Risk factors related to inflammation and endothelial dysfunction in the DCCT/EDIC cohort and their relationship with nephropathy and macrovascular complications

Because endothelial cell dysfunction and inflammation are key contributors to the development of complications in type 1 diabetes, we studied risk factors related to endothelial dysfunction and inflammation (C-reactive protein and fibrinogen, soluble vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin, and fibrinolytic markers) in a subgroup of patients from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) study cohort.

Non-steroidal anti-inflammatory drug use and cervical cancer risk: a case-control study using the Clinical Practice Research Datalink

Non-steroidal anti-inflammatory drugs (NSAIDs) have many anticarcinogenic properties via the inhibition of cyclooxygenase 2 (COX-2). Only one study, a cohort study examining risk of all cancers, investigated their role in cervical cancer with inconsistent findings between non-aspirin NSAIDs and aspirin. The aim of this study was to further investigate NSAID/aspirin use and cervical cancer risk.

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study:preeclampsia

Objective: The purpose of this study was to examine associations of fasting C-peptide, body mass index (BMI), and maternal glucose with the risk of preeclampsia in a multicenter multinational study. Study Design: We conducted a secondary analysis of a blinded observational cohort study. Subjects underwent a 75-g oral glucose tolerance test at 24-32 weeks' gestation. Associations of preeclampsia with fasting C-peptide, BMI, and maternal glucose were assessed with the use of multiple logistic regression analyses and adjustment for potential confounders. Results: Of 21,364 women who were included in the analyses, 5.2% had preeclampsia. Adjusted odds ratios for preeclampsia for 1 SD higher fasting C-peptide (0.87 ug/L), BMI (5.1 kg/m), and fasting (6.9 mg/dL), 1-hour (30.9 mg/dL), and 2-hour plasma glucose (23.5 mg/dL) were 1.28 (95% confidence interval [CI], 1.20-1.36), 1.60 (95% CI, 1.60-1.71), 1.08 (95% CI, 1.00-1.16), 1.19 (95% CI, 1.11-1.28), and 1.21 (95% CI,1.13-1.30), respectively. Conclusion: Results indicate strong, independent associations of fasting C-peptide and BMI with preeclampsia. Maternal glucose levels (below diabetes mellitus) had weaker associations with preeclampsia, particularly after adjustment for fasting C-peptide and BMI. © 2010 Mosby, Inc. All rights reserved.

Development and Application of Medication Appropriateness Indicators for Persons with Advanced Dementia: A Feasibility Study

Background: No studies have been conducted in the UK context to date that categorise medications in terms of appropriateness for patients with advanced dementia, or that examine medication use in these vulnerable patients.

Objectives: The objectives of this study were to categorise the appropriateness of a comprehensive list of medications and medication classes for use in patients with advanced dementia; examine the feasibility of conducting a longitudinal prospective cohort study to collect clinical and medication use data; and determine the appropriateness of prescribing for nursing home residents with advanced dementia in Northern Ireland (NI), using the categories developed.

Methods: A three-round Delphi consensus panel survey of expert clinicians was used to categorise the appropriateness of medications for patients with advanced dementia [defined as having Functional Assessment Staging (FAST) scores ranging from 6E to 7F]. This was followed by a longitudinal prospective cohort feasibility study that was conducted in three nursing homes in NI. Clinical and medication use for participating residents with advanced dementia (FAST scores ranging from 6E to 7F) were collected and a short test of dementia severity administered. These data were collected at baseline and every 3 months for up to 9 months or until death. For those residents who died during the study period, data were also collected within 14 days of death. The appropriateness ratings from the consensus panel survey were retrospectively applied to residents’ medication data at each data collection timepoint to determine the appropriateness of medications prescribed for these residents.

Results: Consensus was achieved for 87 (90 %) of the 97 medications and medication classes included in the survey. Fifteen residents were recruited to participate in the longitudinal prospective cohort feasibility study, four of whom died during the data collection period. Mean numbers of medications prescribed per resident were 16.2 at baseline, 19.6 at 3 months, 17.4 at 6 months and 16.1 at 9 months. Fourteen residents at baseline were taking at least one medication considered by the consensus panel to be never appropriate, and approximately 25 % of medications prescribed were considered to be never appropriate. Post-death data collection indicated a decrease in the proportion of never appropriate medications and an increase in the proportion of always appropriate medications for those residents who died.

Conclusions: This study is the first to develop and apply medication appropriateness indicators for patients with advanced dementia in the UK setting. The Delphi consensus panel survey of expert clinicians was a suitable method of developing such indicators. It is feasible to collect information on quality of life, functional performance, physical comfort, neuropsychiatric symptoms and cognitive function for this subpopulation of nursing home residents with advanced dementia.

Long-Term Follow-Up of a Large Active Surveillance Cohort of Patients With Prostate Cancer

PURPOSE: Active surveillance is increasingly accepted as a treatment option for favorable-risk prostate cancer. Long-term follow-up has been lacking. In this study, we report the long-term outcome of a large active surveillance protocol in men with favorable-risk prostate cancer.

PATIENTS AND METHODS: In a prospective single-arm cohort study carried out at a single academic health sciences center, 993 men with favorable- or intermediate-risk prostate cancer were managed with an initial expectant approach. Intervention was offered for a prostate-specific antigen (PSA) doubling time of less than 3 years, Gleason score progression, or unequivocal clinical progression. Main outcome measures were overall and disease-specific survival, rate of treatment, and PSA failure rate in the treated patients.

RESULTS: Among the 819 survivors, the median follow-up time from the first biopsy is 6.4 years (range, 0.2 to 19.8 years). One hundred forty-nine (15%) of 993 patients died, and 844 patients are alive (censored rate, 85.0%). There were 15 deaths (1.5%) from prostate cancer. The 10- and 15-year actuarial cause-specific survival rates were 98.1% and 94.3%, respectively. An additional 13 patients (1.3%) developed metastatic disease and are alive with confirmed metastases (n = 9) or have died of other causes (n = 4). At 5, 10, and 15 years, 75.7%, 63.5%, and 55.0% of patients remained untreated and on surveillance. The cumulative hazard ratio for nonprostate-to-prostate cancer mortality was 9.2:1.

CONCLUSION: Active surveillance for favorable-risk prostate cancer is feasible and seems safe in the 15-year time frame. In our cohort, 2.8% of patients have developed metastatic disease, and 1.5% have died of prostate cancer. This mortality rate is consistent with expected mortality in favorable-risk patients managed with initial definitive intervention.

Investigating clinical predictors of arteriovenous fistula functional patency in a European cohort

Background: Arteriovenous fistula (AVF) failure to mature (FTM) rates contribute to excessive dependence on central venous catheters for haemodialysis. Choosing the most appropriate vascular access site for an individual patient is guided largely by their age, co-morbidities and clinical examination. We investigated the clinical predictors of AVF FTM in a European cohort of patients and applied an existing clinical risk prediction model for AVF FTM to this population.
Methods: A prospective cohort study was designed that included all patients undergoing AVF creation between January 2009 and December 2014 in a single centre (Belfast City Hospital) who had a functional AVF outcome observed by March 2015.
Results: A total of 525 patients had a functional AVF outcome recorded and were included in the FTM analysis. In this cohort, 309 (59%) patients achieved functional AVF patency and 216 (41%) patients had FTM. Female gender [P < 0.001, odds ratio (OR) 2.03 (CI 1.37–3.02)] and lower-arm AVF [P < 0.001, OR 4.07 (CI 2.77–5.92)] were associated with AVF FTM. The Lok model did not predict FTM outcomes based on the associated risk stratification in our population.
Conclusions: In this European study, female gender was associated with twice the risk of AVF FTM and a lower-arm AVF with four times the risk of FTM. The FTM risk prediction model was not found to be discriminative in this population. Clinical risk factors for AVF FTM vary between populations;we would recommend that units investigate their own clinical predictors of FTM to maximize AVF functional patency and ultimately survival in dialysis patients. Clinical predictors of AVF FTM may not be sufficient on their own to improve vascular access functional patency rates.

Predictive Value of Depressive Symptoms for All-Cause Mortality: Findings From the PRIME Belfast Study Examining the Role of Inflammation and Cardiovascular Risk Markers

OBJECTIVES: To improve understanding about the potential underlying biological mechanisms in the link between depression and all-cause mortality and to investigate the role that inflammatory and other cardiovascular risk factors may play in the relationship between depressive symptoms and mortality.

METHODS: Depression and blood-based biological markers were assessed in the Belfast PRIME prospective cohort study (N = 2389 men, aged 50-59 years) in which participants were followed up for 18 years. Depression was measured using the 10-item Welsh Pure Depression Inventory. Inflammation markers (C-reactive protein [CRP], neopterin, interleukin [IL]-1 receptor antagonist [IL-1Ra], and IL-18) and cardiovascular-specific risk factors (N-terminal pro-b-type natriuretic peptide, midregion pro-atrial natriuretic peptide, midregion pro-adrenomedullin, C-terminal pro-endothelin-1 [CT-proET]) were obtained at baseline. We used Cox proportional hazards modeling to examine the association between depression and biological measures in relation to all-cause mortality and explore the mediating effects.

RESULTS: During follow-up, 418 participants died. Higher levels of depressive symptoms were associated with higher levels of CRP, IL-1Ra, and CT-proET. After adjustment for socioeconomic and life-style risk factors, depressive symptoms were significantly associated with all-cause mortality (hazard ratio = 1.10 per scale unit, 95% confidence interval = 1.04-1.16). This association was partly explained by CRP (7.3%) suggesting a minimal mediation effect. IL-1Ra, N-terminal pro-b-type natriuretic peptide, midregion pro-atrial natriuretic peptide, midregion pro-adrenomedullin, and CT-proET contributed marginally to the association between depression and subsequent mortality.

CONCLUSIONS: Inflammatory and cardiovascular risk markers are associated with depression and with increased mortality. However, depression and biological measures show additive effects rather than a pattern of meditation of biological factors in the association between depression and mortality.

Age-related prevalence and met need for correctable and uncorrectable near vision impairment in a multi-country study

Purpose: To estimate the prevalence, potential determinants, and proportion of met need for near vision impairment (NVI) correctable with refraction approximately 2 years after initial examination of a multi-country cohort. Design: Population-based, prospective cohort study. Participants: People aged ≥35 years examined at baseline in semi-rural (Shunyi) and urban (Guangzhou) sites in China; rural sites in Nepal (Kaski), India (Madurai), and Niger (Dosso); a semi-urban site (Durban) in South Africa; and an urban site (Los Angeles) in the United States. Methods: Near visual acuity (NVA) with and without current near correction was measured at 40 cm using a logarithm of the minimum angle of resolution near vision tumbling E chart. Participants with uncorrected binocular NVA ≤20/40 were tested with plus sphere lenses to obtain best-corrected binocular NVA. Main Outcome Measures: Prevalence of total NVI (defined as uncorrected NVA ≤20/40) and NVI correctable and uncorrectable to >20/40, and current spectacle wearing among those with bilateral NVA ≤20/63 improving to >20/40 with near correction (met need). Results: Among 13 671 baseline participants, 10 533 (77.2%) attended the follow-up examination. The prevalence of correctable NVI increased with age from 35 to 50-60 years and then decreased at all sites. Multiple logistic regression modeling suggested that correctable NVI was not associated with gender at any site, whereas more educated persons aged >54 years were associated with a higher prevalence of correctable NVI in Nepal and India. Although near vision spectacles were provided free at baseline, wear among those who could benefit was <40% at all but 2 centers (Guangzhou and Los Angeles). Conclusions: Prevalence of correctable NVI is greatest among persons of working age, and rates of correction are low in many settings, suggesting that strategies targeting the workplace may be needed.

Test-retest variability in structural and functional parameters of glaucoma damage in the glaucoma imaging longitudinal study.

PURPOSE:

To determine the test-retest variability in perimetric, optic disc, and macular thickness parameters in a cohort of treated patients with established glaucoma.

PATIENTS AND METHODS:

In this cohort study, the authors analyzed the imaging studies and visual field tests at the baseline and 6-month visits of 162 eyes of 162 participant in the Glaucoma Imaging Longitudinal Study (GILS). They assessed the difference, expressed as the standard error of measurement, of Humphrey field analyzer II (HFA) Swedish Interactive Threshold Algorithm fast, Heidelberg retinal tomograph (HRT) II, and retinal thickness analyzer (RTA) parameters between the two visits and assumed that this difference was due to measurement variability, not pathologic change. A statistically significant change was defined as twice the standard error of measurement.

RESULTS:

In this cohort of treated glaucoma patients, it was found that statistically significant changes were 3.2 dB for mean deviation (MD), 2.2 for pattern standard deviation (PSD), 0.12 for cup shape measure, 0.26 mm for rim area, and 32.8 microm and 31.8 microm for superior and inferior macular thickness, respectively. On the basis of these values, it was estimated that the number of potential progression events detectable in this cohort by the parameters of MD, PSD, cup shape measure, rim area, superior macular thickness, and inferior macular thickness was 7.5, 6.0, 2.3, 5.7, 3.1, and 3.4, respectively.

CONCLUSIONS:

The variability of the measurements of MD, PSD, and rim area, relative to the range of possible values, is less than the variability of cup shape measure or macular thickness measurements. Therefore, the former measurements may be more useful global measurements for assessing progressive glaucoma damage.

Ocular comorbidities among cataract-operated patients in rural China: the caring is hip Study of Cataract Outcomes and Uptake of Services (SCOUTS), report No. 3.

PURPOSE: To determine the prevalence and impact on vision and visual function of ocular comorbidities in a rural Chinese cataract surgical program, and to devise strategies to reduce their associated burden. DESIGN: Cross-sectional cohort study. PARTICIPANTS: Persons undergoing cataract surgery by one of two recently trained local surgeons at a government-run village-level hospital in rural Guangdong between August 8 and December 31, 2005. INTERVENTIONS: Eligible subjects were invited to return for a comprehensive ocular examination and visual function interview 10 to 14 months after surgery. Prevalent ocular comorbid conditions were identified. MAIN OUTCOME MEASURES: Presenting and best-corrected vision, visual function, and treatability of the comorbidity. RESULTS: Of 313 persons operated within the study window, 242 (77%) could be contacted by telephone; study examinations and interviews were performed on 176 (74%). Examined subjects had a mean age of 69.4+/-10.5 years, 116 (66%) were female, and 149 (85%) had been blind (presenting vision < or = 6/60) in the operative eye before surgery. Among unoperated eyes, 89 of 109 (81.7%) had > or =1 ocular comorbidities, whereas for operated eyes the corresponding proportion was 72 of 211 (34.1%). The leading comorbidity among operated eyes was refractive error (43/72 [59.7%]), followed by glaucoma/glaucoma suspect (14/72 [19.4%]), whereas for unoperated eyes, it was cataract (80/92 [87.0%]), followed by refractive error (12/92 [13.0%]). Among operated eyes with comorbidities, 90.3% (65/72) had > or =1 comorbidities that were treatable. In separate models adjusting for age and gender, persons with > or =1 comorbidities in the operated eye had significantly worse presenting vision (P<0.001) than those without such findings, but visual function (P = 0.197) and satisfaction with surgery (P = 0.796) were unassociated with comorbidities. CONCLUSIONS: Ocular comorbidities are highly prevalent among persons undergoing cataract surgery in this rural Asian setting, and their presence is significantly associated with poorer visual outcomes. The fact that the great majority of comorbidities encountered in this program are treatable suggests that strategies to reduce their impact can be successful.

Corneal hysteresis and axial length among Chinese secondary school children: the Xichang Pediatric Refractive Error Study (X-PRES) report no. 4.

PURPOSE: To evaluate the association between corneal hysteresis and axial length/refractive error among rural Chinese secondary school children. DESIGN: Cross-sectional cohort study. METHODS: Refractive error (cycloplegic auto-refraction with subjective refinement), central corneal thickness (CCT) and axial length (ultrasonic measurement), intraocular pressure (IOP), and corneal hysteresis (Reichert Ocular Response Analyzer) were measured on a rural school-based cohort of children. RESULTS: Among 1,233 examined children, the mean age was 14.7 +/- 0.8 years and 699 (56.7%) were girls. The mean spherical equivalent (n = 1,232) was -2.2 +/- 1.6 diopters (D), axial length (n = 643) was 23.7 +/- 1.1 mm, corneal hysteresis (n = 1,153) was 10.7 +/- 1.6 mm Hg, IOP (n = 1,153) was 17.0 +/- 3.4 mm Hg, and CCT (n = 1,226) was 553 +/- 33 microns. In linear regression models, longer axial length was significantly (P < .001 for both) associated with lower corneal hysteresis and higher IOP. Hysteresis in this population was significantly (P < .001) lower than has previously been reported for normal White children (n = 42, 12.3 +/- 1.3 mm Hg), when adjusting for age and gender. This difference did not appear to depend on differences in axial length between the populations, as it persists when only Chinese children with normal uncorrected vision are included. CONCLUSIONS: Prospective studies will be needed to determine if low hysteresis places eyes at risk for axial elongation secondary or if primary elongation results in lower hysteresis.

The relationship between time attitudes profiles and self-efficacy, sensation seeking, and alcohol use: An exploratory study

A growing body of research has begun to report on time attitudes which specifically refers to an individual's emotional and evaluative feelings toward the past, the present, and the future. The present study used data from the first wave of a longitudinal cohort study in the United Kingdom. Sample 1 consisted of 1580 adolescents (40% female, 1.7% unreported) in Northern Ireland, while Sample 2 consisted of 813 adolescents (46.7% female, 1.4% unreported) in Scotland. Five similar time attitudes profiles emerged in both countries, with one additional "balanced" profile in Scotland. Results show that there were no substantive differences between profiles in terms of socio-demographic indicators. However, in respect of academic, social and emotional self-efficacy, best results were observed for those with Positive, Ambivalent, and Balanced profiles, with the reverse true for those with Negative, Past Negative, and Pessimistic profiles. Positives were also less likely to report using alcohol.

Patterns and predictors of help-seeking contacts with health services and general practitioner detection of suicidality prior to suicide: a cohort analysis of suicides occurring over a two-year period

Background: Contact with primary care and psychiatric services prior to suicide may be considerable, presenting
opportunities for intervention. However, there is scant knowledge on the frequency, nature and determinants of
contact.
Method: Retrospective cohort study-an analysis of deaths recorded as suicide by the Northern Ireland Coroner’s
Office linked with data from General Practice patient records over a 2 year period
Results: Eighty-seven per cent of suicides were in contact with General Practice services in the 12 months before
suicide. The frequency of contact with services was considerable, particularly among patients with a common
mental disorder or substance misuse problems. A diagnosis of psychiatric problems was absent in 40 % of suicides.
Excluding suicide attempts, the main predictors of a noted general practitioner concern for patient suicidality are
male gender, frequency of consultations, diagnosis of mental illness and substance misuse.
Conclusions: Despite widespread and frequent contact, a substantial proportion of suicidal people were
undiagnosed and untreated for mental health problems. General Practitioner alertness to suicidality may be too
narrowly focused.

Low-Dose Aspirin Use After Diagnosis of Colorectal Cancer Does Not Increase Survival: A Case–Control Analysis of a Population-Based Cohort

BACKGROUND & AIMS: Individuals who began taking low-dose aspirin before they were diagnosed with colorectal cancer were reported to have longer survival times than patients who did not take this drug. We investigated survival times of patients who begin taking low-dose aspirin after a diagnosis of colorectal cancer in a large population-based cohort study.

METHODS: We performed a nested case-control analysis using a cohort of 4794 patients diagnosed with colorectal cancer from 1998 through 2007, identified from the UK Clinical Practice Research Datalink and confirmed by cancer registries. There were 1559 colorectal cancer-specific deaths, recorded by the Office of National Statistics; these were each matched with up to 5 risk-set controls. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI), based on practitioner-recorded aspirin usage.

RESULTS: Overall, low-dose aspirin use after a diagnosis of colorectal cancer was not associated with colorectal cancer-specific mortality (adjusted OR = 1.06; 95% CI: 0.92-1.24) or all-cause mortality (adjusted OR = 1.06; 95% CI: 0.94-1.19). A dose-response association was not apparent; for example, low-dose aspirin use for more than 1 year after diagnosis was not associated with colorectal cancer-specific mortality (adjusted OR = 0.98; 95% CI: 0.82-1.19). There was also no association between low-dose aspirin usage and colon cancer-specific mortality (adjusted OR = 1.02; 95% CI: 0.83-1.25) or rectal cancer-specific mortality (adjusted OR = 1.10; 95% CI: 0.88-1.38).

CONCLUSIONS: In a large population-based cohort, low-dose aspirin usage after diagnosis of colorectal cancer did not increase survival time.

Overweight duration in older adults and cancer risk: a study of cohorts in Europe and the United States

Recent studies have shown that cancer risk related to overweight and obesity is mediated by time and might be better approximated by using life years lived with excess weight. In this study we aimed to assess the impact of overweight duration and intensity in older adults on the risk of developing different forms of cancer. Study participants from seven European and one US cohort study with two or more weight assessments during follow-up were included (n = 329,576). Trajectories of body mass index (BMI) across ages were estimated using a quadratic growth model; overweight duration (BMI ≥ 25) and cumulative weighted overweight years were calculated. In multivariate Cox models and random effects analyses, a longer duration of overweight was significantly associated with the incidence of obesity-related cancer [overall hazard ratio (HR) per 10-year increment: 1.36; 95 % CI 1.12-1.60], but also increased the risk of postmenopausal breast and colorectal cancer. Additionally accounting for the degree of overweight further increased the risk of obesity-related cancer. Risks associated with a longer overweight duration were higher in men than in women and were attenuated by smoking. For postmenopausal breast cancer, increased risks were confined to women who never used hormone therapy. Overall, 8.4 % of all obesity-related cancers could be attributed to overweight at any age. These findings provide further insights into the role of overweight duration in the etiology of cancer and indicate that weight control is relevant at all ages. This knowledge is vital for the development of effective and targeted cancer prevention strategies.