Peritoneal dialysate effluent and serum CA125 concentrations in stable peritoneal dialysis patients

INTRODUCTION: CA125 in peritoneal dialysis (PD) effluent dialysate has been used as a surrogate biomarker for the health of the peritoneum in PD patients. However CA125 is synthesised by epithelial cells and as such is not specific for the peritoneum, and most studies have only measured peritoneal CA125, without serum CA125 values. As such we wished to determine the factors which influenced PD effluent CA125 in a large contemporaneous cohort. METHODS: We measured dialysate effluent CA125 in PD patients attending for routine assessment of peritoneal membrane function with a peritoneal equilibration test (PET), with corresponding serum CA125. RESULTS: Serum and dialysate CA125 were measured in 205 PD patients; 59.0 ± 16.8 years, median PD treatment 3 (2–20) months, 59 % male, 42.4 % diabetic, with 31.2 % treated by continuous ambulatory peritoneal dialysis, 22 % by automated overnight peritoneal dialysis cycler (APD) and 46.8 % by APD with a day time exchange. The median serum CA125 was 21 (13–38) U/ml, with an effluent 4 h PD PET effluent of 20 (11.5–36.5) U/ml. PET PD effluent dialysate was associated with PET dialysate total protein (β 12.9, p < 0.001), serum CA125 (β 0.109, p = 0.002), residual renal function (β 0.53, p = 0.018) and age (β 0.145, p = 0.042) and negatively with the number of PD cycles/day (β −2.19, p = 0.001). There was no association with prior peritonitis episodes. CONCLUSION: PD effluent CA125 concentrations were associated with peritoneal protein losses and increased by the usage of higher glucose dialysates to compensate for loss of residual renal function

Association between a large change between the minimum and maximum monthly values of solar insolation and a history of suicide attempts in bipolar I disorder

Background: The rate of suicide attempts by patients with bipolar disorder is high. In addition to patient and country specific factors, environmental factors may contribute to suicidal behavior. Sunlight has multiple diverse impacts on human physiology and behavior. Solar insolation is defined as the electromagnetic energy from the sun striking a surface area on earth. We previously found that a large change in solar insolation between the minimum and maximum monthly values was associated with an increased risk of suicide attempts in patients with bipolar I disorder. Methods: The association between solar insolation and a history of suicide attempts in bipolar disorder was again investigated using an international database with 15% more data and more sites at diverse locations and countries. Results: Data were available from 5641 patients with bipolar I disorder living at a wide range of latitudes in 41 countries in both hemispheres. A large change in solar insolation between the minimum and maximum monthly values was associated with a history of suicide attempts in patients with bipolar I disorder, a replication of our prior analysis. The estimated model also associated state sponsored religion in the onset country, female gender, a history of alcohol or substance abuse, and being part of a younger birth cohort with a history of suicide attempts. Conclusions: A large change between the minimum and maximum monthly values of solar insolation was associated with a history of suicide attempts in bipolar I disorder, replicating our prior research. Physicians should be aware that daylight has wide ranging physiological and psychiatric impacts, and that living with large changes in solar insolation may be associated with an increased suicide risk

Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder

Background: Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about &gt; 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. Methods: Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. Results: The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6&nbsp;years. Of the onset locations, 34.0% had at least 1&nbsp;month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66&nbsp;years younger. Conclusion: UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition

Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p &lt; 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed

Supplementary Material for: Biomarker Predictors of Adverse Acute Kidney Injury Outcomes in Critically Ill Patients: The Dublin Acute Biomarker Group Evaluation Study

Background: The Dublin Acute Biomarker Group Evaluation (DAMAGE) Study is a prospective 2-center observational study investigating the utility of urinary biomarker combinations for the diagnostic and prognostic assessment of acute kidney injury (AKI) in a heterogeneous adult intensive care unit (ICU) population. The objective of this study is to evaluate whether serial urinary biomarker measurements, in combination with a simple clinical model, could improve biomarker performance in the diagnostic prediction of severe AKI and clinical outcomes such as death and need for renal replacement therapy (RRT). Methods: Urine was collected daily from patients admitted to the ICU, for a total of 7 post-admission days. Urine biomarker concentrations (neutrophil gelatinase-associated lipocalin [NGAL], α-glutathione S-transferase [GST], π-GST, kidney injury molecule-1 [KIM-1], liver-type fatty acid-binding protein [L-FABP], Cystatin C, creatinine, and albumin) were measured. Urine biomarkers were combined with a clinical prediction of AKI model, to determine ability to predict AKI (any stage, within 2 days or 7 days of ICU admission), or a ­30-day composite clinical outcome (RRT – or death). Results: A total of 257 (38%) patients developed AKI within 7 days of ICU admission. Of those who developed AKI, 106 (41%) patients met stage 3 AKI within 7 days of ICU admission and 208 patients of the entire study cohort (31%) met the composite clinical endpoint of in-hospital mortality or RRT within 30 days of ICU admission. The addition of urinary NGAL/albumin to the clinical model modestly improved the prediction of AKI, in particular severe stage 3 AKI (area under the curve [AUC] of 0.9 from 0.87, p = 0.369) and the prediction of 30-day RRT or death (AUC 0.83 from 0.79, p = 0.139). Conclusion: A clinical model incorporating severity of illness, patient demographics, and chronic illness with currently available clinical biomarkers of renal function was strongly predictive of development of AKI and associated clinical outcomes in a heterogeneous adult ICU population. The addition of urinary NGAL/albumin to this simple clinical model improved the prediction of severe AKI, need for RRT and death, but not at a statistically or clinically significant level, when compared to the clinical model alone