Time-dependent vaccine efficacy estimation quantified by a mathematical model.

In this paper we calculate the variation of the estimated vaccine efficacy (VE) due to the time-dependent force of infection resulting from the difference between the moment the Clinical Trial (CT) begins and the peak in the outbreak intensity. Using a simple mathematical model we tested the hypothesis that the time difference between the moment the CT begins and the peak in the outbreak intensity determines substantially different values for VE. We exemplify the method with the case of the VE efficacy estimation for one of the vaccines against the new coronavirus SARS-CoV-2.

Time-dependent vaccine efficacy estimation quantified by a mathematical model

In this paper we calculate the variation of the estimated vaccine efficacy (VE) due to the time-dependent force of infection resulting from the difference between the moment the Clinical Trial (CT) begins and the peak in the outbreak intensity. Using a simple mathematical model we tested the hypothesis that the time difference between the moment the CT begins and the peak in the outbreak intensity determines substantially different values for VE. We exemplify the method with the case of the VE efficacy estimation for one of the vaccines against the new coronavirus SARS-CoV-2.

The Estimate of the Impact of Coccyx Resection in Surgical Field Exposure During Abdominal Perineal Resection Using Preoperative High-Resolution Magnetic Resonance.

OBJECTIVE: To estimate the improvement in surgical exposure by removal of the coccyx, during abdomino-perineal resection (APR), in rectal cancer patients. METHODS: Retrospective study of 29 consecutive patients with rectal cancer was carried out. Using MR T2 sagittal series, the solid angle was estimated using the angle determined by the anterior resection margin and the tip of coccyx (no coccyx resection) or the tip of last sacral vertebra (coccyx resection). The solid angle provides an estimate of the tridimensional surface area provided by an original angle resulting in the best estimate of the surgeon's view/exposure to the critical dissecting point of choice (anterior rectal wall). The difference ("Gain") in surgical field exposure by removal of the coccyx was compared by the solid angle variation between the two estimates (with and without the coccyx). RESULTS: Routine removal of the coccyx determines an average 42% (95% CI 27-57%) gain in surgical field exposure area facing the anterior rectal wall at the level of the prostate/vagina by the surgeon. Fifteen (51%) patients had ≥30% (median) estimated gain in surgical field exposure by coccygectomy. There was no association between BMI, age or gender and estimated gain in surgical field exposure area. CONCLUSIONS: Routine removal of the coccyx during APR may result in an average increase in 42% in surgical field exposure during APR's perineal dissection. Precise estimation of surgical field exposure gain by removal of the coccyx may be predicted by MR sagittal series for each individual patient.

Age and regional differences in clinical presentation and risk of hospitalization for dengue in Brazil, 2000-2014.

OBJECTIVES: Dengue cases range from asymptomatic to severe, eventually leading to hospitalization and death. Timely and appropriate management is critical to reduce morbidity. Since 1980, dengue has spread throughout Brazil, affecting an increasing number of individuals. This paper describes age and regional differences in dengue's clinical presentation and associated risk of hospitalization based on more than 5 million cases reported to the Brazilian Ministry of Health from 2000-2014. METHODS: We performed a retrospective analysis of ∼5,450,000 dengue cases, relating clinical manifestations and the risk of hospitalization to age, gender, previous infection by dengue, dengue virus serotype, years of formal education, delay to first attendance and the occurrence of dengue during outbreaks and in different Brazilian regions. RESULTS: Complicated forms of dengue occurred more frequently among those younger than 10 years (3.12% vs 1.92%) and those with dengue virus 2 infection (7.65% vs 2.42%), with a delay to first attendance >2 days (3.18% vs 0.82%) and with ≤4 years of formal education (2.02% vs 1.46%). The risk of hospitalization was higher among those aged 6-10 years old (OR 4.57; 95% CI 1.43-29.96) and those who were infected by dengue virus 2 (OR 6.36; 95% CI 2.52-16.06), who lived in the Northeast region (OR 1.38; 95% CI 1.11-2.10) and who delayed first attendance by >5 days (composite OR 3.15; 95% CI 1.33-8.9). CONCLUSIONS: In Brazil, the occurrence of severe dengue and related hospitalization is associated with being younger than 10 years old, being infected by dengue virus 2 or 3, living in the Northeast region (the poorest and the second most populated) and delaying first attendance for more than 2 days.

A mathematical model for optimizing the indications of liver transplantation in patients with hepatocellular carcinoma.

BACKGROUND: The criteria for organ sharing has developed a system that prioritizes liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) who have the highest risk of wait-list mortality. In some countries this model allows patients only within the Milan Criteria (MC, defined by the presence of a single nodule up to 5 cm, up to three nodules none larger than 3 cm, with no evidence of extrahepatic spread or macrovascular invasion) to be evaluated for liver transplantation. This police implies that some patients with HCC slightly more advanced than those allowed by the current strict selection criteria will be excluded, even though LT for these patients might be associated with acceptable long-term outcomes. METHODS: We propose a mathematical approach to study the consequences of relaxing the MC for patients with HCC that do not comply with the current rules for inclusion in the transplantation candidate list. We consider overall 5-years survival rates compatible with the ones reported in the literature. We calculate the best strategy that would minimize the total mortality of the affected population, that is, the total number of people in both groups of HCC patients that die after 5 years of the implementation of the strategy, either by post-transplantation death or by death due to the basic HCC. We illustrate the above analysis with a simulation of a theoretical population of 1,500 HCC patients with tumor size exponentially. The parameter λ obtained from the literature was equal to 0.3. As the total number of patients in these real samples was 327 patients, this implied in an average size of 3.3 cm and a 95% confidence interval of [2.9; 3.7]. The total number of available livers to be grafted was assumed to be 500. RESULTS: With 1500 patients in the waiting list and 500 grafts available we simulated the total number of deaths in both transplanted and non-transplanted HCC patients after 5 years as a function of the tumor size of transplanted patients. The total number of deaths drops down monotonically with tumor size, reaching a minimum at size equals to 7 cm, increasing from thereafter. With tumor size equals to 10 cm the total mortality is equal to the 5 cm threshold of the Milan criteria. CONCLUSION: We concluded that it is possible to include patients with tumor size up to 10 cm without increasing the total mortality of this population.

Cost risk benefit analysis to support chemoprophylaxis policy for travellers to malaria endemic countries.

BACKGROUND: In a number of malaria endemic regions, tourists and travellers face a declining risk of travel associated malaria, in part due to successful malaria control. Many millions of visitors to these regions are recommended, via national and international policy, to use chemoprophylaxis which has a well recognized morbidity profile. To evaluate whether current malaria chemo-prophylactic policy for travellers is cost effective when adjusted for endemic transmission risk and duration of exposure. a framework, based on partial cost-benefit analysis was used. METHODS: Using a three component model combining a probability component, a cost component and a malaria risk component, the study estimated health costs avoided through use of chemoprophylaxis and costs of disease prevention (including adverse events and pre-travel advice for visits to five popular high and low malaria endemic regions) and malaria transmission risk using imported malaria cases and numbers of travellers to malarious countries. By calculating the minimal threshold malaria risk below which the economic costs of chemoprophylaxis are greater than the avoided health costs we were able to identify the point at which chemoprophylaxis would be economically rational. RESULTS: The threshold incidence at which malaria chemoprophylaxis policy becomes cost effective for UK travellers is an accumulated risk of 1.13% assuming a given set of cost parameters. The period a travellers need to remain exposed to achieve this accumulated risk varied from 30 to more than 365 days, depending on the regions intensity of malaria transmission. CONCLUSIONS: The cost-benefit analysis identified that chemoprophylaxis use was not a cost-effective policy for travellers to Thailand or the Amazon region of Brazil, but was cost-effective for travel to West Africa and for those staying longer than 45 days in India and Indonesia.

Modeling the risk of malaria for travelers to areas with stable malaria transmission.

BACKGROUND: Malaria is an important threat to travelers visiting endemic regions. The risk of acquiring malaria is complex and a number of factors including transmission intensity, duration of exposure, season of the year and use of chemoprophylaxis have to be taken into account estimating risk. MATERIALS AND METHODS: A mathematical model was developed to estimate the risk of non-immune individual acquiring falciparum malaria when traveling to the Amazon region of Brazil. The risk of malaria infection to travelers was calculated as a function of duration of exposure and season of arrival. RESULTS: The results suggest significant variation of risk for non-immune travelers depending on arrival season, duration of the visit and transmission intensity. The calculated risk for visitors staying longer than 4 months during peak transmission was 0.5% per visit. CONCLUSIONS: Risk estimates based on mathematical modeling based on accurate data can be a valuable tool in assessing risk/benefits and cost/benefits when deciding on the value of interventions for travelers to malaria endemic regions.

Forecasting versus projection models in epidemiology: the case of the SARS epidemics.

In this work we propose a simple mathematical model for the analysis of the impact of control measures against an emerging infection, namely, the severe acute respiratory syndrome (SARS). The model provides a testable hypothesis by considering a dynamical equation for the contact parameter, which drops exponentially with time, simulating control measures. We discuss the role of modelling in public health and we analyse the distinction between forecasting and projection models as assessing tools for the estimation of the impact of intervention strategies. The model is applied to the communities of Hong Kong and Toronto (Canada) and it mimics those epidemics with fairly good accuracy. The estimated values for the basic reproduction number, R0, were 1.2 for Hong Kong and 1.32 for Toronto (Canada). The model projects that, in the absence of control, the final number of cases would be 320,000 in Hong Kong and 36,900 in Toronto (Canada). In contrast, with control measures, which reduce the contact rate to about 25% of its initial value, the expected final number of cases is reduced to 1778 in Hong Kong and 226 in Toronto (Canada). Although SARS can be a devastating infection, early recognition, prompt isolation, and appropriate precaution measures, can be very effective to limit its spread.