Prognosis and Survival of Older Patients With Dizziness in Primary Care:a 10-year prospective cohort study

Purpose: The prognosis of dizzy older patients in primary care is unknown. Our objective was to determine the prognosis and survival of patients with different subtypes and causes of dizziness. Methods: In a primary care prospective cohort study, 417 older adults with dizziness (mean age 75.5 years) received a full diagnostic workup in 2006-2008. A panel of physicians classified their dizziness subtype and primary cause of dizziness. Presyncope was the most common dizziness subtype (69.1%), followed by vertigo (41.0%), disequilibrium (39.8%), and other dizziness (1.7%). The most common primary causes of dizziness were cardiovascular disease (56.8%) and peripheral vestibular disease (14.4%). Main outcome measures were mortality and dizziness-related impairment assessed at 10-year follow-up.Results: At 10-year follow-up 169 patients (40.5%) had died. Multivariable adjusted Cox models showed a lower mortality rate for patients with the subtype vertigo compared to other subtypes (HR 0.62 (95% CI 0.40 to 0.96)), and for peripheral vestibular disease versus cardiovascular disease as primary cause of dizziness (HR 0.46 (95% CI 0.25 to 0.84)). After 10 years, 47.7% of patients who filled out the follow-up measurement experienced substantial dizziness-related impairment. No significant difference in substantial impairment was seen between different subtypes and primary causes of dizziness. Conclusions: The 10-year mortality rate was lower for the dizziness subtype vertigo compared to other subtypes. Patients with dizziness primarily caused by peripheral vestibular disease had a lower mortality rate than patients with cardiovascular disease. Substantial dizziness-related impairment in older dizzy patients 10 years later is high, and indicates that current treatment strategies by FPs may be suboptimal.<br/

Synthesis and structure-activity relationships of 4-fluorophenyl-imidazole p38 alpha MAPK, CK1 delta and JAK2 kinase inhibitors

The synthesis and structure-activity relationships of novel 4-(4 '-fluorophenyl)imidazoles as selective p38 alpha MAPK, CK1 delta and JAK2 inhibitors with improved water solubility are described. Microwave-assisted multicomponent reactions afforded 4-fluorophenyl-2,5-disubstituted imidazoles. Carboxylate and phosphonate groups were introduced via 'click' reactions. The kinase selectivity was influenced by the heteroaryl group at imidazole C-5 and the position of a carboxylic acid or tetrazole at imidazole C-2. For example, pyrimidines 15 and 34 inhibited p38 alpha MAPK with IC50 = 250 nM and 96 nM, respectively. Pyridine 3 gave CK1 delta inhibition with IC50 = 89 nM and pyridin-2-one 31 gave JAK2 inhibition with IC50 = 62 nM. (C) 2014 Elsevier Ltd. All rights reserved

Prognose van duizeligheid in de huisartsenpraktijk

Ouderen met duizeligheid door een perifere vestibulaire aandoening leven langer dan ouderen met duizeligheid door een cardiovasculaire aandoening. Bijna de helft van de ouderen met duizeligheidsklachten ondervindt na 10 jaar nog steeds of opnieuw ernstige beperkingen door de duizeligheid. Beschouw duizeligheid bij ouderen in de huisartsenpraktijk daarom als een klacht die niet vanzelf verdwijnt en behandel proactief

Syntheses and structure-activity relationships for some triazolyl p38 alpha MAPK inhibitors

The design, synthesis and biological evaluation of novel triazolyl p38 alpha MAPK inhibitors with improved water solubility for formulation in cationic liposomes (SAINT-O-Somes) targeted at diseased endothelial cells is described. Water-solubilizing groups were introduced via a 'click' reaction of functional azides with 2-alkynyl imidazoles and isosteric oxazoles to generate two small libraries of 1,4-disubstituted 1,2,3-triazolyl p38 alpha MAPK inhibitors. Triazoles with low IC50 values and desired physicochemical properties were screened for in vitro downregulation of proinflammatory gene expression and were formulated in SAINT-O-Somes. Triazolyl p38 alpha MAPK inhibitor 88 (IC50 = 0.096 mu M) displayed the most promising in vitro activity. (C) 2014 Elsevier Ltd. All rights reserved