| 1. |
|
|
| 2. |
|
|
| 3. |
- Friman, S., et al.
(författare)
-
Sotrastaurin, a Novel Small Molecule Inhibiting Protein-Kinase C : Randomized Phase II Study in Renal Transplant Recipients
- 2011
-
Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 11:7, s. 1444-1455
-
Tidskriftsartikel (refereegranskat)abstract
- Sotrastaurin, a selective protein-kinase-C inhibitor, blocks early T-cell activation through a calcineurin-independent mechanism. In this study, de novo renal transplant recipients with immediate graft function were randomized 1: 2 to tacrolimus (control, n = 44) or sotrastaurin (300 mg b.i.d.; n = 81). All patients received basiliximab, mycophenolic acid (MPA) and steroids. The primary endpoint was the composite of treated biopsy-proven acute rejection (BPAR), graft loss, death or lost to follow-up at month 3. The main safety assessment was estimated glomerular filtration rate (eGFR); modification of diet in renal disease (MDRD) at month 3. Composite efficacy failure at month 3 was higher for the sotrastaurin versus control regimen (25.7% vs. 4.5%, p = 0.001), driven by higher BPAR rates (23.6% vs. 4.5%, p = 0.003), which led to early study termination. Median (+/- standard deviation [SD]) eGFR was higher for sotrastaurin versus control at all timepoints from day 7 (month 3: 59.0 +/- 22.3 vs. 49.5 +/- 17.7 mL/min/1.73 m(2), p = 0.006). The most common adverse events were gastrointestinal disorders (control: 63.6%; sotrastaurin: 88.9%) which led to study-medication discontinuation in two sotrastaurin patients. This study demonstrated a lower degree of efficacy but better renal function with the calcineurin-inhibitor-free regimen of sotrastaurin+MPA versus the tacrolimus-based control. Ongoing studies are evaluating alternative sotrastaurin regimens.
|
|
| 4. |
- Irwin, Debra E, et al.
(författare)
-
Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction.
- 2011
-
Ingår i: BJU international. - 1464-410X.
-
Tidskriftsartikel (refereegranskat)abstract
- Study Type - Symptom prevalence (prospective cohort) Level of Evidence1b OBJECTIVE To estimate and predict worldwide and regional prevalence of lower urinary tract symptoms (LUTS), overactive bladder (OAB), urinary incontinence (UI) and LUTS suggestive of bladder outlet obstruction (LUTS/BOO) in 2008, 2013 and 2018 based on current International Continence Society symptom definitions in adults aged ≥20 years. PATIENTS AND METHODS Numbers and prevalence of individuals affected by each condition were calculated with an estimation model using gender- and age-stratified prevalence data from the EPIC study along with gender- and age-stratified worldwide and regional population estimates from the US Census Bureau International Data Base. RESULTS An estimated 45.2%, 10.7%, 8.2% and 21.5% of the 2008 worldwide population (4.3 billion) was affected by at least one LUTS, OAB, UI and LUTS/BOO, respectively. By 2018, an estimated 2.3 billion individuals will be affected by at least one LUTS (18.4% increase), 546 million by OAB (20.1%), 423 million by UI (21.6%) and 1.1 billion by LUTS/BOO (18.5%). The regional burden of these conditions is estimated to be greatest in Asia, with numbers of affected individuals expected to increase most in the developing regions of Africa (30.1-31.1% increase across conditions, 2008-2018), South America (20.5-24.7%) and Asia (19.7-24.4%). CONCLUSIONS This model suggests that LUTS, OAB, UI and LUTS/BOO are highly prevalent conditions worldwide. Numbers of affected individuals are projected to increase with time, with the greatest increase in burden anticipated in developing regions. There are important worldwide public-health and clinical management implications to be considered over the next decade to effectively prevent and manage these conditions.
|
|
