archives@tulane.edu / Background Few studies have examined the association between parenting quality and behavioral adjustment in children and asthma incidence. Medication non-adherence is a proposed mechanism for the association between caregiver stress and asthma morbidity, but research on the association is limited. Aims To examine the association between parent-child relationship and child’s behavioral adjustment and asthma incidence, and to explore the association between caregiver stress and medication non-adherence in children with asthma. Methods Secondary analyses were conducted in two study populations: a birth cohort study in the United Kingdom and an intervention trial of children with asthma in inner-city New Orleans. The first two analyses defined asthma by parent report and current asthma medication use at five or seven years. Mother-child relationship and child’s behavioral adjustment were measured with the Child-Parent Relationship Scale (CPRS) and the Strengths and Difficulties Questionnaire (SDQ), respectively, at three years. Caregiver stress and medication non-adherence were measured using Cohen’s Perceived Stress Scale (PSS-4) and caregiver self-report, respectively, at baseline and twelve months. Results Among families with the most major life events, children with mothers reporting poorest compared to best CPRS had an adjusted OR=2.8 (95% CI: 2.3-3.6) for asthma. Adjusted odds ratios for the association between abnormal versus normal SDQ at 3 years and asthma at 5 or 7 years was 1.2 (95% CI: 1.0-1.5). Adjusted odds ratios for non-adherence due to running out of medications were 6.8 (95% CI: 1.0-47.6) in high versus normal stress caregivers. Conclusions Increased risk of asthma was observed among those with the poorest mother-child relationships and the most major life events, and in children with abnormal behavioral adjustment. A statistically significant adjusted association between caregiver stress and overall medication non-adherence was not observed, but an association between increased caregiver stress and non-adherence due to running out of medications was suggested. / 1 / Fritha Morrison

Microsporidia are an obligate, intracellular fungal pathogen that can cause devastating, disseminating infections in the immunocompromised. Because of the limitations of current medications, microsporidia’s abundant presence in the environment, and an increasing number of at-risk populations, investigation into decreasing microsporidia infectivity is needed. As an intracellular pathogen, microspridial attachment is a vital first step to infection, and if attachment is reduced, previous work shows that infectivity is mitigated. An in silico analysis of Encephalitozoon intestinalis revealed a predicted protein similar in sequence to ADAM (A Disintegrin And Metalloproteinase) proteins. This predicted protein is termed microsporidia ADAM or MADAM. ADAM proteins contain an integrin binding region, which is well known to bind to integrin proteins. Integrins are important receptors for attachment and cell signaling, and several pathogens utilize host integrins as a receptor to aid in attachment during infection. Immunoelectron microscopy demonstrates that MADAM protein is found on the plasma membrane, anchoring disk, and polar tube of E. intestinalis spores. Our hypothesis is that MADAM is involved in the key role of host cell attachment. To this end, a 17 amino acid long section of the MADAM protein was generated that surrounded the integrin binding domain. During spore adherence assays, pretreating host cells with this small peptide protein, significantly decreased E. intestinalis spore attachment to host cells as compared to control samples. These results suggest E. intestinalis cleverly exploits host integrins as a means to bind to host cells before infection.

No description available.

The infection process of intracellular opportunistic microsporidia involves the forcible eversion of a coiled hollow polar filament that pierces the host cell membrane, allowing the passage of infectious sporoplasm into the host cell cytoplasm. Although the exact mechanism of spore activation leading to polar filament discharge is unknown, we have shown that spore adherence to host cells, which is mediated by sulfated glycosaminoglycans, may play a vital role. When adherence is inhibited, host cell infection decreases, indicating a direct link between adherence and infection. The goal of this study was to evaluate the effects of exogenous divalent cations on microsporidia spore adherence and infection. Data generated using an in vitro spore adherence assay show that spore adherence is augmented by manganese (Mn2+) and magnesium (Mg2+), but not by calcium (Ca2+). However, each of the three divalent cations contributed to increased host cell infection when included in the assay. Finally, we show that Mn2+ and Mg2+ may activate a constituent on the microsporidia spore, not on the host cell, leading to higher infection efficiency. This report further supports recent evidence that spore adherence to the host cell surface is an important aspect of the microsporidial infection process.

Microsporidia are obligate intracellular, spore-forming, fungal-related pathogens that employ a unique organelle, the polar tube, to transfer infectious spore contents into host cells to initiate infection. Spore adherence to host cells may provide the proximity required for polar tube/host cell interaction during in vivo infection. In previous in vitro studies, host sulfated glycosaminoglycans (GAGs) or recombinant microsporidia endospore protein (EnP1) was implicated in the pathogen adherence and infection process; however, complete ablation of spore adherence and infection could not be achieved, suggesting that additional or alternative spore and host cell determinants of adherence and infection may exist. Analysis of the Encephalitozoon intestinalis genome revealed about 100 predicted proteins containing the canonical integrin-binding motif arginine-glycine-aspartic acid (RGD); and, many pathogens have been shown to engage integrin molecules on cell surfaces. We hypothesized that host cell integrins play a role in microsporidia adherence and infection. In this study, we demonstrated that addition of exogenous integrin ligands or recombinant alpha 3 beta 1 integrin or alpha 5 beta 1 integrin to assays of E. intestinalis adherence and infection significantly reduced spore adherence and infection of host cells, supporting our hypothesis and implicating these specific integrins as putative host cell receptors for E. intestinalis spores.

No description available.

Background Research has shown varying and uncertain effects of oral nutritional supplements (ONS) and descriptions on the use of ONS in studies have been incomplete. To get valid study results on the effects of ONS, it is important that study participants adhere to ONS interventions. However, it is unclear how adherence have affected study results on ONS in earlier studies.  Aim To map characteristics of quantitative studies from the 21st century investigating adherence to ONS in patients with malnutrition. Method The general structure of systematic reviews was chosen. In the literature search, articles that investigated patients with malnutrition or risk for malnutrition as target population, ONS as intervention and adherence to ONS as outcome, were inspected. A PICO-question was formulated for the literature search. For the data extraction, a variable key document with variables and codes, that were to be extracted from the included articles, were explicitly created for this thesis. A pilot study with thirteen (10%) articles was conducted to test and adjust the variable key document. The result was presented using descriptive statistics. Results Out of the 134 included articles, the majority were RCTs (60.0%) from industrialized countries. Most of the articles investigated solely the effect of some kind of ONS intervention (51.4%), more precisely a milk-based industrial ONS (56.0%). Many of the variables of interest, were not reported in the articles. Other terms than ‘oral nutritional supplements’ (60.4%) were used more frequently than ‘oral nutritional supplements’ (39.6%). The term ‘compliance’ was used in 68.7% of the articles and ‘adherence’ in 27.0%. Adherence was most often studied as a secondary outcome (47.8%) and measured in different ways but most frequently with diaries or daily records of ONS intake (21.6%). Conclusion Future studies investigating ONS should aim for completeness and accuracy in descriptions of the study method regarding ONS and adherence to ONS to better facilitate comparison between studies. The present review could be used to guide researchers during the process when planning studies on ONS and adherence to ONS. / Bakgrund Studier som undersökt effekten av näringsdrycker har visat på varierande och osäkra resultat och beskrivningen av hur näringsdryck används har varit bristfällig. För att få studieresultat med hög validitet om effekten av näringsdrycker är det viktigt att studiedeltagare är följsamma till ordinationen av näringsdryck. Det är oklart hur följsamheten till ordination av näringsdryck har påverkat studieresultaten hittills.  Syfte Att kartlägga studiedetaljer i kvantitativa studier från 2000-talet som undersökt följsamhet till ordinationer av näringsdrycker bland patienter med malnutrition.  Metod Den generella strukturen för systematisk litteraturöversikt valdes. I litteratursökningen granskades artiklar som undersökte patienter med malnutrition eller risk för malnutrition som målgrupp, näringsdrycker som intervention och följsamhet till ordination av näringsdryck som utfall. För dataextraheringen formulerades en variabelnyckel, specifikt för denna litteraturöversikt, med variabler och koder som skulle extraheras ur inkluderade artiklar. En pilotstudie med tretton (10%) artiklar gjordes för att testa och anpassa variabelnyckeln. Resultatet presenterades med deskriptiv statistik. Resultat Av de 134 inkluderade studierna var majoriteten RCT-studier (60,0%) från industrialiserade länder. Största delen av studierna undersökte enbart effekten av näringsdrycker (51,4%), närmare bestämt mjölkbaserade industriframställda näringsdrycker (56,0%). Många av de variabler som var av intresse att studera rapporterades inte i artiklarna. Andra termer än ‘oral nutritional supplements’ (60,4%) användes mer frekvent än ‘oral nutritional supplements’ (39,6%). Termen ‘compliance’ användes i 68,7% av studierna och ‘adherence’ användes i 27,0%. Följsamheten till näringsdrycker undersöktes oftast som ett sekundärt utfall (47,8%) och det undersöktes på olika sätt men oftast med dagbok eller daglig registrering av intaget av näringsdryck (21,6%). Slutsats Framtida studier som undersöker näringsdrycker bör försöka uppnå fullständig och noggrann rapportering av studiemetoden relaterad till användandet av näringsdryck och följsamhet till ordination av näringsdryck för att bättre kunna jämföra resultat mellan studier. Denna litteraturöversikt skulle kunna användas för att vägleda forskare under processen när de planerar studier på näringsdrycker och följsamhet till ordination av näringsdrycker.

<p> This work is an investigation of user acceptance of a prototype solution utilizing wireless text messaging (or SMS - i.e., short messaging service) to improve people's adherence. Insufficient adherence, also known as medical non-compliance, is a major cause of failure in self-management programs, causing significant losses to all healthcare stakeholders.</p> <p> Innovative mobile healthcare solutions, based on portable devices like cell phones, may address some non-adherence aspects by helping outpatients to follow treatments agreed with their health providers. Although this seems a win-win situation, a verdict on the overall usefulness of such an approach cannot be formulated before exploring outpatient acceptance, as this is a novel technology that targets a new area of implementation. Accordingly, this research investigates key factors that may influence the acceptance of a mobile healthcare solution based on SMS to support improved adherence to healthy behaviour, with special attention to motivation (the 'pro' factors) and perceived risk (the 'con' factors).</p> <p> As a means of investigation, a one-month longitudinal experiment with two groups of subjects (an intervention group and a control group) was utilized. Data were analyzed with quantitative and qualitative techniques: descriptive statistics, partial least squares modelling, and content analysis.</p> <p> Findings show that users are aware of the potential usefulness of such a pioneering application. However, enjoyment is the unique reason for adopting, and perceived financial and psychological risks the main obstacles against adopting, an SMS-based solution for improving adherence to healthy behaviour. Furthermore, a business analysis shows that users are concerned about usefulness features, even when asked about financial aspects.</p> <p> These results, together with encouraging findings about the effectiveness of the application, open the way for medical-led research to investigate if long-term mobile healthcare initiatives customized to patient needs are also beneficial for outpatient adherence and health outcomes.</p> / Thesis / Doctor of Philosophy (PhD)

The Human Immunodeficiency Virus (HIV) epidemic remains a major global public health problem, with sub-Saharan Africa (SSA) at its epicentre. Despite the use of antiretroviral therapy (ART) to reduce new infections and deaths, SSA reports the highest HIV incidence, constituting two-thirds of global new infections. Cameroon is one of SSA countries where HIV care decentralization is enforced as a national policy but follow up of people living with HIV (PLWH) is provider-oriented, with limited patient involvement in clinical monitoring. The purpose of this dissertation was to explore predominant barriers and facilitators influencing ART adherence and identify effective interventions enhancing ART adherence across SSA. Furthermore, we sought to assess the prevalence and predictors of ART non-adherence among PLWH, and factors influencing non-adherence among PLWH who have experienced ART non-adherence in Cameroon. We conducted a comprehensive systematic review and meta-analysis on studies examining barriers to ART adherence and interventions boosting adherence. Forty-five studies were selected (30 for narrative synthesis and 15 for meta-analysis). Identified barriers and facilitators to ART adherence were categorized into seven principal factors: patient-related, health system-related, medication-related, stigma, poor mental health, socioeconomic and socio-cultural-related factors. Adherence-enhancing interventions encompassed counselling, incentives, mobile phone short message service, peer delivered behavioral intervention, community ART delivery, electronic adherence service monitoring device, lay health worker lead group intervention and food assistance. The meta-analysis revealed a statistically significant difference in ART adherence between intervention and control groups (pooled OR=1.56, 95%CI:1.35 - 1.80, p=<0.01). Using a cross-sectional study of adult PLWH in HIV treatment centres in Cameroon, we explored the prevalence and predictors of ART non-adherence. A total of 451 participants with mean age 43.42 years (SD: 10.42), were enrolled. Overall, ART non-adherence was 37.78%. Reasons for missing ART include forgetfulness, business and traveling without drugs. Significant factors associated with ART non-adherence include age, education, and alcohol consumption. In a qualitative study of 43 adult PLWH who had experienced ART non-adherence, adherence barriers included those related to patient, medication, health service, stigma, use of alternative treatment, resource limitation, environmental/social, and political instability. Adherence facilitators included social support, aligning treatment with patient’s daily routines, use of reminders, health sector/caregiver support, and awareness of HIV status/ART knowledge. To harness full potential of ART and mitigate HIV burden in SSA countries, stakeholders engaged in HIV management must recognize and integrate barriers, facilitators, and adherence-enhancing interventions when formulating policies or crafting treatment strategies. Continuous information provision and unflinching support both from patients’ families and caregivers are needed to improve adherence. Future studies focusing on specific underrepresented demographics - HIV-infected children, adolescents, and pregnant women in SSA are needed to uncover appropriate barriers, facilitators and interventions tailored to each group’s unique needs. Other studies focusing on assessing long-term non-adherence trends and determinants using larger samples of PLWH in many regions are necessary. Also, studies using both in-depth and focused group discussions, and quantitative approaches are required to uncover the ART non-adherence-related burden.

Background: Canada is the only developed country with universal healthcare but no universal prescription drug coverage. Prescription drug coverage in Canada is often described as a “patchwork” system; eligibility for coverage varies by province and influenced by circumstance. Subsets of the population are eligible for partial or full provincial coverage for their prescription medications through public and/or private coverage. Methods: The extent and factors associated with misreporting of drug insurance and cost-related non-adherence (CRNA) to prescribed medicines were investigated in three study populations: Ontario seniors 65 and over, Quebec seniors 65 and over, and Quebec adults 25-64 using pooled data from the 2015/2016 Canadian Community Health Survey (CCHS). The rationale for these study cohorts was that the vast majority had partial or full coverage for prescription medications from a public and/or private source. The factors associated with CRNA to prescribed medicines were also explored in these three subgroups. Results: There is a degree of misreporting of drug insurance among Ontario seniors (17%), Quebec seniors (18%) and Quebec adults (9%). Quebec adults who declared CRNA to prescribed drugs had twice the odds of misreporting prescription drug coverage (OR 2.1 95% CI 1.3-3.4). Lower-income earners among Ontario seniors (OR 1.8, 95% CI 1.3-2.6), Quebec seniors (OR 1.7 95% CI 1.2-2.6), and Quebec adults (OR 3.4, 95% CI 2.3-5.1) were more likely to misreport coverage. Quebec seniors were more likely to misreport if they had less than a secondary school education (OR 1.4, 95% CI 1.1-1.8). Ontario seniors who were immigrants were more likely to misreport coverage (OR 1.5, 95% CI 1.2-1.8), as were Quebec seniors who were immigrants (OR 2.2, 95% CI 1.4-3.5). Ontario seniors who had a flu shot in the past 12 months (OR 0.7, 95% CI 0.5-9.9) and Quebec adults who had visited a GP in the past 12 months (OR 0.6, 95% CI 0.45,0.77) were less likely to misreport coverage. CRNA to prescribed drugs was reported by Ontario seniors (3.3%), Quebec seniors (2.5%), and Quebec adults (5.3%). Low-income Ontario seniors (OR 2.9, 95% CI 1.5-5.7) and Quebec adults (2.5, 95% CI 1.6-3.8) were more likely to report CRNA to prescribed medicines. Quebec adults with chronic conditions (OR 1.7, 95% CI 1.2-2.4) and those in self-reported poor health (OR 2.4, 95% CI 1.3-4.4) were also more likely to report CRNA to prescribed drugs. Conclusions: There appears to be a socio-economic gradient in misreporting and CRNA among Ontario seniors, Quebec seniors, and Quebec adults. Given most of these subgroups will have coverage, we hypothesize a degree of measurement error among responses. More specifically, respondents who report CRNA to prescribed medicines may reflect measurement error. / Thesis / Master of Science (MSc) / Canada is a country that prides itself on universal healthcare yet lacks an important component - universal prescription drug coverage. Hence, it is often described as a “patchwork system” whereby Canadians must rely on a combination of public and private drugs plans depending upon circumstance. As a result, a proportion of Canadians lack prescription drug coverage and may be unable to afford prescription medications. This study aimed to investigate self-reported knowledge of prescription drug insurance in three populations: Ontario seniors 65 years and over, Quebec seniors 65 years and older, and Quebec adults 25-64 years old. The determinants of misreporting of drug insurance among these study populations was the primary objective of this analysis. The association between cost-related nonadherence (CRNA) to prescribed drugs and misreporting was a key variable in the analysis. Although only a small proportion of respondents reported CRNA to prescribed drugs, Quebec adults 25-64 were more likely to misreport drug coverage if they also reported CRNA. This study has provided some clarity on the factors that influence misreporting of drug insurance by Ontario seniors, Quebec seniors, and Quebec adults. Given health policy decisions are often guided by studies based on this data, researchers may consider a degree of misreporting in responses. Policy should aim to reduce misunderstandings about their drug coverage.