Using a stochastic continuous-time Markov chain model to examine alternative timing and duration of the COVID-19 lockdown in Kuwait: what can be done now?

BACKGROUND: Kuwait had its first COVID-19 in late February, and until October 6, 2020 it recorded 108,268 cases and 632 deaths. Despite implementing one of the strictest control measures-including a three-week complete lockdown, there was no sign of a declining epidemic curve. The objective of the current analyses is to determine, hypothetically, the optimal timing and duration of a full lockdown in Kuwait that would result in controlling new infections and lead to a substantial reduction in case hospitalizations. METHODS: The analysis was conducted using a stochastic Continuous-Time Markov Chain (CTMC), eight state model that depicts the disease transmission and spread of SARS-CoV 2. Transmission of infection occurs between individuals through social contacts at home, in schools, at work, and during other communal activities. RESULTS: The model shows that a lockdown 10 days before the epidemic peak for 90 days is optimal but a more realistic duration of 45 days can achieve about a 45% reduction in both new infections and case hospitalizations. CONCLUSIONS: In the view of the forthcoming waves of the COVID19 pandemic anticipated in Kuwait using a correctly-timed and sufficiently long lockdown represents a workable management strategy that encompasses the most stringent form of social distancing with the ability to significantly reduce transmissions and hospitalizations.

Analysis of intervention effectiveness using early outbreak transmission dynamics to guide future pandemic management and decision-making in Kuwait.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a World Health Organization designated pandemic that can result in severe symptoms and death that disproportionately affects older patients or those with comorbidities. Kuwait reported its first imported cases of COVID-19 on February 24, 2020. Analysis of data from the first three months of community transmission of the COVID-19 outbreak in Kuwait can provide important guidance for decision-making when dealing with future SARS-CoV-2 epidemic wave management. The analysis of intervention scenarios can help to evaluate the possible impacts of various outbreak control measures going forward which aim to reduce the effective reproduction number during the initial outbreak wave. Herein we use a modified susceptible-exposed-asymptomatic-infectious-removed (SEAIR) transmission model to estimate the outbreak dynamics of SARS-CoV-2 transmission in Kuwait. We fit case data from the first 96 days in the model to estimate the effective reproduction number and used Google mobility data to refine community contact matrices. The SEAIR modelled scenarios allow for the analysis of various interventions to determine their effectiveness. The model can help inform future pandemic wave management, not only in Kuwait but for other countries as well.

Modeling the effect of lockdown timing as a COVID-19 control measure in countries with differing social contacts.

The application, timing, and duration of lockdown strategies during a pandemic remain poorly quantified with regards to expected public health outcomes. Previous projection models have reached conflicting conclusions about the effect of complete lockdowns on COVID-19 outcomes. We developed a stochastic continuous-time Markov chain (CTMC) model with eight states including the environment (SEAMHQRD-V), and derived a formula for the basic reproduction number, R0, for that model. Applying the [Formula: see text] formula as a function in previously-published social contact matrices from 152 countries, we produced the distribution and four categories of possible [Formula: see text] for the 152 countries and chose one country from each quarter as a representative for four social contact categories (Canada, China, Mexico, and Niger). The model was then used to predict the effects of lockdown timing in those four categories through the representative countries. The analysis for the effect of a lockdown was performed without the influence of the other control measures, like social distancing and mask wearing, to quantify its absolute effect. Hypothetical lockdown timing was shown to be the critical parameter in ameliorating pandemic peak incidence. More importantly, we found that well-timed lockdowns can split the peak of hospitalizations into two smaller distant peaks while extending the overall pandemic duration. The timing of lockdowns reveals that a "tunneling" effect on incidence can be achieved to bypass the peak and prevent pandemic caseloads from exceeding hospital capacity.

Analysis of the Healthcare MERS-CoV Outbreak in King Abdulaziz Medical Center, Riyadh, Saudi Arabia, June-August 2015 Using a SEIR Ward Transmission Model.

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonotic coronavirus that has a tendency to cause significant healthcare outbreaks among patients with serious comorbidities. We analyzed hospital data from the MERS-CoV outbreak in King Abdulaziz Medical Center, Riyadh, Saudi Arabia, June-August 2015 using the susceptible-exposed-infectious-recovered (SEIR) ward transmission model. The SEIR compartmental model considers several areas within the hospital where transmission occurred. We use a system of ordinary differential equations that incorporates the following units: emergency department (ED), out-patient clinic, intensive care unit, and hospital wards, where each area has its own carrying capacity and distinguishes the transmission by three individuals in the hospital: patients, health care workers (HCW), or mobile health care workers. The emergency department, as parameterized has a large influence over the epidemic size for both patients and health care workers. Trend of the basic reproduction number (R0), which reached a maximum of 1.39 at the peak of the epidemic and declined to 0.92 towards the end, shows that until added hospital controls are introduced, the outbreak would continue with sustained transmission between wards. Transmission rates where highest in the ED, and mobile HCWs were responsible for large part of the outbreak.

A stochastic model of the bovine spongiform encephalopathy epidemic in Canada.

Bovine spongiform encephalopathy (BSE) appeared in the United Kingdom in the mid 1980s, and has been attributed to the use of meat and bone meal (MBM) in cattle feed contaminated with a scrapie-like agent. Import of infectious materials from a country where BSE has occurred is believed to be the major factor underlying the spread of the BSE epidemic to other countries. This study presents a new stochastic model developed to estimate risk of BSE from importation of cattle infected with the BSE agent. The model describes the propagation of the BSE agent through the Canadian cattle herd through rendering and feeding processes, following importation of cattle with infectious prions. This model was used estimate the annual number of newly infected animals each year over the period 1980-2019. Model predictions suggested that the number of BSE infections in Canada might have been approximately 40-fold greater than the actual number of clinically diagnosed cases. Under complete compliance with the 2007 ban on feeding MBM, this model further predicts that BSE is disappearing from the Canadian cattle system. A series of sensitivity analyses was also conducted to test the robustness of model predictions to alternative assumptions about factors affecting the evolution of the Canadian BSE epidemic.

Using expert judgments to improve chronic wasting disease risk management in Canada.

ABSTARCT Chronic wasting disease (CWD) is a neurodegenerative, protein misfolding disease affecting cervids in North America in epidemic proportions. While the existence of CWD has been known for more than 40 years, risk management efforts to date have not been able to curtail the spread of this condition. An expert elicitation exercise was carried out in May 2011 to obtain the views of international experts on both the etiology of CWD and possible CWD risk management strategies. This study presents the results of the following three components of the elicitation exercise: (1) expert views of the most likely scenarios for the evolution of the CWD among cervid populations in Canada, (2) ranking analyses of the importance of direct and indirect transmission routes, and (3) rating analyses of CWD control measures in farmed and wild cervids. The implications of these findings for the development of CWD risk management strategies are described in a Canadian context.

Expert elicitation on the uncertainties associated with chronic wasting disease.

A high degree of uncertainty exists for chronic wasting disease (CWD) transmission factors in farmed and wild cervids. Evaluating the factors is important as it helps to inform future risk management strategies. Expert opinion is often used to assist decision making in a number of health, science, and technology domains where data may be sparse or missing. Using the "Classical Model" of elicitation, a group of experts was asked to estimate the most likely values for several risk factors affecting CWD transmission. The formalized expert elicitation helped structure the issues and hence provide a rational basis for estimating some transmission risk factors for which evidence is lacking. Considered judgments regarding environmental transmission, latency of CWD transmission, management, and species barrier were provided by the experts. Uncertainties for many items were determined to be large, highlighting areas requiring more research. The elicited values may be used as surrogate values until research evidence becomes available.

Mathematical Models for Estimating the Risks of Bovine Spongiform Encephalopathy (BSE).

When the bovine spongiform encephalopathy (BSE) epidemic first emerged in the United Kingdom in the mid 1980s, the etiology of animal prion diseases was largely unknown. Risk management efforts to control the disease were also subject to uncertainties regarding the extent of BSE infections and future course of the epidemic. As understanding of BSE increased, mathematical models were developed to estimate risk of BSE infection and to predict reductions in risk in response to BSE control measures. Risk models of BSE-transmission dynamics determined disease persistence in cattle herds and relative infectivity of cattle prior to onset of clinical disease. These BSE models helped in understanding key epidemiological features of BSE transmission and dynamics, such as incubation period distribution and age-dependent infection susceptibility to infection with the BSE agent. This review summarizes different mathematical models and methods that have been used to estimate risk of BSE, and discusses how such risk projection models have informed risk assessment and management of BSE. This review also provides some general insights on how mathematical models of the type discussed here may be used to estimate risks of emerging zoonotic diseases when biological data on transmission of the etiological agent are limited.

Relationship of erythrocyte transfusion with short- and long-term mortality in a population-based surgical cohort.

BACKGROUND: When comparing transfused versus nontransfused patients, erythrocyte transfusion is consistently associated with increased mortality. Nonetheless, unmeasured confounding may unduly influence this comparison. This unmeasured risk may have less influence on comparisons of patients undergoing surgery at hospitals with differing transfusion rates. METHODS: Administrative databases were used to conduct a population-based cohort study of patients who underwent elective hip- or knee-replacement surgery from 1999 to 2008 in Ontario, Canada. The authors used Cox proportional-hazards models to determine the adjusted association of hospital-specific erythrocyte transfusion rates (i.e., comparing hospitals with differing transfusion rates) with postoperative mortality. For comparison, they also determined the adjusted association of patient receipt of transfusion (i.e., comparing transfused vs. nontransfused patients) with mortality. RESULTS: Of 162,190 patients, 23% (n=37,015) were transfused. Hospital-specific transfusion rates at the 66 included hospitals ranged from 10.3 to 57.9%. Compared with nontransfused patients, transfused patients experienced increased adjusted 30-day (hazard ratio 2.32; 95% CI, 1.91-2.83) and 1-yr mortality (hazard ratio 1.75; 95% CI, 1.60-1.91). However, when hospitals were categorized into quartiles based on hospital-specific transfusion rates, mortality rates were similar (highest transfusion quartile vs. lowest transfusion quartile: 30-day mortality, hazard ratio 1.11, 95% CI 0.82-1.50; 1-yr mortality, hazard ratio 1.02, 95% CI 0.82-1.26). CONCLUSIONS: The association of transfusion with postoperative mortality differed significantly when comparing transfused versus nontransfused patients, as opposed to comparing hospitals with differing transfusion rates. This discrepancy raises questions about the true relationship between transfusion and mortality.

Expert elicitation for the judgment of prion disease risk uncertainties.

There is a high level of uncertainty surrounding the potential for iatrogenic prion transmission through transplantation, medical instrument reuse, blood transfusion, and blood product use due to a lack of evidence-based research on this important risk issue. A group of specialists was enlisted to evaluate some of the knowledge gaps in this area using the "Classical Model," a structured elicitation procedure for weighting and pooling expert judgment. The elicitation exercise was undertaken in March 2009 with 11 transmissible spongiform encephalopathy (TSE) experts who were first calibrated using a series of seed questions for which the answers are known; they were then asked to answer a number of target questions that are important for risk assessment purposes, but for which there remains high uncertainty at this time. The target questions focused on variant Creutzfeldt-Jakob disease (vCJD) prevalence, incubation times for vCJD, genetic susceptibility to prion disease, blood infectivity, prion reduction of blood and blood products, surgical instrument risks, and interspecies transmission of TSEs. The experts were also asked to perform pairwise risk rankings for 12 different potential routes of infection. Dura mater transplantation was seen as having the highest risk, while dental tissue grafts were viewed as presenting the lowest risk of iatrogenic transmission. The structured elicitation procedure provides a rational, auditable, and repeatable basis for obtaining useful information on prion disease risk issues, for which data are sparse.

Documenting a transfusion: how well is it done?

BACKGROUND: Current practice in transfusion medicine promotes clear documentation of transfusion-related events including the fact that the patient has been informed of the related risks and benefits. STUDY DESIGN AND METHODS: A retrospective review of 1005 patient charts was carried out to determine documentation. RESULTS: Most patients were from general surgery (10.8%) and cardiac surgery (14.1%). In 75 percent of cases the physician had not documented that any discussion had occurred regarding the risks and/or benefits or alternatives. Only 12 percent of charts included information that the patient was subsequently told what blood components were given to them. The discharge summary recorded transfusion information in 32.1 percent of cases whereas the consult note had this information in 26.3 percent. Chart records matched the transfusion medicine records in 60.6 percent of cases. The most common error was in the blood unit identification number. CONCLUSIONS: While accepted in theory, the practice of documenting patient information on transfusion is not well done.

Epidemiology of hepatocellular carcinoma in Canada, 1995: analysis of death certificates.

A descriptive analysis of hepatocellular carcinoma (HCC) deaths in Canada for 1995 was undertaken. Cases (ICD-9 155.0) were identified from the Statistics Canada annual mortality file; age-adjusted death rates by age, sex and province were calculated. Antecedent causes and conditions leading to death listed on the death certificate, including viral hepatitis infection and cirrhosis, were examined, in addition to birthplace information. The 403 cases identified resulted in an annual age-standardized mortality rate of 2.11 deaths per 100,000 persons among men and 0.64 deaths per 100,000 persons among women. Mean age at death was 65.5 years with male-to-female ratio approximately 3:1. Compared to the age-standardized rate for birthplace of Canada of 0.96 per 100,000 (95 percent CI: 0.84, 1.10), the age-standardized mortality rates were significantly elevated for birthplace of Europe 1.72 (95 percent CI: 1.37, 2.28), Asia 5.17 (95 percent CI: 4.11, 6.44), and non-significantly elevated for all other countries 1.54 (95 percent CI: 0.94, 2.39). In total, 60 patients (15 percent) were reported to have had viral hepatitis; sufficient information was not provided for the remainder. Of the total population, 8.7 percent were reported to have had viral hepatitis B and 5.2 percent had viral hepatitis C. Information on cirrhosis was provided in 103 (26 percent) of cases. Of these, the largest proportion (45 percent) was of unknown type while 23 patients (22 percent) had alcohol-related cirrhosis. Prevalence of antecedent causes was slightly lower than reported previously and may be considered minimum estimates since inadequate information was provided in over 50 percent of deaths.

Epidemiological study of Creutzfeldt-Jakob disease death certificates in Canada, 1979-2001.

INTRODUCTION: A descriptive epidemiological analysis to update trends of Creutzfeldt-Jakob disease (CJD) deaths, from 1979-2001, was undertaken. METHODS: Cases with CJD as underlying cause were extracted. Age-adjusted death rates by age, sex, and province were calculated. Information on birthplace, autopsy indications and type of work were examined for death certificates from 1979 to 1997. RESULTS: 462 cases were identified between 1979 and 1997. The average annual age-standardized mortality rate was 0.93 deaths per million persons during this period and 1.03 for 1998-2001. Persons 60 years or older demonstrated the highest average annual mortality rate. Rates were slightly higher among males and increased with age. Persons born in Canada accounted for 72% of deaths. Cause of death was verified by autopsy for 9.1% of patients while 21% of deaths indicated that additional information relating to underlying cause was expected. The service industry occupation represented the largest mortality (Quebec does not capture these data). CONCLUSIONS: Canadian rates are consistent with those of the United States and slightly higher than those of certain European countries. Approximately 44% of CJD cases had an autopsy record, though many were incomplete. We are unable to determine a relation with occupation. We recommend annual analysis of CJD death registrations for updated surveillance of trends, as mortality data are an efficient tool for monitoring incidence.

Hepatitis A, B, and C in Canada. Results from the National Sentinel Health Unit Surveillance System, 1993-1995.

OBJECTIVES: To estimate the incidence of and to describe the risk factors that were associated with the acquisition of hepatitis A, B, and C in well-defined Canadian populations from the Sentinel Health Unit Surveillance System (SHUSS). METHODS: We used the 1993 to 1995 data on hepatitis A, B, and C infection in Canada, collected by SHUSS, a national surveillance system established by the Laboratory Centre for Disease Control in Health Canada in 1993, through consultation and collaboration with provincial partners. We calculated the rates of, and described and discussed the risk factors that were associated with, hepatitis A, B, and C infection, based on the SHUSS surveillance data. RESULTS: From 1993 to 1995, SHUSS reported 92 cases of hepatitis A, 89 hepatitis B, and 720 hepatitis C, yielding a rate of 3.9, 3.8, and 30.3 per 100,000, respectively. The reported rates varied substantially among participating health units, ranging from 0.8 to 8.1 per 100,000 for hepatitis A, 0.0 to 9.0 for hepatitis B, and 5.4 to 73.3 for hepatitis C. The most frequently reported risk factor for hepatitis A was a history of street drug use, followed by recent international travel and household contact with a hepatitis A case, household crowding, and a history of raw or undercooked shellfish consumption. The most frequently reported risk factors for the acquisition of hepatitis B included history of street drug use and occupational exposure. The most frequently reported risk factor for the acquisition of hepatitis C was a history of street drug use, followed by health care exposure and occupational exposure. Only 5% of persons with hepatitis B infection had a history of hepatitis B immunization. INTERPRETATION: Despite the limitations of possible bias due to selective participation of SHUSS and the lack of information on risk factors among controls, the high exposure to known risk factors and the low rate of vaccination among hepatitis patients can provide useful information for the development of public health policies to control hepatitis A, B, and C infection in Canada.

An epidemiologic study of hepatocellular carcinoma in Canada.

BACKGROUND AND METHODS: To provide information on poorly described Canadian hepatocellular cancer epidemiology, we analyzed incident cases abstracted from the Canadian Cancer Registration Database (1969-1997) and Canadian annual death data (1969-1998). Age, sex, geographic distribution, and secular trends were described. Projection models were developed for the next decade. RESULTS: Results indicated much higher incidence and mortality rates in males than females, with substantial increases for both with age. Age-standardized incidence rates increased an average of 3.4% per year in males, 1.2% per year in females (1969-1997). Age-standardized mortality rates increased an average of 1.48% in males, but decreased an average of 0.46% per year in females (1969-1998). Join-point analysis of the linear trends in the age-standardized incidence and mortality rates suggested that a new trend started to emerge about 1991. The fitted non-linear multiplicative model predicted the occurrence of 1,565 new cases and 802 deaths in the year 2010. HCC incidence was the highest in British Colombia, followed by Quebec, and the lowest in the Atlantic region. CONCLUSIONS: Incidence rates of hepatocellular carcinoma have increased substantially, consistent with the reported increase in the prevalence of Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) infections in recent decades.

Development of a computer linkage system for a blood recipient notification program in Nova Scotia.

OBJECTIVES: To assess the potential uses of computer-assisted record linkage in the surveillance of infectious diseases, using the Nova Scotia blood recipient notification program as the example. METHODS: We developed a computer-assisted, multiple-pass, probabilistic record linkage to link records for blood recipients identified by the Nova Scotia notification program (Nova Scotia Phase I Blood Bank File information) with corresponding Nova Scotia Health Card Registration File records to obtain current mailing addresses to contact potentially living recipients. We used variables available from both files (e.g., name, date of birth, gender, and health care registration number) to link records, after eliminating duplicates/deceased cases. RESULTS: Among 23,925 eligible records in the Nova Scotia Phase I Blood Bank File (1984-1990), there were 1,818 (7.8%) duplications and 8,675 deceased cases, leaving 13,432 cases for linkage. 8,713 (65%) cases were successfully linked to the 1998 Health Card Registration Data File for current mailing addresses. INTERPRETATION: Multiple-pass linkage seems acceptable for maximizing detection of correctly matched records for look-back projects. To overcome quality/lack of information obstacles, future look-back linkages should explore the use of supplementary data files (tax files, voter lists, license files, other provincial databases) to obtain most current addresses.