Predictors of Fatal Outcome in Hospitalised Adult Patients with Acute Kidney Injury at Two Tertiary Hospitals in Sub-Saharan Africa

Introduction: Data on mortality in acute kidney injury (AKI) derives from high-income countries where AKI is hospital-acquired and occurs in elderly patients with a high burden of cardiovascular disease. In sub-Saharan Africa (SSA), AKI is community-acquired occurring in healthy young adults. We aimed to identify predictors of fatal outcomes in patients with AKI in two tertiary hospitals in Cameroon. Methods: Medical records of adults with confirmed AKI, from January 2018 to March 2020 were retrieved. The outcomes of interest were in-hospital deaths and presumed causes of death. We used multiple logistic regressions modeling to identify predictors of death. The study was approved by the ethics boards of both hospitals. Values were considered significant for a p-value of 0.05. Results: We included 285 patient records (37.2% females). The mean (SD) age was 50.1 (19.0) years. Hypertension (n = 97, 34.0%), organ failure (n = 88, 30.9%), and diabetes (n = 60, 21.1%) were the main comorbidities. The majority of patients had community-acquired AKI (78.6%, n = 224), were KDIGO stage 3 (88.8%, n = 253), and needed dialysis (52.6%, n = 150). Up to 16.7% (n = 25) did not receive what was needed. The in-hospital mortality rate was 29.1% (n = 83). Lack of access to dialysis (OR = 27.8;CI: 5.2 - 149.3, p = 0.001), hypotension (OR = 11.8;CI: 1.3 - 24.8;p = 0.001) and ICU admission (OR = 5.7;CI: 1.3 - 24.8, p = 0.001) were predictors of mortality. The presence of co-morbidities or underlying diseases (n = 46, 55%) were the main causes of death. Conclusions: In-hospital AKI mortality is high, as in other low- and middle-income economies. Lack of access to dialysis and the severity of the underlying illness are major predictors of death.

Country-based modelling of COVID-19 case fatality rate:A multiple regression analysis

BACKGROUND The spread of the severe acute respiratory syndrome coronavirus 2 outbreak worldwide has caused concern regarding the mortality rate caused by the infection.The determinants of mortality on a global scale cannot be fully understood due to lack of information.AIM To identify key factors that may explain the variability in case lethality across countries.METHODS We identified 21 Potential risk factors for coronavirus disease 2019(COVID-19)case fatality rate for all the countries with available data.We examined univariate relationships of each variable with case fatality rate(CFR),and all independent variables to identify candidate variables for our final multiple model.Multiple regression analysis technique was used to assess the strength of relationship.RESULTS The mean of COVID-19 mortality was 1.52±1.72%.There was a statistically significant inverse correlation between health expenditure,and number of computed tomography scanners per 1 million with CFR,and significant direct correlation was found between literacy,and air pollution with CFR.This final model can predict approximately 97%of the changes in CFR.CONCLUSION The current study recommends some new predictors explaining affect mortality rate.Thus,it could help decision-makers develop health policies to fight COVID-19.

An In-Depth Analysis of Road Fatal Crash Patterns and Discussions in Ho Chi Minh City

Although there has been a slight decrease in road traffic crashes, fatalities, and injuries in recent years, HCMC (Ho Chi Minh City) will continue to encounter challenges in mitigating and preventing road crashes. This study analyzes road crash data from the past five years, obtained from the Road-Railway Police Bureau (PC08) and TSB (Traffic Safety Board) in HCMC. This analysis gives us valuable insights into road crash patterns, characteristics, and underlying causes. This comprehensive understanding serves as a scientific foundation for developing cohesive strategies and implementing targeted solutions to address road traffic safety issues more effectively in the future.

Clinical and Familial Characteristics of Ten Chinese Patients with Fatal Family Insomnia

Objective Fatal familial insomnia （FFI） is an autosomal dominant prion disease characterized clinically by inattention, sleep loss, dysautonomia, and motor signs. This study is aimed to investigate clinical and familial characteristics often Chinese Patients with FFI. Methods We identified ten FFI cases from the surveillance network for Creutafeldt- Jakob disease （CJD） in China.Final diagnosis of FFI cases was made in accordance with the WHO criteria for CJD.The main clinical features and family histories of these ten FFI cases were analyzed. Results The median age of ten cases at onset was 38 years （from 19 to 55）. The foremost symptoms seemed to be various, including sleep disturbances, vision disorder, dizziness and anorexia. Sleep disturbances appeared in all cases and lasted in the whole clinical courses. Progressive sympathetic symptoms, memory loss, movement disturbances, myoclonus and hypertension were also frequently observed. The median duration of the disease was 9.5 months. EEG and MRI did not figure out special abnormality. 14-3-3 protein in CSF was positive in five out of eight tested patients. Clear family histories were identified in 8 patients. Conclusion The data from our study confirm that the Chinese FFI cases have similar clinical characteristics as that of the Caucasian cases. Compared with other genetic CJD associated mutations, the genetic frequencies of D178N in PRNP are apparently high among the Chinese cases.

Indicators of fatal outcome in severe Plasmodium falciparum malaria:a study in a tertiary-care hospital in Thailand

Objective:To illustrate the clinical features and investigate the indicators associated with a fatal outcome in adult patients with severe Plasmodium falciparum malaria admitted to the Hospital for Tropical Diseases,Bangkok,Thailand.Methods:We studied 202 adult malaria patients admitted to the Intensive Care Unit.A total of 43 clinical variables were identified by univariate and logistic regression analyses,to eliminate confounding factors.Results:Regarding the statistical methods,only 6 variables-jaundice,cerebral malaria,metabolic acidosis,body mass index,initial respiratory rate,and white blood cell count-were significant indicators of death, with adjusted odds ratios(95%CI) of 15.2(2.1-32.3).4.3(2.3-12.6),3.3(2.3-5.7),2.4(1.9-3.5),2.2 (1.5-2.6),and 1.7(1.2-3.1),respectively.Conclusions:Our study found that jaundice,cerebral malaria,metabolic acidosis,body mass index,initial respiratory rate and white blood cell count were indicators of fatal outcome in severe Plasmodium falciparum malaria.Further studies on the fatal indicators in severe malaria need to be compared with data from different geographical areas,to construct practical measures to address potentially fatal indicators in different settings.

Epidemiological Survey of the Prevalence of Non-fatal Injury among Children Aged 5-14 Years in China

Objective To determine the prevalence of non-fatal injuries among children aged 5-14 years in China. Methods Data of 21 973 children aged 5-14 years were extracted from the Fourth National Health Service Survey of China carried out between June 15 and July 10, 2008. Injury-related indicators included： history of ever having had an injury, and injury frequency, cause, location and severity. Results The overall prevalence of non-fatal injuries among the children in the previous 12 months was 17.0 per 1000 subjects. The leading causes of non-fatal injuries were falls, animal bites, traffic accidents, falling objects and burns. The majority of children sustained only one injury. The main place of injury was at home in 40% and 54% of urban boys and girls, respectively, at school in 48% of rural boys, and at home and at school each in 33% of rural girls. Medical treatment for one day was the main option for 80% of urban boys and girls, 84% of rural boys, and 72% of rural girls. Conclusion Nonfatal injuries among children aged 5-14 years are a serious public health concern in China.

Fatality in Kikuchi-Fujimoto disease: A rare phenomenon

Kikuchi-Fujimoto disease(KFD), also known as histiocytic necrotizing lymphadenitis, is an uncommon condition, typically characterized by lymphadenopathy and fevers. It usually has a benign course; however, it may progress to fatality in extremely rare occasions. The diagnosis is made via lymph node biopsy and histopathology. Our patient was a young female who presented with shortness of breath, fever, and malaise. Physical examination revealed significant cervical and axillary lymphadenopathy. Chest X-ray displayed multilobar pneumonia. She required intubation and mechanical ventilation for progressive respiratory distress. Histopathology of lymph nodes demonstrated variable involvement of patchy areas of necrosis within the paracortex composed of karyorrhectic debris with abundant histiocytes consistent with KFD. After initial stabilization, the patient's condition quickly deteriorated with acute anemia, thrombocytopenia and elevated prothrombin time, partial prothrombin time, and D-dimer levels. Disseminated intravascular coagulopathy(DIC) ensued resulting in the patient's fatality. DIC in KFD is not well understood, but it is an important cause of mortality in patients with aggressive disease.

Fatality from Road Traffic Accident in Guinea: A Retrospective Descriptive Analysis

Objectives: Causes and risk factors that result in fatal road traffic accident have not been described at the national level in Guinea yet. The goal of this study is to explore the causes and risk factors related to fatal road traffic accident, identified most vulnerable road users, and inform the road traffic prevention policy in Guinea. Methods: We made a retrospective descriptive analysis based on national fatal road traffic accident data from the Department of Health Information at the Guinean Ministry of Health for year 2011. Results: In 2011, road traffic accident was responsible for an aggregate number of 1655 deaths with an overall death rate of 15.3 per 100,000 population. Male experienced more than twice the risk of death from road traffic accidents (21.9 deaths per 100,000 population) compared with female (9.0 deaths per 100,000 population). While taking the population as a whole, the highest death rate was found among the middle aged in 35 - 49 age group accounting for (29.7 deaths per 100,000 population), followed successively by young adults age group 25 - 34 years (24.6 deaths per 100,000 population), and the middle aged in 50 - 64 age group (22.9 deaths per 100,000 population). Principally, occupants, motorcyclists and pedestrians sustained considerable burden of deaths respectively (9.2;2.9;2.2 per 100,000 population). In re-gional setting, the highest death rate was found in Upper Guinea (19.5 per 100,000 population), followed by Forest Guinea (18.7 per 100,000 population) and Middle Guinea (16.8 per 100,000 population). A large proportion of male was killed as motorcyclist than female while high per-centage of female died as occupant than male for all age group. The regional distribution showed that when a remarkable number of occupant death were observed in Upper and Forest Guinea, more people died as pedestrian and pedal cyclist in Conakry. Conclusions: This study demonstrated that most of the deaths were among occupants, motorcyclists and pedestrians, and the productive workforce aged 25 - 49 years. It was found that majority of the deaths happened in Upper Guinea followed by Forest Guinea. Improvement of roads design, strict enforcement of road safety laws and raising the awareness of general public about the causes and risks factors of road traffic accident through various channels are highly required which will promote economic growth in the local communities and then help people escape the poverty trap.

Giant Asian honeybee or Bambara stings causing myocardial infarction,bowel gangrene and fatal anaphylaxis in Sri Lanka:a case series

The sting of Giant Asian honeybee(Apis dorsata) or Bambara in Sinhala and Kanmge Kulavi in Tamil is a common environmental hazard in Sri Lanka known to cause immediate allergic reactions,which could be fatal in sensitized individuals.We reported myocardial infarction, bowel gangrene and fatal anaphylaxis in a prospectively proven case series and the association of these uncommon complications with delayed removal of stingers from the patients’skin.

Crizotinib-induced acute fatal liver failure in an Asian ALK-positive lung adenocarcinoma patient with liver metastasis: A case report

BACKGROUND Crizotinib-induce hepatotoxicity is rare and non-specific, and severe hepatotoxicity can develop into fatal liver failure. Herein, we report a case of fatal crizotinib-induced liver failure in a 37-year-old Asian patient.CASE SUMMARY The patient complained of dyspnea and upper abdominal pain for a week in August 2017. He was diagnosed with anaplastic lymphoma kinase-rearranged lung adenocarcinoma combined with multiple distant metastases. Crizotinib was initiated as a first-line treatment at a dosage of 250 mg twice daily. No adverse effects were seen until day 46. On day 55, he was admitted to the hospital with elevated liver enzymes aspartate aminotransferase(AST)(402 IU/L), alanine aminotransferase(ALT)(215 IU/L) and total bilirubin(145 μmol/L) and was diagnosed with crizotinib-induced fulminant liver failure. Despite crizotinib discontinuation and intensive supportive therapy, the level of AST(1075 IU/L),ALT(240 IU/L) and total bilirubin(233 μmol/L) continued to rapidly increase,and he died on day 60.CONCLUSION Physicians should be aware of the potential fatal adverse effects of crizotinib.

Pathogen characteristics and its sensitivity against antimicrobial agents in fatal bacterial granuloma after eyelid trauma in vitro

AIM: To understand the pathogen characteristics and its sensitivity against antimicrobial agents in fatal bacterial granuloma after eyelid trauma (FBGT) in vitro, and to provide laboratory evidence for diagnosis. METHODS: The FBGT pathogens were isolaated and cultured with reformed rabbit-brain anaerobic enriched broth (RRAB), and identified by ATB/API 20A system. The minimum inhibiting concentration (MIC) was determined by anaerobic broth dilution method. RESULTS: A total of 22 strains of pathogen were separated from 21 patients with FBGT and identified as Propionibacterium acnes (PA) by ATB/API 20A system. The MIC of ciprofloxacin for 22 PA strains was 0.0625-0.5mg/L, the MIC of penicillin, ampicillin, ampicillin/sulbactam, cefoperazone, lincomycin, and imipenem/cilastatin were 0.125-0.5mg/L, the MIC of ticarcillin/clavulanic acid was 0.250-1.000mg/L, and the MIC of metronidazole was 64-256mg/L. The pathogen of FBGT was strictly anaerobic PA, which growed slowly and better in nutritious RRAB broth. All PA were resistant to metronidazole, but susceptive to other routine antimicrobial agents, such as penicillin, ampicillin and lincomycin. CONCLUSION: FBGT should not be treated with metronidazole. Clinicians should choose combined use of drugs or operation to treat FBGT according to patients' individual condition and the results of drug sensitivity test.

Mast cell tryptase and carboxypeptidase A expression in body fluid and gastrointestinal tract associated with drug-related fatal anaphylaxis

AIM: To investigate the expression of mast cell tryptase and carboxypeptidase A in drug-related fatal anaphylaxis.METHODS: The expression of mast cell tryptase and carboxypeptidase A in 15 autopsy cases of drugrelated fatal anaphylaxis and 20 normal autopsy cases were detected. First, the expression of mast cell tryptase was determined in stomach, jejunum, lung, heart, and larynx by immunofluorescence. Different tissues were removed and fixed in paraformaldehyde solution, then paraffin sections were prepared for immunofluorescence. Using specific mast cell tryptase and carboxypeptidase A antibodies, the expression of tryptase and carboxypeptidase A in gastroenterology tract and other tissues were observed using fluorescent microscopy. The postmortem serum and pericardial fluid were collected from drug-related fatal anaphylaxis and normal autopsy cases. The level of mast cell tryptase and carboxypeptidase A in postmortem serum and pericardial fluid were measured using fluor enzyme linked immunosorbent assay(FEIA) and enzyme linked immunosorbent assay(ELISA) assay. The expression of mast cell tryptase and carboxypeptidase A was analyzed in drug-related fatal anaphylaxis cases and compared to normal autopsy cases.RESULTS: The expression of carboxypeptidase A was less in the gastroenterology tract and other tissues from anaphylaxis-related death cadavers than normal controls. Immunofluorescence revealed that tryptase expression was significantly increased in multiple organs, especially the gastrointestinal tract, from anaphylaxis-related death cadavers compared to normal autopsy cases(46.67 ± 11.11 vs 4.88 ± 1.56 in stomach, 48.89 ± 11.02 vs 5.21 ± 1.34 in jejunum, 33.72 ± 5.76 vs 1.30 ± 1.02 in lung, 40.08 ± 7.56 vs 1.67 ± 1.03 in larynx, 7.11 ± 5.67 vs 1.10 ± 0.77 in heart, P < 0.05). Tryptase levels, as measured with FEIA, were significantly increased in both sera(43.50 ± 0.48 μg/L vs 5.40 ± 0.36 μg/L, P < 0.05) and pericardial fluid(28.64 ± 0.32 μg/L vs 4.60 ± 0.48 μg/L, P < 0.05) from the anaphylaxis group in comparison with the control group. As measured by ELISA, the concentration of carboxypeptidase A was also increased more than 2-fold in the anaphylaxis group compared to control(8.99 ± 3.91 ng/m L vs 3.25 ± 2.30 ng/m L in serum, 4.34 ± 2.41 ng/m L vs 1.43 ± 0.58 ng/m L in pericardial fluid, P < 0.05).CONCLUSION: Detection of both mast cell tryptase and carboxypeptidase A could improve the forensic identification of drug-related fatal anaphylaxis.

Use of Finite Element Analysis for the Prediction of Driver Fatality Ratio Based on Vehicle Intrusion Ratio in Head-On Collisions

To estimate the aggressivity of vehicles in frontal crashes, national highway traffic safety administration (NHTSA) has introduced the driver fatality ratio, DFR, for different vehicle-to-vehicle categories. The DFR proposed by NHTSA is based on the actual crash statistical data, which makes it difficult to evaluate for other vehicle categories newly introduced to the market, as they do not have sufficient crash statistics. A finite element (FE) methodology is proposed in this study based on computational reconstruction of crashes and some objective measures to predict the relative risk of DFR associated with any vehicle-to-vehicle crash. The suggested objective measures include the ratios of maximum intrusion in the passenger compartments of the vehicles in crash, and the transmitted peak deceleration of the vehicles’ center of gravity, which are identified as the main influencing parameters on occupant injury. The suitability of the proposed method is established for a range of bullet light truck and van (LTV) categories against a small target passenger car with published data by NHTSA. A mathematical relation between the objective measures and DFR is then developed. The methodology is then extended to predict the relative risk of DFR for a crossover category vehicle, a light pick-up truck, and a mid-size car in crash against a small size passenger car. It is observed that the ratio of intrusions produces a reasonable estimate for the DFR, and that it can be utilized in predicting the relative risk of fatality ratios in head-on collisions. The FE methodology proposed in this study can be utilized in design process of a vehicle to reduce the aggressivity of the vehicle and to increase the on-road fleet compatibility in order to reduce the occupant injury out- come.

Design of Cusum Scheme for Monitoring Road Accident Fatalities

In recent years, road accident fatalities in Nigeria have continued to be on the increase. Thus, urgent attention is needed to reduce or eliminate road accidents fatalities. To achieve this goal, the cumulative sum (Cusum) control chart scheme was designed for monitoring the road accident fatalities using the recorded occurrence of road accident fatalities in a state in the western part of Nigeria. The designed Cusum detects the period of the years when the highest occurrence of road accident fatalities occurred. These periods were observed to be festive periods such as Christmas, Easter, Eid-el- Kabir, and Eid-el-Moluod. Therefore, the festive periods of the year should be used as benchmark by road managers as periods where more attention or precaution measure should be put in place on the roads to drastically reduce or eliminate high occurrence of road accident fatalities. The designed Cusum control chart can be adapted for other states in the country and also for the larger society for detecting the periods when the rate of death as a result of road accidents was prevalent.

SEIHCRD Model for COVID-19 Spread Scenarios,Disease Predictions and Estimates the Basic Reproduction Number,Case Fatality Rate,Hospital,and ICU Beds Requirement

We have proposed a new mathematical method,the SEIHCRD model,which has an excellent potential to predict the incidence of COVID-19 diseases.Our proposed SEIHCRD model is an extension of the SEIR model.Three-compartments have added death,hospitalized,and critical,which improves the basic understanding of disease spread and results.We have studiedCOVID-19 cases of six countries,where the impact of this disease in the highest are Brazil,India,Italy,Spain,the United Kingdom,and the United States.After estimating model parameters based on available clinical data,the modelwill propagate and forecast dynamic evolution.Themodel calculates the Basic reproduction number over time using logistic regression and the Case fatality rate based on the selected countries’age-category scenario.Themodel calculates two types of Case fatality rate one is CFR daily,and the other is total CFR.The proposed model estimates the approximate time when the disease is at its peak and the approximate time when death cases rarely occur and calculate how much hospital beds and ICU beds will be needed in the peak days of infection.The SEIHCRD model outperforms the classic ARXmodel and the ARIMA model.RMSE,MAPE,andRsquaredmatrices are used to evaluate results and are graphically represented using Taylor and Target diagrams.The result shows RMSE has improved by 56%–74%,and MAPE has a 53%–89%improvement in prediction accuracy.

A study of mining fatalities and coal price variation

It has long been postulated that a relationship exists between commodity price cycles and fatalities in the mining industry.Previous studies have found only weak correlations in this area.This study analyses the fatalities recorded in coal mines over the period 1985-2016 in the State of Queensland as a function of thermal coal price variation.The study finds that the relationship between fatalities and coal prices is not linear.One to two fatalities occur in most years independent of the thermal coal price.When the price of coal falls below AUD 55/tonne(non-inflation adjusted),the likelihood of an incident involving multiple fatalities increases.The probability can be estimated at 2 in 18 events(equivalent to 11%).This paper postulates that in difficult economic times,mining companies react by downsizing direct employees.If not carefully managed,this can result in loss of knowledge around safety systems,and reduced effectiveness of safety supervision.Because of labour cost advantages,some jobs previously undertaken by direct employees will be replaced by contractors.Increased contractor numbers contribute to increased risk of fatalities occurring,as contractors are over-represented in accident categories involving vehicle accidents,tire handling and crushing incidents.Mine inspectorates,mining,and mining contractor companies need to be especially vigilant to enforce health and safety management systems during periods of low coal prices.

Fatal cases of animal-mediated human rabies: Looking beyond sectoral prism to One Health

This issue of Asian Pacific Journal of Tropical Medicine has published a case report[1].This report detailed an atypical fatal case of fox-mediated human rabies.It once again reemphasized the importance of zoonotic disease transmission by animals(including wildlife),and a need to look introspectively in order to consider innovative solutions aimed at reducing the burden of zoonoses.Rabies continues to significantly impact human lives.

Case Fatality Rate of Severe Acute Respiratory Syndromes in Beijing

To describe the case fatality rate of SARS in Beijing. Methods Data of SARS cases notified from Beijing Center for Disease Control and Prevention （BCDC） and supplemented by other channels were collected. The data were analyzed by rate calculation. Results The case fatality rate of SARS in Beijing was 7.66%, and had an ascending trend while the age of cases was getting older, and a descending trend while the epidemic developmem. The case fatality rate in Beijing was lower than that in other main epidemic countries or regions. Conclusions The risk of death increases with the increment of age of SARS patients. Beijing is successful in controlling and treating SARS.

A cohort study of hospitalized adult dengue patients with fatality in Taiwan: The elderly and febrile characteristics matter for prognosis

Objective:To identify the febrile characteristics and clinical presentations associated with fatality in hospitalized adult patients with dengue virus(DENV)infections.Methods:A total of 289 adult hospitalized patients with laboratoryconfirmed DENV infections were examined,of which 22 were fatal and 267 were non-fatal.A comparison of the clinical and laboratory characteristics was retrospectively conducted of the deceased and surviving individuals.Multivariate logistic regression and receiver operating characteristic curve analysis were performed to identify predictors of fatality.Results:Fatal patients exhibited significantly more comorbidities,particularly renal and cardiac comorbidities,and they were,in general,older than control individuals(P<0.0001).The results of logistic regression analysis showed that febrile duration of less than four days before arriving in the Emergency Department(OR=5.34;95%CI:1.39–20.6),episode of hypotension in the Emergency Department(OR=6.95;95%CI:2.40–20.1),and comorbidity with congestive heart failure(OR=11.26;95%CI:2.31–54.79)were all significantly associated with inpatient fatality due to DENV infection.The ROC curve analysis indicated that the final prognostic model yielded an area under the curve of 0.87(95%CI:0.79–0.97)for fatality.Conclusions:The aforementioned clinical findings may help clinicians predict fatality among adult inpatients with DENV infection.

No Effects of Meteorological Factors on the SARS-CoV-2 Infection Fatality Rate

Objective Previous studies have shown that meteorological factors may increase COVID-19 mortality,likely due to the increased transmission of the virus.However,this could also be related to an increased infection fatality rate(IFR).We investigated the association between meteorological factors(temperature,humidity,solar irradiance,pressure,wind,precipitation,cloud coverage)and IFR across Spanish provinces(n=52)during the first wave of the pandemic(weeks 10–16 of 2020).Methods We estimated IFR as excess deaths(the gap between observed and expected deaths,considering COVID-19-unrelated deaths prevented by lockdown measures)divided by the number of infections(SARS-CoV-2 seropositive individuals plus excess deaths)and conducted Spearman correlations between meteorological factors and IFR across the provinces.Results We estimated 2,418,250 infections and 43,237 deaths.The IFR was 0.03%in<50-year-old,0.22%in 50–59-year-old,0.9%in 60–69-year-old,3.3%in 70–79-year-old,12.6%in 80–89-year-old,and26.5%in≥90-year-old.We did not find statistically significant relationships between meteorological factors and adjusted IFR.However,we found strong relationships between low temperature and unadjusted IFR,likely due to Spain’s colder provinces’aging population.Conclusion The association between meteorological factors and adjusted COVID-19 IFR is unclear.Neglecting age differences or ignoring COVID-19-unrelated deaths may severely bias COVID-19 epidemiological analyses.