MS

thesisThe early detection of infectious disease outbreaks is key to their management and initiation of mitigation strategies. This is true whether the disease is naturally occurring or due to intentional release as an act of terrorism. In recent times, this has become evident with the anthrax bioterrorism attacks of October 2001, the occurrence of emerging infections such as West Nile Virus and Severe Acute Respiratory Syndrome of the concern for a new pandemic of influenza based on H5N1 avian influenza. Public health surveillance efforts at the University of Utah have been place for several years and came to the forefront during the 2002 Winter Olympic Games. At that time, an electronic medical record-based system was developed and deployed to perform daily surveillance of patients visiting the clinics and emergency department of the University of Utah Health Care System. This effort was then followed by a detailed validation of the computer rules used in the surveillance system, with special emphasis on the early detection of central nervous system (CNS) syndromes such as meningitis and encephalitis. These syndromes are of importance to both emerging infections such as West Nile Virus and for NIH/CDC Category B threat agents such as Eastern and Western Equine Encephalitis. True CNS syndromes caused by infectious agents represent a small proportion of patients seen at the emergency department of a large tertiary hospital. "Reason for visit" chief complaint data were poor predictors for the early detection of CNS syndromes. Orders and early results from the laboratory testing of cerebro-spinal fluid were useful for the early detection of meningitis and encephalitis. Overall, computer-based surveillance methods have a role to play in the early detection of infectious diseases. In particular, this project has contributed to public health surveillance by moving the field beyond complaint data and has shown the validity of suing computer-based rules for the detection of meningitis and encephalitis

Can near real-time monitoring of emergency department diagnoses facilitate early response to sporadic meningococcal infection? - prospective and retrospective evaluations

<p>Abstract</p> <p>Background</p> <p>Meningococcal infection causes severe, rapidly progressing illness and reporting of cases is mandatory in New South Wales (NSW), Australia. The NSW Department of Health operates near real-time Emergency Department (ED) surveillance that includes capture and statistical analysis of clinical preliminary diagnoses. The system can provide alerts in response to specific diagnoses entered in the ED computer system. This study assessed whether once daily reporting of clinical diagnoses of meningococcal infection using the ED surveillance system provides an opportunity for timelier public health response for this disease.</p> <p>Methods</p> <p>The study involved a prospective and retrospective component. First, reporting of ED diagnoses of meningococcal infection from the ED surveillance system prospectively operated in parallel with conventional surveillance which requires direct telephone reporting of this scheduled medical condition to local public health authorities by hospitals and laboratories when a meningococcal infection diagnosis is made. Follow-up of the ED diagnoses determined whether meningococcal infection was confirmed, and the time difference between ED surveillance report and notification by conventional means. Second, cases of meningococcal infection reported by conventional surveillance during 2004 were retrospectively matched to ED visits to determine the sensitivity and positive predictive value (PPV) of ED surveillance.</p> <p>Results</p> <p>During the prospective evaluation, 31 patients were diagnosed with meningococcal infection in participating EDs. Of these, 12 had confirmed meningococcal disease, resulting in a PPV of 38.7%. All confirmed cases were notified earlier to public health authorities by conventional reporting.</p> <p>Of 149 cases of notified meningococcal disease identified retrospectively, 130 were linked to an ED visit. The sensitivity and PPV of the ED diagnosis for meningococcal infection was 36.2% and 36.7%, respectively.</p> <p>Conclusions</p> <p>Based on prospective evaluation, it is reassuring that existing mechanisms for reporting meningococcal infection perform well and are timely. The retrospective evaluation found low sensitivity and PPV of ED diagnoses for meningococcal disease. Even if more rapid forwarding of ED meningococcal diagnoses to public health authorities were possible, the low sensitivity and PPV do not justify this. In this study, use of an ED surveillance system to augment conventional surveillance of this scheduled medical condition did not demonstrate a benefit.</p

Utility of chloride and adenosine deaminase measurement in cerebrosphinal fluid for the early presumptive diagnosis of tuberculous meningitis

Background: Chloride and adenosine deaminase measurements in cerebrospinal fluid are still sporadically requested as part of tuberculous meningitis work-up. In the literature, evidence is contradictory and opinion is divided on their utility in clinical practice. The accuracy of both for the early presumptive diagnosis of tuberculous meningitis was investigated in patients in a region with high prevalence of tuberculosis and HIV infection in order to inform a decision on whether to continue offering these tests to clinicians. Methods: A retrospective descriptive study of diagnostic accuracy was conducted at the National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa. Data were collected on all cerebrospinal fluid specimens submitted for tuberculosis culture between 1 January 2012 and 31 December 2014. Chloride and adenosine deaminase concentrations were compared with automated liquid culture for Mycobacterium tuberculosis as the reference standard. Findings: There were 2531 cerebrospinal fluid specimens submitted for tuberculosis culture during the study period; exclusion of duplicates yielded 2081 specimens. Chloride was requested on 711 (34·2%) specimens; 44 (6·2%) were tuberculosis culture-positive. Adenosine deaminase was requested on 152 (7·3%) specimens; 20 (13·2%) were culture-positive. Chloride sensitivity (6 U/L) was 70% (45·7-88·1), specificity 89·4% (82·8-94·1), positive predictive value 50% (30·6-69·4), negative predictive value 95·2% (89·8-98·2), positive likelihood ratio 6·6 (3·72-11·7), and negative likelihood ratio 0·336 (0·171-0·657). Interpretation: In this patient population chloride and adenosine deaminase showed at best only modest performance as markers of tuberculous meningitis. However, very good negative predictive values could serve to identify patients highly unlikely to have the disease

Infectious Disease Epidemiology in the Asia-Pacific Region

My Master of Philosophy in Applied Epidemiology (MAE) placement at the National Centre for Immunisation Research and Surveillance (NCIRS) focused on various vaccine preventable diseases from a state, national and international lens. In response to a rise in invasive meningococcal serogroup W disease in Australia, I performed a comprehensive epidemiological review of the disease. My findings informed the decision of the Australian Technical Advisory Group on Immunisation to support the addition of the quadrivalent meningococcal vaccine onto the National Immunisation Program, providing immunity for meningococcal serogroups A, C, W and Y in infants and young adults. A small outbreak of varicella among children in an outside of school hours care facility provided the opportunity to conduct an outbreak investigation and a vaccine effectiveness study. Although underpowered, this study demonstrated the occurrence of breakthrough varicella despite high one-dose coverage among primary school-aged children, and evidence for consideration of a two-dose nationally funded program. I performed another vaccine effectiveness study following a state-wide outbreak of rotavirus in New South Wales in 2017. This was accompanied by an epidemiological analysis of rotavirus notifications and a genetic profile analysis of hospitalised rotavirus cases. The rotavirus outbreak occurred despite high vaccine effectiveness and vaccine coverage. The findings indicated that rotavirus is increasing among the older population who do not have vaccine-induced immunity. I conducted the first evaluation of the Paediatric Active Enhanced Disease Surveillance (PAEDS) system. PAEDS is an NCIRS-led initiative and actively finds hospitalised cases of serious childhood conditions and adverse events following immunisation. I evaluated this system using a mixed methods study design involving data analysis and stakeholder questionnaires. This evaluation provided practical recommendations for the progression and continuation of PAEDS in a time where the future of PAEDS is unknown. As part of the international response to the diphtheria outbreak among refugees in Bangladesh, I assisted the response of the World Health Organization in Cox's Bazar. As an epidemiologist, I analysed communicable disease alerts and trends in the refugee camps as well as investigated disease reports and conducted risk assessments. I gained further international experience by assisting in an applied field epidemiology research study: 'Surveillance and Monitoring to Eliminate Lymphatic Filariasis and Scabies from Samoa'. I conducted field visits to dozens of households in remote villages of Samoa to collect mosquitoes for testing the prevalence of lymphatic filariasis antibodies and antigens. The works within this thesis fulfil the requirements of the MAE. This thesis reports analyses of the epidemiology of invasive meningococcal disease in Australia, vaccine effectiveness of varicella among highly vaccinated children in Brisbane, epidemiology and vaccine effectiveness of rotavirus in New South Wales, evaluation of a surveillance system of serious childhood conditions in Australia, as well as describes the response to a humanitarian emergency in Bangladesh and assistance in a field research study in Samoa. These projects contribute to the work of NCIRS in informing the National Immunisation Program and vaccine policy and practice, as well as to the evidence base of vaccine preventable diseases and international epidemiological research

Predicting infections using computational intelligence – A systematic review

Infections encompass a set of medical conditions of very diverse kinds that can pose a significant risk to health, and even death. As with many other diseases, early diagnosis can help to provide patients with proper care to minimize the damage produced by the disease, or to isolate them to avoid the risk of spread. In this context, computational intelligence can be useful to predict the risk of infection in patients, raising early alarms that can aid medical teams to respond as quick as possible. In this paper, we survey the state of the art on infection prediction using computer science by means of a systematic literature review. The objective is to find papers where computational intelligence is used to predict infections in patients using physiological data as features. We have posed one major research question along with nine specific subquestions. The whole review process is thoroughly described, and eight databases are considered which index most of the literature published in different scholarly formats. A total of 101 relevant documents have been found in the period comprised between 2003 and 2019, and a detailed study of these documents is carried out to classify the works and answer the research questions posed, resulting to our best knowledge in the most comprehensive study of its kind. We conclude that the most widely addressed infection is by far sepsis, followed by Clostridium difficile infection and surgical site infections. Most works use machine learning techniques, from which logistic regression, support vector machines, random forest and naive Bayes are the most common. Some machine learning works provide some ideas on the problems of small data and class imbalance, which can be of interest. The current systematic literature review shows that automatic diagnosis of infectious diseases using computational intelligence is well documented in the medical literature.publishedVersio

Rurality or distance to care and the risk of homelessness among Afghanistan and Iraq veterans

INTRODUCTION: To date, no studies have examined the relationship of rurality and distance to nearest VA facility to risk of homelessness. METHODS: We examined differences in the rate of homelessness within a year of a Veteran's first encounter with the VA following last military separation based on rurality and distance to the nearest VA facility using multivariable log-binomial regressions. RESULTS: In our cohort of 708,120 Veterans, 73% were determined to have a forwarding address in urban areas, 59.2% and 86.7% lived within 40 miles of the nearest VA medical center (VAMC), respectively. Veterans living in a rural area and those living between 20+ miles away from the nearest VAMC were at a lower risk for homelessness. CONCLUSIONS: Our unique dataset allowed us to explore the relationship between geography and homelessness. These results are important to policy makers in understanding the risk factors for homelessness among Veterans and planning interventions

Neurodevelopmental Outcomes Following Severe Hand Foot and Mouth Disease in Vietnam

In 2011, more than 160 children died in an unprecedented outbreak of Hand foot and mouth disease (HFMD) in Vietnam, predominantly associated with enterovirus 71 (EV-A71). The occurrence of encephalitis outbreaks in children at vulnerable developmental stages raised concerns of long-term consequences. Limited retrospective outcome studies in the literature lack either a healthy comparison group or a locally validated neurodevelopmental assessment tool. Brain MRI retrospective observations identified stereotypical patterns of brainstem lesions predominantly in severe EV-A71 HFMD cases with conflicting opinions on the prognostic role of MRI. I adapted the “Bayley Scales of Infant and Toddler Development (3rd edition)” for Vietnam and demonstrated that the adaptation was reliable and valid. I conducted a prospective observational cohort study to test the hypothesis that children with severe HFMD, graded per Vietnam Ministry of Health classification, would have lower cognitive, language and motor Z scores than a healthy comparison group. All HFMD cases had virological samples taken and a sample of severe HFMD cases had brain MRI scans. All Z score 95% confidence intervals were within 2 standard deviations of the comparative healthy cohort mean suggesting outcomes at six months were not significantly lower than the healthy comparative group. I identified novel nonspecific brain white matter abnormalities on MRI in all severity grades, lower motor Z scores in grade 2b children with MRI abnormalities and that Coxsackievirus A10 (CV-A10) was significantly associated with MRI abnormalities. These findings support surveillance of all enteroviruses during HFMD outbreaks and suggest MRI may be predictive of motor impairment in a subset of severe HFMD cases. No significant impairment was identified at six months follow-up, but more complex developmental skills are yet to emerge. Hence the study continues for an eighteen-month follow up to robustly determine emergence of long-term sequelae

Serious conditions in patients presenting with non-specific chief complaints to the Emergency Medical Service (EMS)

BACKGROUND Ambulance clinicians encounter patients presenting with non-specific chief complaints on a daily basis. Such complaints can also be described as “decreased general health condition” “general malaise” and “sense of sickness”. These symptoms are often accompanied by vital signs within the normal reference range. It is known that one in three patients in the emergency department presenting with non-specific chief complaints have underlying serious conditions. In the context of ambulance care, there is a lack of knowledge in the group of patients and the identification of serious conditions within that group. AIM The overall aim was for patients with non-specific complaints in the pre-hospital setting; to describe the population for both those who are transported to hospitals or not i.e., conveyed, or non-conveyed, to investigate whether biomarkers can contribute to the identification of those who develop a serious condition, and to describe the experiences of pre-hospital emergency nurses in caring for the patient. METHODS Four sub-studies were performed. Study I was a retrospective, population-based study with the aim to describe the population and establish the prevalence of serious conditions as well as mortality rates among patients presenting with non-specific chief complaints and who were transported to the ED. Patients were identified via the electronic ambulance medical records (CAK-net, Region Stockholm) and data was retrieved from the National Patient Register and Causes of death register at Sweden’s National Board of Health and Welfare. Descriptive statistics was performed. Study II was a retrospective, population-based study with the aim to describe the population, establish the prevalence of serious condition as well as mortality rates and to compare between the groups of patients who were conveyed or non-conveyed. Descriptive statistics and regression analysis was performed. Study III was a qualitative interview study of prehospital emergency nurses experiences in caring for patients presenting with non-specific chief complaints. Qualitative content analysis according to Elo and Kyng s was performed. Study IV was a prospective, double-blind, multicenter study with the aim to determine if the biomarkers suPAR and lactate could identify serious conditions, as well as the predictive value on mortality. Ambulance care systems from Stockholm Region and two regions of Helsinki, Finland participated. Two blood tests were drawn after index ambulance assessment. Descriptive statistics as well as regression and likelihood analyses were performed. RESULT In Study I, 3780 patients were included and had a median age of 77 years. Serious condition was prevalent in 35.3%. Admittance to hospital care was 67.7%. Patients with prevalent serious conditions had 20.2% 30-day mortality compared to 4.2% in the group without serious conditions. The majority of the patients had low triage scores according to Rapid Emergency Triage and Treatment System (RETTS) (60.7%) and National Early Warning Score (NEWS) (76.3%) and 23.9% and 28.3% had prevalent serious conditions respectively. 30-day mortality was 13.0% and 14.1% respectively. In Study II, a total of 4744 patients were included, with a median age of 76 years. A serious condition was present in 29.5% of the patients. Among those who were non-conveyed, serious conditions was present in 6.6% compared to 35.3% among those conveyed. 30-day mortality was 17.2% for those with prevalent serious conditions and who were non-conveyed, compared to 20.2% in the group who were conveyed. In Study III the prehospital emergency nurses expressed that an indepth systematic assessment may reduce suffering and increase patient safety. The systematic assessment is based on acknowledging the unexplained suffering, a systematic approach and experience, and that organizational processes such as feedback on given care are key for a meaningful caring encounter and optimal assessment. In Study IV, a total of 414 patients were included. The median age was 82 years of age. 15.2% of the patients had a serious condition. A positive likelihood ratio (LR+) of 1.17 and a positive predictive value (PPV) of 17.3% as being predictive of a serious condition was observed when suPAR was elevated above 3 ng/ml. A LR+ of 4.67 and a PPV of 16.7% was observed for suPAR levels above 9 ng/ml as being predictive of 30-day mortality. Lactate was not significantly predictive. CONCLUSIONS Several conclusions stem from the findings in the four sub-studies. The results indicate that the identification of serious conditions among patients presenting with non-specific chief complaints to the ambulance service is still complicated. Serious conditions are present in both high and low triage levels. These triage systems are based on vital signs and may therefore be insufficient tools with which to identify serious conditions. The patients who are non-conveyed after index assessment do not differ from the patients conveyed in term of symptoms, sex or age. However, they differ in terms of prevalence of serious conditions and mortality, which is in both cases lower. The biomarkers, suPAR and lactate cannot differentiate between patients with or without serious conditions, but the association with mortality could add value to the clinical assessment. Prehospital emergency nurses experience that this patient group benefits from an in-depth systematic assessment that can reduce suffering and increase patient safety, and that organizational factors such as feedback and differentiated levels of care could have positive effects on care in general and for patients with non-specific chief complaints in particular. The results indicate that the assessments are complex and that the objective parameters used are not sufficient to identify serious conditions. Identification of serious conditions among patients presenting with NSCs to the ambulance service remains a challenge. Increased education and feedback on given care would likely increase the identification. However, an enhanced understanding of the atypical presentations of NSCs and the process of clinical reasoning could strengthen the ACs in performing person-centered car

An Evaluation of Mandatory Communicable Disease Reporting in North Carolina

The current communicable disease surveillance system in the United States largely relies on reporting of communicable diseases and conditions by both physicians and laboratories. Incomplete or inaccurate reporting of these diseases impairs the estimation of incidence rates from surveillance systems as well as hinders the implementation and evaluation of public health control measures. The extent of incomplete reporting has not been quantified for a large geographic area over time or for more than a few diseases. Therefore, the completeness of communicable disease reporting was studied using a retrospective cohort study at 8 large healthcare systems in North Carolina (NC) spanning a ten-year time period. The NC Department of Health and Human Services (NC DHHS) communicable disease surveillance system is based on mandatory reporting of more than 60 diseases and conditions and is a passive surveillance system. Diagnostic codes from healthcare system billing records were used to ascertain the eligible cases to be reported to the communicable disease surveillance system, and a unique identifier was used to match these eligible patients to the case-patients who were reported to the NC DHHS surveillance system. In addition, a validation study was also conducted to estimate positive predictive values of the diagnostic codes for communicable disease case ascertainment because these codes are widely used for both public health surveillance and research. Quantification of communicable disease reporting completeness is critical to understanding the impact on two public health surveillance system goals, that is, disease incidence rate estimation and public health initiation of disease transmission control measures. In addition, these analyses may guide the development of local, state and national strategies for improvement of disease reporting and surveillance