Episode 365: 366. Association of dose of inhaled corticosteroids and frequency of adverse events

Bloom CI et al. Association of dose of inhaled corticosteroids and frequency of adverse events. Am J Respir Crit Care Med 2025 Jan; 211:54. (https://doi.org/10.1164/rccm.202402-0368OC)  Bloom and colleagues' study, published in the American Journal of Respiratory and Critical Care Medicine in January 2025, provides significant insights into the safety profile of inhaled corticosteroids (ICS) for asthma patients7. The research, which analyzed data from two large UK databases, reveals important associations between ICS dosage and adverse events.  GINA GUIDELINES+ step 1 is ics formoterol OR low dose ICS--- as you move up ICS is always in the picture like a bad ex girlfriend in the family picture…. You can never just cut it out—sure you can go on photo shop and make em bigger or smaller like you can go with ICS but you cant cut them out. Key Findings Low-dose ICS: No significant increase in adverse events7. Medium to high-dose ICS: Associated with increased risks of: Major adverse cardiovascular events (MACE) Cardiac arrhythmia Pulmonary embolism (PE) Hospitalization for pneumonia71 Risk-Benefit Analysis: Absolute risk of adverse events was low Number needed to harm (NNH) for 12 months of ICS use: Medium dose (201-599 mcg): MACE (473), arrhythmia (567), PE (1221), pneumonia (230) High dose (≥600 mcg): MACE (224), arrhythmia (396), PE (577), pneumonia (93)3 Time-dependent risks: Highest risk observed at 12 months MACE risks increased in the first 60 days but returned to baseline after ICS cessation1 Implications for Asthma Management Guideline adherence: Use the lowest effective ICS dose37. Risk assessment: Consider patient-specific factors when prescribing medium to high-dose ICS. Monitoring: Increased vigilance for potential adverse events in patients on higher ICS doses. Step-down approach: Consider dose reduction once asthma is well-controlled1. Alternative strategies: Explore options like low-dose ICS/formoterol for maintenance and relief, or biologics for frequent exacerbators1. This study underscores the importance of balancing asthma control with potential risks of higher ICS doses. While ICS remain a cornerstone of asthma treatment, clinicians should aim for the lowest effective dose and regularly reassess the need for high-dose therapy.

Gao FM et al. A systematic review and meta-analysis on the safety and efficacy of sodium–glucose cotransporter 2 inhibitor use in hospitalized patients. Diabetes Care 2024 Dec 1; 47:2275. (https://doi.org/10.2337/dc24-0946) Trial ResultsSGLT-2 inhibitors, crucial in managing diabetes, kidney disease, and heart failure, have shown promising results in hospitalized patients1. The meta-analysis, covering 23 randomized controlled trials with 20,000 participants, revealed:No significant increase in ketoacidosis rates (0.21 vs. 0.14 per 100 person-years)1Lower mortality and fewer readmissions in heart failure patients1Reduced incidence of acute kidney injury overall1These findings suggest that SGLT-2 inhibitors can be safely continued or initiated in hospitalized patients, particularly those with heart failure1.LimitationsHowever, it's important to note some limitations: Potential underpowering: The study might not have had enough statistical power to detect small differences in ketoacidosis rates1. Risk underestimation: Including outpatient follow-up periods may have diluted the true risk of ketoacidosis during hospitalization1. Patient diversity: Only 30% of participants had diabetes, which might not fully represent the typical hospital population1.ConclusionWhile the results are encouraging, caution is still advised. The study supports current recommendations for SGLT-2 inhibitor use in hospitalized patients, especially those with heart failure, but emphasizes the need for careful monitoring and individualized decision-making1.This concludes our brief podcast on SGLT-2 inhibitors in hospitalized patients. Thank you for listening, and stay tuned for more updates on diabetes care and management.

Is accelerated surgery for hip fracture better for high-risk patients? A recent substudy of the HIP ATTACK trial has shed new light on this topic. The original trial, published in 2020, compared accelerated surgery (within 6 hours) to standard-timing surgery (within 24 hours) for hip fracture patients. While the initial results showed only marginal benefits, this new analysis focuses on a specific group: patients with elevated cardiac troponin levels at hospital arrival--- THE SICK GUYS7.Here's what the researchers found:For patients with elevated troponin levels - about a quarter of those tested - accelerated surgery was associated with significantly lower mortality. The numbers are striking: 10% mortality in the accelerated surgery group compared to 23% in the standard surgery group. This translates to a number needed to treat of just 87.Interestingly, for patients with normal troponin levels, there was no significant difference in mortality between the two surgical approaches7.These findings suggest that for high-risk patients - those with elevated troponin levels - immediate surgery without further work-up or delay could lead to better outcomes. It's a paradigm shift in how we approach these cases .However, it's important to note that we're still awaiting results from the HIP ATTACK-2 study, which will provide more definitive evidence on whether accelerated surgery is superior to standard timing in these patients7.In conclusion, this study highlights the potential benefits of tailoring surgical timing to individual patient risk factors. For those with elevated troponin levels, rapid intervention could be life-saving.   Borges FK et al. Myocardial injury in patients with hip fracture: A HIP ATTACK randomized trial substudy. J Bone Joint Surg Am 2024 Dec 18; 106:2303. (https://doi.org/10.2106/JBJS.23.01459)Cornell C. Patients presenting with acute myocardial injury with hip fracture have greater survival with rapid surgical care. J Bone Joint Surg Am 2024 Dec 18; 106:e50. (https://doi.org/10.2106/JBJS.24.00583)

Today, we're discussing two groundbreaking studies from 2024 that challenge our understanding of β-blocker therapy for secondary prevention after myocardial infarction, or MI.Let's start with a Swedish study Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction | New England Journal of Medicine that included over 5,000 patients with normal left ventricular ejection fraction after an MI5. The researchers compared long-term beta-blocker therapy with no beta-blocker treatment. Surprisingly, after 3.5 years, there was no significant difference in the primary endpoint of all-cause death or recurrent MI between the two groups5. This suggests that for patients with preserved heart function after an MI, long-term beta-blocker use may not provide additional benefits.  Now, let's turn to a French study involving 3,700 patients who were already on β-blockers following an MI Beta-Blocker Interruption or Continuation after Myocardial Infarction | New England Journal of Medicine7. This trial compared continuing β-blocker therapy to stopping it. After three years, the results showed a slightly higher incidence of adverse events in the group that stopped β-blockers, primarily due to more hospitalizations for cardiovascular reasons7.What do these studies tell us? Well, they suggest that the benefits of β-blockers might be more modest in our current era of advanced revascularization techniques and modern medical therapies for post-MI patients8. However, it's crucial to note that the Swedish study focused on low-risk patients with normal heart function and they say well there was a lower event rate than expected!!! That is EXPECTED WHEN THE OTHER MEDICATIONS WORK!!! ,8.It's important to remember that these findings don't necessarily apply to all post-MI patients. Those with reduced heart function or other specific indications may still benefit significantly from β-blocker therapy7.In conclusion, while these studies provide valuable insights, there are other trials currently being done to help us better answer this question of what to do with the betablocker post mi

Methods Monday  --- Accuracy of Event Rate and Effect Size Estimation in Major Cardiovascular Trials: A Systematic Review | Cardiology | JAMA Network Open | JAMA Network  During the design of a randomized clinical trial (RCT), estimation of the expected event rate and effect size is a key component to calculating the sample size. Overly optimistic estimation of event rates and effect sizes may lead to underpowered trials. If you expect 1 event per 100 people and you are looking for 5 events then you only need to enroll….. 500 people but if the actual event rate is 1 per 200 people then in order to get 5 events you need to enroll 1000 people!! You can see enrolling 500 people instead of 1000 would underpower your trial  This article, published in JAMA Network Open in April 2024, presents a systematic review of 344 contemporary cardiovascular randomized clinical trials (RCTs) to evaluate the accuracy of estimated event rates and effect sizes1. The key findings are:Event rates were frequently overestimated: Median observed event rate: 9.0% (IQR, 4.3%-21.4%) Median estimated event rate: 11.0% (IQR, 6.0%-25.0%) 61.1% of trials overestimated the event rate 1Effect sizes were often overestimated: Median observed effect size: 0.91 (IQR, 0.74-0.99) Median estimated effect size: 0.72 (IQR, 0.60-0.80) 82.1% of trials overestimated the effect size The drug companies think their drug is way better than it is or observed to be in trials1Device trials were independently associated with decreased accuracy of event rate estimation compared to drug trials1.The study concludes that the frequent overestimation of event rates and effect sizes in cardiovascular RCTs may contribute to underpowered trials and the inability to adequately test trial hypotheses1. This finding has implications for trial design—if we are not accurate or realistic about the interventions we are likely to underpower the study which means you have to do the whole thing all over again or likely all over again and risk FDA rejecting you drug.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2821168A team of researchers set out to change that by developing a comprehensive algorithm.The process involved a multidisciplinary panel of 11 expertss with extensive experience in managing urinary retention. These experts evaluated about 100 clinical scenarios to create an initial flow sheet. The algorithm was then refined through interviews with 33 frontline clinicians from various specialties.So, what does this new algorithm recommend? Let's break it down:First, bladder scanning is the preferred method for evaluating patients with urinary retention symptoms. It's also recommended for asymptomatic patients who haven't voided in 3 hours.If a bladder scanner isn't available, the algorithm suggests using either an intermittent straight catheter (ISC) or an indwelling urinary catheter (IUC), with a preference for ISC initially.Now, let's talk about when to catheterize based on bladder scanner volumes. For symptomatic patients, catheterization is recommended when the volume is 300 mL or more. For asymptomatic patients, the threshold is higher at 500 mL or more.Lastly, the algorithm provides guidance on when to transition from intermittent to indwelling catheterization. If a patient needs an ISC more frequently than every 4 hours, or if their output is 500 mL or more every 4 hours, it's appropriate to switch to an IUC

https://jamanetwork.com/journals/jama/article-abstract/2822097Design, Setting, and Participants  Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not.Exposure  Various classes of oral antibiotics.Main Outcomes and Measures  Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group.Results  During the 20-year study period, we identified 21 758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87 025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital.Conclusion and Relevance  Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate.

https://www.nejm.org/doi/full/10.1056/NEJMoa2407001ConclusionsNo participants receiving twice-yearly lenacapavir acquired HIV infection. HIV incidence with lenacapavir was significantly lower than background HIV incidence and HIV incidence with F/TDF. Among 5338 participants who were initially HIV-negative, 55 incident HIV infections were observed: 0 infections among 2134 participants in the lenacapavir group (0 per 100 person-years; 95% confidence interval [CI], 0.00 to 0.19), 39 infections among 2136 participants in the F/TAF group (2.02 per 100 person-years; 95% CI, 1.44 to 2.76), and 16 infections among 1068 participants in the F/TDF group (1.69 per 100 person-years; 95% CI, 0.96 to 2.74)

Allaudeen N et al. Medications for alcohol-use disorder and follow-up after hospitalization for alcohol withdrawal: A multicenter study. J Hosp Med 2024 Dec; 19:1122. (https://doi.org/10.1002/jhm.13458)   Hospital admission for alcohol withdrawal is a problem when it comes to readmission. They just come back--- In this retrospective study of ≈600 patients (96% men) admitted for alcohol withdrawal at 19 Veterans Affairs hospitals during 1 year (2018–2019), researchers evaluated prescription rates of medications for alcohol use disorder (AUD; e.g., naltrexone, acamprosate, disulfiram, gabapentin, topiramate) and scheduled follow-up appointments.The objective of this study was to evaluate the effects of medications for AUD and follow-up appointments on readmission and abstinence.Neither prescription of AUD agents (to 51% of patients) at hospital discharge nor scheduled follow-up appointments at discharge were associated with 30-day readmissions or 6-month alcohol abstinence.Only direct discharge to residential AUD treatment programs was associated significantly with fewer readmissions (odds ratio, 0.4) and alcohol abstinence (OR, 2.5). Additionally, being discharged with a primary care appointment and actually attending the appointment was associated with fewer hospital readmissions (OR, 0.3).

Real‐world use of glucocorticoids and clinical outcomes in adults hospitalized with community‐acquired pneumonia on medical wards - Malecki - 2024 - Journal of Hospital Medicine - Wiley Online Library This was a retrospective cohort study of 11,500 patients with CAP who were admitted to general medicine units in 7 Canadian hospitals, researchers compared outcomes for patients who received systemic corticosteroids. Patients were excluded if they were admitted to the intensive care units or had COPD or COVID-19 infection. Between those that got steroids and those that didn’t get steroids there was no differences in intensive care admissions, hospital length of stay, or 30-day readmissions. HOWEVER, In an adjusted analysis, patients who received systemic corticosteroids were significantly more likely to die in the hospital than were patients who didn't receive steroids (8.0% vs. 6.3%; P=0.03).  LET’S BE CLEAR THIS IS FOR NON-SEVERE PNA!! If you have severe pna and are going to the ICU then the evidence and guidelines clearly indicate steroids are appropriate. Critical Care Medicine (lww.com)