Cellular injury leading to oxidative stress in acute poisoning with potassium permanganate/oxalic acid, paraquat, and glyphosate surfactant herbicide.

Previous studies on human acute kidney injury (AKI) following poisoning with potassium permanganate/oxalic acid (KMnO4/H2C2O4), paraquat, and glyphosate surfactant herbicide (GPSH) have shown rapid and large increases in serum creatinine (sCr) that cannot be entirely explained by direct nephrotoxicity. One plausible mechanism for a rapid increase in sCr is oxidative stress. Thus, we aimed to explore biomarkers of oxidative stress, cellular injury, and their relationship with sCr, after acute KMnO4/H2C2O4, paraquat, and GPSH poisonings. Serum biomarkers [sCr, creatine (sCn), cystatin C (sCysC)] and urinary biomarkers [cytochrome C (CytoC), 8-isoprostane (8-IsoPs)] were evaluated in 105 patients [H2C2O4/KMnO4 (N = 57), paraquat, (N = 21), GPSH (N = 27)] recruited to a multicenter cohort study. We used area under the receiver operating characteristics curve (AUC-ROC) to quantify the extent of prediction of moderate to severe AKI (acute kidney injury network stage 2/3 (AKIN2/3)). Patients with AKIN2/3 showed increased levels of CytoC. Early high CytoC predicted AKIN2/3 in poisoning with KMnO4/H2C2O4 (AUC-ROC4-8h: 0.81), paraquat (AUC-ROC4-8h: 1.00), and GPSH (AUC-ROC4-8h: 0.91). 8-Isoprostane levels were not significantly elevated. Reduced sCn and increased sCr/sCn ratios were observed for 48 h post KMnO4/H2C2O4 ingestion. Paraquat exhibited a similar pattern (N = 11), however only 3 were included in our study. Increased CytoC suggests there is mitochondrial injury coupled with energy depletion. The increased sCr within 24 h could be due to increased conversion of cellular creatine to creatinine during the process of adenosine triphosphate (ATP) generation and then efflux from cells. Later increases of sCr are more likely to represent a true decrease in kidney function.

Antidepressant therapy in cancer patients: initiation and factors associated with treatment.

PURPOSE: We assessed the impact of a cancer diagnosis and its timing on antidepressant initiation. We also examined patterns of, and factors associated with, new antidepressant treatment in cancer patients. METHODS: We followed 61 067 antidepressant-naive Australian Government Department of Veterans' Affairs clients. We used multivariable Cox proportional hazards models with time-varying covariates to compare antidepressant initiation in clients with and without cancer and to assess how initiation varies with time from diagnosis, adjusting for sociodemographic characteristics, health service use and co-morbidities. RESULTS: 17.2% (995/5795) of cancer patients initiated antidepressants and, on average, was more likely to initiate treatment than non-cancer controls with similar characteristics (initiation rate 9/100 person-years, 95% confidence interval: 8.5-9.6 vs 6.6/100 person-years, 95% confidence interval: 6.5-6.7). The peak initiation period was 12 weeks before and 16 weeks after diagnosis; cancer patients were 42% more likely to commence therapy than non-cancer patients (adjusted hazard ratio = 1.4, 1.2 to 1.7). Cancer patients with co-morbid disease, dispensed opioids, corticosteroids or anxiolytics and to whom death was approaching were more likely to initiate treatment. Median duration of antidepressant therapy was 16 weeks. CONCLUSION: New antidepressant treatment is more common in cancer populations than in cancer-free populations. Treatment was most commonly initiated around diagnosis time, a period when cancer drug treatments also commence. The timing of peak antidepressant uptake suggests treatment may be for short-term adjustment reactions, better managed without drugs. Durations of treatment are shorter than recommended for depression.

A simple quantitative bedside test to determine methemoglobin.

STUDY OBJECTIVE: Methemoglobinemia after pesticide poisoning is associated with a mortality of 12% in Sri Lanka. Treatment is complicated by the lack of laboratory facilities. We aimed to develop and validate a low-cost bedside test for quantitative estimation of clinically significant methemoglobin to be used in settings of limited resources. METHODS: A method to reliably produce blood samples with 10% to 100% methemoglobin was developed. Freshly prepared methemoglobin samples were used to develop the color chart. One drop (10 microL) of prepared methemoglobin sample was placed on white absorbent paper and scanned using a flatbed Cannon Scan LiDE 25 scanner. The mean red, green, and blue values were measured with ImageJ 1.37v. These color values were used to prepare a color chart to be used at the bedside. Interobserver agreement was assessed against prepared samples. The results from clinical use were compared with formal methemoglobin measurements. RESULTS: The red color value was linearly related to percentage methemoglobin (R(2)=0.9938), with no effect of absolute hemoglobin concentration. Mean interobserver (N=21) agreement and weighted kappa for scanned methemoglobin spots using the color chart were 94% and 0.83, respectively. Mean interobserver (N=9) agreement and weighted kappa for a freshly prepared methemoglobin sample with the chart were 88% and 0.71, respectively. Clinical use of the color chart also showed good agreement with spectrometric measurements. CONCLUSION: A color chart can be used to give a clinically useful quantitative estimate of methemoglobinemia.