influence the course of the skin disease, as in acne. In others, dietary change may serve as one aspect of prevention, such as in skin cancer and aging of the skin. In others, dermatological disease may be linked to systemic disease, and dietary changes may affect health outcomes, as in psoriasis. Lastly, systemic medications prescribed for dermatological disease, such as steroids, are known to raise the risk of other diseases, and dietary change may reduce this risk.

Linking costs to health outcomes for allocating scarce public health resources.

INTRODUCTION: Resources for public health (PH) are scarce and policymakers face tough decisions in determining their funding priorities. The difficulty of making these decisions is compounded by current PH accounting systems, which are ill-equipped to link fiscal resources to PH outcomes. This paper examines the types of revenues and expenditures, health services, and health outcomes that are being tracked at the local and state PH levels. The authors provide recommendations for strengthening the ability of local and state governments to link expenditures to PH outcomes, both within and across jurisdictions. FRAMEWORK AND NEXT STEPS: The source of revenue data for most local jurisdictions is the accounting systems used for the budgeting and auditing of fiscal activities, and these are primarily linked to specific PH programs. In contrast, expenditure data are mostly generic and typically span multiple PH programs with no link to specific PH activities. Many challenges exist to then link PH activities to health outcomes data, which are often collected through separate reporting systems at the local, state, and national levels. Policy change at the state level and implementation strategies that are standardized across local health departments are required to assess the costs and health outcomes of PH activities. CONCLUSION: Information linking PH expenditures to health outcomes of PH services could greatly inform the decision-making process. This information will allow investments in PH to be better understood and will provide a strong foundation for the PH services and systems research community to understand variation and drive improvement. Ultimately, these data could be used to improve accountability at the local and state PH department levels.

Role of sonography-guided lithotripsy in renal stone with angiomyolipoma.

Treatment of angiomyolipoma (AML) of kidney with stone has been challenging for urologists. We present our experience of treating the renal stone in the presence of AML with shockwave lithotripsy (SWL). Position of the patient with respect to the direction of the shockwaves and accurate knowledge of the dimension of the focal zone are critical aspects of SWL. Keeping the AML safely away from the focal zone at all times during the procedure is only possible by usage of real-time ultrasonography in lieu of fluoroscopy.

Utility of SOFA and APACHE II score in sepsis in rural set up MICU.

AIMS AND OBJECTIVES: To assess morbidity and mortality as well as to prognosticate the patients by using SOFA and APACHE II scores of patients with sepsis, severe sepsis and multi-organ dysfunction syndrome (MODS) in rural setup ICU. MATERIAL AND METHODOLOGY: We carried out prospective study on patients with sepsis as per ACCP guidelines and analysed their clinical and microbiological profile. We calculated SOFA score on day 1, 3 and 7. APACHE II score was also calculated on day of admission. We used both the scores for predicting the outcome. RESULTS: The mortality rate was 48% in our study group which had alarming proportion of MODS patients (78%). The most common organ involved was lung and the most common organism causing sepsis was Klebseilla. On day 3, the mortality rate of patients with SOFA score less than nine was 9.1%, while the mortality rate of patients with score more than nine was 78%. The trend of mean SOFA score was progressively declining in survivor group. The mean APACHE II score was marginally higher in non-survivor group compared to survivor group, however the difference was not statistically significant. CONCLUSIONS: Serial measurement of SOFA score during first week is very useful tool in predicting the outcome. The APACHE II score on day of admission was not reliable in predicting the mortality rate in this study and we believe that it may need modification in set up like ours.

Synchronous hepatocellular carcinoma with renal cell carcinoma: a case report and review of literature of multiple synchronous primary malignancies.

Multiple synchronous primary malignancies have been reported since the 19th century. A number of proposed theories as to the predisposing factors have been discussed. The criteria to diagnose multiple primary malignancies have been revised by Warren and Gates. We hereby present a case of an asymptomatic individual detected with a synchronous hepatocellular carcinoma and a renal cell carcinoma, its presentation, diagnosis, and the management. The occurrence of synchronous hepatocellular carcinoma with renal cell carcinoma is very rare and only a few cases have been reported. Synchronous extrahepatic primary malignancies have been reported in a few studies across the world though with a varied incidence rate. The occurrence seems to be in the older age group without gender differentiation. The extrahepatic malignancies were more common in cirrhotic livers though the overall survival does not differ between patients with hepatocellular carcinoma alone and hepatocellular carcinoma with synchronous extrahepatic malignancies.

Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with long-term follow-up.

PURPOSE: Cancer patients who undergo radiotherapy remain at life-long risk of radiation-induced injury to normal tissues. We conducted a randomized, controlled, double-blind crossover trial with long-term follow-up to evaluate the effectiveness of hyperbaric oxygen for refractory radiation proctitis. METHODS AND MATERIALS: Patients with refractory radiation proctitis were randomized to hyperbaric oxygen at 2.0 atmospheres absolute (Group 1) or air at 1.1 atmospheres absolute (Group 2). The sham patients were subsequently crossed to Group 1. All patients were re-evaluated by an investigator who was unaware of the treatment allocation at 3 and 6 months and Years 1-5. The primary outcome measures were the late effects normal tissue-subjective, objective, management, analytic (SOMA-LENT) score and standardized clinical assessment. The secondary outcome was the change in quality of life. RESULTS: Of 226 patients assessed, 150 were entered in the study and 120 were evaluable. After the initial allocation, the mean SOMA-LENT score improved in both groups. For Group 1, the mean was lower (p = 0.0150) and the amount of improvement nearly twice as great (5.00 vs. 2.61, p = 0.0019). Similarly, Group 1 had a greater portion of responders per clinical assessment than did Group 2 (88.9% vs. 62.5%, respectively; p = 0.0009). Significance improved when the data were analyzed from an intention to treat perspective (p = 0.0006). Group 1 had a better result in the quality of life bowel bother subscale. These differences were abolished after the crossover. CONCLUSION: Hyperbaric oxygen therapy significantly improved the healing responses in patients with refractory radiation proctitis, generating an absolute risk reduction of 32% (number needed to treat of 3) between the groups after the initial allocation. Other medical management requirements were discontinued, and advanced interventions were largely avoided. Enhanced bowel-specific quality of life resulted.