STRATEGIC ALLIANCES: FROM SUCCES TO FAILURE

Over the past few years, the strategic alliances had been increasingly common. The term “strategic alliance” can mean many different things, but the commonly used meaning entails a joint corporative effort by two or more companies working towards agreed ustrategic alliances, benefits, risk of failure

NEUROBLASTOMUL CU DISEMINARE METASTATICĂ, PREZENTARE NEONATALĂ-CASE REPORT

Neuroblastoamele sunt tumori cu origine in celule sușe ale sistemului nervos simpatic, derivate din crestele neurale, reprezentând70% dintre tumorile cu localizare la nivelul glandei suprarenale. Neuroblastomul este cea mai frecventă tu- moră solidă la sugar, cu o prevalență de 1:70000 de nou-născuți, insumând aproximativ 20% din cancerele neonatale. Rata de mortalitate se situează la 15%, având ca factor cauzal dificultățile de diagnostic precoce. 1-2% din cazuri prezintă istoric familiar. Neuroblastoamele caracteristici genetice, biologice și morfologice heterogene si un comportament clinic divers.Lucrarea prezintă cazul unui nou-născut de sex feminin, 8 ore de viată, provenit din sarcină nedispensarizată, naștere dificilă cu aplicare de forceps, transferat in sectia de Chirurgie cu suspiciunea diagnostică de hemoperitoneu. Explorările imagistice efectuate in urgență confirmă diagnosticul de hemoperitoneu și relevă prezența unei tumori de glandă suprare- nală dreaptă, multiple diseminări hepatice si hepatomegalie importantă. La internare pacienta prezintă stare generala gravă, abdomen mărit de volum pe seama hepatomegaliei, circulație colaterală abdominală. Se intervine chirurgical, dupa stabilizarea hemodinamică a pacientei, practicându-se laparotomie subcostală dreaptă. Se constată prezența unei rupturi de lob drept hepatic, fără hmoragie activă pe tranșa de ruptură și se practică biopsie metastază tumorală hepatică, tumorsu- prarenalectomie dreaptă, controlul hemostazei. Evoluția postoperatorie este lent nefavorabilă pacienta prezentând anemie importantă, edeme generalizate, oligoanurie și in ciuda tratamentului suportiv maximal dezvoltă stop cardiocircultator ce nu răspunde la manevrele de resuscitare.Neuroblastomul este una dintre cele mai enigmatice tumori în perioada neonatală, putând regresa spontan sau progre- sa fulminant in absența unui plan terapeutic adecvat sau in prezența unui stadiu avansat. Diagnosticul precoce reprezintă o provocare in practica medicală curentă, ca in cazul prezentat in care afecțiunea a debutat in utero, iar pacienta nu a beneficiat de ecografie antenatală. Descoperirea unui neuroblastom fetal crează oportunitatea fie a unui tratament in utero, fie a unor precauții in ceea ce privește momentul nașterii

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

INFLUENCES ON THE QUANTUM OF DAMAGES AWARDED AT ICSID

The present paper is part of a larger study that aims to identify some of the factors that have a great impact on the quantum of the damages awarded in ICSID cases. The driver of this study is the high level of the damages awarded in this sort of disputes between foreign investors and the host state. In 2012 the ICSID tribunal awarded more than 1.77 billion USD for a breach of Fair and Equitable Treatment standard and indirect expropriation by Ecuador. Another reason for choosing this subject is the increasing number of the cases judged at this Centre. The analytical method used for analysing the determination relation between the identified factors and the quantum of the damages is the linear regression analysis. For the data collection were used as many cases’ awards as could been found published on the official site, from which were selected the cases were damages were awarded, in number of 30. For all the analysis made the statistical signification was followed and additional statistics trimming methods used, were necessary. The first factor that had been chosen was the value of damages requested, the calculations showing the impact assumed for it. The reasons beside this selection are pretty obvious: it is the most obvious factor on which the arbitrator can rely, it has the same nature of value, and it’s based on an expert’s report of damages’ valuation. There is plenty room for further analysis, this only representing the starting point, but is very important step in configuring the data base on which the following analysis will be set. For each case studied there are other characteristics, beside the value of damages requested, that were extracted and presented in order to determinate there impact or the lack of impact. For these factors is needed a preparation operation of pondering because of their nature, non-numerical, so that these will be the subject of a further analysis. The importance of this paper is also given by the definitions of the elements used in the factors’ impact analysis

ICSID CASES IN WHICH DAMAGES WERE AWARDED BASED ON MARKET APPROACH

The foreign direct investments had encountered the need of a special organism to protect the investors and their rights. This organism was founded by the World Bank and it is called The International Centre for Settlement of Investment Disputes – ICSID. After the recognition of ICSID by the states, the foreign investment flow grew and the number of disputes start growing as well. If the host state is in breach of the Bilateral Investment Treaty, it will have to pay damages to the investor. In order to determine the quantum of the damages, a business valuation is needed. Enterprise valuation has become particularly important with business development, especially as a result of the development of stock market transactions. Business development has, among other things, led to the diversification of funding sources, so stock listing has become essential for many firms that require capital for their underlying investment projects. Besides the role of attracting capital for business development, the stock exchange is also the place for the creation, development and diversification of the investment portfolio of the various investors and, at the same time, the 'playground' of the speculators. None of these roles could be successfully accomplished in the absence of documented business reviews. Around these assessments, three main approaches were outlined: asset, revenue and market approach. Each of these approaches is based on a fundamental concept from which it proposes a mathematical computation method that results in an informative sum representing the estimated value of the evaluated business. These three methods are also the methods accepted by ICSID in establishing the damages that will be awarded in the judged cases. There are some conditions that have to be met in order to use one method instead of other. Usually the selection of the method it is dome by the evaluator, but the arbitrators that are judging the case can reject one method and select another one, based on their professional judgement

Forecasting in Business

There is little managementliterature on forecasting at national level and scarcepractical issues. We are told only that there are severalforecasting methods and that forecasting is a tool ofstrategic management. After addressing several claimsabout forecasting made in management literature, thispaper presents several forecasting methods used inoperational management

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]).CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791

Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting & Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (<60, 60-69, and >_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 & PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages <60, 60-69, and >_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791