Questioning Medicine

Questioning Medicine
Questioning Medicine

Join Andrew on a medical rollercoaster as we ask a medical question and answer it based on recent published papers.  

  1. 13H AGO

    383. What is the GFR at which we stop metforin?

    Metformin while not necessarily first line therapy for diabetes depending on the patients co-morbid conditions it is certainly highly ranked on the list of medications! I know often metformin is stopped while coming into the hospital for fear of potentially lactic acidosis or an increase in AKI with contrast studies however this ‘belief’ is largely based on myth and misconception. Metformin's contraindications should be contraindicated - PMC I also know that often metformin is held at discharge if the patients GFR is near or around 30 However, two new studies. Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation Study - ClinicalKey 4,278 Scottish residents with a diagnosis of type 2 diabetes were identified as prevalent metformin users with incident CKD stage 4. (it was stopped when they reached CKD 5) Results:Compared with continuing metformin, stopping metformin was associated with a lower 3-year survival (63.7% [95% CI, 60.9-66.6] vs 70.5% [95% CI, 68.0-73.0]; HR, 1.26 [95% CI, 1.10-1.44])    (THAT WOULD BE ROUGHLY A NNT OF 14) Interestingly the thing we think metformin prevents (MACE) was the same in both groups  (HR, 1.05 [95% CI, 0.88-1.26]). Could it be possible that metformin saves your life on some other mechanism that we don’t totally understand?? Discontinuing metformin was associated with a higher risk of death from respiratory diseases (HR, 1.51 [95% CI, 1.06-2.12]) MAYBE THAT IS THE SECRET!?  Trial 2Clinical outcomes following discontinuation of metformin in patients with type 2 diabetes and advanced chronic kidney disease in Hong Kong: a territory-wide, retrospective cohort and target trial emulation study - ScienceDirect 33,586 metformin users with new-onset eGFR 30 ml/min/1.73 m2 were included in the study and 7500 (22.3%) of whom discontinued metformin within 6 months whereas 26,086 (77.7%) continued use of metformin. They were followed for a median duration of 3.8 (IQR: 2.2–6.1) years, This time, those in which metformin was discontinued had higher risk of MACE (weighted and adjusted HR = 1.40, 95% CI: 1.29–1.52),AND once again if you stopped the metformin you had a higher incidence of death  (HR = 1.22, 1.18–1.27). BUT get this, if you stopped the metformin you had higher rates of progression to END STAGE KIDNEY DISEASE (HR = 1.52, 1.42–1.62)!!!Yes, stopping metformin was associated with all the badness of the heart and kidneys  PS- no association observed for the risk of lactic acidosis (still) Obviously, these are both observational studies so there could be unaccounted for confounders that can only truly be ruled out with an RCT. Now that metformin is $4 a month at Walmart and the new fancy diabetic drugs are $20-$40 per day it is very unlikely we will see the proper drug company run trial anytime in the near future. However it does seem possible and even reasonable we continue metformin even at smaller doses (500mg daily or 500mg BID) may actually decrease the one thing we are all trying to fight against…..death

    11 min
  2. FEB 27

    381. Relative efficacy of prehabilitation interventions and their components

    https://www.bmj.com/content/388/bmj-2024-081164systematic review and meta-analysis on prehabilitation before surgery, published in the BMJ in February 2025.Prehabilitation aims to prepare patients for surgery through interventions like exercise, nutrition, and psychological support. This study looked at which prehabilitation components are most effective for improving key outcomes after surgery.The researchers analyzed 186 randomized trials with over 15,000 participants. They used advanced statistical methods to compare different prehabilitation approaches.The key findings were:Exercise-only prehabilitation reduced complications by about 50% compared to usual care.Nutritional prehabilitation alone reduced complications by about 38%.Combining exercise, nutrition, and psychosocial support reduced complications by about 36%.For hospital length of stay, exercise plus psychosocial support was most effective, reducing stays by about 2.5 days on average.Multicomponent prehabilitation including exercise, nutrition and psychosocial support was best for improving quality of life and physical recovery after surgery.When looking at individual components, exercise and nutrition consistently showed the most benefit across all outcomes.However, there are important limitations to consider. The overall certainty of evidence was low to very low for most comparisons. This was mainly due to potential bias in the original trials and imprecision in the results.So what does this mean for clinical practice? While not definitive, this study suggests that exercise and nutritional prehabilitation, either alone or as part of multicomponent programs, likely benefit surgical patients. Clinicians should consider incorporating these approaches when preparing patients for surgery.However, we still need large, high-quality trials to confirm these findings before making strong recommendations. Future research should focus on well-designed studies looking at the outcomes that matter most to patients and healthcare systems.In summary, this study provides promising evidence for prehabilitation, particularly exercise and nutrition-based approaches.

    7 min
  3. FEB 12

    378. What is the Best Way To Treat Ductal Carcinoma In Situ

    https://jamanetwork.com/journals/jama/article-abstract/2828218DCIS is a non-invasive form of breast cancer, meaning the abnormal cells are contained within the milk ducts. For years, the standard treatment has been surgery, often followed by radiation and/or hormone therapy - the same treatments used for invasive breast cancer. But is this aggressive approach always necessary for low-risk DCIS?(Transition Music - Short and subtle - 2 seconds) Host: That's the question the COMET trial, or Comparing an Operation to Monitoring, With or Without Endocrine Therapy for Low-Risk DCIS, set out to answer. This large, randomized trial enrolled nearly 1000 women with newly diagnosed, low-risk DCIS across 100 centers in the US between 2017 and 2023. Participants were randomly assigned to either guideline-concordant care, meaning surgery with or without radiation, or active monitoring, involving regular check-ups with imaging and physical exams, reserving surgery only if the DCIS progressed to invasive cancer. The study focused on women who had hormone receptor-positive, grade 1 or 2 DCIS without evidence of invasive cancer.(Transition Music - Short and subtle - 2 seconds)  Host: The Major Finding: After a median follow-up of about 3 years, the study found that active monitoring was not inferior to surgery in terms of the rate of invasive cancer developing in the same breast. Specifically, the 2-year cumulative rate of ipsilateral invasive cancer was 4.2% in the active monitoring group and 5.9% in the guideline-concordant care group. This difference was statistically non-significant, meeting the pre-defined criteria for non-inferiority.(Transition Music - Short and subtle - 2 seconds) Host: This means that, at least in the short term, women with low-risk DCIS who chose active monitoring did not have a higher risk of developing invasive cancer compared to those who underwent surgery.(Transition Music - Short and subtle - 2 seconds  )Host: So, how should this change practice? For carefully selected women with low-risk DCIS, active monitoring could be a reasonable and safe alternative to immediate surgery. This approach could avoid the risks and side effects associated with surgery, radiation, and hormone therapy, such as pain, altered body image, and other long-term complications.(Transition Music - Short and subtle - 2 seconds) Host: Important Considerations: This study focused on low-risk DCIS. Active monitoring requires strict adherence to follow-up appointments and imaging. Further research is needed to determine the long-term outcomes of active monitoring and to identify which patients are most suitable for this approach. Patients considering active monitoring should have a thorough discussion with their healthcare provider to weigh the risks and benefits and make an informed decision.(Transition Music - Short and subtle - 2 seconds)

    8 min
  4. FEB 11

    377. Does How Long You Have Hypertension Matter?

    Association of Duration of Recognized Hypertension and Stroke Risk: The REGARDS Study   (Transition Music - Short and subtle - 2 seconds)Host:  Hypertension is a well-known risk factor for stroke, but this study, led by Dr. George Howard and colleagues, asks a fascinating question: Does the duration of hypertension matter, even when blood pressure is managed? (Transition Music - Short and subtle - 2 seconds)Host: The researchers used data from the REGARDS study, a large, long-term study looking at racial and geographic differences in stroke. They followed over 27,000 stroke-free participants for over 12 years, tracking who developed stroke and how long they had been diagnosed with hypertension. Participants were grouped by duration of hypertension: normotensive (no hypertension), 5 years or less, 6 to 20 years, and 21 years or more. (Transition Music - Short and subtle - 2 seconds)Host:  So, what did they find? Several key findings emerged. First, people with longer durations of hypertension were taking more antihypertensive medications, suggesting it becomes harder to manage blood pressure over time. Second, even with medication, their average systolic blood pressure (the top number) was higher. (Transition Music - Short and subtle - 2 seconds)  Host: Most importantly, the study found a clear association between the duration of hypertension and stroke risk. Compared to people with normal blood pressure, those with hypertension for 5 years or less had a 31% increased risk of stroke. That risk jumped to 50% for those with hypertension for 6 to 20 years, and a staggering 67% for those with hypertension for 21 years or more. These increased risks remained even after the researchers accounted for factors like age, race, sex, and other stroke risk factors.(Transition Music - Short and subtle - 2 seconds) Host: Key Takeaway: This study strongly suggests that the duration of hypertension significantly impacts stroke risk, independent of blood pressure levels at a single point in time.(Transition Music - Short and subtle - 2 seconds)  Host: What does this mean for you? It reinforces the importance of preventing or delaying the onset of hypertension in the first place. Early lifestyle interventions, such as diet and exercise, can play a crucial role. If you're already diagnosed with hypertension, work closely with your doctor to manage your blood pressure effectively and consider how long you've had the condition as part of your overall risk assessment. The longer you have hypertension, the more vigilant you may need to be.

    7 min
  5. FEB 7

    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 FindingsLow-dose ICS: No significant increase in adverse events7.Medium to high-dose ICS: Associated with increased risks of:Major adverse cardiovascular events (MACE)Cardiac arrhythmiaPulmonary embolism (PE)Hospitalization for pneumonia71Risk-Benefit Analysis:Absolute risk of adverse events was lowNumber 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)3Time-dependent risks:Highest risk observed at 12 monthsMACE risks increased in the first 60 days but returned to baseline after ICS cessation1Implications for Asthma ManagementGuideline 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.

    6 min
4.9
out of 5
71 Ratings

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Join Andrew on a medical rollercoaster as we ask a medical question and answer it based on recent published papers.  

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