Recommendations for the management of hyperkalemia in patients receiving renin-angiotensin-aldosterone system inhibitors.

Hyperkalemia is common in clinical practice and can be caused by medications used to treat cardiovascular diseases, particularly renin-angiotensin-aldosterone system inhibitors (RAASis). This narrative review discusses the epidemiology, etiology, and consequences of hyperkalemia, and recommends strategies for the prevention and management of hyperkalemia, mainly focusing on guideline recommendations, while recognizing the gaps or differences between the guidelines. Available evidence emphasizes the importance of healthcare professionals (HCPs) taking a proactive approach to hyperkalemia management by prioritizing patient identification and acknowledging that hyperkalemia is often a long-term condition requiring ongoing treatment. Given the risk of hyperkalemia during RAASi treatment, it is advisable to monitor serum potassium levels prior to initiating these treatments, and then regularly throughout treatment. If RAASi therapy is indicated in patients with cardiorenal disease, HCPs should first treat chronic hyperkalemia before reducing the dose or discontinuing RAASis, as reduction or interruption of RAASi treatment can increase the risk of adverse cardiovascular and renal outcomes or death. Moreover, management of hyperkalemia should involve the use of newer potassium binders, such as sodium zirconium cyclosilicate or patiromer, as these agents can effectively enable optimal RAASi treatment. Finally, patients should receive education regarding hyperkalemia, the risks of discontinuing their current treatments, and need to avoid excessive dietary potassium intake.

Sex differences in excessive oral corticosteroid exposure in poor adherent adult asthmatics overusing short-acting ß-2 agonists.

BACKGROUND: We know that excessive short-acting ß2-agonists (SABA) use in asthma may be associated to high exacerbation risks. We studied whether such excessive SABA consumption is connected with different higher oral corticosteroid (OC) prescriptions in the two sexes. METHODS: In our prescribing database, we searched subjects aged 18-40 years that were prescribed at least one SABA package/year and/or at least two ICS or two ICS/LABA boxes/year to identify asthmatics. Their OC prescriptions/year were also examined. Subjects were divided into 4 groups according to SABA packages/year prescribed (0, 1-2,3-6 and ≥7), considering sexes separately. RESULTS: Individuals recruited were 9,102. Subjects with at least one OC prescription were higher in each group and were females (P<0.001). The OC packages/year number was also more elevated in women especially those with >7 SABA prescriptions/year (0.96 in males vs. 2.64 in females, P<0.001). 94.7%/93.6% males/females, who never used SABA, took at least one ICS/LABA (mean 5.84/5.48 packages/year), while the subject percentage adhering to ICS/LABA dropped to 28-47% (mean 0.94-3.82 packages/year) in those who used SABA (P<0.001). Higher SABA prescriptions were associated with an increasing OC dispensation (ß=0.057, P<0.0001). We observed also a greater risk of using >3 OC packages/year in subjects with 3-6 (OR: 2.98 [95% CI: 2.19-4.06], P<0.001) and ≥7 (OR: 3.49 [95% CI: 2.39-5.10], P<0.001) SABA prescriptions compared to those that never used SABA. Besides, we found that using ICS (OR:0.51 [95% CI: 0.35-0.75], P<0.001) or ICS/LABA (OR:0.07 [95% CI: 0.05-0.09], P<0.001) may significantly reduce SABA prescriptions. CONCLUSIONS: Poor adherence to maintenance treatment appears to associated with excessive SABA prescriptions that may lead to a higher OC consumption particularly noticeable in women.

Hospitalization and mortality for acute exacerbation of asthma: an Italian population-based study.

Asthma is an ever-increasing disease with a highly variable prevalence among different ethnic groups. Information on hospital admission for acute exacerbation of asthma in adult patients and data regarding short-term prognosis of these patients are limited. We, thus, performed an epidemiological study on hospital admission for asthma acute exacerbation in Italy using hospital discharge database records derived from all Italian hospitals. Patients > 15 years old were identified using clinical Modification (ICD-9-CM) codes. Information on baseline characteristics, vital status at discharge, duration of hospitalization, and up to five secondary discharge diagnoses was collected. Comorbidity was evaluated using the Charlson comorbidity index (CCI). During the observation period (2013-2014), 20,056 patients with asthma acute exacerbation were hospitalized. Median length of hospitalization was 7.9 days (interquartile range 4-10) and mean in-hospital mortality was 0.8%. In-hospital mortality and length of hospitalization varied among different regions (from 0 to 2.9% and from 6.5 to 8.9 days, respectively). Old age, invasive and non-invasive mechanical ventilation, and CCI resulted as significantly associated with higher in-hospital mortality. Our study results, on a large sample of patients, confirm that hospitalization for asthma acute exacerbation is not uncommon among Italian current population. Older age, high CCI, and use of ventilator support were associated with a higher mortality rate. These findings should be analyzed to set up appropriate health care policies on patients with asthma.

Should a prescription database be used to search uncontrolled severe asthmatics?

INTRODUCTION: Many uncontrolled severe asthmatics are not on biologic therapy. We hypothesized that using a prescription database could help us identify them. MATERIAL AND METHODS: 3,309 patients who received at least one Montelukast prescription in 2019 were extracted from our prescription database. Number of packages/year, types and dosages of ICS, LABA, ICS/LABA, LAMA and monoclonal antibodies were considered for each patient. In our analysis, for subjects that took > 7 packages of ICS/LABA + LTRA +/- LAMA (high adherent) the number of oral corticosteroids (OC) packets prescribed for each of them was also looked upon. RESULTS: Patients that took ICS/LABA or ICS/LABA + LAMA continuously with high ICS doses were 188 (25.6%) and 117 (39.3%) respectively (total: 305 - 29.5%). Among them, 58 (30.9%) and 53 (45.3%) (total: 111 - 36.4%) were prescribed more than 2 OC packages. Whereas, 21 (11.2%) and 24 (20.5%) patients (total: 45 - 14.75%) received at least 4 OC package prescriptions. CONCLUSION: Approximately 36% of patients in continuous step-4/5 of GINA guidelines treatment may have severe uncontrolled asthma (overusing OC) which needed biologic treatment. In our opinion, a prescription archiving database may be a tool that can help us identify such uncontrolled asthma patients.

Optimization of RAASi Therapy with New Potassium Binders for Patients with Heart Failure and Hyperkalemia: Rapid Review and Meta-Analysis.

(1) Background: The objective of this rapid review is to assess whether new potassium binders (NPBs) could enable the optimization of RAASi therapy more than usual care or placebo in patients with or at risk of heart failure and hyperkalemia. (2) Methods: We searched for RCTs that included patients with or at risk of hyperkalemia and patients treated with Patiromer or sodium zirconium cyclosilicate (ZSC). The comparators were placebo, usual care, and potassium binders with different doses or different treatment protocols. We searched the Cochrane CENTRAL, MEDLINE, and ClinicalTrials.gov databases. The risk of bias was assessed using the Cochrane risk of bias tool for RCTs. Data were pooled using the random effects model, and the fixed effects model was used for sensitivity analysis. (3) Results: We included 12 studies with 2800 enrolled patients. Only three of these trials (412 patients) were included in the meta-analysis. NPBs seemed to have an effect on the optimization of MRA therapy, with an RR (95% CI) of 1.24 (1.09, 1.42) (moderate certainty evidence); Patiromer seemed to have an effect on MRA optimization, with an RR (95% CI) or 1.25 (1.08, 1.45) (high certainty evidence). ZSC seemed to have no effect on enabling MRA therapy, with an RR (95% CI) of 1.19 (0.89, 1.59) (low certainty evidence). The AEs in HF patients with hyperkalemia treated with Patiromer were GI disorders and hypomagnesemia. ZSC The AEs included chronic cardiac failure, hypokalemia, and edema. (4) Conclusions: This meta-analysis included three studies with a small number of patients and a short follow-up period (1-3 months). The evidence of the effect of NPBs on MRA optimization had a moderate certainty for imprecision. Data on the effect on MRA optimization and less severe AEs in long-term treatment seem to suggest the use of Patiromer for the optimization of MRA therapy in patients with or at risk of heart failure and hyperkalemia. Future adequately powered RCTs are needed to assess the benefits and potential harms of potassium binders.

Which LABA/LAMA should be chosen in COPD patients in real life?

BACKGROUND: Given COPD heterogeneity, we do not know if some LABA/LAMAs are more suitable for some COPD phenotypes. This real-life database study aimed to evaluate retrospectively the 4 LABA/LAMA effectiveness and highlight possible specificities that could better guide us in choosing the right LABA/LAMA to be used. METHODS: We searched for subjects (1,779) adherent to umeclidinium/vilanterol (UM/VI), indacaterol/glycopyrronium (IND/GLY), aclidinium/formoterol (ACLI/FOR) and tiotropium/olodaterol (TIO/OLO) treatments in our prescribing/dispensing database. Prescriptions for systemic corticosteroids (SC), antibiotics and salbutamol during one year of LABA/LAMA treatment were analyzed. RESULTS: A better adherence was found in individuals taking IND/GLY (10.42 ± 1.86 packages/year) compared with UM/VI (10.09 ± 1.9; p = 0.008), ACLI/FOR (9.8 ± 1.8; p = 0.001) and TIO/OLO (10.1 ± 2.1; p = 0.047). The number of patients that were prescribed at least one package of SC/year and their package numbers/year were similar in males/females, across age groups and in "non-frequent exacerbators" with the 4 LABA/LAMAs. More SC were taken by frequent exacerbators, whereas fewer SC/antibiotic packages were prescribed to subjects aged >80 years with all treatments. In patients treated with ACLI/FOR or TIO/OLO, lower risks to having antibiotic prescriptions were observed when UM/VI (0.698[0.516-0.945] and 0.696[0.491-0.985; p = 0.020 and p = 0.041) and IND/GLY (0.597[0.445-0.802] and 0.595[0.423-0.836]; p = 0.001 and p = 0.003) were considered as landmarks. Lower risks for salbutamol prescriptions were detected with UM/VI (0.678[0.480-0.958]; p = 0.027) and TIO/OLO (0.585[0.365-0.937]; p = 0.026) when ACLI/FOR was used as a reference. CONCLUSION: According to our retrospective database study, each LABA/LAMA could have a specific efficacy profile in COPD that might be considered for personalized therapy. However, head-to-head targeted trials aimed to assess the impact of different LABA/LAMAs on COPD are needed to confirm/disprove such results.

FDG-PET/CT Assessment of Pulmonary Sarcoidosis: A Guide for Internists.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography integrated with computed tomography (18-F-FDG-PET/CT) is getting wide consensus in the diagnosis and staging of neoplastic disorders and represents a useful tool in the assessment of various inflammatory conditions. DISCUSSION: Sarcoidosis is an uncommon disease characterized by the systemic formation of noncaseating granulomas. Lungs are the sites most often affected, and investigation with high resolution computed tomography and biopsy is essential to achieve a correct diagnosis. 18-F-FDGPET/ CT is effective in the assessment of pulmonary sarcoidosis by demonstrating pulmonary and extrathoracic involvement and findings correlate well with pulmonary function in patients affected. CONCLUSION: This review would illustrate the usefulness and limits of 18-F-FDG-PET/CT in the assessment of pulmonary sarcoidosis.

Bisphosphonates, atherosclerosis and vascular calcification: update and systematic review of clinical studies.

BACKGROUND: Epidemiologic and clinical data have suggested the existence of a biologic linkage between the bone system and the vascular system. Bisphosphonates (BPs) are effective inhibitors of bone resorption and are currently considered the drugs of choice for the prevention and treatment of osteoporosis and related fractures. Data from several publications have suggested that BPs may also be effective in reducing the atherosclerotic process and vascular calcification, but the results of these studies are contrasting. This review aimed to allow a better understanding of the relationships between BPs and atherosclerosis in humans. MATERIALS AND METHODS: Electronic databases of Pubmed-Medline, Cochrane Library and SCOPUS from inception to June 30, 2016 were searched. The full texts of the articles potentially eligible were carefully assessed and reviewed. Finally, 20 studies were found to be eligible and were included in the systematic review. All included studies were published between 2000 and 2014. RESULTS: In several studies, etidronate limited the progression of aortic and coronary calcification in hemodialysis patients, whereas the nitrogen-containing-BPs given orally did not significantly reduce vascular calcifications in patients with chronic kidney disease, kidney trasplant or in those with osteoporosis. Nitrogen-containing-BPs present favorable effects both on vessel wall thickness and on arterial elasticity due to both a reduction in serum lipids and the interaction of BPs with the bone tissue, with the consequent release of bone turnover markers and cytokines into the bloodstream. CONCLUSION: To sum up, the BPs seem to have the potential of influencing atherosclerosis and calcium homeostasis at the level of vascular walls with several possible mechanisms which may differ according to the type, potency, dosage and administration route of BPs. Additional studies are needed to specifically address the mechanism by which BP use could influence cardiovascular morbidity and mortality.

Spontaneous dissection of the celiac artery in the young: a case report and systematic review of the literature.

INTRODUCTION: The spontaneous isolated celiac artery dissection (siCAD) represents a challenging cause of abdominal pain and complete information regarding incidence, etiology and risk factors in the young is still lacking. In this study, we report a case of siCAD occurred in a young woman and we systematically searched for information on siCADs in literature databases. METHODS: PubMed/Embase and Cochrane were searched for, using the following terms: Isolated celiac trunk dissection, isolated celiac artery dissection, celiac artery dissection, celiac trunk dissection, spontaneous isolated visceral artery dissection, spontaneous isolated dissection of visceral arteries, isolated celiac artery dissection in the young, isolated celiac trunk dissection in the young. Patients were included if they were younger than 50 years, if they had a spontaneous etiology and a selective involvement of the celiac artery (with or without involvement of its branches). RESULTS: 180 studies were found, and 18 remained after screening. Twenty-one patients (male = 19, female = 2) with siCADs were included. Mean age was 44.71 ± 3.61 years. Hypertension was the most prevalent comorbidity. All patients presented with abdominal pain, more often located in the epigastrium (n = 11). Almost all patients underwent CT to confirm the diagnosis. A conservative treatment was adopted in 13 patients while an invasive approach was adopted in 8 patients (endovascular approach in 7). DISCUSSION: siCADs represent a rare but important cause of vascular dissection in the young. Uncomplicated cases can be safely treated with conservative strategies. The surgical or endovascular repair is indicated when dissections complicate or symptoms persist despite an adequate conservative treatment.

Bone anabolics in osteoporosis: Actuality and perspectives.

Vertebral and nonvertebral fractures prevention is the main goal for osteoporosis therapy by inhibiting bone resorption and/or stimulating bone formation. Antiresorptive drugs decrease the activation frequency, thereby determining a secondary decrease in bone formation rate and a low bone turnover. Bisphosphonates are today's mainstay among antiresorptive treatment of osteoporosis. Also, oral selective estrogen receptor modulators and recently denosumab have a negative effect on bone turnover. Agents active on bone formation are considered a better perspective in the treatment of severe osteoporosis. Recombinant-human parathyroid hormone (PTH) has showed to increase bone formation and significantly decrease vertebral fractures in severe patients, but with a modest effect on nonvertebral fractures. The study of Wnt signaling pathway, that induces prevalently an osteoblastic activity, opens large possibilities to antagonists of Wnt-inhibitors, such as sclerostin antibodies and dickkopf-1 antagonists, with potential effects not only on trabecular bone but also on cortical bone.

Osteoporosis and risk of fracture in patients with diabetes: an update.

Diabetes mellitus (DM) and osteoporotic fractures are two of the most important causes of mortality and morbidity in older subjects. Recent data report a close association between fragility fracture risk and DM of both type 1 (DM1) and type 2 (DM2). However, DM1 is associated with reduced bone mineral density (BMD), whereas patients with DM2 generally have normal or increased BMD. This apparent paradox may be explained by the fact that, at a given level of BMD, diabetic patients present lower bone quality with respect to non-diabetics, as shown by several studies reporting that diabetes may affect bone tissue by means of various mechanisms, including hyperinsulinemia, deposition of advanced glycosylation endproducts (AGEs) in collagen, reduced serum levels of IGF-1, hypercalciuria, renal failure, microangiopathy and inflammation. In addition, the propensity to fall and several comorbidities may further explain the higher fracture incidence in DM patients with respect to the general population. It is reasonable to expect that close metabolic control of diabetes may improve bone status, although its effect on reduction of fracture risk has not yet been demonstrated. However, metformin has a direct effect on bone tissue by reducing AGE accumulation, whereas insulin acts directly on osteoclast activity, and thiazolidinediones (TZD) may have a negative effect by switching mesenchymal progenitor cells to adipose rather than bone tissue. New prospects include the incretins, a class of antidiabetic drugs which may play a role linking nutrition and bone metabolism. Better knowledge on how diabetes and its treatments influence bone tissue may lie at the basis of effective prevention of bone fracture in diabetic patients. Thus, close glycemic control, adequate intake of calcium and vitamin D, screening for low BMD, and prevention and treatment of diabetic complications are key elements in the management of osteoporosis in both DM1 and DM2. Attention should be paid to treating diabetes with TZD in women with DM2, particularly if elderly. Lastly, patients with osteoporosis and diabetes should be offered the same pharmacological treatments as non-diabetics, although specific trials on the effects of anti-osteoporotic drugs in the diabetic population are lacking.

Calcium bioavailability from a new calcium-fortified orange beverage, compared with milk, in healthy volunteers.

The recommended dietary calcium intake may be difficult to reach using dairy products only. This study aimed to evaluate the absorbability of calcium of a new orange beverage in comparison with that of milk. Ten healthy adults, 5 males and 5 females, were randomly divided to receive, under fasting conditions, an orange beverage enriched either with calcium or milk. Both the beverages had been labelled the previous evening with a 44Ca solution. After a two-month interval the subjects underwent a crossover of beverages. Total and ionized calcium, parathyroid (PTH) hormone, and 44Ca were evaluated. The 44Ca was measured by inductively coupled plasma spectrometry. The relative changes in calcium absorption from the two test drinks were similar (23.0 +/- 6.4% for milk and 20.9 +/- 9.1% for the orange beverage). No significant differences were found between the two test groups. Both milk and orange beverage determined a similar and significant (p < 0.001) decrease in serum PTH two hours after the beginning of the test (-22.1 +/- 14.0% for milk and -27.9 +/- 15.3% for orange beverage). We can conclude that the bioavailability of calcium from this new calcium-enriched orange beverage is similar to that of milk.

In vivo performance evaluation of the Achilles Insight QUS device.

Achilles plus (GE, Lunar) has been widely used worldwide for more than a decade, and for its precision, ability to predict fragility fractures and comparability to central DXA, it can be considered a reference standard among quantitative ultrasound devices. As a water-bath system, Achilles plus has obvious practical drawbacks. Achilles Insight is a new-generation device that gives ultrasound parameters in less than 1 min, providing real-time imaging of the os calcis. The aim of this study was to evaluate the in vivo performance of Achilles Insight in comparison to Achilles plus. The precision showed a coefficient of variation (CV) of 0.5 and 0.4%, 4.1 and 3.0%, 2.7 and 2.1%, respectively, for speed of sound (SOS), broadband ultrasound attenuation (BUA), and Stiffness obtained with Achilles plus and Achilles Insight. We also studied 117 postmenopausal women (mean age: 67.1+/-8.8 yr), 47 with and 70 without fragility fractures. Ultrasound parameters obtained by the two devices significantly (p<0.001) correlated and resulted in agreement according to the Bland and Altman method. Achilles plus and Achilles Insight showed similar values of areas under receiver operating characteristics (ROC) curves in discriminating patients with or without fractures (0.884, 0.82, and 0.879 for SOS, BUA, and Stiffness, respectively, with Achilles plus, and 0.882, 0.828, and 0.889, respectively, for Achilles Insight). In conclusion, the better precision of the Achilles Insight with respect to Achilles plus could be explained by the fact that the measurement with Achilles Insight needs less time and gives a consequent reduction in motion artifacts. The high correlation and the similar ability to identify postmenopausal women with vertebral fracture suggest the possibility of using the database of Achilles plus for Achilles Insight.

Quantitative ultrasound and dual-energy X-ray absorptiometry in the prediction of fragility fracture in men.

Fragility fractures in men represent a major health problem, and this prompts a necessity for reliable tools for the identification of men at risk of fracture. In order to assess the ability of dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) in the prediction of fracture risk in men and whether their combination might be useful in a clinical setting, we studied 401 men (age range 45-82 years, mean 60.3+/-12.5), of whom 133 had osteoporotic fractures and 268 did not. In all subjects we measured bone mineral density at the lumbar spine (BMD-LS) and at the femur, calculating thereafter the standard femoral subregions: neck (BMD-FN), total hip (BMD-T), trochanter (BMD-TR), intertrochanter (BMD-ITR), and Ward's triangle (BMD-W), by DXA. We also performed ultrasound parameters at the calcaneus: speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness, by Achilles plus, and at the phalanxes: amplitude dependent speed of sound (AD-SoS) and the parameters of the graphic trace: bone transmission time (BTT), fast wave amplitude (FWA), signal dynamic (SDy) and ultrasound bone profile index (UBPI), by Bone Profiler. All DXA and QUS parameters, apart from FWA, were significantly (P<0.001) lower in patients with a history of fracture. BMD at the proximal femur showed the best ability in discriminating men with or without fractures. QUS at the heel showed discriminatory ability significantly better than QUS at the fingers. By logistic regression analysis, adjusted for age and BMI, BMD-T showed the best association with fragility fracture [odds ratio (OR)=3.43, 95% confidence interval (CI)=2.47-4.77]. Among QUS parameters, the highest value of the OR was shown by stiffness (OR=3.18, CI=2.27-4.48). FWA and SDy were not associated with fragility fractures in men. If DXA and QUS were combined, the prediction of the OR of fragility fracture events in men increases; in fact Stiffness was able to increase the OR when added to BMD-LS (OR=5.44, CI=3.16-10.13) and BMD-T (OR=6.08, CI=2.63-14.27). SOS and BUA showed a similar pattern. AD-SoS improved the prediction of fracture only when combined with BMD-LS (OR=4.36, CI=1.99-9.57). If BMD-LS and BMD-FN or BMD-T were combined, the value of the OR increases (OR=4.59, CI=2.27-9.25 and OR=4.68, CI=2.24-9.76), respectively. Our study supports the effectiveness of QUS in the identification of osteoporotic fractures in men. QUS seems to play an independent and complementary role, with respect to DXA, in order to enhance the power for predicting osteoporotic fractures in men.