Modelling the impact of delaying vaccination against SARS-CoV-2 assuming unlimited vaccine supply.

BACKGROUND: At the moment we have more than 177 million cases and 3.8 million deaths (as of June 2021) around the world and vaccination represents the only hope to control the pandemic. Imperfections in planning vaccine acquisition and difficulties in implementing distribution among the population, however, have hampered the control of the virus so far. METHODS: We propose a new mathematical model to estimate the impact of vaccination delay against the 2019 coronavirus disease (COVID-19) on the number of cases and deaths due to the disease in Brazil. We apply the model to Brazil as a whole and to the State of Sao Paulo, the most affected by COVID-19 in Brazil. We simulated the model for the populations of the State of Sao Paulo and Brazil as a whole, varying the scenarios related to vaccine efficacy and compliance from the populations. RESULTS: The model projects that, in the absence of vaccination, almost 170 thousand deaths and more than 350 thousand deaths will occur by the end of 2021 for Sao Paulo and Brazil, respectively. If in contrast, Sao Paulo and Brazil had enough vaccine supply and so started a vaccination campaign in January with the maximum vaccination rate, compliance and efficacy, they could have averted more than 112 thousand deaths and 127 thousand deaths, respectively. In addition, for each month of delay the number of deaths increases monotonically in a logarithmic fashion, for both the State of Sao Paulo and Brazil as a whole. CONCLUSIONS: Our model shows that the current delay in the vaccination schedules that is observed in many countries has serious consequences in terms of mortality by the disease and should serve as an alert to health authorities to speed the process up such that the highest number of people to be immunized is reached in the shortest period of time.

Estimating the effects of reopening of schools on the course of the epidemic of COVID-19.

In this paper, we present a method to estimate the risk of reopening of schools illustrated with the case of the State of São Paulo, Brazil. The model showed that, although no death of children would result from the reopening of the schools in the three cities analysed, the risk of asymptomatic and symptomatic cases and secondary cases among teachers, school staff and relatives of the children is not negligible. Although the epidemic hit different regions with different intensities, our model shows that, for regions where the incidence profile is similar to the cities analysed, the risk of reopening of schools is still too high. This in spite of the fact that incidences in these cities were declining in the period of the time considered. Therefore, although we cannot extend the result to the entire country, the overall conclusion is valid for regions with a declining incidence and it is even more valid for regions where incidence is increasing. We assumed a very conservative level of infection transmissibility of children of just 10% as that of adults. In spite of the very low level of transmissibility is assumed, the number of secondary cases caused by infected children among teachers, school staff and relatives varied from 2 to 85. It is, therefore, too soon to have any degree of confidence that reopening of schools before the advent of a vaccine is the right decision to take. The purpose of our model and simulations is to provide a method to estimate the risk of school reopening, although we are sure it could be applied as a guide to public health strategies.

Two complementary model-based methods for calculating the risk of international spreading of a novel virus from the outbreak epicentre. The case of COVID-19.

We present two complementary model-based methods for calculating the risk of international spread of the novel coronavirus SARS-CoV-2 from the outbreak epicentre. One model aims to calculate the number of cases that would be exported from an endemic country to disease-free regions by travellers. The second model calculates the probability that an infected traveller will generate at least one secondary autochthonous case in the visited country. Although this paper focuses on the data from China, our methods can be adapted to calculate the risk of importation and subsequent outbreaks. We found an average R0 = 5.31 (ranging from 4.08 to 7.91) and a risk of spreading of 0.75 latent individuals per 1000 travellers. In addition, one infective traveller would be able to generate at least one secondary autochthonous case in the visited country with a probability of 23%.

Modelling an optimum vaccination strategy against ZIKA virus for outbreak use.

We present a model to optimise a vaccination campaign aiming to prevent or to curb a Zika virus outbreak. We show that the optimum vaccination strategy to reduce the number of cases by a mass vaccination campaign should start when the Aedes mosquitoes' density reaches the threshold of 1.5 mosquitoes per humans, the moment the reproduction number crosses one. The maximum time it is advisable to wait for the introduction of a vaccination campaign is when the first ZIKV case is identified, although this would not be as effective to minimise the number of infections as when the mosquitoes' density crosses the critical threshold. This suboptimum strategy, however, would still curb the outbreak. In both cases, the catch up strategy should aim to vaccinate at least 25% of the target population during a concentrated effort of 1 month immediately after identifying the threshold. This is the time taken to accumulate the herd immunity threshold of 56.5%. These calculations were done based on theoretical assumptions that vaccine implementation would be feasible within a very short time frame.

Is vaccinating monkeys against yellow fever the ultimate solution for the Brazilian recurrent epizootics?

Vaccinating monkeys against yellow fever (YF) has been a common practice in the beginning of the 17D vaccine development. Although it may seem strange at first sight, vaccinating monkeys as a public health strategy is, we think, feasible and theoretically could eliminate the infection among non-human primates, interrupting the virus circulation (or significantly reducing it) and therefore reducing the risk of spilling over to the human population. We propose a series of studies that could demonstrate (or not) the efficacy and feasibility of vaccinating non-human primates YF reservoirs living in green areas of urban centres to cut off or curb the virus circulation that recurrently spill over to the human population. Therefore, vaccinating monkeys in relatively small green areas of the urban centres is perhaps the ultimate solution for the Brazilian recurrent YF epizootics.

The risk of urban yellow fever resurgence in Aedes-infested American cities.

Aedes aegypti, historically known as yellow fever (YF) mosquito, transmits a great number of other viruses such as Dengue, West Nile, Chikungunya, Zika, Mayaro and perhaps Oropouche, among others. Well established in Africa and Asia, Aedes mosquitoes are now increasingly invading large parts of the American continent, and hence the risk of urban YF resurgence in the American cities should because of great concern to public health authorities. Although no new urban cycle of YF was reported in the Americas since the end of an Aedes eradication programme in the late 1950s, the high number of non-vaccinated individuals that visit endemic areas, that is, South American jungles where the sylvatic cycle of YF is transmitted by canopy mosquitoes, and return to Aedes-infested urban areas, increases the risk of resurgence of the urban cycle of YF. We present a method to estimate the risk of urban YF resurgence in dengue-endemic cities. This method consists in (1) to estimate the number of Aedes mosquitoes that explains a given dengue outbreak in a given region; (2) calculate the force of infection caused by the introduction of one infective individual per unit area in the endemic area under study; (3) using the above estimates, calculate the probability of at least one autochthonous YF case per unit area produced by one single viraemic traveller per unit area arriving from a YF endemic or epidemic sylvatic region at the city studied. We demonstrate that, provided the relative vector competence, here defined as the capacity to being infected and disseminate the virus, of Ae. aegypti is greater than 0.7 (with respect to dengue), one infected traveller can introduce urban YF in a dengue endemic area.

Eating disorders-Related hospitalizations in Portugal: A nationwide study from 2000 to 2014.

INTRODUCTION: Recent evidence suggests that incidence of Anorexia nervosa (AN) has remained stable over the last decades in Western Europe, while decreasing for Bulimia nervosa (BN). It is well-known that most individuals with an ED (Eating disorder) do not seek medical treatment. OBJECTIVE: The present study analyses hospitalizations related with EDs held in mainland Portuguese public hospitals between 2000 and 2014. METHOD: A retrospective observational study was performed gathering all inpatient episodes with primary or secondary diagnosis of ED. Number of patients, gender, mean age at discharge, suicide-attempts related hospitalizations, in-hospital mortality, length of stay, and mean charges were analyzed. RESULTS: There were a total of 4,485 hospitalizations with an associated ED. AN was the most frequent ED (n = 2,806). Suicide attempt-related hospitalizations were most common among patients with BN (10.1% of BN hospitalizations) or AN (5.2% of AN hospitalizations). DISCUSSION: AN has higher in-hospital mortality than BN. We observed a higher proportion of suicide related hospitalizations in BN when compared to AN. Although pica, rumination disorder, and psychogenic vomiting represent a smaller portion of all EDs, this study was the first to describe hospitalization trends for this set of EDs for a 15-year period, to the best of our knowledge.

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.

Estimating the prevalence of infectious diseases from under-reported age-dependent compulsorily notification databases.

BACKGROUND: National or local laws, norms or regulations (sometimes and in some countries) require medical providers to report notifiable diseases to public health authorities. Reporting, however, is almost always incomplete. This is due to a variety of reasons, ranging from not recognizing the diseased to failures in the technical or administrative steps leading to the final official register in the disease notification system. The reported fraction varies from 9 to 99% and is strongly associated with the disease being reported. METHODS: In this paper we propose a method to approximately estimate the full prevalence (and any other variable or parameter related to transmission intensity) of infectious diseases. The model assumes incomplete notification of incidence and allows the estimation of the non-notified number of infections and it is illustrated by the case of hepatitis C in Brazil. The method has the advantage that it can be corrected iteratively by comparing its findings with empirical results. RESULTS: The application of the model for the case of hepatitis C in Brazil resulted in a prevalence of notified cases that varied between 163,902 and 169,382 cases; a prevalence of non-notified cases that varied between 1,433,638 and 1,446,771; and a total prevalence of infections that varied between 1,597,540 and 1,616,153 cases. CONCLUSIONS: We conclude that the model proposed can be useful for estimation of the actual magnitude of endemic states of infectious diseases, particularly for those where the number of notified cases is only the tip of the iceberg. In addition, the method can be applied to other situations, such as the well-known underreported incidence of criminality (for example rape), among others.

The risk of dengue for non-immune foreign visitors to the 2016 summer olympic games in Rio de Janeiro, Brazil.

BACKGROUND: Rio de Janeiro in Brazil will host the Summer Olympic Games in 2016. About 400,000 non-immune foreign tourists are expected to attend the games. As Brazil is the country with the highest number of dengue cases worldwide, concern about the risk of dengue for travelers is justified. METHODS: A mathematical model to calculate the risk of developing dengue for foreign tourists attending the Olympic Games in Rio de Janeiro in 2016 is proposed. A system of differential equation models the spread of dengue amongst the resident population and a stochastic approximation is used to assess the risk to tourists. Historical reported dengue time series in Rio de Janeiro for the years 2000-2015 is used to find out the time dependent force of infection, which is then used to estimate the potential risks to a large tourist cohort. The worst outbreak of dengue occurred in 2012 and this and the other years in the history of Dengue in Rio are used to discuss potential risks to tourists amongst visitors to the forthcoming Rio Olympics. RESULTS: The individual risk to be infected by dengue is very much dependent on the ratio asymptomatic/symptomatic considered but independently of this the worst month of August in the period studied in terms of dengue transmission, occurred in 2007. CONCLUSIONS: If dengue returns in 2016 with the pattern observed in the worst month of August in history (2007), the expected number of symptomatic and asymptomatic dengue cases among tourists will be 23 and 206 cases, respectively. This worst case scenario would have an incidence of 5.75 (symptomatic) and 51.5 (asymptomatic) per 100,000 individuals.

Modeling Importations and Exportations of Infectious Diseases via Travelers.

This paper is an attempt to estimate the risk of infection importation and exportation by travelers. Two countries are considered: one disease-free country and one visited or source country with a running endemic or epidemic infectious disease. Two models are considered. In the first model (disease importation), susceptible individuals travel from their disease-free home country to the endemic country and come back after some weeks. The risk of infection spreading in their home country is then estimated supposing the visitors are submitted to the same force of infection as the local population but do not contribute to it. In the second model (disease exportation), it is calculated the probability that an individual from the endemic (or epidemic) country travels to a disease-free country in the condition of latent infected and eventually introduces the infection there. The input of both models is the force of infection at the visited/source country, assumed known. The models are deterministic, but a preliminary stochastic formulation is presented as an appendix. The models are exemplified with two distinct real situations: the risk of dengue importation from Thailand to Europe and the risk of Ebola exportation from Liberia to the USA.

Estimating the Size of the HCV Infection Prevalence: A Modeling Approach Using the Incidence of Cases Reported to an Official Notification System.

In this paper we propose two methods to give a first rough estimate of the actual number of hepatitis C virus (HCV)-infected individuals (prevalence) taking into account the notification rate of newly diagnosed infections (incidence of notification) and the size of the liver transplantation waiting list (LTWL) of patients with liver failure due to chronic HCV infection. Both approaches, when applied to the Brazilian HCV situation converge to the same results, that is, the methods proposed reproduce both the prevalence of reported cases and the LTWL with reasonable accuracy. We use two methods to calculate the prevalence of HCV that, as a first, and very crude approximation, assumes that the actual prevalence of HCV in Brazil is proportional to the reported incidence to the official notification system with a constant denoted [Formula: see text]. In the paper we discuss the limitations and advantages of this assumption. With the two methods we calculated [Formula: see text], which reproduces both the reported incidence and the size of the LTWL. With the value of [Formula: see text] we calculated the prevalence I(a) (the integral of which resulted in 1.6 million people living with the infection in Brazil, most of whom unidentified). Other variables related to HCV infection (e.g., the distribution of the proportion of people aged a who got infected n years ago) can be easily calculated from this model. These new variables can then be measured and the model can be recursively updated, improving its accuracy.

Overactive bladder - 18 years - Part I.

Overactive bladder syndrome is one of the lower urinary tract dysfunctions with the highest number of scientific publications over the past two decades. This shows the growing interest in better understanding this syndrome, which gathers symptoms of urinary urgency and increased daytime and nighttime voiding frequency, with or without urinary incontinence and results in a negative impact on the quality of life of approximately one out of six individuals - including both genders and almost all age groups. The possibility of establishing the diagnosis just from clinical data made patients' access to specialized care easier. Physiotherapy resources have been incorporated into the urological daily practice. A number of more selective antimuscarinic drugs with consequent lower adverse event rates were released. Recently, a new class of oral drugs, beta-adrenergic agonists has become part of the armamentarium for Overactive Bladder. Botulinum toxin injections in the bladder and sacral neuromodulation are routine modalities of treatment for refractory cases. During the 1st Latin-American Consultation on Overactive Bladder, a comprehensive review of the literature related to the evolution of the concept, epidemiology, diagnosis, and management was conducted. This text corresponds to the first part of the review Overactive Bladder 18-years.

Overactive bladder - 18 years - Part II.

Traditionally, the treatment of overactive bladder syndrome has been based on the use of oral medications with the purpose of reestablishing the detrusor stability. The recent better understanding of the urothelial physiology fostered conceptual changes, and the oral anticholinergics - pillars of the overactive bladder pharmacotherapy - started to be not only recognized for their properties of inhibiting the detrusor contractile activity, but also their action on the bladder afference, and therefore, on the reduction of the symptoms that constitute the syndrome. Beta-adrenergic agonists, which were recently added to the list of drugs for the treatment of overactive bladder, still wait for a definitive positioning - as either a second-line therapy or an adjuvant to oral anticholinergics. Conservative treatment failure, whether due to unsatisfactory results or the presence of adverse side effects, define it as refractory overactive bladder. In this context, the intravesical injection of botulinum toxin type A emerged as an effective option for the existing gap between the primary measures and more complex procedures such as bladder augmentation. Sacral neuromodulation, described three decades ago, had its indication reinforced in this overactive bladder era. Likewise, the electric stimulation of the tibial nerve is now a minimally invasive alternative to treat those with refractory overactive bladder. The results of the systematic literature review on the oral pharmacological treatment and the treatment of refractory overactive bladder gave rise to this second part of the review article Overactive Bladder - 18 years, prepared during the 1st Latin-American Consultation on Overactive Bladder.

A public health risk assessment for yellow fever vaccination: a model exemplified by an outbreak in the state of São Paulo, Brazil.

We propose a method to analyse the 2009 outbreak in the region of Botucatu in the state of São Paulo (SP), Brazil, when 28 yellow fever (YF) cases were confirmed, including 11 deaths. At the time of the outbreak, the Secretary of Health of the State of São Paulo vaccinated one million people, causing the death of five individuals, an unprecedented number of YF vaccine-induced fatalities. We apply a mathematical model described previously to optimise the proportion of people who should be vaccinated to minimise the total number of deaths. The model was used to calculate the optimum proportion that should be vaccinated in the remaining, vaccine-free regions of SP, considering the risk of vaccine-induced fatalities and the risk of YF outbreaks in these regions.

A comparative analysis of the relative efficacy of vector-control strategies against dengue fever.

Dengue is considered one of the most important vector-borne infection, affecting almost half of the world population with 50 to 100 million cases every year. In this paper, we present one of the simplest models that can encapsulate all the important variables related to vector control of dengue fever. The model considers the human population, the adult mosquito population and the population of immature stages, which includes eggs, larvae and pupae. The model also considers the vertical transmission of dengue in the mosquitoes and the seasonal variation in the mosquito population. From this basic model describing the dynamics of dengue infection, we deduce thresholds for avoiding the introduction of the disease and for the elimination of the disease. In particular, we deduce a Basic Reproduction Number for dengue that includes parameters related to the immature stages of the mosquito. By neglecting seasonal variation, we calculate the equilibrium values of the model's variables. We also present a sensitivity analysis of the impact of four vector-control strategies on the Basic Reproduction Number, on the Force of Infection and on the human prevalence of dengue. Each of the strategies was studied separately from the others. The analysis presented allows us to conclude that of the available vector control strategies, adulticide application is the most effective, followed by the reduction of the exposure to mosquito bites, locating and destroying breeding places and, finally, larvicides. Current vector-control methods are concentrated on mechanical destruction of mosquitoes' breeding places. Our results suggest that reducing the contact between vector and hosts (biting rates) is as efficient as the logistically difficult but very efficient adult mosquito's control.

Risk of symptomatic dengue for foreign visitors to the 2014 FIFA World Cup in Brazil.

Brazil will host the FIFA World Cup™, the biggest single-event competition in the world, from June 12-July 13 2014 in 12 cities. This event will draw an estimated 600,000 international visitors. Brazil is endemic for dengue. Hence, attendees of the 2014 event are theoretically at risk for dengue. We calculated the risk of dengue acquisition to non-immune international travellers to Brazil, depending on the football match schedules, considering locations and dates of such matches for June and July 2014. We estimated the average per-capita risk and expected number of dengue cases for each host-city and each game schedule chosen based on reported dengue cases to the Brazilian Ministry of Health for the period between 2010-2013. On the average, the expected number of cases among the 600,000 foreigner tourists during the World Cup is 33, varying from 3-59. Such risk estimates will not only benefit individual travellers for adequate pre-travel preparations, but also provide valuable information for public health professionals and policy makers worldwide. Furthermore, estimates of dengue cases in international travellers during the World Cup can help to anticipate the theoretical risk for exportation of dengue into currently non-infected areas.

When Addressing Trauma Makes a Difference: A Case Report of Undiagnosed Complex Post-traumatic Stress Disorder.

Complex post-traumatic stress disorder (C-PTSD) is an emergent diagnosis, which acknowledges the impact of prolonged interpersonal abuse on affect regulation, interpersonal functioning, and self-concept. We present the case of a 59-year-old woman who remained undiagnosed and untreated for this condition for three decades while under follow-up in mental health services for the diagnosis of personality disorder and bipolar disorder. The patient suffered repeated sexual abuse in her childhood, resulting in intrusive traumatic memories she emotionally and cognitively avoided, dissociative amnesia, a persistent inability to experience positive emotions, a persistent sense of guilt, re-experiencing phenomena, and hypervigilance toward others and their intentions to harm her. She persistently believed herself to be worthless, defective, inferior, and lacking value; had a history of affective dysregulation resulting in suspicion of bipolar disorder; and displayed a pattern of relationship avoidance. Addressing chronic trauma and assessing its impact offered deeper contextualization of the patient's symptoms and proved pivotal in redefining her diagnosis and providing access to trauma-focused psychotherapy, which is the mainstay of treatment for C-PTSD.

Partial Implant Rehabilitations in the Posterior Regions of the Jaws Supported by Short Dental Implants (7.0 mm): A 7-Year Clinical and 5-Year Radiographical Prospective Study.

Background: Short implants have been used in the restoration of edentulous jaws in the past several years. However, some studies have suggested that short implants are less successful than standard implants. The aim of this study is to investigate the outcome of short implants placed in the posterior maxilla or mandible following one-stage or immediate-function protocols with a follow-up of 7 years (clinically) and 5 years (radiographically). Methods: This study included 127 patients rehabilitated with 217 implants measuring 7 mm and supporting 157 fixed prostheses in the posterior segments of both jaws. Final abutments were delivered at the surgery stage and were loaded after 4 months in 116 patients (199 implants). The primary outcome measure was implant survival measured through life tables. Secondary outcome measures were marginal bone loss and the incidence of biological and mechanical complications at the patient level and implant level (evaluated through descriptive statistics). Results: Twenty-four patients (18.9%) with 45 implants (20.7%) were lost to the follow-up. In total, 32 implants failed (14.8%) in 22 patients (17.3%), resulting in a cumulative survival rate at 7 years of 81.2% for 7 mm implants in the rehabilitation of the posterior regions of the maxilla and mandible. The average (standard deviation) marginal bone loss was 1.47 mm (0.99 mm) at 5 years. The incidence rate of biological complications was 12.6% and 10.6% at the patient and implant levels, respectively. The incidence rate of mechanical complications was 21.3% for patients and 16.1% for implants. A higher failure rate was registered in smokers and in implant arrangements with a sequence of three fixtures in proximity. Conclusions: Within the limitations of this study, it can be concluded that the placement of 7 mm long implants for the partial implant-supported rehabilitation of atrophic posterior jaws is possible in the long term, judging by the survival rate and stable average marginal bone loss. Nevertheless, strict case selection should be performed, especially in smokers and with implant arrangements that provide a minimum of one unit in inter-implant distance.