ROSIGLIATAZONE EVALUATED FOR CARDIOVSCULAR OUTCOMES IN ORAL AGENT COMBINATION THERAPY FOR TYPE 2 DIABETES (RECORD): & MULTICENTRE, RANDOMISED, OPEN -LABEL TRIAL. PHILIP D HOME DM, STUART J POCOCK PHD. AND COLLEAGUES. ROSIGLITAZONE IS AN INSULIN SENSITISER USED IN COMBINATION WITH MEFORMIN, A SULFONYLUREA, OR BOTH, FOR LOWERING BLOOD GLUCOSE IN PEOPLE WITH TYPE 2 DIABETES. WE ASSESSED CARDIOVASCULAR OUTCOMES AFTER ADDITION OF ROSIGLITAZONE TO EITHER METFORMIN OR SULFONYLUREA COMPARED WITH THE COMBINATION OF THE OVER S-7 YEARS OF FOLLOW UP. WE ALSO ASSESSED COMPARATIVE SAFETY METHODS. IN A MULTICENTRE, OPEN-LABEL TRIAL, 4447 PATIENTS WITH TYPE 2 DIABETES ON METFORMIN OR SULFONYLUREA MONOTHERAPY WITH MEAN HAEMOGLOBIN ALC (HB A1C) OF 7-9% WERE RANDOMLY ASSIGNED TO ADDITION OF ROSIGLITAZONE (N=2220) OR TO A COMBINATION OF METFORMIN AND SULFONYLUREA (ACTIVE CONTROL GROUP, N=2227). ‘THE PRIMARY ENDPOINT WAS CARDIOVASCULAR HOSPITALISATION OR CARDIOVASCULAR DEATH, WITH A HAZARD RATIO (HR) NON INFERIORITY MARGIN OF 1.20. ANALYSIS WAS BY INTENTION TO TREAT. THIS STUDY IS REGISTERED WITH GOVERNMENT CLINICAL TRIALS NUMBER NCTO0379769. FINDINGS. 321 PEOPLE IN THE ROSIGLITAZONE GROUP AND 323 IN THE ACTIVE CONTROL GROUP EXPERIENCED THE PRIMARY OUTCOME DURING A MEAN 5-5 YEAR FOLLOW UP, MEETING THE CRITERION ON NON-INFERIORITY (HR 0.93, 95% CL 0.85-1.16), HR WAS 0-84 (0-59) FOR CARDOVASCULAR DEATH, 1-14 (0.80 - 1.63) FOR MYOCARDIAL INFARCTION, AND 0.72 (0.49-1.06) FOR STROKE. HEART FAILURE CAUSING ADMISSION TO HOSPITAL OR DEATH OCCURRED IN 61 PEOPLE IN THE ROSIGLITAZONE GROUP AND 29 IN THE ACTIVE CONTROL GROUP (HR2.10, 1.35 ~ 3.27, RISK DIFFERENCE PER 1000 PERSON-YEARS 2.6, 1.1-4.1). UPPER AND DISTAL LOWER, LIMB FRACTURE RATES WERE INCREASED MAINLY IN WOMEN RANDOMLY ASSIGNED TO RSIGLITAZONE. MEAN HBALC WAS LOWER IN THE ROSIGLITAZONE GROUP THAN IN THE CONTROL GROUP AT 5 YEARS. INTERPRETATION. ADDITION ROSIGLITAZONE TO GLUCOSE LOWERING THERAPY IN PEOPLE WITH TYPE 2 DIABETES IS CONFIRMED TO INCREASE THE RISK OF HEART FAILURE AND OF SOME FRACTURES, MAINLY IN WOMEN. ALTHOUGH THE DATA ARE INCONCLUSIVE ABOUT ANY POSSIBLE EFFECT ON MYOCARDIAL INFARCTION, ROSIGLITAZONE DOES NOT INCREASE THE RISK OF OVERALL CARDIVASCULAR MORBIDITY OR MORTALITY COMPARED WITH STANDARD GLUCOSE -LOWERING DRUGS.WHAT WAS THE MAIN PURPOSE OF THE STUDY? ake afr ‘TO TREAT PATIENTS WITH TYPE 2 DIABETES. To DETERMINE THE INCIDENCE OF HOSPITALIZATION IN PATIENTS TAKING ROSIGLITAZONE, ‘To DISCOVER THE EFFECTS THAT ROSIGLITAZONE HAS ON HEART FAILURE IN PATIENTS WITH TYPE 2 UMBETES, TO GET GOVERNMENT APPROVAL FOR ROSIGLITAZONE, LOWER DISULINE IN PEOPLE WITH TYPE 2 DIABETES LOWER 81000 GLUCOSE IN PEOPLE WITH TYPE 2 DIABETES INCREASE BLOOD GLUCOSE IN PECPLE WITH TYPE 2 DIABETES. [DIMINISH ISULINE IN PEOPLE WITH TYPE 1 OTAEETES. PARTICIPANTS WERE GIVEN SULFONYLUREA. PARTICIPANTS WERE GIVEN ROSISLITAZONE. PARTICIPANTS HAD NEARLY SIMILAR LEVELS OF HBAIC. PARTICIPANTS WERE ALL FROM THE SAME CENTRE. WHAT DOBS THE AUTHOR CONCLUDE REGARDING THE SAFETY OF ROSIGUTAZONE IN GLUCOSE-LOWERING ‘THERAPY FOR PATIENTS WITH TYPE-2 DIABETES? ona ‘THE PERCENTAGE OF PATIENTS RESULTING IN HEART FAILURE WAS VERY HIGH FOR BOTH GROUPS, ROSIGLITAZONE, IN GENERAL CAUSES HEART FAILURE ROSIGUTAZONE 15 GENERALLY SAFE, BUT NOT FOR WOMEN, ROSIGLATAZONE SHOULD BE USED ONLY FOR MALE PATIENTS. ADDITION ROSIGUTAZONE TO GLUCOSE LOWERING THERAPY IN PEOPLE WITH TYPE 2 DIABETES 15 ‘CONFIRMED To: oor INCREASE THE RISK OF HEART FAILURE AND OF SOME FRACTURES, MAINLY IN MEN. INCREASE THE RISK OF HEART FAILURE AND OF SOME FRACTURES, MAINLY IN WOMEN. ‘THE DATA ARE CONCLUSIVE ABOUT ANY POSSIBLE EFFECT ON MYOCARDIAL INFARCTION, ROSIGLITAZONE INCREASES THE RISK OF OVERALL CARDIVASCULAR MORBIDITY.PIGMENTARY DISORDERS IN LATIN AMERICA FALABELLA, RAFAEL DERMATOLOGIC CLINICS - VOLUME 25, ISSUE 3 W. 8. SAUNDERS COMPANY JULY 2007 PITYRIASIS ALBA (PA) IS A COMMON DISORDER, ‘OBSERVED IN LATIN AMERICAN PATIENTS. LESIONS DISCLOSE HYPOPIGMENTATION, MAINLY OBSERVED (ON FACIAL AREAS AND SUNLIGHT EXPOSED SURFACE OF ARMS AND FOREARMS; THOSE ON THE TRUNK AND LOWER EXTREMITIES ARE LESS COMMON. AN ATOPIC DIATHESIS IS PRESENT IN MOST PATIENTS, AND THE CONDITION FREQUENTLY DEVELOPS IN CHILDREN AND YOUNG ADULTS. THE AVERAGE LESION BEGINS WITH A SLIGHTLY HYPOPIGMENTED MACULE THAT ENLARGES GRADUALLY FROM 1 CM TO 3 CM AND MAY COALESCE WITH NEIGHBORING MACULES, RESULTING IN LARGER HYPOPIGMENTED DEFECTS. A FINE DESQUAMATION AND DRYNESS OF SKIN ARE CHARACTERISTIC AND THE CLINICAL PICTURE USUALLY WORSENS DURING SUMMER OR DURING FREQUENT WATERSPORT ACTIVITIES. & FOLLICULAR VARIETY WITH MILD HYPERKERATOSIS AT THE HAIR FOLLICLE OSTIUM FREQUENTLY OCCURS. ON HISTOLOGIC EXAMINATION, EPIDERMAL AND FOLLICULAR SPONGIOSIS, FOCAL PARAKERATOSIS, SLIGHT ACANTHOSIS, AND MILD SUPERFICIAL PERIVASCULAR INFILTRATES ARE SEEN. IN A STUDY, ULTRASTRUCTURAL, EXAMINATION DISCLOSED SMALL AND REDUCED NUMBERS OF MELANOCYTES AND MELANOSOMES. ALTHOUGH PA IMPROVES SPONTANEOUSLY AFTER PUBERTY, LOW POTENCY CORTICOSTEROIDS, SUCH AS 1% HYDROCORTISONE OR 0.5% DESONIDE, FREQUENT EMOLLIENT APPLICATION, AND SUNLIGHT AVOIDANCE/PROTECTION ARE USEFUL TO CONTROL THIS DISORDER. SKIN CONTACT WITH DIVERSE CHEMICALS MAY INDUCE ACQUIRED HYPOPIGMENTATION, WHICH MAY OCCUR EITHER DURING PROFESSIONAL ACTIVITIES OR AS AN INCIDENTAL EVENT. AREAS OF CONTACT, SUCH AS HANDS AND. FEET, MAY BECOME AFFECTED WITH OR WITHOUT INITIAL DERMATITIS, AND THEREAFTER HYPOPIGMENTATION OCCURS. SOME OF THE INVOLVED CHEMICALS ARE CATECHOL AND BENZENE DERIVATIVES USED AS ANTISEPTICS AND CLEANSERS, PESTICIDES, AND EPOXY RESINS COMMONLY USED IN HOUSEHOLD WORK. MACULAR LESIONS SHOW DIFFERENT GRADES OF HYPOPIGMENTATION OR ‘TRUE DEPIGMENTATION INDISTINGUISHABLE FROM VITILIGO; A PREVIOUS HISTORY OF SUBSTANCE CONTACT AND DERMATITIS ARE IN FAVOR OF THE CHEMICAL NATURE OF DEPIGMENTATION . ON HISTOLOGIC EXAMINATION, JUST A FEW MELANOCYTES ARE PRESENT AND REDUCED OR ABSENT MELANIN IS OBSERVED. TREATMENT OF DEPIGMENTATION IS DIFFICULT, BECAUSE MOST OF THE TIME ACRAL AREAS ARE INVOLVED AND MELANOCYTES IN AFFECTED AREAS ARE SCARCE. IF VITILIGO-LIKE DEPIGMENTATION BECOMES REFRACTORY TO MEDICAL THERAPY, MELANOCYTE GRAFTING MAY BE AN, IMPORTANT THERAPEUTIC SOLUTION.