Accuracy of algorithms to identify patients with a diagnosis of major cancers and cancer-related adverse events in an administrative database: a validation study in an acute care hospital in Japan.

OBJECTIVES: Validation studies in oncology are limited in Japan. This study was conducted to evaluate the accuracy of diagnosis and adverse event (AE) definitions for specific cancers in a Japanese health administrative real-world database (RWD). DESIGN AND SETTING: Retrospective observational validation study to assess the diagnostic accuracy of electronic medical records (EMRs) and claim coding regarding oncology diagnosis and AEs based on medical record review in the RWD. The sensitivity and positive predictive value (PPV) with 95% CIs were calculated. PARTICIPANTS: The validation cohort included patients with lung (n=2257), breast (n=1121), colorectal (n=1773), ovarian (n=216) and bladder (n=575) cancer who visited the hospital between January 2014 and December 2018, and those with prostate cancer (n=3491) visiting between January 2009 and December 2018, who were identified using EMRs. OUTCOMES: Key outcomes included primary diagnosis, deaths and AEs. RESULTS: For primary diagnosis, sensitivity and PPV for the respective cancers were as follows: lung, 100.0% (96.6 to 100.0) and 81.0% (74.9 to 86.2); breast, 100.0% (96.3 to 100.0) and 74.0% (67.3 to 79.9); colorectal, 100.0% (96.6 to 100.0) and 80.5% (74.3 to 85.8); ovarian, 89.8% (77.8 to 96.6) and 75.9% (62.8 to 86.1); bladder, 78.6% (63.2 to 89.7) and 67.3% (52.5 to 0.1); prostate, 100.0% (93.2 to 100.0) and 79.0% (69.7 to 86.5). Sensitivity and PPV for death were as follows: lung, 97.0% (84.2 to 99.9) and 100.0% (84.2 to 100.0); breast, 100.0% (1.3 to 100.0) and 100.0% (1.3 to 100.0); colorectal, 100.0% (28.4 to 100.0) and 100.0% (28.4 to 100.0); ovarian, 100.0% (35.9 to 100.0) and 100.0% (35.9 to 100.0); bladder, 100.0% (9.4-100.0) and 100.0% (9.4 to 100.0); prostate, 75.0% (19.4 to 99.4) and 100.0% (19.4 to 100.0). Overall, PPV tended to be low, with the definition based on International Classification of Diseases, 10th revision alone for AEs. CONCLUSION: Diagnostic accuracy was not so high, and therefore needs to be further investigated. TRIAL REGISTRATION NUMBER: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000039345).

Mitochonic Acid 5 (MA-5), a Derivative of the Plant Hormone Indole-3-Acetic Acid, Improves Survival of Fibroblasts from Patients with Mitochondrial Diseases.

Mitochondria are key organelles implicated in a variety of processes related to energy and free radical generation, the regulation of apoptosis, and various signaling pathways. Mitochondrial dysfunction increases cellular oxidative stress and depletes ATP in a variety of inherited mitochondrial diseases and also in many other metabolic and neurodegenerative diseases. Mitochondrial diseases are characterized by the dysfunction of the mitochondrial respiratory chain, caused by mutations in the genes encoded by either nuclear DNA or mitochondrial DNA. We have hypothesized that chemicals that increase the cellular ATP levels may ameliorate the mitochondrial dysfunction seen in mitochondrial diseases. To search for the potential drugs for mitochondrial diseases, we screened an in-house chemical library of indole-3-acetic-acid analogs by measuring the cellular ATP levels in Hep3B human hepatocellular carcinoma cells. We have thus identified mitochonic acid 5 (MA-5), 4-(2,4-difluorophenyl)-2-(1H-indol-3-yl)-4-oxobutanoic acid, as a potential drug for enhancing ATP production. MA-5 is a newly synthesized derivative of the plant hormone, indole-3-acetic acid. Importantly, MA-5 improved the survival of fibroblasts established from patients with mitochondrial diseases under the stress-induced condition, including Leigh syndrome, MELAS (myopathy encephalopathy lactic acidosis and stroke-like episodes), Leber's hereditary optic neuropathy, and Kearns-Sayre syndrome. The improved survival was associated with the increased cellular ATP levels. Moreover, MA-5 increased the survival of mitochondrial disease fibroblasts even under the inhibition of the oxidative phosphorylation or the electron transport chain. These data suggest that MA-5 could be a therapeutic drug for mitochondrial diseases that exerts its effect in a manner different from anti-oxidant therapy.