Mkaya Mwamburi

Rates of progression in diabetic retinopathy during different time periods: a systematic review and meta-analysis

OBJECTIVE This meta-analysis reviews rates of progression of diabetic retinopathy to proliferative diabetic retinopathy (PDR) and/or severe visual loss (SVL) and temporal trends. RESEARCH DESIGN AND METHODS This systematic literature review and meta-analysis of prospective studies assesses progression of retinopathy among diabetic patients without treatment for retinopathy at baseline. Studies published between 1975 to February 2008 were identified. Outcomes of interest were rates of progression to PDR and/or SVL. Pooled baseline characteristics and outcome measures were summarized using weighted averages of counts and means. Baseline characteristics and outcomes were compared between two periods: 1975–1985 and 1986–2008. RESULTS A total of 28 studies comprising 27,120 diabetic patients (mean age 49.8 years) were included. After 4 years, pooled incidence rates for PDR and SVL were 11.0 and 7.2%, respectively. Rates were lower among participants in 1986–2008 than in 1975–1985. After 10 years, similar patterns were observed. Participants in 1986–2008 studies had lower proportions of PDR and non-PDR at all time points than participants in 1975–1985 studies. CONCLUSIONS Since 1985, diabetic patients have lower rates of progression to PDR and SVL. These findings may reflect an increased awareness of retinopathy risk factors; earlier identification and initiation of care for patients with retinopathy; and improved medical management of glucose, blood pressure, and serum lipids. Differences in baseline characteristics, particularly in the prevalence and severity of retinopathy, could also have contributed to these temporal differences.

Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer's disease.

Amylin, a pancreatic peptide, and amyloid-beta peptides (Aβ), a major component of Alzheimer’s disease (AD) brain, share similar β-sheet secondary structures, but it is not known whether pancreatic amylin affects amyloid pathogenesis in the AD brain. Using AD mouse models, we investigated the effects of amylin and its clinical analog, pramlintide, on AD pathogenesis. Surprisingly, chronic intraperitoneal (i.p.) injection of AD animals with either amylin or pramlintide reduces the amyloid burden as well as lowers the concentrations of Aβ in the brain. These treatments significantly improve their learning and memory assessed by two behavioral tests, Y maze and Morris water maze. Both amylin and pramlintide treatments increase the concentrations of Aβ1-42 in cerebral spinal fluid (CSF). A single i.p. injection of either peptide also induces a surge of Aβ in the serum, the magnitude of which is proportionate to the amount of Aβ in brain tissue. One intracerebroventricular injection of amylin induces a more significant surge in serum Aβ than one i.p. injection of the peptide. In 330 human plasma samples, a positive association between amylin and Aβ1-42 as well as Aβ1-40 is found only in patients with AD or amnestic mild cognitive impairment. As amylin readily crosses the blood–brain barrier, our study demonstrates that peripheral amylin’s action on the central nervous system results in translocation of Aβ from the brain into the CSF and blood that could be an explanation for a positive relationship between amylin and Aβ in blood. As naturally occurring amylin may play a role in regulating Aβ in brain, amylin class peptides may provide a new avenue for both treatment and diagnosis of AD.

Residential Traffic Exposure, Pulse Pressure, and C-reactive Protein: Consistency and Contrast among Exposure Characterization Methods

Background Traffic exposure may increase cardiovascular disease (CVD) risk via systemic inflammation and elevated blood pressure, two important clinical markers for managing disease progression. Objectives We assessed degree and consistency of association between traffic exposure indicators as predictors of C-reactive protein (CRP) and pulse pressure (PP) in an adult U.S. Puerto Rican population (n = 1,017). Methods Cross-sectional information on health and demographics and blood data was collected. Using multiple linear regression, we tested for associations between CRP, PP, and six traffic exposure indicators including residential proximity to roads with > 20,000 vehicles/day and traffic density [vehicle miles traveled per square mile (VMT/mi2)]. Diabetes and obesity [body mass index (BMI) ≥ 30 kg/m2] were tested as effect modifiers. Results CRP was positively associated with traffic density in the total population [36% CRP difference with 95% confidence interval (CI) 2.5–81%] for residence within the highest versus lowest VMT/mi2 level. With BMI ≥ 30, CRP showed significant positive associations with five of six traffic indices including residence ≤ 200 m versus > 200 m of a roadway [22.7% CRP difference (95% CI, 3.15–46.1)] and traffic density in the third highest versus lowest VMT/mi2 level [28.1% difference (95% CI, 1.0–62.6)]. PP was positively associated with residence within ≤ 100 m of a roadway for the total population [2.2 mmHg (95% CI, 0.13–4.3 mmHg)] and persons with BMI ≥ 30 [3.8 mmHg (95% CI, 0.88–6.8)]. Effect estimates approximately doubled for residence within ≤ 200 m of two or more roadways, particularly in persons with diabetes [8.1 mmHg (95% CI, 2.2–14.1)]. Conclusions Traffic exposure at roadway volumes as low as 20,000–40,000 vehicles/day may increase CVD risk through adverse effects on blood pressure and inflammation. Individuals with elevated inflammation profiles, that is, BMI ≥ 30, may be more susceptible to the effects of traffic exposure.

Is there an association between aspirin dosing and cardiac and bleeding events after treatment of acute coronary syndrome? A systematic review of the literature

BACKGROUND Current acetylsalicylic acid (ASA) dosing algorithms for the prevention of secondary thrombotic events in acute coronary syndrome (ACS) patients are inconsistent and lack sufficient data support. METHODS We performed a systematic review of the literature for studies that assessed clinical outcomes in patients with ACS following coronary stent insertion (SI) or medical treatment (MT). Acetylsalicylic acid dosing was stratified into low- (<160 mg) and high- (≥ 160 mg) dose categories. Outcomes were assessed at 1, 6, and 12 months and included major bleeding, myocardial infarction, and all-cause death. A random-effects meta-analysis was used to estimate the value of the mean for each outcome variable. RESULTS Of 12,472 publications identified, 136 studies with 289,330 patients were analyzed. In the 1-month SI analysis, proportions of patients (95% CI) in the low- and high-dose ASA categories experiencing major bleeding were 2.1% (1.5-2.6) and 1.9% (0.0-3.8); proportions with myocardial infarction were 2.1% (1.3-2.8) and 1.8% (0.9-2.6); and proportions of all-cause death were 2.8% (2.2-3.4) and 2.4% (1.3-3.5), respectively. Results were similar in the MT analysis, except that major bleeding rates for low and high doses were 1.7% (1.3-2.2) and 4.0% (2.2-5.8), respectively. Regression analyses suggested that the proportion of patients reporting each of the outcomes evaluated were not significantly different between the low- and high-dose categories, with the exception of the 1-month major bleeding following MT. CONCLUSIONS Our results suggest no improved clinical outcomes associated with higher ASA maintenance doses in ACS patients receiving SI or MT. In the MT analysis, there was more major bleeding in the first month after an ACS event with high-dose ASA.

A community participatory study of cardiovascular health and exposure to near-highway air pollution: study design and methods

Abstract Current literature is insufficient to make causal inferences or establish dose-response relationships for traffic-related ultrafine particles (UFPs) and cardiovascular (CV) health. The Community Assessment of Freeway Exposure and Health (CAFEH) is a cross-sectional study of the relationship between UFP and biomarkers of CV risk. CAFEH uses a community-based participatory research framework that partners university researchers with community groups and residents. Our central hypothesis is that chronic exposure to UFP is associated with changes in biomarkers. The study enrolled more than 700 residents from three near-highway neighborhoods in the Boston metropolitan area in Massachusetts, USA. All participants completed an in-home questionnaire and a subset (440+) completed an additional supplemental questionnaire and provided biomarkers. Air pollution monitoring was conducted by a mobile laboratory equipped with fast-response instruments, at fixed sites, and inside the homes of selected study participants. We seek to develop improved estimates of UFP exposure by combining spatiotemporal models of ambient UFP with data on participant time-activity and housing characteristics. Exposure estimates will then be compared with biomarker levels to ascertain associations. This article describes our study design and methods and presents preliminary findings from east Somerville, one of the three study communities.

Angiotensin converting enzyme inhibitors and the reduced risk of Alzheimer's disease in the absence of apolipoprotein E4 allele.

Our cross-sectional study showed that the interaction between apolipoprotein E4 (ApoE4) and angiotensin converting enzyme (ACE) inhibitors was associated with Alzheimer’s disease (AD). The aim of this longitudinal study was to differentiate whether ACE inhibitors accelerate or reduce the risk of AD in the context of ApoE alleles. Using the longitudinal data from the National Alzheimer’s Coordinating Center (NACC) with ApoE genotyping and documentation of ACE inhibitors use, we found that in the absence of ApoE4, subjects who had been taking central ACE inhibitor use (χ2 test: 21% versus 27%, p = 0.0002) or peripheral ACE inhibitor use (χ2 test: 13% versus 27%, p < 0.0001) had lower incidence of AD compared with those who had not been taking an ACE inhibitor. In contrast, in the presence of ApoE4, there was no such association between ACE inhibitor use and the risk of AD. After adjusting for the confounders, central ACE inhibitor use (OR = 0.68, 95% CI = 0.55, 0.83, p = 0.0002) or peripheral ACE inhibitor use (OR = 0.33, 95% CI = 0.33, 0.68, p < 0.0001) still remained inversely associated with a risk of developing AD in ApoE4 non-carriers. In conclusion, ACE inhibitors, especially peripherally acting ones, were associated with a reduced risk of AD in the absence of ApoE4, but had no such effect in those carrying the ApoE4 allele. A double-blind clinical trial should be considered to determine the effect of ACE inhibitors on prevention of AD in the context of ApoE genotype.

Positional error and time-activity patterns in near-highway proximity studies: an exposure misclassification analysis

BackgroundThe growing interest in research on the health effects of near-highway air pollutants requires an assessment of potential sources of error in exposure assignment techniques that rely on residential proximity to roadways.MethodsWe compared the amount of positional error in the geocoding process for three different data sources (parcels, TIGER and StreetMap USA) to a “gold standard” residential geocoding process that used ortho-photos, large multi-building parcel layouts or large multi-unit building floor plans. The potential effect of positional error for each geocoding method was assessed as part of a proximity to highway epidemiological study in the Boston area, using all participants with complete address information (N = 703). Hourly time-activity data for the most recent workday/weekday and non-workday/weekend were collected to examine time spent in five different micro-environments (inside of home, outside of home, school/work, travel on highway, and other). Analysis included examination of whether time-activity patterns were differentially distributed either by proximity to highway or across demographic groups.ResultsMedian positional error was significantly higher in street network geocoding (StreetMap USA = 23 m; TIGER = 22 m) than parcel geocoding (8 m). When restricted to multi-building parcels and large multi-unit building parcels, all three geocoding methods had substantial positional error (parcels = 24 m; StreetMap USA = 28 m; TIGER = 37 m). Street network geocoding also differentially introduced greater amounts of positional error in the proximity to highway study in the 0–50 m proximity category. Time spent inside home on workdays/weekdays differed significantly by demographic variables (age, employment status, educational attainment, income and race). Time-activity patterns were also significantly different when stratified by proximity to highway, with those participants residing in the 0–50 m proximity category reporting significantly more time in the school/work micro-environment on workdays/weekdays than all other distance groups.ConclusionsThese findings indicate the potential for both differential and non-differential exposure misclassification due to geocoding error and time-activity patterns in studies of highway proximity. We also propose a multi-stage manual correction process to minimize positional error. Additional research is needed in other populations and geographic settings.

Cryptosporidiosis in HIV/AIDS Patients in Kenya: Clinical Features, Epidemiology, Molecular Characterization and Antibody Responses

We investigated the epidemiological and clinical features of cryptosporidiosis, the molecular characteristics of infecting species and serum antibody responses to three Cryptosporidium-specific antigens in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients in Kenya. Cryptosporidium was the most prevalent enteric pathogen and was identified in 56 of 164 (34%) of HIV/AIDS patients, including 25 of 70 (36%) with diarrhea and 31 of 94 (33%) without diarrhea. Diarrhea in patients exclusively infected with Cryptosporidium was significantly associated with the number of children per household, contact with animals, and water treatment. Cryptosporidium hominis was the most prevalent species and the most prevalent subtype family was Ib. Patients without diarrhea had significantly higher serum IgG levels to Chgp15, Chgp40 and Cp23, and higher fecal IgA levels to Chgp15 and Chgp40 than those with diarrhea suggesting that antibody responses to these antigens may be associated with protection from diarrhea and supporting further investigation of these antigens as vaccine candidates.

Falls, poisonings, burns, and road traffic injuries in urban Peruvian children and adolescents: a community based study

Objectives: To identify individual and household characteristics associated with serious falls, poisonings, burns and road traffic injuries (RTIs) for children in Lima, Peru. Methods: 5061 households consisting of 10 210 children were included in this community based, cross-sectional study in San Juan de Miraflores (SJM), a low income, urban district of Lima, Peru. Households were eligible if there was a consenting adult and at least one resident child aged ⩽18 years. A door to door survey was conducted in SJM, collecting childhood injury, demographic, and socioeconomic data. Analysis was done at the individual and household level for injuries severe enough to have required medical consultation. Results: The greatest burden of injury was from falls and RTIs. For individuals, male gender and age were the most important predictors of injuries. Households in which multiple injuries were reported were more likely to be poor (odds ratio (OR) 1.66, 95% CI 1.24 to 2.22) and overcrowded (OR 1.88, 95% CI 1.20 to 2.94). The occurrence of serious falls, poisonings, burns, and pedestrian RTIs significantly increased the likelihood of a second serious injury in the home (adjusted ORs ranged between 1.88 and 2.99). Conclusion: All children from households in which an unintentional injury has occurred appear to have an increased likelihood of future injury; such high risk households may be readily identifiable in the clinical setting. Interventions in this environment designed to prevent subsequent injuries merit further investigation.

Effect of time-activity adjustment on exposure assessment for traffic-related ultrafine particles

Exposures to ultrafine particles (<100 nm, estimated as particle number concentration, PNC) differ from ambient concentrations because of the spatial and temporal variability of both PNC and people. Our goal was to evaluate the influence of time-activity adjustment on exposure assignment and associations with blood biomarkers for a near-highway population. A regression model based on mobile monitoring and spatial and temporal variables was used to generate hourly ambient residential PNC for a full year for a subset of participants (n=140) in the Community Assessment of Freeway Exposure and Health study. We modified the ambient estimates for each hour using personal estimates of hourly time spent in five micro-environments (inside home, outside home, at work, commuting, other) as well as particle infiltration. Time-activity adjusted (TAA)-PNC values differed from residential ambient annual average (RAA)-PNC, with lower exposures predicted for participants who spent more time away from home. Employment status and distance to highway had a differential effect on TAA-PNC. We found associations of RAA-PNC with high sensitivity C-reactive protein and Interleukin-6, although exposure-response functions were non-monotonic. TAA-PNC associations had larger effect estimates and linear exposure-response functions. Our findings suggest that time-activity adjustment improves exposure assessment for air pollutants that vary greatly in space and time.