Background Respiratory viruses are a leading cause of acute lower respiratory infections (ALRI) in young children. The role of seasonal influenza virus in childhood ALRI is generally underappreciated. This is because the global burden of disease due to ALRI attributable to seasonal influenza virus in children is unknown. This thesis aims to estimate the global and regional hospital admissions for seasonal influenzaassociated ALRI and the possible boundaries for influenza-associated ALRI mortality in children younger than five years. The WHO has developed guidelines for influenza surveillance using severe acute respiratory infections (SARI) sentinel surveillance network. However, data from sentinel surveillance are not routinely used in estimating disease burden in a population. This thesis also aims to provide tools for estimating influenza disease burden using data from SARI sentinel surveillance in developing country settings. Methods Incidence data for influenza-associated ALRI (from passive, hospital-based studies) were collected using a systematic review of studies published between January 1, 1995 and October 31, 2010. These data were supplemented by unpublished data from 15 population-based studies that were obtained by forming a consortium of researchers (Influenza Study Group) working in developing countries. The incidence meta-estimates were applied to global and regional population estimates for 2008 to calculate the estimated number of hospitalised influenza-associated ALRI cases that year. The possible bounds for influenza-associated mortality were estimated by combining incidence estimates with in-hospital case fatality ratios and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality. The data to estimate the incidence of all-cause hospitalised ALRI were collected using a systematic literature review that was supplemented with unpublished data from 24 population-based studies that were obtained by collaborating with research sites in developing countries (Severe ALRI Working Group). The hospitalised ALRI incidence meta-estimates were applied to global and regional population estimates for 2008 to calculate the estimated number of all-cause hospitalised ALRI cases that year. Data on the proportion of hospitalised ALRI cases that were positive for influenza were collected using a systematic review of the studies published between January 1, 1995 and December 31, 2011. The meta-estimates of the proportion of hospitalised ALRI cases positive for influenza were applied to the estimated number of hospitalised ALRI cases in the year 2008 to estimate the number of hospitalised influenza-associated ALRI cases globally and for the six WHO regions using this alternative method. The tools for estimating influenza disease burden using surveillance data were developed after a literature review and a survey of 27 end-users (influenza epidemiologists) in 24 countries. Results Thirty nine studies (21 from developing and 18 from industrialised regions) satisfying the eligibility criteria, provided data on the incidence of influenza-associated hospitalised ALRI. The incidence is highest in infants in the first six months of life, both in developing as well as industrialised countries. It is estimated that the incidence of hospitalised influenza-associated ALRI in children under the age of five years was about 1.5 (95% CI 1.0 to 2.3) and 1.2 (95% CI 0.9 to 1.6) per 1000 children in developing and industrialised countries respectively. This translates to about 911,000 (95% CI 617,000 to 1.4 million) hospitalisations worldwide due to influenza-associated ALRI in children younger than five years in 2008, 93% of the cases occurring in developing countries (where 90% of the global under-5 population reside). An estimated 21,500 (based on 20 studies) to 115,000 deaths (based on only 1 study) in under-five children were attributable to influenza-associated ALRI in 2008. Incidence and mortality varied substantially from year to year in any one setting. Eighty five studies (61 from developing and 24 from industrialised) reported incidence of hospitalised ALRI in children aged 0 to 4 years. It is estimated that about 11.3 (95% CI 9.5 to 13.5) million episodes of ALRI resulting in hospitalisation occurred worldwide in children aged 0 to 4 years in 2008, 92% of these occurring in developing countries. Twenty three studies (19 from developing and 4 from industrialised) reported data on proportion of hospitalised ALRI cases testing positive for influenza using laboratory tests. The estimated proportion of influenza-positive hospitalised ALRI cases was about 5.0 (95% CI 3.6 to 7) percent and 8.4 (95% CI 4.2 to 16.7) percent in developing and industrialised countries respectively. This translates to about 772,000 (95% CI 343,000 to 1.8 million) cases of influenza-associated hospitalised ALRI in children younger than five years worldwide in the year 2008. A manual (targeted at developing countries) describing the methods to estimate the disease burden associated with seasonal influenza using the various surveillance data was developed after considering the results of the preliminary survey. An electronic tool (based on a spread sheet model) to help the end-users (epidemiologists at sentinel surveillance sites and Ministries of Health) to estimate the disease burden at local and national levels was developed as an adjunct to the manual. The manual along with the electronic tool were piloted at three different sites in two developing countries (India and Ghana) and feedback from the end-users was obtained to make the version more user-friendly. The final draft of the manual along with the tool has been submitted to the WHO for final clearance. The member states and the WHO Eastern Mediterranean Regional Office decided to adopt the manual and in the first instance estimate the influenza disease burden in 8 member states having the requisite data for undertaking disease burden estimation. Conclusions Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on hospital inpatient services worldwide. There are significant gaps in published data from developing countries (especially the African and Eastern Mediterranean regions of the WHO). Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not presently available. Effective use of sentinel surveillance data for disease burden estimation would greatly improve the quality and precision of disease burden estimates (especially those resulting in hospitalisation). Improved disease burden estimates (particularly at the national level) would inform policy makers and national governments in formulating immunization policies for vaccinating high-risk groups, and planning annual requirements for vaccines and anti-viral drugs against seasonal influenza.

published_or_final_version / Community Medicine / Master / Master of Public Health

Herpes zoster is a common disease, affecting up to 30% of the population in their lifetime. We examined the burden of this disease over the period of 1997-2013 using administrative healthcare data to determine changes over time. Key medications used to treat herpes zoster and postherpetic neuralgia became generic, resulting in costs reductions, where was offset by increased drug utilization leaving drug-episode costs unchanged. Mean per-episode medical costs increased moderately. Combined, these resulted in increased outpatient costs over time. However, dramatic reduction in HZ-related hospitalizations countered these trends, resulting in no net change in overall burden. The total healthcare cost of treating HZ and PHN in Manitoba in 2011/12 was $1,997,183, slightly less than the $2,095,633 burden determined for 1997/98, the first study year. Long-term demographic projections suggest the population will continue to grow and age, likely driving the future burden upwards. / October 2016

Research has demonstrated that taking care of a patient with schizophrenia has serious mental health costs to caregivers including high levels of burden and poorer overall mental health. Research also indicates that caregivers from certain ethnic/racial groups may fare better in this process. Specifically, prior research indicates that African American and Hispanic caregivers often exhibit better mental health than their Caucasian counterparts. Using a sample of 176 caregivers of patients with schizophrenia, the present study was specifically aimed at examining whether three variables (caregiver burden, family cohesion and interdependence) may account for part of the formerly observed ethnic/racial differences in psychological outcomes. Study hypotheses pertaining to ethnicity/race and family cohesion were not supported. For the most part, minorities in this study did not demonstrate better mental health outcomes than Caucasians and family cohesion did not predict mental health outcomes. However, in line with study hypotheses, we did find that subjective burden mediated the relationship between objective burden and mental health. In other words, subjective appraisals of caregiving appear to partially underlie the association between concrete costs of caregiving and psychological outcomes in schizophrenia caregivers. Also as expected, we found that interdependence moderated the relationship between objective burden and subjective burden. This finding suggests that helping caregivers to value harmony and connection with others over individual self-interests may reduce the likelihood that objective stressors (which are often inevitable in schizophrenia) will result in subjective distress.

Bakalauro baigiamajame darbe nagrinėjama įmonėms tenkanti mokesčių našta. Nestabilios ekonomikos periodu, kai verslas turi prisitaikyti prie pablogėjusių rinkos sąlygų, mokesčių naštos rodiklis tampa vienu iš svarbiausių veiksnių lemiančių verslo patrauklumą. Teorinėje dalyje apžvelgiama mokesčių naštos sąvoka, raida, skaičiavimas ir įmonių mokami mokesčiai. Praktinėje darbo dalyje nagrinėjama įmonių rinkos struktūra, sumokėtų mokesčių dinamika, atskirų mokesčių rūšių ir svarbiausių mokesčių sukeliama našta įmonėms. Taip pat analizuojama kokia dalis bendrosios mokesčių naštos tenka įmonėms ir kokią administracinę naštą sukelia mokesčių mokėjimas. Detaliau analizuotas pelno mokestis ir mokesčio sumą lemiančių veiksnių įtaka. Atlikus tyrimą nustatyta, kad didžioji dalis bendrosios mokesčių naštos tenka įmonėms, o santykiniams mokesčių naštos kitimo rodikliams didesnį poveikį padarė bendrojo vidaus produkto kitimas nei mokestinės sumos. / The tax burden on companies is analysed in this research. The period of economic instability, when the business needs to adapt to worsen market conditions, the tax burden indicator becomes one of the most important factors determining the attractiveness of the business. The theoretical part provides an overview of the conception, development, and calculation of tax burden and taxes paid by companies. The structure of companies market, the dynamics of paid taxes, types of individual taxes and the most important tax burden on companies are analysed in the practical part of the research. It also analyses what part of a general tax burden falls on companies and what kind of administrative burden is created after the payment of taxes. An income tax and influence of factors on tax amount are analysed in more detail. The investigation revealed that the biggest part of tax burden falls on companies and a gross domestic product had bigger influence on indicators of the changes in a relative tax burden than the amount of tax.

Infectious disease outbreaks can have a significant impact on healthcare resources and are disruptive to routine healthcare programs and services. There is very little literature on the economic burden of infectious disease outbreaks; thus, this research attempts to provide insight into the healthcare resources used to contain a mumps outbreak. The Nova Scotia 2007 mumps outbreak provides an opportunity to produce a costing framework to capture the economic burden an outbreak has on the Nova Scotia healthcare system. The costing framework for this study used an accounting model to costing; in particular, it used an activity-based costing approach. The total mumps outbreak cost is estimated at $2,478,500 or $3,511 per mumps case. Given the significant impact an infectious disease outbreak has on healthcare resources, more economic evaluations should be done to help guide policies around infectious disease prevention strategies, and to maximize the allocation of healthcare resources.

Cognitive impairment in Parkinson’s disease (PD) can impact negatively on caregivers and is associated with carer distress and feelings of burden. To investigate this relationship we examined level of burden, coping strategies, depression, anxiety and potential positive aspects of caregiving in the caregivers of 104 PD patients. The PD patients were classified as either showing normal cognition (PD-N; n=57), with mild cognitive impairment (PD-MCI; n=31) or with dementia (PD-D; n=16). The key finding was that mean Zarit burden score increased between carers of PD-N (M=14.1, SD=12.0) through to PD-MCI (M=21.1, SD=9.86) and PD-D (M=27.8, SD=10.61); F (2,101) =9.96, p<0.001. Post hoc tests (Newman-Keuls) identified significantly higher Zarit burden scores in PD-D caregivers compared to both PD-N (p<.001) and PD-MCI patients (p<.05), but carers of PD-MCI patients also showed increased burden scores relative to those of PD-N patients (p<.05). The proportion of carers showing significant levels of burden (Zarit burden score ≥21) also increased as cognition declined (21% for PD-N; 58% for PD-MCI; and 81% for PD-D). Time spent providing care and problem-focused, emotion-focused and dysfunctional coping strategies also increased with worsening cognition. While caregiver use of problem-focused coping mediated the association between patient cognitive status and caregiver burden, we could not be confident about this relationship as the inverse model was also significant. Caregiver Zarit burden was independent of caregiver depression, anxiety and positive attributions of caregiving. The study highlights the impact of Parkinson’s disease on those providing care when the patients’ cognition is poor, including those with MCI. Caregiver well-being has important implications for nursing home placement and disease course.

Risken att drabbas av demens ökar med stigande ålder. Antalet demenssjuka kommer att öka beroende på att befolkningen blir allt äldre. I och med detta ökar även antalet anhöriga som har en viktig roll i vården av den sjuke. I Sverige finns det ca 1,3 miljoner personer som ger stöd eller vård till närstående regelbundet. Demens är en diagnos för en rad symtom, med bland annat sviktande minne och nedsättning av andra kognitiva funktioner, vilket i sin tur har allvarliga konsekvenser för individer, familjer och hälso- sjukvårdssystem. De vanligaste formerna av demens är Alzheimers sjukdom, vaskulär demens och frontallobsdemens. En demenssjukdom medför ofta en stor fysisk, psykisk och social påfrestning. Syftet med litteraturstudien var att belysa anhörigvårdares upplevelse av att leva med en närstående som drabbats av demens. Studien baseras på nio kvalitativa och två kvantitativa artiklar. Analysen resulterade i tre huvudkategorier: "Upplevelse av förändrad relation", "Upplevelse av förändrad vardag" och "Upplevelse av stödbehov". I resultatet framkom det att anhöriga upplevde en rollförändring vilket påverkade såväl relationer som anhörigas hälsa. Upplevelser av ensamhet, bundenhet och isolering var stor samt känslan av att förlora kontrollen över sitt liv. Resultatet visar även på att anhöriga kan uppleva meningsfullhet i vårdandet. Personen med demens blir ofta allt mer beroende av familjemedlemmars stöd för att klara sin dagliga livsföring. Anhöriga behöver i sin tur stöd för att hantera vardagen och för att öka känslan av trygghet i deras omsorgssituation. En sjuksköterska behöver goda grundläggande kunskaper om den kliniska bilden och symtomatologi av kognitiv nedgång för att kunna ge anhöriga värdefulla råd och information.

Thesis (M. A.)--Roger Williams University, 2009. / Title from title page screen (viewed on Oct. 29, 2009) Includes bibliographical references.

Recombinant protein technologies have emerged as important tools for the production of proteins with industrial, academic and biopharmaceutical applications. However, current process development for a target protein is hindered by the burden recombinant protein expression places on the host system, with the level of this negative effect and the ideal production conditions varying from protein to protein. As a result current process optimisation relies on trial and error to determine the optimal set up for a given target protein. The work presented here will examine two mechanisms by which this burden acts on the cell, contributing towards making the overall burden effect and the optimal process conditions more predictable. Flux Balance Analysis was used to examine the effect of amino acid supplementation on the metabolic cost of a recombinant protein to predict which supplements would improve the efficiency of production, predictions supported elsewhere in the literature. However, experimental validation in batch and fed batch cultures for the production of human Granulocyte Colony Stimulating Factor demonstrated that these supplementation strategies do not lead to an increase in yield or performance. The results from the computational modelling alongside similar studies in the literature suggest that the more important factor may be optimisation for better growth generally rather than targeted attempts based on the protein composition. The sensitivity of native E. coli proteins to a loss of chaperone activity was predicted using the solubility data of the eSol database, identifying rrmJ as a protein of interest. The possible significance of rrmJ for chaperone saturation was examined alongside examining the effect of recombinant protein solubility using Green Fluorescent Protein (GFP) and its mutant GFP_A which have differing solubility. However, neither an effect through rrmJ nor a negative effect of recombinant protein solubility on growth was identified. Kinetic modelling for a mechanistic examination of the chaperone network suggests this is because the poorly folding protein is preferentially shifted to the insoluble fraction while the better performing proteins, i.e. the native proteins, are relatively unperturbed despite saturation of the chaperones. Overall the study was not able to make these areas more predictable. However, the observations made within this study contribute to an improvement in our understanding of two key mechanisms of interest in the field. Of particular interest is the identification of two logical hypotheses within the literature to be, at least in the cases tested, false.