The risk for urinary tract infections with sodium-glucose cotransporter 2 inhibitors: No longer a cause of concern?

Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve cardiovascular and renal outcomes in patients with type 2 diabetes, including those with diabetic kidney disease. However, the US Food and Drug Administration and European Medicines Agency warnings about potential adverse effects, such as urosepsis and pyelonephritis, based on post-marketing case reports, may deter physicians from prescribing these drugs. A recent evaluation of two large US-based databases of commercial claims failed to find evidence for an increased risk of urinary tract infection (UTI) or severe UTI in type 2 diabetes patients who were prescribed an SGLT2.Research by A.O. is supported by FIS PI16/02057, PI19/00588, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018, KIDNEY ATT ACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, FRIAT, Sociedad Española de Nefrología, Comunidad de Madrid B2017/BMD- 3686 CIFRA2-CM

Carvedilol in hypertension treatment

Although β-blockers have been previously shown to effectively reduce blood pressure (BP) and have been used for hypertension treatment for over 40 years, their effect on cardiovascular morbidity and mortality in hypertensive patients remains controversial and its use in uncomplicated hypertension is currently under debate. However, data on the above field derive mainly from studies which were conducted with older agents, such as atenolol and metoprolol, while considerable pharamacokinetic and pharmacodynamic heterogeneity is present within the class of β-blockers. Carvedilol, a vasodilating non-cardioselective β-blocker, is a compound that seems to give the opportunity to the clinician to use a cardioprotective agent without the concerning hemodynamic and metabolic actions of traditional β-blocker therapy. In contrast with conventional β-blockers, carvedilol maintains cardiac output, has a less extended effect on heart rate and reduces BP by decreasing vascular resistance. Further, several studies has shown that carvedilol has a beneficial or at least neutral effect on metabolic parameters, such as glycemic control, insulin sensitivity, and lipid metabolism, suggesting that they could be used in subjects with the metabolic syndrome or diabetes without negative consequences. This article summarizes the distinct pharmacologic, hemodynamic, and metabolic properties of carvedilol in relation to conventional β-blockers, attempting to examine the potential use of this agent for hypertension treatment

A Linear Estimator for Factor-Augmented Fixed-T Panels with Endogenous Regressors

Supplementary Materials: The supplementary appendix to this article provides additional results about the method developed in the present article. In particular, Section S1 analyses several extensions of the model analyzed in the main text, including unbalanced panels, observed factors, and consistency of the GMM estimator under an alternative set of assumptions, in which the factor loadings are treated as a sequence of constants. Section S2 provides descriptive statistics for the data used in the empirical illustration. Section S3 reports additional Monte Carlo results. Finally, Section S4 provides proofs of the main theoretical results put forward in the article. The supplemental materials are available online at: https://ndownloader.figstatic.com/files/22658501 .Copyright © 2020 The Authors.. A novel method-of-moments approach is proposed for the estimation of factor-augmented panel data models with endogenous regressors when T is fixed. The underlying methodology involves approximating the unobserved common factors using observed factor proxies. The resulting moment conditions are linear in the parameters. The proposed approach addresses several issues which arise with existing nonlinear estimators that are available in fixed T panels, such as local minima-related problems, a sensitivity to particular normalization schemes, and a potential lack of global identification. We apply our approach to a large panel of households and estimate the price elasticity of urban water demand. A simulation study confirms that our approach performs well in finite samples.NWO VENI grant number 451-17-002; Australian Research Council, under research grant number DP-170103135

New results on asymptotic properties of likelihood estimators with persistent data for small and large T

Data Availability Statement: Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.Copyright © The Author(s) 2023. This paper revisits the panel autoregressive model, with a primary emphasis on the unit-root case. We study a class of misspecified Random effects Maximum Likelihood (mRML) estimators when T is either fixed or large, and N tends to infinity. We show that in the unit-root case, for any fixed value of T, the log-likelihood function of the mRML estimator has a single mode at unity as N→ ∞ . Furthermore, the Hessian matrix of the corresponding log-likelihood function is non-singular, unless the scaled variance of the initial condition is exactly zero. As a result, mRML is consistent and asymptotically normally distributed as N tends to infinity. In the large-T setup, it is shown that mRML is asymptotically equivalent to the bias-corrected FE estimator of Hahn and Kuersteiner (Econometrica 70(4):1639–1657, 2002). Moreover, under certain conditions, its Hessian matrix remains non-singular

A European Renal Association (ERA) synopsis for nephrology practice of the 2023 European Society of Hypertension (ESH) Guidelines for the Management of Arterial Hypertension.

In June 2023, the European Society of Hypertension (ESH) presented and published the new 2023 ESH Guidelines for the Management of Arterial Hypertension, a document that was endorsed by the European Renal Association (ERA). Following the evolution of evidence in recent years, several novel recommendations relevant to the management of hypertension in patients with chronic kidney disease (CKD) appeared in these Guidelines. These include recommendations for target office blood pressure (BP) <130/80 mmHg in most and against target office BP <120/70 mmHg in all patients with CKD; recommendations for use of spironolactone or chlorthalidone for patients with resistant hypertension with estimated glomerular filtration rate (eGFR) higher or lower than 30 mL/min/1.73 m2, respectively; use of a sodium-glucose cotransporter 2 inhibitor for patients with CKD and estimated eGFR ≥20 mL/min/1.73 m2; use of finerenone for patients with CKD, type 2 diabetes mellitus, albuminuria, eGFR ≥25 mL/min/1.73 m2 and serum potassium <5.0 mmol/L; and revascularization in patients with atherosclerotic renovascular disease and secondary hypertension or high-risk phenotypes if stenosis ≥70% is present. The present report is a synopsis of sections of the ESH Guidelines that are relevant to the daily clinical practice of nephrologists, prepared by experts from ESH and ERA. The sections summarized are those referring to the role of CKD in hypertension staging and cardiovascular risk stratification, the evaluation of hypertension-mediated kidney damage and the overall management of hypertension in patients with CKD

Meropenem vs standard of care for treatment of neonatal late onset sepsis (NeoMero1): A randomised controlled trial.

BACKGROUND: The early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide. We hypothesized that efficacy of meropenem as a broad-spectrum antibiotic is superior to standard of care regimens (SOC) in empiric treatment of LOS and aimed to compare meropenem to SOC in infants aged 44 weeks meeting the Goldstein criteria of sepsis, were randomized in a 1:1 ratio to receive meropenem or one of the two SOC regimens (ampicillin+gentamicin or cefotaxime+gentamicin) chosen by each site prior to the start of the study for 8-14 days. The primary outcome was treatment success (survival, no modification of allocated therapy, resolution/improvement of clinical and laboratory markers, no need of additional antibiotics and presumed/confirmed eradication of pathogens) at test-of-cure visit (TOC) in full analysis set. Stool samples were tested at baseline and Day 28 for meropenem-resistant Gram-negative organisms (CRGNO). The primary analysis was performed in all randomised patients and in patients with culture confirmed LOS. Proportions of participants with successful outcome were compared by using a logistic regression model adjusted for the stratification factors. From September 3, 2012 to November 30th 2014, total of 136 patients (instead of planned 275) in each arm were randomized; 140 (52%) were culture positive. Successful outcome at TOC was achieved in 44/136 (32%) in the meropenem arm vs. 31/135 (23%) in the SOC arm (p = 0.087). The respective numbers in patients with positive cultures were 17/63 (27%) vs. 10/77 (13%) (p = 0.022). The main reason of failure was modification of allocated therapy. Treatment emergent adverse events occurred in 72% and serious adverse events in 17% of patients, the Day 28 mortality was 6%. Cumulative acquisition of CRGNO by Day 28 occurred in 4% of patients in the meropenem and 12% in the SOC arm (p = 0.052). CONCLUSIONS: Within this study population, we found no evidence that meropenem was superior to SOC in terms of success at TOC, short term hearing disturbances, safety or mortality were similar in both treatment arms but the study was underpowered to detect the planned effect. Meropenem treatment did not select for colonization with CRGNOs. We suggest that meropenem as broad-spectrum antibiotic should be reserved for neonates who are more likely to have Gram-negative LOS, especially in NICUs where microorganisms producing extended spectrum- and AmpC type beta-lactamases are circulating

Pirfenidone in idiopathic pulmonary fibrosis:expert panel discussion on the management of drug-related adverse events

Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose.Correction in: Advances in Therapy, Volume 31, Issue 5, pp 575-576 , doi: 10.1007/s12325-014-0118-8</p

A Case of Pulmonary-Renal Syndrome Leading to the Diagnosis of Legionnaires’ Disease

We report a case of a 51-year-old Caucasian man referred at our department due to acute renal failure (ARF) complicating respiratory failure during hospitalization in a regional hospital. The patient was previously started on steroids due to the suspicion of rapidly progressive glomerulonephritis (RPGN) in the context of Goodpasture syndrome. However, clinical and laboratory findings did not support this diagnosis; instead a careful evaluation limited differential diagnosis of the renal insult to acute tubular necrosis or acute interstitial nephritis (AIN) following respiratory infection. With lung function fully improved but renal function not recovering, a renal biopsy revealed AIN, a finding leading to further diagnostic testing and finally to the diagnosis of Legionnaires’ disease as a cause of this patient’s pulmonary-renal syndrome. The management consisted of progressive tapering of oral steroids associated with full recovery of the patient’s renal function. This is a rare case of Legionnaires’ disease causing immune-mediated AIN and highlights the possibility of Legionella infection as a cause of pulmonary-renal syndrome

Rapid Millifluidic Synthesis of Stable High Magnetic Moment FexCy Nanoparticles for Hyperthermia

A millifluidic reactor with a 0.76 mm internal diameter was utilized for the synthesis of monodisperse, high magnetic moment, iron carbide (FexCy) nanoparticles by thermal decomposition of iron pentacarbonyl (Fe(CO)5) in 1-octadecene in the presence of oleylamine at 22 min nominal residence time. The effect of reaction conditions (temperature and pressure) on the size, morphology, crystal structure, and magnetic properties of the nanoparticles was investigated. The system developed facilitated the thermal decomposition of precursor at reaction conditions (up to 265 °C and 4 bar) that cannot be easily achieved in conventional batch reactors. The degree of carbidization was enhanced by operating at elevated temperature and pressure. The nanoparticles synthesized in the flow reactor had size 9–18 nm and demonstrated high saturation magnetization (up to 164 emu/gFe). They further showed good stability against oxidation after 2 months of exposure in air, retaining good saturation magnetization values with a change of no more than 10% of the initial value. The heating ability of the nanoparticles in an alternating magnetic field was comparable with other ferrites reported in the literature, having intrinsic loss power values up to 1.52 nHm2 kg–1