VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO

DR. NORMAN CLINICAL EFFECTIVENESS AND IMPLEMENTATION OF MASSED PRO:OVER TWENTY WELL-CONTROLLED CLINICAL TRIALS HAVE DEMONSTRATED THE EFFICACY AND EFFECTIVENESS OF PROLONGED EXPOSURE (PE) FOR PTSD, INCLUDING SEVERAL WITH SERVICE MEMBERS AND VETERANS. PE IS A TIME-LIMITED (ABOUT 12 SESSION) PSYCHOTHERAPY THAT HELPS PEOPLE CHANGE TRAUMA-RELATED COGNITIONS SUCH AS "THE WORLD IS COMPLETELY DANGEROUS AND "I AM INCOMPETENT" THROUGH IN-VIVO EXPOSURE TO TRAUMA REMINDERS AND IMAGINAL EXPOSURE TO THE TRAUMA MEMORY. OVER TIME, EXPOSURE TO THESE AVOIDED BUT SAFE STIMULI HELPS PATIENTS REDUCE THEIR BELIEF IN THEIR TRAUMA-RELATED COGNITIONS WHICH IS ASSOCIATED WITH RECOVERY FROM PTSD. IN ONE OF THE LARGEST STUDY OF PE TO DATE, PE RESULTED IN LARGE EFFECT SIZES WITH 73% OF PATIENTS RESPONDING TO TREATMENT AND 40% LOSING THEIR PTSD DIAGNOSIS. PE HAS BEEN SHOWN TO BE EFFECTIVE WITH A VARIETY OF COMPLEX AND COMORBID POPULATIONS AND ALL FIVE MAJOR U.S. AND INTERNATIONAL CLINICAL PRACTICE GUIDELINES FOR PTSD TREATMENT GIVE PE THEIR HIGHEST RATING. GIVEN THE STRENGTH OF THIS EVIDENCE, PE HAS BEEN IMPLEMENTED IN MULTIPLE HEALTHCARE SYSTEMS OVER THE PAST DECADE, SUCH AS THE DEPARTMENT OF DEFENSE (DOD), VETERANS AFFAIRS (VA). UNFORTUNATELY, PATIENTS WITH CURRENT COMORBID SUBSTANCE USE DISORDERS (SUD) HAVE BEEN HISTORICALLY EXCLUDED FROM PTSD TREATMENT TRIALS, SLOWING THEIR SPREAD INTO SUD TREATMENT SETTINGS AND LEAVING PE LARGELY UNAVAILABLE TO THOSE WITH ARGUABLY THE GREATEST NEED.

DR. IX - KIDNEY TUBLAR DAMAGE AND DYSFUNCTION IDENTIFY A NOVEL AXIS OF CHRONIC KIDNEY:PATHOLOGIC STUDIES DEMONSTRATE THAT KIDNEY TUBULE INJURY, ATROPHY, AND FIBROSIS ARE COMMON FEATURES OF CHRONIC KIDNEY DISEASE (CKD) AND ARE HIGHLY PREDICTIVE OF PROGRESSION TO DIALYSIS. ESTABLISHED CKD RISK FACTORS INCLUDING HYPERTENSION AND ADVANCED AGE ARE ASSOCIATED WITH TUBULAR INJURY AND FIBROSIS ON BIOPSY. HOWEVER, CURRENT CLINICAL ASSESSMENT OF CKD EVALUATES ONLY GLOMERULAR FUNCTION (GFR) AND GLOMERULAR INJURY (ALBUMINURIA), BUT NOT KIDNEY TUBULAR DYSFUNCTION OR INJURY. THE OVERALL HYPOTHESIS OF THIS APPLICATION IS THAT KIDNEY TUBULAR DYSFUNCTION AND INJURY ARE MEASURABLE CONTRIBUTORS TO CKD PATHOGENESIS AND PROGNOSIS. DYSFUNCTION OF THE KIDNEY TUBULES WILL BE ASSESSED BY THREE INDICES: (1) RENAL TUBULE RESISTANCE TO HORMONE ACTIONS OF FGF23 AND PTH; (2) ACID/BASE HOMEOSTASIS; AND (3) URINE RE-ABSORPTIVE CAPACITY.WE WILL: (1) DETERMINE THE ASSOCIATION OF KIDNEY TUBULAR DYSFUNCTION AND INJURY WITH RISK OF CVD EVENTS, (2) DETERMINE THE ASSOCIATION OF KIDNEY TUBULAR DYSFUNCTION AND INJURY WITH CKD PROGRESSION, AND (3) DETERMINE WHETHER RANDOMIZATION TO INTENSIVE BLOOD PRESSURE MANAGEMENT ARM OF THE TRIAL SLOWS PROGRESSION OF KIDNEY TUBULAR DYSFUNCTION AND INJURY OVER TIME COMPARED WITH STANDARD BLOOD PRESSURE MANAGEMENT.