Renal Blood Oxygenation Level-dependent Imaging in Longitudinal Follow-up of Donated and Remaining Kidneys

Purpose To determine renal oxygenation changes associated with uninephrectomy and transplantation in both native donor kidneys and transplanted kidneys by using blood oxygenation level-dependent (BOLD) MR imaging. Materials and Methods The study protocol was approved by the local ethics committee. Thirteen healthy kidney donors and their corresponding recipients underwent kidney BOLD MR imaging with a 3-T imager. Written informed consent was obtained from each subject. BOLD MR imaging was performed in donors before uninephrectomy and in donors and recipients 8 days, 3 months, and 12 months after transplantation. R2* values, which are inversely related to tissue partial pressure of oxygen, were determined in the cortex and medulla. Longitudinal R2* changes were statistically analyzed by using repeated measures one-way analysis of variance with post hoc pair-wise comparisons. Results R2* values in the remaining kidneys significantly decreased early after uninephrectomy in both the medulla and cortex (P < .003), from 28.9 sec(-1) ± 2.3 to 26.4 sec(-1) ± 2.5 in the medulla and from 18.3 sec(-1) ± 1.5 to 16.3 sec(-1) ± 1.0 in the cortex, indicating increased oxygen content. In donors, R2* remained significantly decreased in both the medulla and cortex at 3 (P < .01) and 12 (P < .01) months. In transplanted kidneys, R2* remained stable during the first year after transplantation, with no significant change. Among donors, cortical R2* was found to be negatively correlated with estimated glomerular filtration rate (R = -0.47, P < .001). Conclusion The results suggest that BOLD MR imaging may potentially be used to monitor renal functional changes in both remaining and corresponding transplanted kidneys. (©) RSNA, 2016.

Long-term results of endoscopic third ventriculostomy: an outcome analysis.

OBJECT Endoscopic third ventriculostomy (ETV) is the procedure of choice in the treatment of obstructive hydrocephalus. The excellent clinical and radiological success rates are well known. Nevertheless, very few papers have addressed the very long term outcomes of the procedure in very large series. The authors present a large case series of 113 patients who underwent 126 ETVs, and they highlight the initial postoperative outcome after 3 months and long-term follow-up with an average of 7 years. METHODS All patients who underwent ETV at the Department of Neurosurgery, Mainz University Hospital, between 1993 and 1999 were evaluated. Obstructive hydrocephalus was the causative pathology in all cases. RESULTS The initial clinical success rate was 82% and decreased slightly to 78% during long-term follow-up. Long-term success was analyzed using Kaplan-Meier curves. Overall, ETV failed in 31 patients. These patients underwent a second ETV or shunt treatment. A positive impact on long-term success was seen for age older than 6 months, and for obstruction due to cysts or benign aqueductal stenosis. The complication rate was 9% with 5 intraoperative and 5 postoperative events. CONCLUSIONS The high clinical success rate in short-term and long-term follow-up confirms ETV's status as the gold standard for the treatment of obstructive hydrocephalus, especially for distinct pathologies. The patient's age and underlying pathology may influence the outcome. These factors should be considered carefully preoperatively by the surgeon.

Pitfalls of practicing cancer epidemiology in resource-limited settings: the case of survival and loss to follow-up after a diagnosis of Kaposi's sarcoma in five countries across sub-Saharan Africa.

BACKGROUND Survival after diagnosis is a fundamental concern in cancer epidemiology. In resource-rich settings, ambient clinical databases, municipal data and cancer registries make survival estimation in real-world populations relatively straightforward. In resource-poor settings, given the deficiencies in a variety of health-related data systems, it is less clear how well we can determine cancer survival from ambient data. METHODS We addressed this issue in sub-Saharan Africa for Kaposi's sarcoma (KS), a cancer for which incidence has exploded with the HIV epidemic but for which survival in the region may be changing with the recent advent of antiretroviral therapy (ART). From 33 primary care HIV Clinics in Kenya, Uganda, Malawi, Nigeria and Cameroon participating in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortia in 2009-2012, we identified 1328 adults with newly diagnosed KS. Patients were evaluated from KS diagnosis until death, transfer to another facility or database closure. RESULTS Nominally, 22% of patients were estimated to be dead by 2 years, but this estimate was clouded by 45% cumulative lost to follow-up with unknown vital status by 2 years. After adjustment for site and CD4 count, age <30 years and male sex were independently associated with becoming lost. CONCLUSIONS In this community-based sample of patients diagnosed with KS in sub-Saharan Africa, almost half became lost to follow-up by 2 years. This precluded accurate estimation of survival. Until we either generally strengthen data systems or implement cancer-specific enhancements (e.g., tracking of the lost) in the region, insights from cancer epidemiology will be limited.

Identification of genetic variation influencing apolipoprotein E levels: Follow-up of genome-wide linkage scans in the GENOA study

Apolipoprotein E (ApoE) plays a major role in the metabolism of high density and low density lipoproteins (HDL and LDL). Its common protein isoforms (E2, E3, E4) are risk factors for coronary artery disease (CAD) and explain between 16 to 23% of the inter-individual variation in plasma apoE levels. Linkage analysis has been completed for plasma apoE levels in the GENOA study (Genetic Epidemiology Network of Atherosclerosis). After stratification of the population by lipoprotein levels and body mass index (BMI) to create more homogeneity with regard to biological context for apoE levels, Hispanic families showed significant linkage on chromosome 17q for two strata (LOD=2.93 at 104 cM for a low cholesterol group, LOD=3.04 at 111 cM for a low cholesterol, high HDLC group). Replication of 17q linkage was observed for apoB and apoE levels in the unstratified Hispanic and African-American populations, and for apoE levels in African-American families. Replication of this 17q linkage in different populations and strata provides strong support for the presence of gene(s) in this region with significant roles in the determination of inter-individual variation in plasma apoE levels. Through a positional and functional candidate gene approach, ten genes were identified in the 17q linked region, and 62 polymorphisms in these genes were genotyped in the GENOA families. Association analysis was performed with FBAT, GEE, and variance-component based tests followed by conditional linkage analysis. Association studies with partial coverage of TagSNPs in the gene coding for apolipoprotein H (APOH) were performed, and significant results were found for 2 SNPs (APOH_20951 and APOH_05407) in the Hispanic low cholesterol strata accounting for 3.49% of the inter-individual variation in plasma apoE levels. Among the other candidate genes, we identified a haplotype block in the ACE1 gene that contains two major haplotypes associated with apoE levels as well as total cholesterol, apoB and LDLC levels in the unstratified Hispanic population. Identifying genes responsible for the remaining 60% of inter-individual variation in plasma apoE level, will yield new insights into the understanding of genetic interactions involved in the lipid metabolism, and a more precise understanding of the risk factors leading to CAD. ^

Tobacco use and related psychosocial risk factors among youth in urban India: Assessment of Project MYTRI follow-up surveys

Project MYTRI (Mobilizing Youth for Tobacco-Related Initiatives in India) was a large 2-year randomized school-based trial with a goal to reduce and prevent tobacco use among students in 6th and 8th grades in Delhi and Chennai in India (n=32 schools). Baseline analyses in 2004 showed that 6th grade students reported more tobacco use than 8 th grade students, opposite of what is typically observed in developed countries like the US. The present study aims to study differences in tobacco use and psychosocial risk factors between the 6th grade cohort and 8th grade cohort, in a compliant sub-sample of control students that were present at all 3 surveys from 2004-06. Both in 2004 and 2005, 6th grade cohort reported significantly greater prevalence of ever use of all tobacco products (cigarettes, bidis, chewing tobacco, any tobacco). These significant differences in ever use of any tobacco between cohorts were maintained by gender, city and socioeconomic status. The 6th grade cohort also reported significantly greater prevalence of current use of tobacco products (cigarettes, chewing tobacco, any tobacco) in 2004. Similar findings were observed for psychosocial risk factors for tobacco use, where the 6th grade cohort scored higher risk than 8th grade cohort on scales for intentions to smoke or chew tobacco and susceptibility to smoke or chew tobacco in 2004 and 2005, and for knowledge of health effects of tobacco in all three years.^ The evidence of early initiation of tobacco use in our 6th grade cohort in India indicates the need to target prevention programs and other tobacco control measures from a younger age in this setting. With increasing proportions of total deaths and lost DALYs in India being attributable to chronic diseases, addressing tobacco use among younger cohorts is even more critical. Increase in tobacco use among youth is a cause for concern with respect to future burden of chronic disease and tobacco-related mortality in many developing countries. Similarly, epidemiological studies that aim to predict future death and disease burden due to tobacco should address the early age at initiation and increasing prevalence rates among younger populations. ^

Follow-up care after a health fair screening in three Houston neighborhoods in 2008

Background. Each year thousands of people participate in mass health screenings for diabetes and hypertension, but little is known about whether or not those who receive higher than normal screening results obtain the recommended follow-up medical care, or what barriers they perceive to doing so. ^ Methods. Study participants were recruited from attendees at three health fairs in low-income neighborhoods in Houston, Texas Potential participants had higher than normal blood pressure (> 90/140 mgHg) or blood glucose readings (100 mm/dL fasting or 140 mm/dL random). Study participants were called at one, two, and three months and asked if they had obtained follow-up medical care; those who had not yet obtained follow-up care were asked to identify barriers. Using a modified Aday-Andersen model of health service access, the independent variables were individual and community characteristics and self-perceived need. The dependent variable was obtaining follow-up care, with barriers to care a secondary outcome. ^ Results. Eighty-two study participants completed the initial questionnaire and 59 participants completed the study protocol. Forty-eight participants (59% under an intent to treat analysis, 81% of those completing the study protocol) obtained follow-up care. Those who completed the initial questionnaire and who reported a regular source of care were significantly more likely to obtain follow-up care. For those who completed the study protocol the relationship between having a regular source of care and obtaining follow-up care approached but did not reach significance. For those who completed the initial questionnaire, self-described health status, when examined as a binary variable (good, very good, excellent, or poor, fair, not sure) was associated with obtaining follow-up care for those who rated their health as poor, fair, or not sure. While the group who completed the study protocol did not reach statistical significance, the same relationship between self-described health status of poor, fair, or not sure and obtaining follow-up care was present. The participants who completed the study protocol and described their blood pressure as OK or a little high were statistically more likely to get follow-up care than those who described it as high or very high. All those on oral medications for hypertension (12/12) and diabetes (4/4) who were told to obtain follow-up care did so; however, the small sample size allows this correlation to be of statistical significance only for those treating hypertension. ^ The variables significantly associated with obtaining follow-up care were having a regular source of care, self-described health status of poor, fair, or not sure, self-described blood pressure of OK or a little high, and taking medication for blood pressure. ^ At the follow-up telephone calls, 34 participants identified barriers to care; cost was a significant barrier reported by 16 participants, and 10 reported that they didn’t have time because they were working long hours after Hurricane Ike. ^ The study included the offer of access assistance: information about nearby safety-net providers, a visit to or information from the Health Information Center at their Neighborhood Center location, or information from Project Safety Net (a searchable web site for safety net providers). Access assistance was offered at the health fairs and then again at follow-up telephone calls to those who had not yet obtained follow-up care. Of the 48 participants who reported obtaining follow-up care, 26 said they had made use of the access assistance to do so. The use of access assistance was associated with being Hispanic, not having health insurance or a regular source of care, and speaking Spanish. It was also associated with being worried about blood glucose. ^ Conclusion. Access assistance, as a community enabling characteristic, may be useful in aiding low-income people in obtaining medical care. ^

A review of the published literature on interventions to increase compliance with follow-up outpatient medical appointments in primary care practice

Effective strategies for patient follow-up compliance in family practice are essential for the prevention and early detection of disease with the consequences of decreasing morbidity and mortality. With effective appointment reminder systems in place, physicians can better manage the overall health of their patients by providing preventive care as well. This literature review examines intervention strategies used by the authors, the compliance rate of appointment adherence using these techniques, as well as theories relating to study outcomes. The findings of this study may be used as an educational tool by practices to suggest which intervention strategies might be the most effective for their clinic.^

Metabolic syndrome and cardiovascular mortality among participants of the hypertension detection and follow-up program

Metabolic Syndrome (MetS) is a clustering of cardiovascular (CV) risk factors that includes obesity, dyslipidemia, hyperglycemia, and elevated blood pressure. Applying the criteria for MetS can serve as a clinically feasible tool for identifying patients at high risk for CV morbidity and mortality, particularly those who do not fall into traditional risk categories. The objective of this study was to examine the association between MetS and CV mortality among 10,940 American hypertensive adults, ages 30-69 years, participating in a large randomized controlled trial of hypertension treatment (HDFP 1973-1983). MetS was defined as the presence of hypertension and at least two of the following risk factors: obesity, dyslipidemia, or hyperglycemia. Of the 10,763 individuals with sufficient data available for analysis, 33.2% met criteria for MetS at baseline. The baseline prevalence of MetS was significantly higher among women (46%) than men (22%) and among non-blacks (37%) versus blacks (30%). All-cause and CV mortality was assessed for 10,763 individuals. Over a median follow-up of 7.8 years, 1,425 deaths were observed. Approximately 53% of these deaths were attributed to CV causes. Compared to individuals without MetS at baseline, those with MetS had higher rates of all-cause mortality (14.5% v. 12.6%) and CV mortality (8.2% versus 6.4%). The unadjusted risk of CV mortality among those with MetS was 1.31 (95% confidence interval [CI], 1.12-1.52) times that for those without MetS at baseline. After multiple adjustment for traditional risk factors of age, race, gender, history of cardiovascular disease (CVD), and smoking status, individuals with MetS, compared to those without MetS, were 1.42 (95% CI, 1.20-1.67) times more likely to die of CV causes. Of the individual components of MetS, hyperglycemia/diabetes conferred the strongest risk of CV mortality (OR 1.73; 95% CI, 1.39-2.15). Results of the present study suggest MetS defined as the presence of hypertension and 2 additional cardiometabolic risk factors (obesity, dyslipidemia, or hyperglycemia/diabetes) can be used with some success to predict CV mortality in middle-aged hypertensive adults. Ongoing and future prospective studies are vital to examine the association between MetS and cardiovascular morbidity and mortality in select high-risk subpopulations, and to continue evaluating the public health impact of aggressive, targeted screening, prevention, and treatment efforts to prevent future cardiovascular disability and death.^

THE RELATIONSHIP BETWEEN SERUM CHOLESTEROL AND CANCER INCIDENCE IN THE POPULATION OF THE HYPERTENSION DETECTION AND FOLLOW-UP PROGRAM

The relationship between serum cholesterol and cancer incidence was investigated in the population of the Hypertension Detection and Follow-up Program (HDFP). The HDFP was a multi-center trial designed to test the effectiveness of a stepped program of medication in reducing mortality associated with hypertension. Over 10,000 participants, ages 30-69, were followed with clinic and home visits for a minimum of five years. Cancer incidence was ascertained from existing study documents, which included hospitalization records, autopsy reports and death certificates. During the five years of follow-up, 286 new cancer cases were documented. The distribution of sites and total number of cases were similar to those predicted using rates from the Third National Cancer Survey. A non-fasting baseline serum cholesterol level was available for most participants. Age, sex, and race specific five-year cancer incidence rates were computed for each cholesterol quartile. Rates were also computed by smoking status, education status, and percent ideal weight quartiles. In addition, these and other factors were investigated with the use of the multiple logistic model.^ For all cancers combined, a significant inverse relationship existed between baseline serum cholesterol levels and cancer incidence. Previously documented associations between smoking, education and cancer were also demonstrated but did not account for the relationship between serum cholesterol and cancer. The relationship was more evident in males than females but this was felt to represent the different distribution of occurrence of specific cancer sites in the two sexes. The inverse relationship existed for all specific sites investigated (except breast) although a level of statistical significance was reached only for prostate carcinoma. Analyses after exclusion of cases diagnosed during the first two years of follow-up still yielded an inverse relationship. Life table analysis indicated that competing risks during the period of follow-up did not account for the existence of an inverse relationship. It is concluded that a weak inverse relationship does exist between serum cholesterol for many but not all cancer sites. This relationship is not due to confounding by other known cancer risk factors, competing risks or persons entering the study with undiagnosed cancer. Not enough information is available at the present time to determine whether this relationship is causal and further research is suggested. ^

THE RELATIONSHIP BETWEEN DEGREE OF BLOOD PRESSURE REDUCTION AND MORTALITY AMONG HYPERTENSIVES IN THE HYPERTENSION DETECTION AND FOLLOW-UP PROGRAM

The relationship between degree of diastolic blood pressure (DBP) reduction and mortality was examined among hypertensives, ages 30-69, in the Hypertension Detection and Follow-up Program (HDFP). The HDFP was a multi-center community-based trial, which followed 10,940 hypertensive participants for five years. One-year survival was required for inclusion in this investigation since the one-year annual visit was the first occasion where change in blood pressure could be measured on all participants. During the subsequent four years of follow-up on 10,052 participants, 568 deaths occurred. For levels of change in DBP and for categories of variables related to mortality, the crude mortality rate was calculated. Time-dependent life tables were also calculated so as to utilize available blood pressure data over time. In addition, the Cox life table regression model, extended to take into account both time-constant and time-dependent covariates, was used to examine the relationship change in blood pressure over time and mortality.^ The results of the time-dependent life table and time-dependent Cox life table regression analyses supported the existence of a quadratic function which modeled the relationship between DBP reduction and mortality, even after adjusting for other risk factors. The minimum mortality hazard ratio, based on a particular model, occurred at a DBP reduction of 22.6 mm Hg (standard error = 10.6) in the whole population and 8.5 mm Hg (standard error = 4.6) in the baseline DBP stratum 90-104. After this reduction, there was a small increase in the risk of death. There was not evidence of the quadratic function after fitting the same model using systolic blood pressure. Methodologic issues involved in studying a particular degree of blood pressure reduction were considered. The confidence interval around the change corresponding to the minimum hazard ratio was wide and the obtained blood pressure level should not be interpreted as a goal for treatment. Blood pressure reduction was attributed, not only to pharmacologic therapy, but also to regression to the mean, and to other unknown factors unrelated to treatment. Therefore, the surprising results of this study do not provide direct implications for treatment, but strongly suggest replication in other populations. ^

REGRESSION ANALYSIS FOR STANDARDIZED MORTALITY RATIOS WITH APPLICATION TO OCCUPATIONAL FOLLOW-UP STUDIES

Traditional comparison of standardized mortality ratios (SMRs) can be misleading if the age-specific mortality ratios are not homogeneous. For this reason, a regression model has been developed which incorporates the mortality ratio as a function of age. This model is then applied to mortality data from an occupational cohort study. The nature of the occupational data necessitates the investigation of mortality ratios which increase with age. These occupational data are used primarily to illustrate and develop the statistical methodology.^ The age-specific mortality ratio (MR) for the covariates of interest can be written as MR(,ij...m) = ((mu)(,ij...m)/(theta)(,ij...m)) = r(.)exp (Z('')(,ij...m)(beta)) where (mu)(,ij...m) and (theta)(,ij...m) denote the force of mortality in the study and chosen standard populations in the ij...m('th) stratum, respectively, r is the intercept, Z(,ij...m) is the vector of covariables associated with the i('th) age interval, and (beta) is a vector of regression coefficients associated with these covariables. A Newton-Raphson iterative procedure has been used for determining the maximum likelihood estimates of the regression coefficients.^ This model provides a statistical method for a logical and easily interpretable explanation of an occupational cohort mortality experience. Since it gives a reasonable fit to the mortality data, it can also be concluded that the model is fairly realistic. The traditional statistical method for the analysis of occupational cohort mortality data is to present a summary index such as the SMR under the assumption of constant (homogeneous) age-specific mortality ratios. Since the mortality ratios for occupational groups usually increase with age, the homogeneity assumption of the age-specific mortality ratios is often untenable. The traditional method of comparing SMRs under the homogeneity assumption is a special case of this model, without age as a covariate.^ This model also provides a statistical technique to evaluate the relative risk between two SMRs or a dose-response relationship among several SMRs. The model presented has application in the medical, demographic and epidemiologic areas. The methods developed in this thesis are suitable for future analyses of mortality or morbidity data when the age-specific mortality/morbidity experience is a function of age or when there is an interaction effect between confounding variables needs to be evaluated. ^

Sacred vocation program follow up evaluation at the Baylor healthcare system

Background: The Sacred Vocation Program (SVP) (Amick B, Karff S., 2003) helps workers find meaning, spirituality, and see their job as a sacred vocation. The SVP is based on Participatory Action Research (PAR) (Minkler & Wallerstein, 1997; Parker & Wall, 1998). This study aims to evaluate the SVP implemented at the Baylor Healthcare System, Dallas-Fort Worth. ^ Methods: The study design is a qualitative design. We used data from study participants who have participated in focus groups. During these focus groups specific questions and probes regarding the effectiveness of the SVP have been asked. We analyzed the focus groups and derived themes. ^ Results: Results of this study demonstrate SVP helps graduates feel valued and important. The SVP has improved meaningful work for employees and improved a sense of belonging for participants. The program has also increased participant spirituality. The coping techniques developed during a SVP class helps participants deal with stressful situations. The SVP faces challenges of implementation fidelity, poor communication, program viability in tough economic times and implementation of phase II. Another sustainability challenge for SVP is the perception of the program being a religious one versus a spiritual program. ^ Conclusion: Several aspects of the SVP work. The phase I of SVP is successful in improving meaningful work and a sense of belonging for participants. The coping techniques help participants deal with difficult work situations. The SVP can increase effectiveness through improvements in implementation fidelity, communication and leadership commitment. ^

Fasting blood glucose and 8-year mortality in the hypertension detection follow-up program population

This study analyzed the relationship between fasting blood glucose (FBG) and 8-year mortality in the Hypertension Detection Follow-up Program (HDFP) population. Fasting blood glucose (FBG) was examined both as a continuous variable and by specified FBG strata: Normal (FBG 60–100 mg/dL), Impaired (FBG ≥100 and ≤125 mg/dL), and Diabetic (FBG>125 mg/dL or pre-existing diabetes) subgroups. The relationship between type 2 diabetes was examined with all-cause mortality. This thesis described and compared the characteristics of fasting blood glucose strata by recognized glucose cut-points; described the mortality rates in the various fasting blood glucose strata using Kaplan-Meier mortality curves, and compared the mortality risk of various strata using Cox Regression analysis. Overall, mortality was significantly greater among Referred Care (RC) participants compared to Stepped Care (SC) {HR = 1.17; 95% CI (1.052,1.309); p-value = 0.004}, as reported by the HDFP investigators in 1979. Compared with SC participants, the RC mortality rate was significantly higher for the Normal FBG group {HR = 1.18; 95% CI (1.029,1.363); p-value = 0.019} and the Impaired FBG group, {HR = 1.34; 95% CI (1.036,1.734); p-value = 0.026,}. However, for the diabetic group, 8-year mortality did not differ significantly between the RC and SC groups after adjusting for race, gender, age, smoking status among Diabetic individuals {HR = 1.03; 95% CI (0.816,1.303); p-value = 0.798}. This latter finding is possibly due to a lack of a treatment difference of hypertension among Diabetic participants in both RC and SC groups. The largest difference in mortality between RC and SC was in the Impaired subgroup, suggesting that hypertensive patients with FBG between 100 and 125 mg/dL would benefit from aggressive antihypertensive therapy.^