Utilidad de la ultrafiltración ambulatoria de corta duración por vía periférica en insuficiencia cardíaca refractaria a diuréticos. Experiencia inicial / Usefulness of short-term peripheral ambulatory ultrafiltration in heart failure refractory to diuretics. Initial experience

Introducción y objetivo En la insuficiencia cardíaca la congestión es el síntoma más frecuente y es habitual la resistencia diurética. El objetivo del estudio es analizar si la ultrafiltración (UF) ambulatoria de corta duración por vía periférica es útil y segura en estos pacientes. Material y métodos Se analizaron los 5 primeros pacientes ultrafiltrados por resistencia diurética en una unidad de gestión rápida de un hospital de referencia durante 12h. Resultados Estos pacientes estaban en tratamiento con al menos 3 diuréticos por vía oral; la UF permitió reducir y/o retirar algunos. El volumen extraído durante el procedimiento fue de 1520±271ml. Hubo cambios significativos en la diuresis (pre-UF: 1360±164; post-UF: 1670±254ml; p=0,035); peso (pre-UF: 69,6±14; post-UF: 66,2±15kg; p=0,0001) y creatinina (pre-UF: 2,1±0,3; post-UF: 1,8±0,4mg; p=0,023). Conclusiones En pacientes en régimen ambulatorio con insuficiencia cardíaca y resistencia a los diuréticos, la UF de corta duración por vía periférica resultó efectiva y segura (AU)

Introduction and objective In heart failure congestion is the most common symptom and diuretic resistance is frequent. This study aims to analyse whether short-term peripheral outpatient ultrafiltration (UF) is useful and safe in these patients. Material and methods The first 5 patients ultrafiltrated for diuretic resistance in a fast-track unit of a referral hospital for 12hours were analysed. Results These patients were on treatment with at least 3 oral diuretics; UF made it possible to reduce and/or withdraw some of them. The volume extracted during the procedure was 1520±271ml. There were significant changes in diuresis (PreUF: 1360±164, PostUF: 1670±254ml; P=.035), weight (PreUF: 69.6±14, PostUF: 66.2±15kg; P=.0001) and creatinine (PreUF: 2.1±0.3, PostUF: 1.8±0.4mg; P= 0.023). Conclusions In outpatients with heart failure and diuretic resistance, short-course peripheral UF was effective and safe (AU)

Hydrochlorothiazide and Prevention of Kidney-Stone Recurrence.

BACKGROUND: Nephrolithiasis is one of the most common conditions affecting the kidney and is characterized by a high risk of recurrence. Thiazide diuretic agents are widely used for prevention of the recurrence of kidney stones, but data regarding the efficacy of such agents as compared with placebo are limited. Furthermore, dose-response data are also limited. METHODS: In this double-blind trial, we randomly assigned patients with recurrent calcium-containing kidney stones to receive hydrochlorothiazide at a dose of 12.5 mg, 25 mg, or 50 mg once daily or placebo once daily. The main objective was to investigate the dose-response effect for the primary end point, a composite of symptomatic or radiologic recurrence of kidney stones. Radiologic recurrence was defined as the appearance of new stones on imaging or the enlargement of preexisting stones that had been observed on the baseline image. Safety was also assessed. RESULTS: In all, 416 patients underwent randomization and were followed for a median of 2.9 years. A primary end-point event occurred in 60 of 102 patients (59%) in the placebo group, in 62 of 105 patients (59%) in the 12.5-mg hydrochlorothiazide group (rate ratio vs. placebo, 1.33; 95% confidence interval [CI], 0.92 to 1.93), in 61 of 108 patients (56%) in the 25-mg group (rate ratio, 1.24; 95% CI, 0.86 to 1.79), and in 49 of 101 patients (49%) in the 50-mg group (rate ratio, 0.92; 95% CI, 0.63 to 1.36). There was no relation between the hydrochlorothiazide dose and the occurrence of a primary end-point event (P = 0.66). Hypokalemia, gout, new-onset diabetes mellitus, skin allergy, and a plasma creatinine level exceeding 150% of the baseline level were more common among patients who received hydrochlorothiazide than among those who received placebo. CONCLUSIONS: Among patients with recurrent kidney stones, the incidence of recurrence did not appear to differ substantially among patients receiving hydrochlorothiazide once daily at a dose of 12.5 mg, 25 mg, or 50 mg or placebo once daily. (Funded by the Swiss National Science Foundation and Inselspital; NOSTONE ClinicalTrials.gov number, NCT03057431.).

Tiazidas: lo que el dermatólogo debería saber / What Dermatologists Should Know About Thiazides

La hidroclorotiazida (HCTZ) y otros diuréticos tiazídicos son fármacos que se han empleado desde hace décadas para el tratamiento de la hipertensión arterial, la insuficiencia cardíaca o la enfermedad renal crónica. Las tiazidas se han asociado con reacciones de fotosensibilidad, siendo heterogéneas en cuanto a manifestación clínica y tiempo de recuperación, y en las cuales, el fototest, el fotoparche y la biopsia cutánea nos pueden ser útiles en el diagnóstico. En relación con estos fármacos, en los últimos años se ha evidenciado también un mayor riesgo dosis-dependiente de desarrollar determinados tipos de cáncer cutáneo en pacientes tratados de forma crónica con HCTZ. En esta revisión se comentan, asimismo, otros efectos adversos menos habituales o reconocidos de los diuréticos tiazídicos reportados de forma aislada en la literatura (AU)

Hydrochlorothiazide and other thiazide diuretics have been used for decades to treat high blood pressure, heart failure, and chronic kidney disease. Thiazides have been linked to photosensitivity with heterogeneous clinical manifestations and recovery times. Diagnosis can be aided by phototesting, photopatch testing, and skin biopsy. Long-term use of hydrochlorothiazide has been linked to an increased dose-dependent risk of certain types of skin cancer in recent years. In this review, we also look at other less common or lesser-known adverse effects of thiazide diuretics that have been described in isolated reports (AU)

[Translated article] What Dermatologists Should Know About Thiazides / Tiazidas: lo que el dermatólogo debería sabers

Hydrochlorothiazide and other thiazide diuretics have been used for decades to treat high blood pressure, heart failure, and chronic kidney disease. Thiazides have been linked to photosensitivity with heterogeneous clinical manifestations and recovery times. Diagnosis can be aided by phototesting, photopatch testing, and skin biopsy. Long-term use of hydrochlorothiazide has been linked to an increased dose-dependent risk of certain types of skin cancer in recent years. In this review, we also look at other less common or lesser-known adverse effects of thiazide diuretics that have been described in isolated reports (AU)

La hidroclorotiazida (HCTZ) y otros diuréticos tiazídicos son fármacos que se han empleado desde hace décadas para el tratamiento de la hipertensión arterial, la insuficiencia cardíaca o la enfermedad renal crónica. Las tiazidas se han asociado con reacciones de fotosensibilidad, siendo heterogéneas en cuanto a manifestación clínica y tiempo de recuperación, y en las cuales, el fototest, el fotoparche y la biopsia cutánea nos pueden ser útiles en el diagnóstico. En relación con estos fármacos, en los últimos años se ha evidenciado también un mayor riesgo dosis-dependiente de desarrollar determinados tipos de cáncer cutáneo en pacientes tratados de forma crónica con HCTZ. En esta revisión se comentan, asimismo, otros efectos adversos menos habituales o reconocidos de los diuréticos tiazídicos reportados de forma aislada en la literatura (AU)

Clinical implication of initial intravenous diuretic dose for acute decompensated heart failure.

Although intravenous diuretics is a cornerstone of acute heart failure treatment (AHF), its optimal initial dose is unclear. This is a post-hoc analysis of the REALITY-AHF, a prospective multicentre observational registry of AHF. The initial intravenous diuretic dose used in each patient was categorised into below, standard, or above the recommended dose groups according to guideline-recommended initial intravenous diuretic dose. The recommended dose was individualised based on the oral diuretic dose taken at admission. We compared the study endpoints, including 60-day mortality, diuretics response within six hours, and length of hospital stay (HS). Of 1093 patients, 429, 558, and 106 were assigned to the Below, Standard, and Above groups, respectively. The diuretics response and HS were significantly greater in the Below group than in the Standard group after adjusting for covariates. Kaplan-Meier analysis indicated a significantly higher incidence of 60-day mortality in the Above group than the Standard group. This difference was retained after adjusting for other prognostic factors. Treatment with a lower than guideline-recommended intravenous diuretic dose was associated with longer HS, whereas above the guideline-recommended dose was associated with a higher 60-day mortality rate. Our results reconfirm that the guideline-recommended initial intravenous diuretic dose is feasible for AHF.

Time until onset of acute kidney injury by combination therapy with "Triple Whammy" drugs obtained from Japanese Adverse Drug Event Report database.

Acute kidney injury (AKI) associated with "Triple Whammy" drug therapy consisting of renin-angiotensin system inhibitors, diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs) has been reported. There have been no reports investigating "Triple Whammy" drug therapy and the time to AKI onset using adverse drug events report databases. The aim of this study was to determine the relationship between the time to AKI onset and treatment with "Triple Whammy" drug therapy. We analyzed AKI cases registered in the Japanese Adverse Drug Event Report database. The data were analyzed using the Kaplan-Meier approach, generalized Wilcoxon tests, and Weibull distribution. AKI was reported in 18,415 cases, of which 7,466 cases used Triple Whammy drugs. All combinations of Triple Whammy drugs were associated with significantly higher odds ratios for reporting AKI. In Weibull analysis, AKI onset was early for most combination patterns of Triple Whammy drugs. The Kaplan-Meier approach showed that the treatment duration to AKI onset was much shorter in cases using NSAIDs; median onsets, 8 days for triple combination, 7 days for NSAIDs added to renin-angiotensin system inhibitors, 9 days for NSAIDs added to diuretics, 6 days for diuretics added to NSAIDs, and 9 days for NSAIDs alone. AKI associated with Triple Whammy drugs is likely to occur in the early stages of treatment, especially with concomitant NSAIDs. Patients should be monitored for the occurrence of AKI within the first 2 weeks.

The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial.

AIM: The main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF). METHODS: In a pilot double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion. RESULTS: From July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p = 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53). CONCLUSION: In patients with CRS1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results in renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 on 19/05/2020 retrospectively registered.

Angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers: New-onset diabetes mellitus stratified by statin use.

WHAT IS KNOWN AND OBJECTIVES: Regardless of statin use, which is known to induce hyperglycaemia, comparative studies on the risk of new-onset diabetes mellitus (NODM) with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are needed. This study evaluated the effects of ACEIs and ARBs on NODM in the clinical setting. METHODS: This retrospective cohort study utilized electronic medical record data from Seoul St. Mary's Hospital and Seoul National University Hospital from 2009 to 2012. Patients who were prescribed ACEIs or ARBs for the first time (irrespective of concomitant statin use) were followed up for 5 years. RESULTS AND DISCUSSIONS: A total of 11,703 patients were included, 24.9% (n = 2916) were taking ACEIs and 75.1% (n = 9189) were taking ARBs. Patients on ACEIs had a significantly lower incidence of NODM both with statin use (HR = 0.13, p < 0.001) and without (HR = 0.15, p = 0.009) than patients on ARBs. Age ≥60 years (HR = 1.49, p = 0.010), BMI ≥25 (HR = 1.96, p < 0.010), use of calcium channel blockers (HR = 1.47, p = 0.010), and diuretics (HR = 1.48, p = 0.010) were risk factors for NODM with statin use. WHAT IS NEW AND CONCLUSION: Patients taking ACEIs are less likely to develop NODM than patients taking ARBs, irrespective of statin use. Patients' conditions, including the risk of NODM, should be considered before prescribing ACEIs or ARBs. Future randomized clinical trials are needed to clarify further the relationship between ACEIs and ARBs and their effect on NODM.

Diuretic effect of co-administration of furosemide and albumin in comparison to furosemide therapy alone: An updated systematic review and meta-analysis.

BACKGROUND: It has been a matter of much debate whether the co-administration of furosemide and albumin can achieve better diuresis and natriuresis than furosemide treatment alone. There is inconsistency in published trials regarding the effect of this combination therapy. We, therefore, conducted this meta-analysis to explore the efficacy of furosemide and albumin co-administration and the factors potentially influencing the diuretic effect of such co-administration. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, Medline, and Cochrane databases. Prospective studies with adult populations which comparing the effect of furosemide and albumin co-administration with furosemide alone were included. The outcomes including diuretic effect and natriuresis effect measured by hourly urine output and hourly urine sodium excretion from both groups were extracted. Random effect model was applied for conducting meta-analysis. Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity of treatment effects. RESULTS: By including 13 studies with 422 participants, the meta-analysis revealed that furosemide with albumin co-administration increased urine output by 31.45 ml/hour and increased urine excretion by 1.76 mEq/hour in comparison to furosemide treatment alone. The diuretic effect of albumin and furosemide co-administration was better in participants with low baseline serum albumin levels (< 2.5 g/dL) and high prescribed albumin infusion doses (> 30 g), and the effect was more significant within 12 hours after administration. Diuretic effect of co-administration was better in those with baseline Cr > 1.2 mg/dL and natriuresis effect of co-administration was better in those with baseline eGFR < 60 ml/min/1.73m2. CONCLUSION: Co-administration of furosemide with albumin might enhance diuresis and natriuresis effects than furosemide treatment alone but with high heterogeneity in treatment response. According to the present meta-analysis, combination therapy might provide advantages compared to the furosemide therapy alone in patients with baseline albumin levels lower than 2.5 g/dL or in patients receiving higher albumin infusion doses or in patients with impaired renal function. Owing to high heterogeneity and limited enrolled participants, further parallel randomized controlled trials are warranted to examine our outcome. REGISTRATION: PROSEPRO ID: CRD42020211002; https://clinicaltrials.gov/.

Chlorthalidone for Hypertension in Advanced Chronic Kidney Disease.

BACKGROUND: Little evidence has been available to support the use of thiazide diuretics to treat hypertension in patients with advanced chronic kidney disease. METHODS: We randomly assigned patients with stage 4 chronic kidney disease and poorly controlled hypertension, as confirmed by 24-hour ambulatory blood-pressure monitoring, in a 1:1 ratio to receive chlorthalidone at an initial dose of 12.5 mg per day, with increases every 4 weeks if needed to a maximum dose of 50 mg per day, or placebo; randomization was stratified according to previous use of loop diuretics. The primary outcome was the change in 24-hour ambulatory systolic blood pressure from baseline to 12 weeks. Secondary outcomes were the change from baseline to 12 weeks in the urinary albumin-to-creatinine ratio, N-terminal pro-B-type natriuretic peptide level, plasma renin and aldosterone levels, and total body volume. Safety was also assessed. RESULTS: A total of 160 patients underwent randomization, of whom 121 (76%) had diabetes mellitus and 96 (60%) were receiving loop diuretics. At baseline, the mean (±SD) estimated glomerular filtration rate was 23.2±4.2 ml per minute per 1.73 m2 of body-surface area and the mean number of antihypertensive medications prescribed was 3.4±1.4. At randomization, the mean 24-hour ambulatory systolic blood pressure was 142.6±8.1 mm Hg in the chlorthalidone group and 140.1±8.1 mm Hg in the placebo group and the mean 24-hour ambulatory diastolic blood pressure was 74.6±10.1 mm Hg and 72.8±9.3 mm Hg, respectively. The adjusted change in 24-hour systolic blood pressure from baseline to 12 weeks was -11.0 mm Hg (95% confidence interval [CI], -13.9 to -8.1) in the chlorthalidone group and -0.5 mm Hg (95% CI, -3.5 to 2.5) in the placebo group. The between-group difference was -10.5 mm Hg (95% CI, -14.6 to -6.4) (P<0.001). The percent change in the urinary albumin-to-creatinine ratio from baseline to 12 weeks was lower in the chlorthalidone group than in the placebo group by 50 percentage points (95% CI, 37 to 60). Hypokalemia, reversible increases in serum creatinine level, hyperglycemia, dizziness, and hyperuricemia occurred more frequently in the chlorthalidone group than in the placebo group. CONCLUSIONS: Among patients with advanced chronic kidney disease and poorly controlled hypertension, chlorthalidone therapy improved blood-pressure control at 12 weeks as compared with placebo. (Funded by the National Heart, Lung, and Blood Institute and the Indiana Institute of Medical Research; CLICK ClinicalTrials.gov number, NCT02841280.).

Cardiogenic shock complicating multisystem inflammatory syndrome following COVID-19 infection: a case report.

BACKGROUND: With the high prevalence of COVID-19 infections worldwide, the multisystem inflammatory syndrome in adults (MIS-A) is becoming an increasingly recognized entity. This syndrome presents in patients several weeks after infection with COVID-19 and is associated with thrombosis, elevated inflammatory markers, hemodynamic compromise and cardiac dysfunction. Treatment is often with steroids and intravenous immunoglobulin (IVIg). The pathologic basis of myocardial injury in MIS-A, however, is not well characterized. In our case report, we obtained endomyocardial biopsy that revealed a pattern of myocardial injury similar to that found in COVID-19 cardiac specimens. CASE PRESENTATION: A 26-year-old male presented with fevers, chills, headache, nausea, vomiting, and diarrhea 5 weeks after his COVID-19 infection. His SARS-CoV-2 PCR was negative and IgG was positive, consistent with prior infection. He was found to be in cardiogenic shock with biventricular failure, requiring inotropes and diuretics. Given concern for acute fulminant myocarditis, an endomyocardial biopsy (EMB) was performed, showing an inflammatory infiltrate consisting predominantly of interstitial macrophages with scant T lymphocytes. The histologic pattern was similar to that of cardiac specimens from COVID-19 patients, helping rule out myocarditis as the prevailing diagnosis. His case was complicated by persistent hypoxemia, and a computed tomography scan revealed pulmonary emboli. He received IVIg, steroids, and anticoagulation with rapid recovery of biventricular function. CONCLUSIONS: MIS-A should be considered as the diagnosis in patients presenting several weeks after COVID-19 infection with severe inflammation and multi-organ involvement. In our case, EMB facilitated identification of MIS-A and guided therapy. The patient's biventricular function recovered with IVIg and steroids.

Administration of Subcutaneous Furosemide in Elastomeric Pump vs. Oral Solution for the Treatment of Diuretic Refractory Congestion.

INTRODUCTION: The most common symptom in heart failure (HF) is congestion, which can be refractory to diuretic treatment. AIM: To verify whether, in patients with advanced HF and diuretic resistance, subcutaneous furosemide or furosemide in an oral solution can improve the clinical-analytical status. METHODS: From 2018 to 2020, 27 consecutive outpatients with diuretic resistance, not candidates for other alternatives, were recruited. Patients were treated either with subcutaneous furosemide in elastomeric pump (n: 10) or with oral solution (n: 17) for 5 days. RESULTS: The functional status (NYHA) improved with subcutaneous administration (predose: 3.8 ± 0.5 vs. postdose: 3.1 ± 0.7; p: 0.02) and oral solution (predose: 3.7 ± 0.3 vs. postdose: 2.5 ± 0.7; p: 0.0001). Weight loss was greater with the oral solution (predose: 85.5 ± 19.5 vs. postdose: 81.3 ± 18.8Kg; p: 0.0001) than subcutaneous (predose: 81.6 ± 15.9 vs. postdose: 80.4 ± 15.1kg; p: 0.16). Creatinine showed a non-significant increase in both groups. The number of hospital visits showed no difference between both options. CONCLUSIONS: The administration of furosemide, both subcutaneously by elastomeric pump or drinking the oral solution, is effective for the treatment of congestion in advanced HF refractory to diuretic treatment.

Comparison of continuous infusion and intermittent boluses of furosemide in acute heart failure: A protocol for systematic review and meta-analysis.

BACKGROUND: Acute heart failure (HF) is a common cause of hospital admission. This study aims to compare continuous infusion and intermittent boluses of furosemide in treating acute HF. METHODS: This protocol of systematic review and meta-analysis has been drafted under the guidance of the preferred reporting items for systematic reviews and meta-analyses protocols. Electronic databases including Web of Science, Embase, PubMed, Wanfang, Data, Scopus, Science Direct, and Cochrane Library will be searched in June 2021 by 2 independent reviewers. The main outcomes are post-treatment daily urine output, weight, length of stay, serum sodium, potassium, and creatinine. Two researchers conducted a quality assessment in strict accordance with the risk bias assessment tool recommended by the Cochrane Handbook Version5.3. We performed the meta-analysis by Stata version 10.0 software. RESULTS: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. CONCLUSION: The choice of furosemide regime in acute HF remains physician preference. Both bolus and continuous infusion yields satisfactory outcomes.

Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs.

BACKGROUND: Furosemide, a diuretic that acts on the loop of Henle, is commonly used to treat congestive heart failure in veterinary medicine. Some owners have difficulty in administering oral tablet medication to animal patients, which leads to noncompliance, especially during long-term administration. Oral disintegrating film (ODF) has the advantages of easy administration via a non-invasive route, rapid dissolution, and low suffocating risk. The objective of this study was to research the pharmacokinetic (PK) profiles and diuretic effect of furosemide after intravenous (IV), orally uncoated tablet (OUT), and newly developed ODF administration in healthy beagle dogs. In this study, a furosemide-loaded ODF (FS-ODF) formulation was developed and five beagle dogs were administered a single dose (2 mg/kg) of furosemide via each route using a cross-over design. RESULTS: The most suitable film-forming agent was sodium alginate; thus, this was used to develop an ODF for easy drug administration. No significant differences were detected in the PK profiles between OUT and FS-ODF. In the blood profiles, the concentration of total protein was significantly increased compared to the baseline (0 h), whereas no significant difference was detected in the concentration of creatinine and hematocrit compared to the baseline. FS-ODF resulted in a similar hourly urinary output to OUT during the initial 2 h after administration. The urine specific gravity was significantly decreased compared to the baseline in each group. The peak times of urine electrolyte (sodium and chloride) excretion per hour were 1 h (IV), 2 h (OUT), and 2 h (FS-ODF). CONCLUSIONS: These results suggest that the PK/PD of furosemide after administration of newly developed FS-ODF are similar to those of OUT in healthy dogs. Therefore, the ODF formulation has the benefits of ease and convenience, which would be helpful to owners of companion animals, such as small dogs (< 10 kg), for the management of congestive heart failure.

The Risk of Cutaneous Squamous Cell Carcinoma Among Patients with Type 2 Diabetes Receiving Hydrochlorothiazide: A Cohort Study.

BACKGROUND: Because of continuous hyperglycemia and hyperinsulinemia and the use of photosensitizing drug, hydrochlorothiazide (HCTZ), the risk of cutaneous squamous cell carcinoma (cSCC) might be increased among patients with diabetes. This study aimed to estimate the risk of cSCC among HCTZ users with type 2 diabetes, and to determine whether thiazide-like diuretics, another drug in the same class with HCTZ, would be safer. METHODS: We linked the benchmarking database in Dutch primary care, the Netherlands Cancer Registry, and the Dutch Personal Records Database (1998-2019). All 71,648 patients were included, except for those who had a history of skin cancer prior to cohort entry. We used Cox modeling to estimate the HRs and 95% confidence intervals for cSCC. The model was adjusted by cumulative exposure to each antihypertensive, age, sex, smoking, body mass index, blood pressure, serum creatinine, other confounding drug use at cohort entry, and cohort entry year. RESULTS: There were 1,409 cSCC events (23 among thiazide-like diuretics users), during a follow-up of 679,789 person-years. Compared with no HCTZ use, the adjusted HRs for HCTZ use were 1.18 (1.00-1.40) for ≤2 years, 1.57 (1.32-1.88) for 2 to 4 years, and 2.09 (1.73-2.52) for >4 years. The HR was 0.90 (0.79-1.03) for an additional year of thiazide-like diuretic use. CONCLUSIONS: In patients with diabetes, exposure to HCTZ for >2 years is associated with an increased risk of cSCC, whereas no increased risk associated with thiazide-like diuretics was observed. IMPACT: The potential increased risk of cSCC should be a consideration when prescribing HCTZ, with thiazide-like diuretics offering a safer alternative.

Association Between Adaptive Servo-Ventilation Therapy and Renal Function.

Cardio-renal syndrome is a challenging clinical entity to manage, and is often associated with increased morbidity and mortality. We hypothesized that adaptive servo-ventilation (ASV), non-invasive positive pressure ventilation that ameliorates systemic/pulmonary congestion, may improve renal function in patients with symptomatic heart failure complicated by the cardio-renal syndrome. Patients with symptomatic congestive heart failure who underwent ASV therapy for over 1 month were included in this retrospective study. The trajectory of the estimated glomerular filtration ratio (eGFR) between the pre-1 month period and the post-one-month period (on ASV) were compared. A total of 81 patients (median 65 years old, 65 men) were included. eGFR decreased during the pre-1 month period from 52.7 (41.7, 64.6) down to 49.9 (37.3, 63.5) mL/minute/1.73 m2 (P < 0.001) whereas we observed an increase following one-month of ASV therapy up to 53.4 (38.6, 68.6) mL/minute/1.73 m2 (P = 0.022). A reduction in furosemide equivalent dose following the initiation of ASV therapy was independently associated with increases in eGFR with an adjusted odds ratio of 13.72 (95% confidence interval 3.40-55.3, P < 0.001). In conclusion, short-term ASV therapy was associated with the preservation of renal function, particularly when the dose of loop diuretics was concomitantly reduced.

Involvement of the effect of renal hypoperfusion medications on vancomycin trough concentration: A secondary analysis using a retrospective observational data.

This study examined the association between vancomycin (VCM) trough concentration and confounding factors including renal hypoperfusion medications which include angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, loop/thiazide diuretics, or non-steroidal anti-inflammatory drugs. This secondary analysis included patients aged >15 years who were administered VCM intravenously between June 2015 and August 2017 at the Tokyo Women's Medical University Medical Center East. We investigated predictors for three (initial, mean, and final) dose-normalized VCM trough concentration (dose-normalized VCMtrough ) as outcome using a multiple linear regression analysis. In total, 208 patients were analysed (use of loop/thiazide diuretics: 48 [23%]). Multiple linear regression analysis revealed that the initial dose-normalized VCMtrough was negatively correlated with estimated glomerular filtration rate (eGFR) (p = 0.028) and positively correlated with the use of loop/thiazide diuretics (p = 0.003). Meanwhile, there was a positive correlation between the mean dose-normalized VCMtrough and age (p = 0.023). The mean dose-normalized VCMtrough was negatively correlated with eGFR (p < 0.001) and serum albumin (p < 0.001). The final dose-normalized VCMtrough was positively associated with age (p = 0.034) and negatively associated with eGFR (p = 0.032) and serum albumin (p = 0.007). Clinicians should closely monitor VCM trough concentration while receiving VCM and loop/thiazide diuretics.

Angiotensin receptor neprilysin inhibitor for patients with heart failure and reduced ejection fraction: Real-world experience from Turkey (ARNi-TR).

OBJECTIVE: Heart failure (HF) is a growing public health problem with high morbidity and mortality. Recently, angiotensin receptor neprilysin inhibitor (ARNi) has emerged as a promising treatment for HF with reduced ejection fraction (HFrEF). Here, we shared our experience with the use of ARNi in HFrEF from multiple centers in Turkey. METHODS: The ARNi-TR is a multicenter, noninterventional, retrospective, observational study. Overall, 779 patients with HF from 22 centers in Turkey who were prescribed sacubitril/valsartan were examined. Initial clinical status, biochemical and echocardiographic parameters, and New York Heart Association functional class (NYHA-FC) values were compared with follow-up values after 1 year of ARNi use. In addition, the effect of ARNi on number of annual hospitalizations was investigated, and the patients were divided into 2 groups, depending on whether ARNi was initiated at hospitalization or under outpatient clinic control. RESULTS: N-terminal pro-brain natriuretic peptide (NT-proBNP), left-ventricle ejection fraction (LV-EF), and NYHA-FC values improved significantly in both groups (all parameters, p<0.001) within 1-year follow-up. In both groups, a decrease in hemoglobin A1c (HbA1c) values was observed in ARNi use (p<0.001), and a decrease in daily diuretic doses and hospitalizations owing to HF were observed after ARNi use (all comparisons, p<0.001). Hypotension (16.9%) was the most common side effect in patients using ARN. CONCLUSION: The ARNi-TR study offers comprehensive real-life data for patients using ARNi in Turkey. The use of ARNi has shown significant improvements in FC, NT-proBNP, HbA1c levels, and LV-EF. Likewise, reductions in the number of annual hospitalizations and daily furosemide doses for HF were seen in this study.