Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants.

BACKGROUND: Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. METHODS: We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. FINDINGS: The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. INTERPRETATION: Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings. FUNDING: WHO

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings. Copyright (C) 2021 World Health Organization; licensee Elsevier

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30–79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30–79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306–359) million women and 317 (292–344) million men in 1990 to 626 (584–668) million women and 652 (604–698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55–62) of women and 49% (46–52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43–51) of women and 38% (35–41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20–27) for women and 18% (16–21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings

Canine Visceral Leishmaniasis in Rio de Janeiro, Brazil: clinical, parasitological, therapeutical and epidemiological findings (1977-1983)

Forty dogs from the periphery of the city of Rio de Janeiro were studied. All dogs where diagnosed as positive for leishmaniasis either parasitologically and/or serologically. Among them, 19 came from areas where only Visceral Leishmaniasis (VL) occurs (Realengo, Bangu, Senador Camará). Clinical signs of the disease were seen in 36.8% of the cases, including emaciation - 100%, lymphadenopathy and depilation - 85.7%. The other 21 dogs came from an area (Campo Grande) where both diseases (VL, and American Cutaneous Leishmaniasis - ACL) occur. Clinical signs of the disease, mainly cutaneous or mucocutaneous ulcers were seen in 76.2% of the cases. Leishmania parasites were found in 39 cases: 22% in viscera, 42.5% in viscera and normal skin and 35% in cutaneous or mucocutaneous ulcers. All the Leishmania stocks isolated from dogs which came from Realengo, Bangu, Senador Camará (VL area), and from Campo Grande (VL + ACL area) were characterized as L. donovani (except in one case) according to their schizodeme, zymodeme and serodeme. The only stock characterized as L. b. braziliensis, was isolated from the lymph node of a dog from Campo Grande with visceral disease and without skin lesions. Antimony therapy attempted in eight Leishmania donovani positive dogs was unsuccessful.<br>Durante inquéritos caninos realizados na periferia da cidade do Rio de Janeiro, foram estudados clínica e laboratorialmente 40 cães. Todos apresentavam diagnóstico parasitológico e/ou sorológico de leishmaniose. Dentre esses, 19 procediam de áreas de ocorrência de leishmaniose visceral (LV) - Realengo, Bangu e Senador Camará. Sinais clínicos sugestivos da infecção foram observados em 36,8% deles (incluindo emagrecimento - 100%, linfadenopatia e depilação - 85,7%). Outros 21 cães procediam da área de Campo Grande onde tanto a LV como a leishmaniose tegumentar americana (LTA) ocorrem. Sinais clínicos da infecção por Leishmania, principalmente ulcerações cutâneas e mucocutâneas, foram observadas em 76,2% deles. Em 39 cães foram encontrados leishmanias: 22% em vísceras, 42,5% em vísceras e pele normal e 35% um ulcerações cutâneas ou mucocutâneas. Todos os estoques de Leishmania isolados de cães provenientes das áreas de LV e da área de LV + LTA foram caracterizados como L. donovani (exceto em um caso) conforme seus esquisodemas, zimodemas e serodemas. O único estoque caracterizado como L. braziliensis brazilienzis foi isolado de linfonodo de um cão de Campo Grande, com leishmaniose visceral e sem alterações cutâneas. A tentativa de tratamento pelo antimonial em oito cães positivos para Leishmania donovani não reverteu o curso da doença e um deles apresentou intenso agravamento, morrendo em curto período

Tailoring the synthesis of tantalum-based thin films for biomedical application: Characterization and biological response

The aim of this study was to tailor the deposition parameters of magnetron sputtering to synthetize tantalum oxide (TaxOy) films onto commercially pure titanium (cpTi) surface. The structural and optical properties, morphology, roughness, elemental chemical composition and surface energy were assessed. The impact of TaxOy films on initial Streptococcus sanguinis adhesion was investigated. The morphology and spreading of pre-osteoblastic (MC3T3-E1) cells on a crystalline tantalum oxide film were evaluated. TaxOy films with estimated thickness of 600 nm and different structures (amorphous or crystalline) were produced depending on the various oxygen flow rates and parameters used. X-ray diffraction analysis revealed that the 8 O-2 sccm (600 degrees C/400 W) group showed crystallization corresponding to the beta-TaxO5 phase. Optical analysis showed that the 4 O-2 sccm (200 degrees C 300 W) to 8 O-2 sccm (600 degrees C 300 W) groups and 10 O-2 sccm (200 degrees C 300 W) group presented regular and large-amplitude interference oscillations, suggesting high optical homogeneity of the films. The crystalline beta-TaxO5 coating showed higher roughness and surface energy values than the other groups (P .05). By tailoring the deposition parameters, we synthetized a crystalline beta-TaxO5 coating that improved titanium surface properties and positively affected cell spreading and morphology, making it a promising surface treatment for titanium-based implants101111119COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informação2016/07269-3; 2016/11470-6; 2017/18916-

Three-species biofilm model onto plasma-treated titanium implant surface

In this study, titanium (Ti) was modified with biofunctional and novel surface by micro-arc oxidation (MAO) and glow discharge plasma (GDP) and we tested the development of a three-species periodontopatogenic biofilm onto the treated commercially-pure titanium (cpTi) surfaces. Machined and sandblasted surfaces were used as control group. Several techniques for surface characterizations and monoculture on bone tissue cells were performed. A multispecies biofilm composed of Streptococcus sanguinis, Actinomyces naeslundii and Fusobacterium nucleatum was developed onto cpTi discs for 16.5 h (early biofilm) and 64.5 h (mature biofilm). The number of viable microorganisms and the composition of the extracellular matrix (proteins and carbohydrates) were determined. The biofilm organization was analyzed by scanning electron microscopy (SEM) and Confocal laser scanning microscopy (CLSM). In addition, MC3T3-E1 cells were cultured on the Ti surfaces and cell proliferation (MIT) and morphology (SEM) were assessed. MAO treatment produced oxide films rich in calcium and phosphorus with a volcano appearance while GDP treatment produced silicon-based smooth thin-film. Plasma treatments were able to increase the wettability of cpTi (p 0.05). Plasma treatment did not affect the viable microorganisms counts, but the counts of F. nucleaturn was lower for MAO treatment at early biofilm phase. Biofilm extracellular matrix was similar among the groups, excepted for GDP that presented the lowest protein content. Moreover, cell proliferation was not significantly affected by the experimental, except for MAO at 6 days that resulted in an increased cell proliferative. Together, these findings indicate that plasma treatments are a viable and promising technology to treat bone-integrated dental implants as the new surfaces displayed improved mechanical and biological properties with no increase in biofilm proliferation152354366CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP442786/2014-0; 304908/2015-02013/26145-5; 2013/08451-

LHCb

The LHCb detector is designed to study CP violation and other rare phenomena in decays of hadrons with heavy flavours, in particular $\rm B_s$ mesons. Interest in CP violation comes not only from elementary particle physics but also from cosmology, in order to explain the dominance of matter over antimatter observed in our universe, which could be regarded as the largest CP violation effect ever seen. The LHCb experiment will improve significantly results from earlier experiments both quantitatively and qualitatively, by exploiting the large number of different kinds of b hadrons produced at LHC. This is done by constructing a detector which has \begin{enumerate} \item Good trigger efficiencies for b-hadron final states with only hadrons, as well as those containing leptons. \item Capability of identifying kaons and pions in a momentum range of $\sim 1$ to above 100 GeV/$c$. \item Excellent decay time and mass resolution. \end{enumerate} The LHCb spectrometer shown in the figure consists of the following detector components: \begin{itemize} \item Beam Pipe\\ A 1.8 m-long section of the beam pipe around the interaction point has a large diameter of approximately 120 cm. This accommodates the vertex detector system with its retraction mechanics, and has a thin forward window made of aluminium over the full detector acceptance. This part is followed by two conical sections; the first is 1.5 m long with 25 mrad opening angle, and the second is 16 m long with 10 mrad opening angle. The entire first and most of the second section are made of beryllium in order to reduce the production of the secondary particles. \item Magnet\\ A dipole magnet with the normal conductive Al coil provides a high field integral of 4 Tm. The polarity of the field can be changed to reduce systematic errors in the CP-violation measurements that could result from a left-right asymmetry of the detector. \item Vertex Locator\\ A total of 21 stations made from two layers of silicon detector are used as a vertex detector system (VELO). Additional two stations with only one Si layer are dedicated to the detecting bunch crossings with more than one pp interaction as a part of Level-0 trigger. The closest distance between the active silicon area and the beam is 8 mm. The silicon detectors are placed in Roman pots with 300 $\mu$m thick aluminium windows, which act as a shield against RF pickup from the circulating beam bunches. In order to avoid collapse of the windows, a secondary vacuum is maintained inside the Roman pots. During the injection and acceleration, the Roman pot system will be moved away from the beam to avoid interference with the machine operation and accidental irradiation of the detectors. \item Tracking\\ The LHCb tracking system consists of four stations; one upstream of the magnet (TT) and three just behind the magnet (T1 to T3). No tracking device is positioned in the magnet and most of the tracks are reconstructed by combining the VELO and tracking system. The first station is made of silicon detectors. The stations behind the magnet are split into Inner Tracker (IT) and Outer Tracker (OT) systems due to the high particle density close to the beam pipe. The IT system is made of Si, and drift chambers based on straw technology are used for the OT system. \item Ring Imaging Cherenkov Detectors\\ The RICH system of the LHCb detector consists of two detectors with three different radiators in order to cover the required momentum range, 1-100 GeV/$c$ . The first detector uses aerogel and $\rm C_4 F_ {10}$ gas as radiators. The second detector, used for high momentum particles, is placed after the magnet and has $\rm C F_4$ gas as radiator. The Cherenkov light is detected with planes of Hybrid Photon Detectors (HPD's) placed outside the spectrometer acceptance. \item Calorimeters\\ The calorimeter system consists of a preshower detector followed by electromagnetic and hadronic calorimeters. It also serves as the initial part of the muon filter system. The cells of the Preshower detector are made up from 12 mm-thick lead plates sandwiched by square scintillators, 15 mm thick. For the electromagnetic part a Shashlik calorimeter is used since only modest energy resolution is required. The hadron calorimeter is based on a scintillating tile design similar to that developed for the ATLAS experiment. \item Muon System\\ The Muon system consists of tracking stations and absorber layers. The first tracking station is in front of the calorimeter system, which acts as the first absorber. Behind the calorimeter system, there are four tracking stations with Fe absorber walls in between. An additional Fe absorber is placed after the last tracking station against the muon background from the accelerator tunnel. Multi Wire Proportional Chambers are used everywhere except in the region close to the beam pipe of the first station where Triple-GEM chambers are used. \item Trigger\\ The LHCb trigger has two decision levels. Using custom made electronics, the first decision is made based on high transverse momentum hadrons or electrons found in the calorimeter system, or muons found in the muon system, at the bunch crossing rate of 40 MHz. All data from the detector are then read out at a rate of 1 MHz and sent to a CPU farm for further event reduction. For this purpose, all the detector information is available. With a rate of 2 kHz, events which include calibration data are stored for offline analysis. \end{itemize} Due to the large production cross section for b-$\rm \overline{ b}$ pairs (500~$\rm \mu b$) and efficient trigger, the LHCb experiment requires only a much lower luminosity ($2 \times 10^{32}$~$\rm cm^{-2} s^{-1}$) than the nominal LHC luminosity ($10^{34}$~$\rm cm^{-2}s^{-1}$) for its physics programme. The experiment therefore can reach its full physics potential from the beginning of LHC operation. The luminosity at the LHCb interaction point can be locally tuned so that the experiment is able to continue its physics programme when the machine reaches the nominal operating condition. \end{document