Combination therapy with an ACE inhibitor and an angiotensin receptor blocker for diabetic nephropathy - a meta-analysis

WSTĘP. Inhibitory konwertazy angiotensyny (ACEI) i blokery receptora angiotensyny (ARB) zapobiegają progresji nefropatii cukrzycowej (DN). Wyniki badań sugerują, że połączenie układu renina-angiotensyna-aldosteron (RAAS) i czynników hamujących działa addytywnie w procesie leczenia DN. Ponieważ badania te obejmowały niewielkie grupy chorych, autorzy niniejszej pracy przeprowadzili metaanalizę prób dotyczących leczenia skojarzonego DN. METODY. Badania do metaanalizy wybrano na podstawie baz danych MEDLINE, EMBASE, CINAHL i Cochrane. Włączono wszystkie próby dotyczące skojarzonego leczenia za pomocą ACEI i ARB. Głównym punktem końcowym było dobowe wydalanie białka z moczem, a dodatkowe punkty końcowe obejmowały: wartości ciśnienia tętniczego, stężenia potasu we krwi i współczynnika przesączania kłębuszkowego (GFR). WYNIKI. W 10 włączonych do analizy badaniach 156 chorych otrzymało ACEI i ARB, a 159 jedynie ACEI. Większość badań trwało 8-12 tygodni. U osób leczonych ACEI i ARB uzyskano zmniejszenie proteinurii (p = 0,01), co wiązało się ze znaczną statystyczną heterogenicznością (p = 0,005). Terapia ACEI i ARB była związana ze zmniejszeniem GFR [3,87 ml/min (7,32-0,42); p = 0,03] i tendencją do wzrostu stężenia kreatyniny w surowicy (6,86 umol/l 95% CI -0,76-13,73; p = 0,09). Stężenie potasu zwiększyło się o 0,2 (0,08-0,32) mmol/l (p < 0,01) u chorych leczonych ACEI i ARB. Skurczowe i rozkurczowe ciśnienie krwi obniżyło się odpowiednio o 5,2 mm Hg (2,1-8,4) (p < 0,01) i 5,3 mm Hg (2,2-8,4) (p < 0,01). WNIOSKI. Wyniki metaanalizy sugerują, że łączne stosowanie ACEI + ARB w większym stopniu zmniejsza 24-godzinne wydalanie białka z moczem niż przyjmowanie jedynie ACEI. Korzystne efekty terapii skojarzonej są wynikiem niewielkiego wpływu leków na GFR, stężenie kreatyniny i potasu w surowicy oraz ciśnienie tętnicze. Rezultaty te należy interpretować ostrożnie, ponieważ większość analizowanych badań charakteryzowała się krótkim czasem obserwacji, a w kilku długoterminowych próbach (12 miesięcy) nie wykazano korzystnego wpływu leczenia.AIMS. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) prevent the progression of diabetic nephropathy (DN). Studies suggest that combination renin-angiotensin-aldosterone system (RAAS)-inhibiting therapy provides additive benefit in DN. However, these studies are small in size. We performed a meta-analysis of studies investigating combination therapy for DN. METHODS. Studies were identified through a search of MEDLINE, EMBASE, CINAHL and the Cochrane Database. All trials involving combined ACEI and ARB for slowing progression of DN were included. The primary end point was 24- Blood pressure, serum potassium and glomerular filtration rate (GFR) were secondary end points. RESULTS. In the 10 included trials, 156 patients received ACEI + ARB and 159 received ACEI only. Most studies were 8&#8211;12 weeks in duration. Proteinuria was reduced with ACEI + ARB (p = 0.01). This was associated with significant statistical heterogeneity (p = 0.005). ACEI + ARB was associated with a reduction in GFR [3.87 ml/min (7.32-0.42); p = 0.03] and a trend towards an increase in serum creatinine (6.86 umol/l 95% CI: -0.76-13.73; p = 0.09). Potassium was increased by 0.2 (0.08-0.32) mmol/l (p < 0.01) with ACEI + ARB. Systolic and diastolic blood pressure were reduced by 5.2 (2.1-8.4) mm Hg (p < 0.01) and 5.3 (2.2-8.4) mm Hg (p < 0.01), respectively. CONCLUSIONS. This meta-analysis suggests that ACEI + + ARB reduces 24-h proteinuria to a greater extent than ACEI alone. This benefit is associated with small effects on GFR, serum creatinine, potassium and blood pressure. These results should be interpreted cautiously as most of the included studies were of short duration and the few long-term studies (12 months) have not demonstrated benefi

Noise induced transitions in semiclassical cosmology

A semiclassical cosmological model is considered which consists of a closed Friedmann-Robertson-Walker in the presence of a cosmological constant, which mimics the effect of an inflaton field, and a massless, non-conformally coupled quantum scalar field. We show that the back-reaction of the quantum field, which consists basically of a non local term due to gravitational particle creation and a noise term induced by the quantum fluctuations of the field, are able to drive the cosmological scale factor over the barrier of the classical potential so that if the universe starts near zero scale factor (initial singularity) it can make the transition to an exponentially expanding de Sitter phase. We compute the probability of this transition and it turns out to be comparable with the probability that the universe tunnels from "nothing" into an inflationary stage in quantum cosmology. This suggests that in the presence of matter fields the back-reaction on the spacetime should not be neglected in quantum cosmology.Comment: LaTex, 33.tex pages, no figure

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems