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Summary In this episode of the Pain Exam Podcast, Dr. David Rosenblum provides a comprehensive review of herpes zoster and postherpetic neuralgia (PHN), focusing on pathophysiology, diagnosis, and treatment options. Dr. Rosenblum explains that postherpetic neuralgia affects approximately 25% of patients with acute herpes zoster, causing debilitating unilateral chronic pain in one or more dermatomes. He discusses the three phases of herpes zoster: acute (up to 30 days), subacute (up to 3 months), and postherpetic neuralgia (pain continuing beyond 3 months). Dr. Rosenblum identifies risk factors for developing PHN, including older age, female sex, immunosuppression, prodromal pain, severe rash, and greater acute pain severity. He details the pathophysiology involving peripheral and central sensitization, and explains different phenotypes of PHN that can guide treatment approaches. For treatment, Dr. Rosenblum reviews various options including antiviral medications (which should be started within 72 hours of onset), corticosteroids, opioids, antidepressants (particularly tricyclics and SNRIs), antiepileptics (gabapentin and pregabalin), topical agents (lidocaine and capsaicin), and interventional procedures such as epidural injections and pulsed radiofrequency. He emphasizes that prevention through vaccination with Shingrix is highly effective, with 97% effectiveness in preventing herpes zoster in patients 50-69 years old and 89% effectiveness in those over 70. Dr. Rosenblum mentions that he's currently treating a patient with trigeminal postherpetic neuralgia and is considering a topical sphenopalatine ganglion block as a minimally invasive intervention before attempting more invasive procedures. Chapters Introduction to the Pain Exam Podcast and Topic Overview Dr. David Rosenblum introduces the Pain Exam Podcast, mentioning that it covers painful disorders, alternative treatments, and practice management. He explains that this episode focuses on herpes zoster and postherpetic neuralgia as board preparation for fellows starting their programs, with ABA boards coming up in September. Dr. Rosenblum notes that he's not only preparing listeners for boards but also seeking the latest information to help treat his own patients with this notoriously difficult disease. Upcoming Conferences and Educational Opportunities Dr. Rosenblum announces several upcoming conferences including Aspen in July, Pain Week in September, and events with NYSIP and the Latin American Pain Society. He mentions he'll be teaching ultrasound and regenerative medicine at these events. Dr. Rosenblum invites listeners to sign up at nrappain.org to access a community discussing regenerative medicine, ultrasound-guided pain medicine, regional anesthesia, and board preparation. He also offers ultrasound training in New York and elsewhere, with upcoming sessions in Manhattan on July 12th and October 4th, plus private shadowing opportunities. Overview of Postherpetic Neuralgia Dr. Rosenblum defines postherpetic neuralgia as typically a unilateral chronic pain in one or more dermatomes after acute herpes zoster infection. He states that the incidence of acute herpes zoster ranges between 3-5 patients per thousand person-years, and one in four patients with acute herpes zoster-related pain will transition into postherpetic neuralgia. Dr. Rosenblum emphasizes that while this condition won't kill patients, it can be extremely debilitating and significantly reduce quality of life. Treatment Options Overview Dr. Rosenblum reviews treatment options according to the WHO pain ladder, including tricyclics like nortriptyline and antiepileptic drugs such as gabapentin. He explains that if pain is not significantly reduced, interventional treatments like epidural injections with local anesthetics and corticosteroids or pulsed radiofrequency of the dorsal root ganglion are options. For postherpetic neuralgia specifically, Dr. Rosenblum notes that preferred treatments include transdermal capsaicin, lidocaine, or oral drugs such as antidepressants or antiepileptics. Phases of Herpes Zoster and Definitions Dr. Rosenblum outlines the three phases during herpes zoster reactivation: acute herpes zoster-related pain (lasting maximum 30 days), subacute herpes zoster-related pain (pain after healing of vesicles but disappearing within 3 months), and postherpetic neuralgia (typically defined as pain continuing after 3 months). He mentions that acute herpes zoster pain often begins with prodromal pain starting a few days before the appearance of the rash. Incidence and Risk Factors Dr. Rosenblum states that the incidence of herpes zoster ranges between 3-5 patients per 1,000 person-years, with approximately 5-30% of cases leading to postherpetic neuralgia. He identifies risk factors including older age, female sex, immunosuppression, prodromal pain, severe rash, and greater acute pain severity. Dr. Rosenblum describes the clinical manifestations as a mosaic of somatosensory symptoms including burning, deep aching pain, tingling, itching, stabbing, often associated with tactile and cold allodynia. Impact on Quality of Life Dr. Rosenblum emphasizes that postherpetic neuralgia can be debilitating, impacting both physical and emotional functioning and causing decreased quality of life. He notes that it leads to fatigue, insomnia, depression, anorexia, anxiety, and emotional distress. Dr. Rosenblum stresses the importance of exploring methods for prevention of postherpetic neuralgia and optimizing pain treatment for both subacute herpes zoster-related pain and postherpetic neuralgia. Literature Review and Pathophysiology Dr. Rosenblum mentions that he's discussing a literature review from 2024 that updates previous practical guidelines published in 2011. He explains the pathophysiology of postherpetic neuralgia, which involves sensitization of peripheral and sensory nerves from damage. Dr. Rosenblum describes how inflammatory mediators reduce the stimulus threshold of nociceptors and increase responsiveness, resulting in pathological spontaneous discharges, lower thresholds for thermal and mechanical stimuli, and hyperalgesia. Central Sensitization and Nerve Damage Dr. Rosenblum explains that central sensitization results from peripheral nociceptor hyperactivity leading to plastic changes in the central nervous system, involving amplification of pain signals and reduced inhibition. He describes how nerve damage in postherpetic neuralgia patients results from neuronal death due to severe inflammatory stimuli or secondary to neuronal swelling. Dr. Rosenblum notes that motor defects occur in 0.05% of patients with herpes zoster, observed as abdominal pseudohernias or motor weakness of limbs limited to the affected myotome. Different Phenotypes and Classification Dr. Rosenblum discusses different phenotypes of postherpetic neuralgia and how phenotyping can determine treatment. He explains that there are several ways to classify the phenotypes, with one categorizing patients into three subtypes: sensory loss (most common), thermal gain, and thermal loss with mechanical gain. Dr. Rosenblum describes the mechanistic categorization, including the irritable nociceptive phenotype characterized by preserved sensation, profound dynamic mechanical allodynia, reduced pressure pain threshold, and relief with local anesthetic infiltration. Deafferentation Phenotype Dr. Rosenblum explains that a deafferentation phenotype may arise from destruction of neurons by the virus in the dorsal root ganglion. This phenotype is characterized by sensory loss, including thermal and vibratory sensation without prominent thermal allodynia. He notes that mechanical allodynia can occur secondary to A-beta fibers activating spinothalamic pathways (known as phenotypic switches), along with pressure hyperalgesia and temporal summation suggesting central sensitization. Dr. Rosenblum mentions that in one study, this phenotype was present in 10.8% of individuals, and for those with deafferentation pain, gabapentinoids, antidepressants, and neuromodulatory therapies like repetitive transcranial magnetic stimulation may be beneficial. Diagnosis and Physical Examination Dr. Rosenblum discusses the diagnosis of herpes zoster and postherpetic neuralgia, emphasizing the importance of physical examination. He explains that diagnosis is based on the rash, redness, papules, and vesicles in the painful dermatomes, with healing vesicles showing crust formation. Dr. Rosenblum notes that the rash is generally unilateral and does not cross the midline of the body. In postherpetic neuralgia patients, he mentions that scarring, hyper or hypopigmentation is often visible, with allodynia present in 45-75% of affected patients. Sensory Testing and Assessment Dr. Rosenblum explains that in patients with postherpetic neuralgia, a mosaic of somatosensory alterations can occur, manifesting as hyperalgesia, allodynia, and sensory loss. These can be quantified by quantitative sensory testing, which assesses somatosensory functions, dermal detection thresholds for perception of cold, warmth, and paradoxical heat sensations. He notes that testing can provide clues regarding underlying mechanisms of pain, impaired conditioned pain modulation, temporal summation suggesting central sensitization, and information about the type of nerve damage and surviving afferent neurons. Prevention Through Vaccination Dr. Rosenblum discusses prevention of acute herpes zoster through vaccination, noting that the risk increases with reduced immunity. He highlights studies evaluating Shingrix, a vaccine for herpes zoster, which showed 97% effectiveness in preventing herpes zoster in patients 50-69 years old with healthy immune systems and 89% effectiveness in patients over 70. Dr. Rosenblum states that Shingrix is 89-91% effective in preventing postherpetic neuralgia development in patients with healthy immune systems and 68-91% effective in those with weakened or underlying conditions. Treatment Objectives Dr. Rosenblum outlines the treatment objectives for herpes zoster and postherpetic neuralgia. For acute herpes zoster, objectives include relieving pain, reducing severity and duration of pain, accelerating recovery of epidermal defects, and preventing secondary infections. For postherpetic neuralgia, the objectives are pain alleviation and improved quality of life. Dr. Rosenblum lists available treatments including psychotherapy, opiates, antidepressants, antiepileptics, NMDA antagonists, topical agents, and interventional treatments such as epidurals, pulsed radiofrequency, nerve blocks, and spinal cord stimulation. Antiviral Medications Dr. Rosenblum emphasizes that antiviral drugs should be started within 72 hours of clinical onset, mentioning famciclovir, valacyclovir, and acyclovir. He notes there is no evidence for effectiveness after 72 hours in patients with uncomplicated herpes zoster. Dr. Rosenblum provides dosing information: for immunocompetent patients, famciclovir 500mg and valacyclovir 1000mg three times daily for seven days; for immunocompromised patients, famciclovir 1000mg three times daily for 10 days, while acyclovir should be given IV in the immunocompromised. Benefits of Antiviral Therapy Dr. Rosenblum explains that antiviral medication accelerates the disappearance of vesicles and crusts, promotes healing of skin lesions, and prevents new lesions from forming. By inhibiting viral replication, he notes that antiviral therapy likely reduces nerve damage, resulting in reduced incidence of postherpetic neuralgia, and should be started as soon as possible. Corticosteroids and Opioids Dr. Rosenblum discusses the use of corticosteroids, noting that when added to antiviral medications, they may reduce the severity of acute herpes zoster-related pain, though increased healing of skin lesions was not observed in one study. He mentions that a Cochrane review found oral corticosteroids ineffective in preventing postherpetic neuralgia. Regarding opioids, Dr. Rosenblum states they are commonly used alongside antivirals for controlling acute herpes zoster pain, with tramadol having a number needed to treat (NNT) of 4.7 and strong opioids having an NNT of 4.3 for 50% pain reduction. Methadone and Antidepressants Dr. Rosenblum discusses methadone as an NMDA receptor antagonist used in acute and chronic pain management, though he notes there are no randomized controlled trials determining its efficacy in acute herpes zoster pain or postherpetic neuralgia. He explains that methadone can modulate pain stimuli by inhibiting the uptake of norepinephrine and serotonin, resulting in decreased development of hyperalgesia and opioid tolerance, but has side effects including constipation, nausea, sedation, and QT prolongation that can trigger torsades de pointes. Dr. Rosenblum identifies antidepressants as first-line therapy for postherpetic neuralgia, including tricyclics and SNRIs, with tricyclics having an NNT of 3 and SNRIs an NNT of 6.4 for 50% pain reduction. Antiepileptics and Pharmacological Treatment Summary Dr. Rosenblum discusses antiepileptics like gabapentin and pregabalin for postherpetic neuralgia. He cites two trials measuring gabapentin's effect, concluding it was effective compared to placebo with a pooled NNT of 4.4, while pregabalin had an NNT of 4.9. Dr. Rosenblum summarizes that pharmacological treatment is well established for subacute herpes zoster pain, though new high-quality evidence has been lacking since the last update in 2011. Topical Agents Dr. Rosenblum discusses local anesthetic topical agents including lidocaine and capsaicin creams and patches. He notes that 8% capsaicin provided significant pain reduction during 2-8 weeks, while 5% lidocaine patches provided moderate pain relief after eight weeks of treatment. Dr. Rosenblum also mentions acute herpes zoster intracutaneous injections, citing a study where single intracutaneous injection with methylprednisolone combined with ropivacaine versus saline alone showed significant difference in VAS score at 1 and 4 weeks post-intervention favoring the intervention group. Intracutaneous Injections Dr. Rosenblum discusses the effect of repetitive intracutaneous injections with ropivacaine and methylprednisolone every 48 hours for one week. He cites a randomized control trial comparing antivirals plus analgesics to antivirals plus analgesics and repeat injections, finding the intervention group had significantly shorter duration of pain, lower VAS scores, and lower incidence of postherpetic neuralgia (6.4% vs 28% at 3 months). Dr. Rosenblum notes that a potential side effect of cutaneous methylprednisolone injection is fat atrophy, though this wasn't reported in the study. Summary of Local Anesthetics Dr. Rosenblum summarizes that there are no new studies reporting the efficacy of capsaicin 8% for postherpetic neuralgia, but it remains widely used in clinical practice and is approved in several countries. He notes that lidocaine patches can reduce pain intensity in patients with postherpetic neuralgia but may be more beneficial in patients with allodynia. Dr. Rosenblum adds that intracutaneous injections may be helpful for short periods, while repetitive injections with local anesthetics may reduce VAS scores for up to six months but can cause subcutaneous fat atrophy. Interventional Treatments: Epidural and Paravertebral Injections Dr. Rosenblum discusses interventional treatments, noting that previous guidelines found epidural injection with corticosteroids and local anesthetic as add-on therapy superior to standard care alone for up to one month in managing acute herpes zoster pain. He mentions a randomized controlled trial showing no difference between interlaminar and transforaminal epidural steroid injections for up to three months after the procedure. Dr. Rosenblum adds that previous guidelines reported high-quality evidence that paravertebral injections of corticosteroids or local anesthetic reduces pain in the active phase of herpes zoster. Comparative Studies on Injection Approaches Dr. Rosenblum discusses a trial comparing efficacy of repetitive paravertebral blocks with ropivacaine versus dexmedetomidine to prevent postherpetic neuralgia, which showed significantly lower incidence of zoster-related pain one month after therapy in the dexmedetomidine group, with effects still significant at three months. He also mentions a study comparing steroid injections administered via interlaminar versus transforaminal approaches, finding both groups had significantly lower VAS scores at 1 and 3 months follow-up compared to baseline, though this could align with the natural course of herpes zoster. Timing of Interventions and Continuous Epidural Blockade Dr. Rosenblum cites a retrospective study showing that transforaminal epidural injections administered for acute herpes zoster-related pain were associated with significantly shorter time to pain relief compared to those performed in the subacute phase. He also mentions a randomized controlled trial finding that continuous epidural blockade combined with opioids and gabapentin reduced NRS pain scores more than analgesic drug treatments alone during three-day follow-up, though both studies were low-quality. Interventions for Postherpetic Neuralgia Dr. Rosenblum discusses interventions specifically for postherpetic neuralgia, citing a small randomized controlled trial that demonstrated decreased NRS pain scores six months post-treatment for repeat versus single epidural steroid injections (15mg vs 5mg dexamethasone) administered over 24 days. The trial also found increased likelihood of complete remission during 6-month follow-up in the group receiving repeat epidural dexamethasone, though this was low-quality evidence. Summary of Epidural and Paravertebral Injections Dr. Rosenblum summarizes that epidural or paravertebral injections of local anesthetic and/or glucocorticoids could be considered in treating acute herpes zoster-related pain. For subacute postherpetic neuralgia pain, he notes low-quality evidence supporting epidural injections, while for postherpetic neuralgia, evidence supports continuous epidural infusion, though also of low quality. Dr. Rosenblum emphasizes that none of the included studies for postherpetic neuralgia investigating epidural or paravertebral injections resulted in decreased pain compared to standard therapy. Pulsed Radiofrequency (PRF) Evidence Dr. Rosenblum discusses pulsed radiofrequency (PRF), noting that previous guidelines indicated moderate quality evidence that PRF of the intercostal nerve reduces pain for 6 months in patients with postherpetic neuralgia, and very low-quality evidence that PRF to the dorsal root ganglion (DRG) reduces pain for 6 months. He mentions that multiple studies have been published since then assessing PRF efficacy. PRF Studies for Acute Herpes Zoster Dr. Rosenblum discusses a randomized controlled trial with 60 patients comparing high-voltage bipolar PRF of the cervical sympathetic chain versus sham, with treatment repeated after three days in both groups. He reports that VAS scores in the PRF group at each post-interventional point (1 day, 2 days, 1 month, 2 months, 3 months) were significantly lower than in the sham group, and at 3 months, the incidence of postherpetic neuralgia was 16.7% in the PRF group compared to 40% in the sham group. PRF for Trigeminal Neuralgia Dr. Rosenblum cites another randomized controlled trial evaluating high-voltage long-duration PRF of the Gasserian ganglion in 96 patients with subacute herpes-related trigeminal neuralgia, which found decreased VAS pain scores at all post-interventional time points (3, 7, 14 days and 1, 3, and 6 months) compared to the sham group. He also mentions a randomized comparative effectiveness study in 120 patients with subacute trigeminal herpes zoster, comparing a single application of high-voltage PRF to the Gasserian ganglion versus three cycles of conventional PRF treatment, finding significantly lower mean VAS pain scores for up to six months in the high-voltage PRF group. PRF Compared to Other Interventions Dr. Rosenblum discusses a randomized controlled trial comparing PRF to short-term spinal cord stimulation, which found decreased pain and improved 36-item short-form health survey scores in both groups at six months. He also mentions a randomized controlled trial in 72 patients where PRF of spinal nerves or peripheral branches of cranial nerves combined with five-day infusion of IV lidocaine resulted in greater pain reduction, less rescue analgesia, and reduced inflammatory cytokines at two months compared to PRF with saline infusions. Dr. Rosenblum notes a major limitation of this study was not accounting for the high natural recovery rate. Summary of PRF and Final Recommendations Dr. Rosenblum summarizes that PRF provides significant pain relief lasting over three months in patients with subacute herpes zoster and postherpetic neuralgia. He notes that since few studies have compared PRF versus sham, it's not possible to calculate an accurate number needed to treat. Dr. Rosenblum mentions there are no comparative studies comparing PRF to the intercostal nerves versus PRF of the DRG, but both preclinical and clinical studies suggest superiority of the DRG approach. He adds that evidence for spinal cord stimulation for postherpetic neuralgia is of low quality, and more research is needed given its invasive nature. Sympathetic Blocks and Conclusion Dr. Rosenblum notes there is low-quality evidence for using sympathetic blocks to treat acute herpes zoster-related pain, but no evidence for their use in postherpetic neuralgia. He mentions that risks of treatment with intrathecal methylprednisolone are unclear and therefore not recommended. Dr. Rosenblum concludes by praising the comprehensive article he's been discussing and mentions it provides insight for treating his patients, including a recent case of trigeminal postherpetic neuralgia. Personal Clinical Approach and Closing Dr. Rosenblum shares that he doesn't currently perform PRF in his practice, partly because it's not standard of care and not well reimbursed, creating barriers to implementation. However, he notes that PRF is a very safe procedure as it doesn't involve burning tissue. For his patient with trigeminal neuralgia pain, Dr. Rosenblum plans to try a topical sphenopalatine ganglion block as the least invasive intervention before considering injecting the trigeminal nerves at the foramen, in addition to pharmacotherapy. He concludes by thanking listeners, encouraging them to check the show notes and links, mentioning institutional memberships and shadowing opportunities, and asking listeners to rate and share the podcast. Q&A No Q&A session in this lecture Pain Management Board Prep   Ultrasound Training REGISTER TODAY!   Create an Account and get Free Access to the PainExam- NRAP Academy Community Highlights     David Rosenblum, MD, currently serves as the Director of Pain Management at Maimonides Medical Center and AABP Integrative Pain Care.  As a member of the Department of Anesthesiology, he is involved in teaching, research, CME activities, and was key faculty in developing the anesthesiology residency's regional anesthesia block rotation, as well as institutional wide acute and chronic pain management protocols to ensure safe and effective pain management. He currently is a managing partner in a multi-physician private pain practice, AABP Integrative Pain Care, located in Brooklyn, NY. He is one of the earliest interventional pain physicians to integrate ultrasound guidance to improve the safety and accuracy of interventional pain procedures.   Awards New York Magazine: Top Doctors: 2016, 2017, 2018, 2021, 2022, 2023, 2024, 2025 Schneps Media: 2015, 2016, 2017, 2019, 2020 Top Doctors New York Metro Area (digital guide): 2016, 2017, 2018, 2019, 2020, 2021, 2022, 2023 2025 Schneps Media - Brooklyn Courier Life: 2021, 2022, 2023   Dr. Rosenblum written several book chapters on Peripheral Neuromodulation, Radiofrequency Ablation, and Pharmacology.  He has published numerous noteworthy articles and most recently is developing the ASIPP Guidelines for Peripheral Neuromodulation in the treatment of chronic pain. He has been named several times in NY Magazine's Best Pain Management Doctor List, Nassau County's Best Pain Physician, has appeared on NY1 News, and has made several appearances on XM Radio's Doctor Talk. He currently is lecturing on a national and international level and has partnered with the American Society of Interventional Pain Physicians (ASIPP), American Society of Pain and Neuroscience (ASPN), IASP Mexican Chapter, Eastern Pain Association (EPA), the North American Neuromodulation Society (NANS), World Academy of Pain Medicine United, as well as various other organizations, to support educational events and develop new courses. Since 2008, he has helped over 3000 physicians pass the Pain Management Boards, and has been at the forefront of utilizing ultrasound guidance to perform pain procedures.  He now hosts the PainExam podcast, AnesthesiaExam Podcast, PMRExam Podcasts and uses this platform to promote the safe and effective use of ultrasound in the performance of various procedures such as Peripheral Nerve Stimulation, Caudal Epidurals, Selective Nerve Root Blocks, Cluneal Nerve Blocks, Ganglion impar Blocks, Stellate Ganglion Blocks, Brachial Plexus Blocks, Joint Injections and much more!   Doctor Rosenblum created the NRAP (Neuromodulation Regional Anesthesia and Pain) Academy  and travels to teach various courses focused on Pain Medicine, Regenerative Medicine, Ultrasound Guided Pain Procedures and Regional Anesthesia Techniques.  Dr. Rosenblum is persistent when it comes to eliminating pain and has gained a reputation among his patients for thinking "outside the box" and implements ultrasound guidance to deposit medications, biologics (PRP, Bone Marrow Aspirate, etc.) and Peripheral Nerve Stimulators near pain generators. He is currently treating patients in his great neck and Brooklyn office.  For an appointment go to AABPpain.com or call Brooklyn     718 436 7246 Reference Adriaansen, E. J., Jacobs, J. G., Vernooij, L. M., van Wijck, A. J., Cohen, S. P., Huygen, F. J., & Rijsdijk, M. (2025). 8. Herpes zoster and post herpetic neuralgia. Pain Practice, 25(1), e13423.

Summary In this episode of the Pain Exam Podcast, Dr. David Rosenblum provides a comprehensive review of herpes zoster and postherpetic neuralgia (PHN), focusing on pathophysiology, diagnosis, and treatment options. Dr. Rosenblum explains that postherpetic neuralgia affects approximately 25% of patients with acute herpes zoster, causing debilitating unilateral chronic pain in one or more dermatomes. He discusses the three phases of herpes zoster: acute (up to 30 days), subacute (up to 3 months), and postherpetic neuralgia (pain continuing beyond 3 months). Dr. Rosenblum identifies risk factors for developing PHN, including older age, female sex, immunosuppression, prodromal pain, severe rash, and greater acute pain severity. He details the pathophysiology involving peripheral and central sensitization, and explains different phenotypes of PHN that can guide treatment approaches. For treatment, Dr. Rosenblum reviews various options including antiviral medications (which should be started within 72 hours of onset), corticosteroids, opioids, antidepressants (particularly tricyclics and SNRIs), antiepileptics (gabapentin and pregabalin), topical agents (lidocaine and capsaicin), and interventional procedures such as epidural injections and pulsed radiofrequency. He emphasizes that prevention through vaccination with Shingrix is highly effective, with 97% effectiveness in preventing herpes zoster in patients 50-69 years old and 89% effectiveness in those over 70. Dr. Rosenblum mentions that he's currently treating a patient with trigeminal postherpetic neuralgia and is considering a topical sphenopalatine ganglion block as a minimally invasive intervention before attempting more invasive procedures. Chapters Introduction to the Pain Exam Podcast and Topic Overview Dr. David Rosenblum introduces the Pain Exam Podcast, mentioning that it covers painful disorders, alternative treatments, and practice management. He explains that this episode focuses on herpes zoster and postherpetic neuralgia as board preparation for fellows starting their programs, with ABA boards coming up in September. Dr. Rosenblum notes that he's not only preparing listeners for boards but also seeking the latest information to help treat his own patients with this notoriously difficult disease. Upcoming Conferences and Educational Opportunities Dr. Rosenblum announces several upcoming conferences including Aspen in July, Pain Week in September, and events with NYSIP and the Latin American Pain Society. He mentions he'll be teaching ultrasound and regenerative medicine at these events. Dr. Rosenblum invites listeners to sign up at nrappain.org to access a community discussing regenerative medicine, ultrasound-guided pain medicine, regional anesthesia, and board preparation. He also offers ultrasound training in New York and elsewhere, with upcoming sessions in Manhattan on July 12th and October 4th, plus private shadowing opportunities. Overview of Postherpetic Neuralgia Dr. Rosenblum defines postherpetic neuralgia as typically a unilateral chronic pain in one or more dermatomes after acute herpes zoster infection. He states that the incidence of acute herpes zoster ranges between 3-5 patients per thousand person-years, and one in four patients with acute herpes zoster-related pain will transition into postherpetic neuralgia. Dr. Rosenblum emphasizes that while this condition won't kill patients, it can be extremely debilitating and significantly reduce quality of life. Treatment Options Overview Dr. Rosenblum reviews treatment options according to the WHO pain ladder, including tricyclics like nortriptyline and antiepileptic drugs such as gabapentin. He explains that if pain is not significantly reduced, interventional treatments like epidural injections with local anesthetics and corticosteroids or pulsed radiofrequency of the dorsal root ganglion are options. For postherpetic neuralgia specifically, Dr. Rosenblum notes that preferred treatments include transdermal capsaicin, lidocaine, or oral drugs such as antidepressants or antiepileptics. Phases of Herpes Zoster and Definitions Dr. Rosenblum outlines the three phases during herpes zoster reactivation: acute herpes zoster-related pain (lasting maximum 30 days), subacute herpes zoster-related pain (pain after healing of vesicles but disappearing within 3 months), and postherpetic neuralgia (typically defined as pain continuing after 3 months). He mentions that acute herpes zoster pain often begins with prodromal pain starting a few days before the appearance of the rash. Incidence and Risk Factors Dr. Rosenblum states that the incidence of herpes zoster ranges between 3-5 patients per 1,000 person-years, with approximately 5-30% of cases leading to postherpetic neuralgia. He identifies risk factors including older age, female sex, immunosuppression, prodromal pain, severe rash, and greater acute pain severity. Dr. Rosenblum describes the clinical manifestations as a mosaic of somatosensory symptoms including burning, deep aching pain, tingling, itching, stabbing, often associated with tactile and cold allodynia. Impact on Quality of Life Dr. Rosenblum emphasizes that postherpetic neuralgia can be debilitating, impacting both physical and emotional functioning and causing decreased quality of life. He notes that it leads to fatigue, insomnia, depression, anorexia, anxiety, and emotional distress. Dr. Rosenblum stresses the importance of exploring methods for prevention of postherpetic neuralgia and optimizing pain treatment for both subacute herpes zoster-related pain and postherpetic neuralgia. Literature Review and Pathophysiology Dr. Rosenblum mentions that he's discussing a literature review from 2024 that updates previous practical guidelines published in 2011. He explains the pathophysiology of postherpetic neuralgia, which involves sensitization of peripheral and sensory nerves from damage. Dr. Rosenblum describes how inflammatory mediators reduce the stimulus threshold of nociceptors and increase responsiveness, resulting in pathological spontaneous discharges, lower thresholds for thermal and mechanical stimuli, and hyperalgesia. Central Sensitization and Nerve Damage Dr. Rosenblum explains that central sensitization results from peripheral nociceptor hyperactivity leading to plastic changes in the central nervous system, involving amplification of pain signals and reduced inhibition. He describes how nerve damage in postherpetic neuralgia patients results from neuronal death due to severe inflammatory stimuli or secondary to neuronal swelling. Dr. Rosenblum notes that motor defects occur in 0.05% of patients with herpes zoster, observed as abdominal pseudohernias or motor weakness of limbs limited to the affected myotome. Different Phenotypes and Classification Dr. Rosenblum discusses different phenotypes of postherpetic neuralgia and how phenotyping can determine treatment. He explains that there are several ways to classify the phenotypes, with one categorizing patients into three subtypes: sensory loss (most common), thermal gain, and thermal loss with mechanical gain. Dr. Rosenblum describes the mechanistic categorization, including the irritable nociceptive phenotype characterized by preserved sensation, profound dynamic mechanical allodynia, reduced pressure pain threshold, and relief with local anesthetic infiltration. Deafferentation Phenotype Dr. Rosenblum explains that a deafferentation phenotype may arise from destruction of neurons by the virus in the dorsal root ganglion. This phenotype is characterized by sensory loss, including thermal and vibratory sensation without prominent thermal allodynia. He notes that mechanical allodynia can occur secondary to A-beta fibers activating spinothalamic pathways (known as phenotypic switches), along with pressure hyperalgesia and temporal summation suggesting central sensitization. Dr. Rosenblum mentions that in one study, this phenotype was present in 10.8% of individuals, and for those with deafferentation pain, gabapentinoids, antidepressants, and neuromodulatory therapies like repetitive transcranial magnetic stimulation may be beneficial. Diagnosis and Physical Examination Dr. Rosenblum discusses the diagnosis of herpes zoster and postherpetic neuralgia, emphasizing the importance of physical examination. He explains that diagnosis is based on the rash, redness, papules, and vesicles in the painful dermatomes, with healing vesicles showing crust formation. Dr. Rosenblum notes that the rash is generally unilateral and does not cross the midline of the body. In postherpetic neuralgia patients, he mentions that scarring, hyper or hypopigmentation is often visible, with allodynia present in 45-75% of affected patients. Sensory Testing and Assessment Dr. Rosenblum explains that in patients with postherpetic neuralgia, a mosaic of somatosensory alterations can occur, manifesting as hyperalgesia, allodynia, and sensory loss. These can be quantified by quantitative sensory testing, which assesses somatosensory functions, dermal detection thresholds for perception of cold, warmth, and paradoxical heat sensations. He notes that testing can provide clues regarding underlying mechanisms of pain, impaired conditioned pain modulation, temporal summation suggesting central sensitization, and information about the type of nerve damage and surviving afferent neurons. Prevention Through Vaccination Dr. Rosenblum discusses prevention of acute herpes zoster through vaccination, noting that the risk increases with reduced immunity. He highlights studies evaluating Shingrix, a vaccine for herpes zoster, which showed 97% effectiveness in preventing herpes zoster in patients 50-69 years old with healthy immune systems and 89% effectiveness in patients over 70. Dr. Rosenblum states that Shingrix is 89-91% effective in preventing postherpetic neuralgia development in patients with healthy immune systems and 68-91% effective in those with weakened or underlying conditions. Treatment Objectives Dr. Rosenblum outlines the treatment objectives for herpes zoster and postherpetic neuralgia. For acute herpes zoster, objectives include relieving pain, reducing severity and duration of pain, accelerating recovery of epidermal defects, and preventing secondary infections. For postherpetic neuralgia, the objectives are pain alleviation and improved quality of life. Dr. Rosenblum lists available treatments including psychotherapy, opiates, antidepressants, antiepileptics, NMDA antagonists, topical agents, and interventional treatments such as epidurals, pulsed radiofrequency, nerve blocks, and spinal cord stimulation. Antiviral Medications Dr. Rosenblum emphasizes that antiviral drugs should be started within 72 hours of clinical onset, mentioning famciclovir, valacyclovir, and acyclovir. He notes there is no evidence for effectiveness after 72 hours in patients with uncomplicated herpes zoster. Dr. Rosenblum provides dosing information: for immunocompetent patients, famciclovir 500mg and valacyclovir 1000mg three times daily for seven days; for immunocompromised patients, famciclovir 1000mg three times daily for 10 days, while acyclovir should be given IV in the immunocompromised. Benefits of Antiviral Therapy Dr. Rosenblum explains that antiviral medication accelerates the disappearance of vesicles and crusts, promotes healing of skin lesions, and prevents new lesions from forming. By inhibiting viral replication, he notes that antiviral therapy likely reduces nerve damage, resulting in reduced incidence of postherpetic neuralgia, and should be started as soon as possible. Corticosteroids and Opioids Dr. Rosenblum discusses the use of corticosteroids, noting that when added to antiviral medications, they may reduce the severity of acute herpes zoster-related pain, though increased healing of skin lesions was not observed in one study. He mentions that a Cochrane review found oral corticosteroids ineffective in preventing postherpetic neuralgia. Regarding opioids, Dr. Rosenblum states they are commonly used alongside antivirals for controlling acute herpes zoster pain, with tramadol having a number needed to treat (NNT) of 4.7 and strong opioids having an NNT of 4.3 for 50% pain reduction. Methadone and Antidepressants Dr. Rosenblum discusses methadone as an NMDA receptor antagonist used in acute and chronic pain management, though he notes there are no randomized controlled trials determining its efficacy in acute herpes zoster pain or postherpetic neuralgia. He explains that methadone can modulate pain stimuli by inhibiting the uptake of norepinephrine and serotonin, resulting in decreased development of hyperalgesia and opioid tolerance, but has side effects including constipation, nausea, sedation, and QT prolongation that can trigger torsades de pointes. Dr. Rosenblum identifies antidepressants as first-line therapy for postherpetic neuralgia, including tricyclics and SNRIs, with tricyclics having an NNT of 3 and SNRIs an NNT of 6.4 for 50% pain reduction. Antiepileptics and Pharmacological Treatment Summary Dr. Rosenblum discusses antiepileptics like gabapentin and pregabalin for postherpetic neuralgia. He cites two trials measuring gabapentin's effect, concluding it was effective compared to placebo with a pooled NNT of 4.4, while pregabalin had an NNT of 4.9. Dr. Rosenblum summarizes that pharmacological treatment is well established for subacute herpes zoster pain, though new high-quality evidence has been lacking since the last update in 2011. Topical Agents Dr. Rosenblum discusses local anesthetic topical agents including lidocaine and capsaicin creams and patches. He notes that 8% capsaicin provided significant pain reduction during 2-8 weeks, while 5% lidocaine patches provided moderate pain relief after eight weeks of treatment. Dr. Rosenblum also mentions acute herpes zoster intracutaneous injections, citing a study where single intracutaneous injection with methylprednisolone combined with ropivacaine versus saline alone showed significant difference in VAS score at 1 and 4 weeks post-intervention favoring the intervention group. Intracutaneous Injections Dr. Rosenblum discusses the effect of repetitive intracutaneous injections with ropivacaine and methylprednisolone every 48 hours for one week. He cites a randomized control trial comparing antivirals plus analgesics to antivirals plus analgesics and repeat injections, finding the intervention group had significantly shorter duration of pain, lower VAS scores, and lower incidence of postherpetic neuralgia (6.4% vs 28% at 3 months). Dr. Rosenblum notes that a potential side effect of cutaneous methylprednisolone injection is fat atrophy, though this wasn't reported in the study. Summary of Local Anesthetics Dr. Rosenblum summarizes that there are no new studies reporting the efficacy of capsaicin 8% for postherpetic neuralgia, but it remains widely used in clinical practice and is approved in several countries. He notes that lidocaine patches can reduce pain intensity in patients with postherpetic neuralgia but may be more beneficial in patients with allodynia. Dr. Rosenblum adds that intracutaneous injections may be helpful for short periods, while repetitive injections with local anesthetics may reduce VAS scores for up to six months but can cause subcutaneous fat atrophy. Interventional Treatments: Epidural and Paravertebral Injections Dr. Rosenblum discusses interventional treatments, noting that previous guidelines found epidural injection with corticosteroids and local anesthetic as add-on therapy superior to standard care alone for up to one month in managing acute herpes zoster pain. He mentions a randomized controlled trial showing no difference between interlaminar and transforaminal epidural steroid injections for up to three months after the procedure. Dr. Rosenblum adds that previous guidelines reported high-quality evidence that paravertebral injections of corticosteroids or local anesthetic reduces pain in the active phase of herpes zoster. Comparative Studies on Injection Approaches Dr. Rosenblum discusses a trial comparing efficacy of repetitive paravertebral blocks with ropivacaine versus dexmedetomidine to prevent postherpetic neuralgia, which showed significantly lower incidence of zoster-related pain one month after therapy in the dexmedetomidine group, with effects still significant at three months. He also mentions a study comparing steroid injections administered via interlaminar versus transforaminal approaches, finding both groups had significantly lower VAS scores at 1 and 3 months follow-up compared to baseline, though this could align with the natural course of herpes zoster. Timing of Interventions and Continuous Epidural Blockade Dr. Rosenblum cites a retrospective study showing that transforaminal epidural injections administered for acute herpes zoster-related pain were associated with significantly shorter time to pain relief compared to those performed in the subacute phase. He also mentions a randomized controlled trial finding that continuous epidural blockade combined with opioids and gabapentin reduced NRS pain scores more than analgesic drug treatments alone during three-day follow-up, though both studies were low-quality. Interventions for Postherpetic Neuralgia Dr. Rosenblum discusses interventions specifically for postherpetic neuralgia, citing a small randomized controlled trial that demonstrated decreased NRS pain scores six months post-treatment for repeat versus single epidural steroid injections (15mg vs 5mg dexamethasone) administered over 24 days. The trial also found increased likelihood of complete remission during 6-month follow-up in the group receiving repeat epidural dexamethasone, though this was low-quality evidence. Summary of Epidural and Paravertebral Injections Dr. Rosenblum summarizes that epidural or paravertebral injections of local anesthetic and/or glucocorticoids could be considered in treating acute herpes zoster-related pain. For subacute postherpetic neuralgia pain, he notes low-quality evidence supporting epidural injections, while for postherpetic neuralgia, evidence supports continuous epidural infusion, though also of low quality. Dr. Rosenblum emphasizes that none of the included studies for postherpetic neuralgia investigating epidural or paravertebral injections resulted in decreased pain compared to standard therapy. Pulsed Radiofrequency (PRF) Evidence Dr. Rosenblum discusses pulsed radiofrequency (PRF), noting that previous guidelines indicated moderate quality evidence that PRF of the intercostal nerve reduces pain for 6 months in patients with postherpetic neuralgia, and very low-quality evidence that PRF to the dorsal root ganglion (DRG) reduces pain for 6 months. He mentions that multiple studies have been published since then assessing PRF efficacy. PRF Studies for Acute Herpes Zoster Dr. Rosenblum discusses a randomized controlled trial with 60 patients comparing high-voltage bipolar PRF of the cervical sympathetic chain versus sham, with treatment repeated after three days in both groups. He reports that VAS scores in the PRF group at each post-interventional point (1 day, 2 days, 1 month, 2 months, 3 months) were significantly lower than in the sham group, and at 3 months, the incidence of postherpetic neuralgia was 16.7% in the PRF group compared to 40% in the sham group. PRF for Trigeminal Neuralgia Dr. Rosenblum cites another randomized controlled trial evaluating high-voltage long-duration PRF of the Gasserian ganglion in 96 patients with subacute herpes-related trigeminal neuralgia, which found decreased VAS pain scores at all post-interventional time points (3, 7, 14 days and 1, 3, and 6 months) compared to the sham group. He also mentions a randomized comparative effectiveness study in 120 patients with subacute trigeminal herpes zoster, comparing a single application of high-voltage PRF to the Gasserian ganglion versus three cycles of conventional PRF treatment, finding significantly lower mean VAS pain scores for up to six months in the high-voltage PRF group. PRF Compared to Other Interventions Dr. Rosenblum discusses a randomized controlled trial comparing PRF to short-term spinal cord stimulation, which found decreased pain and improved 36-item short-form health survey scores in both groups at six months. He also mentions a randomized controlled trial in 72 patients where PRF of spinal nerves or peripheral branches of cranial nerves combined with five-day infusion of IV lidocaine resulted in greater pain reduction, less rescue analgesia, and reduced inflammatory cytokines at two months compared to PRF with saline infusions. Dr. Rosenblum notes a major limitation of this study was not accounting for the high natural recovery rate. Summary of PRF and Final Recommendations Dr. Rosenblum summarizes that PRF provides significant pain relief lasting over three months in patients with subacute herpes zoster and postherpetic neuralgia. He notes that since few studies have compared PRF versus sham, it's not possible to calculate an accurate number needed to treat. Dr. Rosenblum mentions there are no comparative studies comparing PRF to the intercostal nerves versus PRF of the DRG, but both preclinical and clinical studies suggest superiority of the DRG approach. He adds that evidence for spinal cord stimulation for postherpetic neuralgia is of low quality, and more research is needed given its invasive nature. Sympathetic Blocks and Conclusion Dr. Rosenblum notes there is low-quality evidence for using sympathetic blocks to treat acute herpes zoster-related pain, but no evidence for their use in postherpetic neuralgia. He mentions that risks of treatment with intrathecal methylprednisolone are unclear and therefore not recommended. Dr. Rosenblum concludes by praising the comprehensive article he's been discussing and mentions it provides insight for treating his patients, including a recent case of trigeminal postherpetic neuralgia. Personal Clinical Approach and Closing Dr. Rosenblum shares that he doesn't currently perform PRF in his practice, partly because it's not standard of care and not well reimbursed, creating barriers to implementation. However, he notes that PRF is a very safe procedure as it doesn't involve burning tissue. For his patient with trigeminal neuralgia pain, Dr. Rosenblum plans to try a topical sphenopalatine ganglion block as the least invasive intervention before considering injecting the trigeminal nerves at the foramen, in addition to pharmacotherapy. He concludes by thanking listeners, encouraging them to check the show notes and links, mentioning institutional memberships and shadowing opportunities, and asking listeners to rate and share the podcast. Q&A No Q&A session in this lecture Pain Management Board Prep   Ultrasound Training REGISTER TODAY!   Create an Account and get Free Access to the PainExam- NRAP Academy Community Highlights     David Rosenblum, MD, currently serves as the Director of Pain Management at Maimonides Medical Center and AABP Integrative Pain Care.  As a member of the Department of Anesthesiology, he is involved in teaching, research, CME activities, and was key faculty in developing the anesthesiology residency's regional anesthesia block rotation, as well as institutional wide acute and chronic pain management protocols to ensure safe and effective pain management. He currently is a managing partner in a multi-physician private pain practice, AABP Integrative Pain Care, located in Brooklyn, NY. He is one of the earliest interventional pain physicians to integrate ultrasound guidance to improve the safety and accuracy of interventional pain procedures.   Awards New York Magazine: Top Doctors: 2016, 2017, 2018, 2021, 2022, 2023, 2024, 2025 Schneps Media: 2015, 2016, 2017, 2019, 2020 Top Doctors New York Metro Area (digital guide): 2016, 2017, 2018, 2019, 2020, 2021, 2022, 2023 2025 Schneps Media - Brooklyn Courier Life: 2021, 2022, 2023   Dr. Rosenblum written several book chapters on Peripheral Neuromodulation, Radiofrequency Ablation, and Pharmacology.  He has published numerous noteworthy articles and most recently is developing the ASIPP Guidelines for Peripheral Neuromodulation in the treatment of chronic pain. He has been named several times in NY Magazine's Best Pain Management Doctor List, Nassau County's Best Pain Physician, has appeared on NY1 News, and has made several appearances on XM Radio's Doctor Talk. He currently is lecturing on a national and international level and has partnered with the American Society of Interventional Pain Physicians (ASIPP), American Society of Pain and Neuroscience (ASPN), IASP Mexican Chapter, Eastern Pain Association (EPA), the North American Neuromodulation Society (NANS), World Academy of Pain Medicine United, as well as various other organizations, to support educational events and develop new courses. Since 2008, he has helped over 3000 physicians pass the Pain Management Boards, and has been at the forefront of utilizing ultrasound guidance to perform pain procedures.  He now hosts the PainExam podcast, AnesthesiaExam Podcast, PMRExam Podcasts and uses this platform to promote the safe and effective use of ultrasound in the performance of various procedures such as Peripheral Nerve Stimulation, Caudal Epidurals, Selective Nerve Root Blocks, Cluneal Nerve Blocks, Ganglion impar Blocks, Stellate Ganglion Blocks, Brachial Plexus Blocks, Joint Injections and much more!   Doctor Rosenblum created the NRAP (Neuromodulation Regional Anesthesia and Pain) Academy  and travels to teach various courses focused on Pain Medicine, Regenerative Medicine, Ultrasound Guided Pain Procedures and Regional Anesthesia Techniques.  Dr. Rosenblum is persistent when it comes to eliminating pain and has gained a reputation among his patients for thinking "outside the box" and implements ultrasound guidance to deposit medications, biologics (PRP, Bone Marrow Aspirate, etc.) and Peripheral Nerve Stimulators near pain generators. He is currently treating patients in his great neck and Brooklyn office.  For an appointment go to AABPpain.com or call Brooklyn     718 436 7246 Reference Adriaansen, E. J., Jacobs, J. G., Vernooij, L. M., van Wijck, A. J., Cohen, S. P., Huygen, F. J., & Rijsdijk, M. (2025). 8. Herpes zoster and post herpetic neuralgia. Pain Practice, 25(1), e13423.

Summary In this episode of the Pain Exam Podcast, Dr. David Rosenblum provides a comprehensive review of herpes zoster and postherpetic neuralgia (PHN), focusing on pathophysiology, diagnosis, and treatment options. Dr. Rosenblum explains that postherpetic neuralgia affects approximately 25% of patients with acute herpes zoster, causing debilitating unilateral chronic pain in one or more dermatomes. He discusses the three phases of herpes zoster: acute (up to 30 days), subacute (up to 3 months), and postherpetic neuralgia (pain continuing beyond 3 months). Dr. Rosenblum identifies risk factors for developing PHN, including older age, female sex, immunosuppression, prodromal pain, severe rash, and greater acute pain severity. He details the pathophysiology involving peripheral and central sensitization, and explains different phenotypes of PHN that can guide treatment approaches. For treatment, Dr. Rosenblum reviews various options including antiviral medications (which should be started within 72 hours of onset), corticosteroids, opioids, antidepressants (particularly tricyclics and SNRIs), antiepileptics (gabapentin and pregabalin), topical agents (lidocaine and capsaicin), and interventional procedures such as epidural injections and pulsed radiofrequency. He emphasizes that prevention through vaccination with Shingrix is highly effective, with 97% effectiveness in preventing herpes zoster in patients 50-69 years old and 89% effectiveness in those over 70. Dr. Rosenblum mentions that he's currently treating a patient with trigeminal postherpetic neuralgia and is considering a topical sphenopalatine ganglion block as a minimally invasive intervention before attempting more invasive procedures. Chapters Introduction to the Pain Exam Podcast and Topic Overview Dr. David Rosenblum introduces the Pain Exam Podcast, mentioning that it covers painful disorders, alternative treatments, and practice management. He explains that this episode focuses on herpes zoster and postherpetic neuralgia as board preparation for fellows starting their programs, with ABA boards coming up in September. Dr. Rosenblum notes that he's not only preparing listeners for boards but also seeking the latest information to help treat his own patients with this notoriously difficult disease. Upcoming Conferences and Educational Opportunities Dr. Rosenblum announces several upcoming conferences including Aspen in July, Pain Week in September, and events with NYSIP and the Latin American Pain Society. He mentions he'll be teaching ultrasound and regenerative medicine at these events. Dr. Rosenblum invites listeners to sign up at nrappain.org to access a community discussing regenerative medicine, ultrasound-guided pain medicine, regional anesthesia, and board preparation. He also offers ultrasound training in New York and elsewhere, with upcoming sessions in Manhattan on July 12th and October 4th, plus private shadowing opportunities. Overview of Postherpetic Neuralgia Dr. Rosenblum defines postherpetic neuralgia as typically a unilateral chronic pain in one or more dermatomes after acute herpes zoster infection. He states that the incidence of acute herpes zoster ranges between 3-5 patients per thousand person-years, and one in four patients with acute herpes zoster-related pain will transition into postherpetic neuralgia. Dr. Rosenblum emphasizes that while this condition won't kill patients, it can be extremely debilitating and significantly reduce quality of life. Treatment Options Overview Dr. Rosenblum reviews treatment options according to the WHO pain ladder, including tricyclics like nortriptyline and antiepileptic drugs such as gabapentin. He explains that if pain is not significantly reduced, interventional treatments like epidural injections with local anesthetics and corticosteroids or pulsed radiofrequency of the dorsal root ganglion are options. For postherpetic neuralgia specifically, Dr. Rosenblum notes that preferred treatments include transdermal capsaicin, lidocaine, or oral drugs such as antidepressants or antiepileptics. Phases of Herpes Zoster and Definitions Dr. Rosenblum outlines the three phases during herpes zoster reactivation: acute herpes zoster-related pain (lasting maximum 30 days), subacute herpes zoster-related pain (pain after healing of vesicles but disappearing within 3 months), and postherpetic neuralgia (typically defined as pain continuing after 3 months). He mentions that acute herpes zoster pain often begins with prodromal pain starting a few days before the appearance of the rash. Incidence and Risk Factors Dr. Rosenblum states that the incidence of herpes zoster ranges between 3-5 patients per 1,000 person-years, with approximately 5-30% of cases leading to postherpetic neuralgia. He identifies risk factors including older age, female sex, immunosuppression, prodromal pain, severe rash, and greater acute pain severity. Dr. Rosenblum describes the clinical manifestations as a mosaic of somatosensory symptoms including burning, deep aching pain, tingling, itching, stabbing, often associated with tactile and cold allodynia. Impact on Quality of Life Dr. Rosenblum emphasizes that postherpetic neuralgia can be debilitating, impacting both physical and emotional functioning and causing decreased quality of life. He notes that it leads to fatigue, insomnia, depression, anorexia, anxiety, and emotional distress. Dr. Rosenblum stresses the importance of exploring methods for prevention of postherpetic neuralgia and optimizing pain treatment for both subacute herpes zoster-related pain and postherpetic neuralgia. Literature Review and Pathophysiology Dr. Rosenblum mentions that he's discussing a literature review from 2024 that updates previous practical guidelines published in 2011. He explains the pathophysiology of postherpetic neuralgia, which involves sensitization of peripheral and sensory nerves from damage. Dr. Rosenblum describes how inflammatory mediators reduce the stimulus threshold of nociceptors and increase responsiveness, resulting in pathological spontaneous discharges, lower thresholds for thermal and mechanical stimuli, and hyperalgesia. Central Sensitization and Nerve Damage Dr. Rosenblum explains that central sensitization results from peripheral nociceptor hyperactivity leading to plastic changes in the central nervous system, involving amplification of pain signals and reduced inhibition. He describes how nerve damage in postherpetic neuralgia patients results from neuronal death due to severe inflammatory stimuli or secondary to neuronal swelling. Dr. Rosenblum notes that motor defects occur in 0.05% of patients with herpes zoster, observed as abdominal pseudohernias or motor weakness of limbs limited to the affected myotome. Different Phenotypes and Classification Dr. Rosenblum discusses different phenotypes of postherpetic neuralgia and how phenotyping can determine treatment. He explains that there are several ways to classify the phenotypes, with one categorizing patients into three subtypes: sensory loss (most common), thermal gain, and thermal loss with mechanical gain. Dr. Rosenblum describes the mechanistic categorization, including the irritable nociceptive phenotype characterized by preserved sensation, profound dynamic mechanical allodynia, reduced pressure pain threshold, and relief with local anesthetic infiltration. Deafferentation Phenotype Dr. Rosenblum explains that a deafferentation phenotype may arise from destruction of neurons by the virus in the dorsal root ganglion. This phenotype is characterized by sensory loss, including thermal and vibratory sensation without prominent thermal allodynia. He notes that mechanical allodynia can occur secondary to A-beta fibers activating spinothalamic pathways (known as phenotypic switches), along with pressure hyperalgesia and temporal summation suggesting central sensitization. Dr. Rosenblum mentions that in one study, this phenotype was present in 10.8% of individuals, and for those with deafferentation pain, gabapentinoids, antidepressants, and neuromodulatory therapies like repetitive transcranial magnetic stimulation may be beneficial. Diagnosis and Physical Examination Dr. Rosenblum discusses the diagnosis of herpes zoster and postherpetic neuralgia, emphasizing the importance of physical examination. He explains that diagnosis is based on the rash, redness, papules, and vesicles in the painful dermatomes, with healing vesicles showing crust formation. Dr. Rosenblum notes that the rash is generally unilateral and does not cross the midline of the body. In postherpetic neuralgia patients, he mentions that scarring, hyper or hypopigmentation is often visible, with allodynia present in 45-75% of affected patients. Sensory Testing and Assessment Dr. Rosenblum explains that in patients with postherpetic neuralgia, a mosaic of somatosensory alterations can occur, manifesting as hyperalgesia, allodynia, and sensory loss. These can be quantified by quantitative sensory testing, which assesses somatosensory functions, dermal detection thresholds for perception of cold, warmth, and paradoxical heat sensations. He notes that testing can provide clues regarding underlying mechanisms of pain, impaired conditioned pain modulation, temporal summation suggesting central sensitization, and information about the type of nerve damage and surviving afferent neurons. Prevention Through Vaccination Dr. Rosenblum discusses prevention of acute herpes zoster through vaccination, noting that the risk increases with reduced immunity. He highlights studies evaluating Shingrix, a vaccine for herpes zoster, which showed 97% effectiveness in preventing herpes zoster in patients 50-69 years old with healthy immune systems and 89% effectiveness in patients over 70. Dr. Rosenblum states that Shingrix is 89-91% effective in preventing postherpetic neuralgia development in patients with healthy immune systems and 68-91% effective in those with weakened or underlying conditions. Treatment Objectives Dr. Rosenblum outlines the treatment objectives for herpes zoster and postherpetic neuralgia. For acute herpes zoster, objectives include relieving pain, reducing severity and duration of pain, accelerating recovery of epidermal defects, and preventing secondary infections. For postherpetic neuralgia, the objectives are pain alleviation and improved quality of life. Dr. Rosenblum lists available treatments including psychotherapy, opiates, antidepressants, antiepileptics, NMDA antagonists, topical agents, and interventional treatments such as epidurals, pulsed radiofrequency, nerve blocks, and spinal cord stimulation. Antiviral Medications Dr. Rosenblum emphasizes that antiviral drugs should be started within 72 hours of clinical onset, mentioning famciclovir, valacyclovir, and acyclovir. He notes there is no evidence for effectiveness after 72 hours in patients with uncomplicated herpes zoster. Dr. Rosenblum provides dosing information: for immunocompetent patients, famciclovir 500mg and valacyclovir 1000mg three times daily for seven days; for immunocompromised patients, famciclovir 1000mg three times daily for 10 days, while acyclovir should be given IV in the immunocompromised. Benefits of Antiviral Therapy Dr. Rosenblum explains that antiviral medication accelerates the disappearance of vesicles and crusts, promotes healing of skin lesions, and prevents new lesions from forming. By inhibiting viral replication, he notes that antiviral therapy likely reduces nerve damage, resulting in reduced incidence of postherpetic neuralgia, and should be started as soon as possible. Corticosteroids and Opioids Dr. Rosenblum discusses the use of corticosteroids, noting that when added to antiviral medications, they may reduce the severity of acute herpes zoster-related pain, though increased healing of skin lesions was not observed in one study. He mentions that a Cochrane review found oral corticosteroids ineffective in preventing postherpetic neuralgia. Regarding opioids, Dr. Rosenblum states they are commonly used alongside antivirals for controlling acute herpes zoster pain, with tramadol having a number needed to treat (NNT) of 4.7 and strong opioids having an NNT of 4.3 for 50% pain reduction. Methadone and Antidepressants Dr. Rosenblum discusses methadone as an NMDA receptor antagonist used in acute and chronic pain management, though he notes there are no randomized controlled trials determining its efficacy in acute herpes zoster pain or postherpetic neuralgia. He explains that methadone can modulate pain stimuli by inhibiting the uptake of norepinephrine and serotonin, resulting in decreased development of hyperalgesia and opioid tolerance, but has side effects including constipation, nausea, sedation, and QT prolongation that can trigger torsades de pointes. Dr. Rosenblum identifies antidepressants as first-line therapy for postherpetic neuralgia, including tricyclics and SNRIs, with tricyclics having an NNT of 3 and SNRIs an NNT of 6.4 for 50% pain reduction. Antiepileptics and Pharmacological Treatment Summary Dr. Rosenblum discusses antiepileptics like gabapentin and pregabalin for postherpetic neuralgia. He cites two trials measuring gabapentin's effect, concluding it was effective compared to placebo with a pooled NNT of 4.4, while pregabalin had an NNT of 4.9. Dr. Rosenblum summarizes that pharmacological treatment is well established for subacute herpes zoster pain, though new high-quality evidence has been lacking since the last update in 2011. Topical Agents Dr. Rosenblum discusses local anesthetic topical agents including lidocaine and capsaicin creams and patches. He notes that 8% capsaicin provided significant pain reduction during 2-8 weeks, while 5% lidocaine patches provided moderate pain relief after eight weeks of treatment. Dr. Rosenblum also mentions acute herpes zoster intracutaneous injections, citing a study where single intracutaneous injection with methylprednisolone combined with ropivacaine versus saline alone showed significant difference in VAS score at 1 and 4 weeks post-intervention favoring the intervention group. Intracutaneous Injections Dr. Rosenblum discusses the effect of repetitive intracutaneous injections with ropivacaine and methylprednisolone every 48 hours for one week. He cites a randomized control trial comparing antivirals plus analgesics to antivirals plus analgesics and repeat injections, finding the intervention group had significantly shorter duration of pain, lower VAS scores, and lower incidence of postherpetic neuralgia (6.4% vs 28% at 3 months). Dr. Rosenblum notes that a potential side effect of cutaneous methylprednisolone injection is fat atrophy, though this wasn't reported in the study. Summary of Local Anesthetics Dr. Rosenblum summarizes that there are no new studies reporting the efficacy of capsaicin 8% for postherpetic neuralgia, but it remains widely used in clinical practice and is approved in several countries. He notes that lidocaine patches can reduce pain intensity in patients with postherpetic neuralgia but may be more beneficial in patients with allodynia. Dr. Rosenblum adds that intracutaneous injections may be helpful for short periods, while repetitive injections with local anesthetics may reduce VAS scores for up to six months but can cause subcutaneous fat atrophy. Interventional Treatments: Epidural and Paravertebral Injections Dr. Rosenblum discusses interventional treatments, noting that previous guidelines found epidural injection with corticosteroids and local anesthetic as add-on therapy superior to standard care alone for up to one month in managing acute herpes zoster pain. He mentions a randomized controlled trial showing no difference between interlaminar and transforaminal epidural steroid injections for up to three months after the procedure. Dr. Rosenblum adds that previous guidelines reported high-quality evidence that paravertebral injections of corticosteroids or local anesthetic reduces pain in the active phase of herpes zoster. Comparative Studies on Injection Approaches Dr. Rosenblum discusses a trial comparing efficacy of repetitive paravertebral blocks with ropivacaine versus dexmedetomidine to prevent postherpetic neuralgia, which showed significantly lower incidence of zoster-related pain one month after therapy in the dexmedetomidine group, with effects still significant at three months. He also mentions a study comparing steroid injections administered via interlaminar versus transforaminal approaches, finding both groups had significantly lower VAS scores at 1 and 3 months follow-up compared to baseline, though this could align with the natural course of herpes zoster. Timing of Interventions and Continuous Epidural Blockade Dr. Rosenblum cites a retrospective study showing that transforaminal epidural injections administered for acute herpes zoster-related pain were associated with significantly shorter time to pain relief compared to those performed in the subacute phase. He also mentions a randomized controlled trial finding that continuous epidural blockade combined with opioids and gabapentin reduced NRS pain scores more than analgesic drug treatments alone during three-day follow-up, though both studies were low-quality. Interventions for Postherpetic Neuralgia Dr. Rosenblum discusses interventions specifically for postherpetic neuralgia, citing a small randomized controlled trial that demonstrated decreased NRS pain scores six months post-treatment for repeat versus single epidural steroid injections (15mg vs 5mg dexamethasone) administered over 24 days. The trial also found increased likelihood of complete remission during 6-month follow-up in the group receiving repeat epidural dexamethasone, though this was low-quality evidence. Summary of Epidural and Paravertebral Injections Dr. Rosenblum summarizes that epidural or paravertebral injections of local anesthetic and/or glucocorticoids could be considered in treating acute herpes zoster-related pain. For subacute postherpetic neuralgia pain, he notes low-quality evidence supporting epidural injections, while for postherpetic neuralgia, evidence supports continuous epidural infusion, though also of low quality. Dr. Rosenblum emphasizes that none of the included studies for postherpetic neuralgia investigating epidural or paravertebral injections resulted in decreased pain compared to standard therapy. Pulsed Radiofrequency (PRF) Evidence Dr. Rosenblum discusses pulsed radiofrequency (PRF), noting that previous guidelines indicated moderate quality evidence that PRF of the intercostal nerve reduces pain for 6 months in patients with postherpetic neuralgia, and very low-quality evidence that PRF to the dorsal root ganglion (DRG) reduces pain for 6 months. He mentions that multiple studies have been published since then assessing PRF efficacy. PRF Studies for Acute Herpes Zoster Dr. Rosenblum discusses a randomized controlled trial with 60 patients comparing high-voltage bipolar PRF of the cervical sympathetic chain versus sham, with treatment repeated after three days in both groups. He reports that VAS scores in the PRF group at each post-interventional point (1 day, 2 days, 1 month, 2 months, 3 months) were significantly lower than in the sham group, and at 3 months, the incidence of postherpetic neuralgia was 16.7% in the PRF group compared to 40% in the sham group. PRF for Trigeminal Neuralgia Dr. Rosenblum cites another randomized controlled trial evaluating high-voltage long-duration PRF of the Gasserian ganglion in 96 patients with subacute herpes-related trigeminal neuralgia, which found decreased VAS pain scores at all post-interventional time points (3, 7, 14 days and 1, 3, and 6 months) compared to the sham group. He also mentions a randomized comparative effectiveness study in 120 patients with subacute trigeminal herpes zoster, comparing a single application of high-voltage PRF to the Gasserian ganglion versus three cycles of conventional PRF treatment, finding significantly lower mean VAS pain scores for up to six months in the high-voltage PRF group. PRF Compared to Other Interventions Dr. Rosenblum discusses a randomized controlled trial comparing PRF to short-term spinal cord stimulation, which found decreased pain and improved 36-item short-form health survey scores in both groups at six months. He also mentions a randomized controlled trial in 72 patients where PRF of spinal nerves or peripheral branches of cranial nerves combined with five-day infusion of IV lidocaine resulted in greater pain reduction, less rescue analgesia, and reduced inflammatory cytokines at two months compared to PRF with saline infusions. Dr. Rosenblum notes a major limitation of this study was not accounting for the high natural recovery rate. Summary of PRF and Final Recommendations Dr. Rosenblum summarizes that PRF provides significant pain relief lasting over three months in patients with subacute herpes zoster and postherpetic neuralgia. He notes that since few studies have compared PRF versus sham, it's not possible to calculate an accurate number needed to treat. Dr. Rosenblum mentions there are no comparative studies comparing PRF to the intercostal nerves versus PRF of the DRG, but both preclinical and clinical studies suggest superiority of the DRG approach. He adds that evidence for spinal cord stimulation for postherpetic neuralgia is of low quality, and more research is needed given its invasive nature. Sympathetic Blocks and Conclusion Dr. Rosenblum notes there is low-quality evidence for using sympathetic blocks to treat acute herpes zoster-related pain, but no evidence for their use in postherpetic neuralgia. He mentions that risks of treatment with intrathecal methylprednisolone are unclear and therefore not recommended. Dr. Rosenblum concludes by praising the comprehensive article he's been discussing and mentions it provides insight for treating his patients, including a recent case of trigeminal postherpetic neuralgia. Personal Clinical Approach and Closing Dr. Rosenblum shares that he doesn't currently perform PRF in his practice, partly because it's not standard of care and not well reimbursed, creating barriers to implementation. However, he notes that PRF is a very safe procedure as it doesn't involve burning tissue. For his patient with trigeminal neuralgia pain, Dr. Rosenblum plans to try a topical sphenopalatine ganglion block as the least invasive intervention before considering injecting the trigeminal nerves at the foramen, in addition to pharmacotherapy. He concludes by thanking listeners, encouraging them to check the show notes and links, mentioning institutional memberships and shadowing opportunities, and asking listeners to rate and share the podcast. Q&A No Q&A session in this lecture Pain Management Board Prep   Ultrasound Training REGISTER TODAY!   Create an Account and get Free Access to the PainExam- NRAP Academy Community Highlights     David Rosenblum, MD, currently serves as the Director of Pain Management at Maimonides Medical Center and AABP Integrative Pain Care.  As a member of the Department of Anesthesiology, he is involved in teaching, research, CME activities, and was key faculty in developing the anesthesiology residency's regional anesthesia block rotation, as well as institutional wide acute and chronic pain management protocols to ensure safe and effective pain management. He currently is a managing partner in a multi-physician private pain practice, AABP Integrative Pain Care, located in Brooklyn, NY. He is one of the earliest interventional pain physicians to integrate ultrasound guidance to improve the safety and accuracy of interventional pain procedures.   Awards New York Magazine: Top Doctors: 2016, 2017, 2018, 2021, 2022, 2023, 2024, 2025 Schneps Media: 2015, 2016, 2017, 2019, 2020 Top Doctors New York Metro Area (digital guide): 2016, 2017, 2018, 2019, 2020, 2021, 2022, 2023 2025 Schneps Media - Brooklyn Courier Life: 2021, 2022, 2023   Dr. Rosenblum written several book chapters on Peripheral Neuromodulation, Radiofrequency Ablation, and Pharmacology.  He has published numerous noteworthy articles and most recently is developing the ASIPP Guidelines for Peripheral Neuromodulation in the treatment of chronic pain. He has been named several times in NY Magazine's Best Pain Management Doctor List, Nassau County's Best Pain Physician, has appeared on NY1 News, and has made several appearances on XM Radio's Doctor Talk. He currently is lecturing on a national and international level and has partnered with the American Society of Interventional Pain Physicians (ASIPP), American Society of Pain and Neuroscience (ASPN), IASP Mexican Chapter, Eastern Pain Association (EPA), the North American Neuromodulation Society (NANS), World Academy of Pain Medicine United, as well as various other organizations, to support educational events and develop new courses. Since 2008, he has helped over 3000 physicians pass the Pain Management Boards, and has been at the forefront of utilizing ultrasound guidance to perform pain procedures.  He now hosts the PainExam podcast, AnesthesiaExam Podcast, PMRExam Podcasts and uses this platform to promote the safe and effective use of ultrasound in the performance of various procedures such as Peripheral Nerve Stimulation, Caudal Epidurals, Selective Nerve Root Blocks, Cluneal Nerve Blocks, Ganglion impar Blocks, Stellate Ganglion Blocks, Brachial Plexus Blocks, Joint Injections and much more!   Doctor Rosenblum created the NRAP (Neuromodulation Regional Anesthesia and Pain) Academy  and travels to teach various courses focused on Pain Medicine, Regenerative Medicine, Ultrasound Guided Pain Procedures and Regional Anesthesia Techniques.  Dr. Rosenblum is persistent when it comes to eliminating pain and has gained a reputation among his patients for thinking "outside the box" and implements ultrasound guidance to deposit medications, biologics (PRP, Bone Marrow Aspirate, etc.) and Peripheral Nerve Stimulators near pain generators. He is currently treating patients in his great neck and Brooklyn office.  For an appointment go to AABPpain.com or call Brooklyn     718 436 7246 Reference Adriaansen, E. J., Jacobs, J. G., Vernooij, L. M., van Wijck, A. J., Cohen, S. P., Huygen, F. J., & Rijsdijk, M. (2025). 8. Herpes zoster and post herpetic neuralgia. Pain Practice, 25(1), e13423.

Lancet 1999;353:2001-07Background: Beta-blockers directly reduce cardiac contractility and myocardial oxygen demand. For decades, they were avoided in patients with acute and chronic heart failure over concerns they would facilitate decompensation of the condition. The therapeutic cornerstones of treatment, prior to the modern era of clinical trials, focused on managing symptoms and quality of life with diuretics and inotropic agents like digoxin; however, new paradigms were arising that focused on addressing neurohormonal mechanisms of chronic disease that were over-activated in the failing heart. The first major success came with inhibition of the renin angiotensin aldosterone system with angiotensin converting enzyme inhibitors whose effect on mortality for patients with mild and severe forms of chronic heart failure were demonstrated in the V-HEFT II, CONSENSUS, and SOLVD trials. Additional benefits were demonstrated with the mineralocorticoid receptor antagonist spironolactone in the RALES trial. These drug classes primarily work by reducing afterload and volume retention. Appreciating why they work for improving cardiac performance and managing symptoms in heart failure patients is straightforward when we consider the major factors that effect cardiac stroke volume - preload, afterload and contractility; however, it is also noteworthy the effects these agents have on sudden death. How beta-blockade benefits the failing heart is less obvious (outside prevention of sudden death). Mechanistic studies in patients with chronic heart failure have consistently shown that when beta blockers are used for more than 1 month, left ventricular function improves. Beta blocker therapy appears to restore the density of beta-adrenergic receptors after they have been downregulated by the chronic overactivity of the sympathetic nervous system. The first major placebo-controlled RCT to demonstrate a mortality benefit used the non-selective beta blocker carvedilol. The trial was small and not originally designed to test mortality and was stopped early without clearly predefined stopping rules. Furthermore, 8% of total patients selected for participation in the trial were excluded prior to randomization after a 2 week, open-label run-in phase with the study drug, which saw 2% of all patients experience worsening heart failure or death representing 24 patients (the difference in total deaths between groups was 9 when the trial was stopped). The Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) was the first large scale trial designed to test the hypothesis that beta-blockade with metoprolol controlled/extended release (CR/XL) added to optimum medical therapy reduces mortality in patients with chronic systolic heart failure.Patients: Patients were recruited from 313 sites in 13 European countries and the United States. Eligible patients were men and women between the age of 40 to 80 years with symptomatic heart failure (NYHA class II-IV) for >/= 3 months before randomization. They had to be on a diuretic and ACE inhibitor for at least 2 weeks. Other drugs, including digoxin, could also be used. Patients also had to have an EF of /=68 beats per minute.Patients were excluded if: they had an MI or unstable angina within 28 days; had an indication or contraindication for treatment with beta-blocker; beta blockade within 6 weeks; heart failure due to systemic disease (i.e., amyloidosis) or alcohol abuse; scheduled or performed cardiac transplant; an ICD; procedures such as CABG or PCI planned or performed in the past 4 months; 2nd or 3rd degree AV block unless a pacemaker was present; unstable or decompensated heart failure defined by pulmonary edema or hypoperfusion or supine systolic BP 25% deviation of the number of observed versus expected consumed placebo tablets during the run-in period.Baseline characteristics: The mean age of patients was 64 years and approximately 78% were male. Slightly more than 30% of patients were above the age of 70. The average EF was 28%. The average SBP was 130 mmHg and heart rate was 82 bpm. Most patients had mild to moderate heart failure, with 41% in NYHA Class II, 56% in Class III, and only 3% in Class IV. Ischemic cardiomyopathy accounted for 65% of cases and nonischemic causes accounted for 35%. Most patients were on an ACE inhibitor or ARB (95%) and diuretic (90%). Digoxin was used in 63%. Trial procedures: Prior to randomization, the study was preceded by a single-blind, 2-week placebo run-in period. Patients meeting eligibility were then randomized to placebo or metoprolol CR/XL. The starting dose of placebo or metoprolol CR/XL was 12.5 mg daily for patients in NYHA class III or IV and 25 mg daily for patients in NYHA class II. The dose was doubled every 2 weeks until the target dose of 200 mg daily was reached. Patients were followed every 3 months.Endpoints: The primary outcome was all-cause mortality. It was estimated that 3,200 patients would need to be followed for 2.4 years to detect a 30% relative reduction in mortality based on annual mortality rate of 9.4% in the placebo group. This would achieve at least 80% power with a 2-sided alpha of 0.04. Patients were recruited faster then planned and so the final sample size of 3,991 patients increased the power of the study.The study was monitored by an independent safety committee and predefined stopping rules for efficacy were based on all-cause mortality, done when 25%, 50%, and 75% of expected deaths had occurred. Results: The trial was stopped early after the 2nd preplanned interim analysis when 50% of expected deaths had occurred. The mean duration of follow-up at the time of stopping was 1 year. The mean daily dose of metoprolol CR/XL was 159 mg once daily, with 87% receiving 100 mg or more and 64% receiving the target dose of 200 mg daily. In the placebo group, the corresponding values were 179 mg daily, 91% and 82%. The study drug was discontinued permanently in 14% of patients in the metoprolol group and 15% in the placebo group. Six months after randomization, heart rate decreased by 14 bpm in the metoprolol group compared to only 3 bpm in the placebo group. Systolic blood pressure decreased less in the metoprolol group (-2.1 vs 3.5 mmHg).Compared to placebo, metoprolol significantly reduced all-cause mortality (7.3% vs 10.8%; RR 0.66; 95% CI 0.53—0.81). Cardiovascular mortality accounted for 91% of all deaths; with sudden death accounting for 58% and death from worsening heart failure accounting for 24% of all deaths. All 3 of these causes of death were significantly reduced by metoprolol. The relative and absolute effects on death were greatest for patients with NYHA class III heart failure.Conclusions: In this trial of stable patients with mild to moderate chronic systolic heart failure, who were optimized on an ACEi or ARB and diuretic, metoprolol CR/XL significantly reduced all-cause mortality. Approximately 30 patients would need to be treated with metoprolol compared to placebo for 1 year to prevent 1 death. This trial represents a significant win for beta blockade in patients with chronic systolic heart failure. While the NNT in this trial is slightly higher than in SOLVD, it is important to appreciate that follow-up time in SOLVD was more than 3x longer. Limitations to external validity in this trial include the run-in period and stringent inclusion and exclusion criteria. Our enthusiasm is also tempered by early stopping, which has been found to be associated with false positive or exaggerated results but this concern is mitigated to some extent in this trial because the rules for early stopping were clearly defined in the protocol.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Robert Pilot and Haley Cherry welcome back Robert Lilligren, President and CEO of NACDI! Then, Rhiana Yazzie, Playwright, Filmmaker, Director, and Artistic Director of New Native Theatre and Amber Ball, Playwright, Director and Visual Artist join to talk about NNT's production of “The Nut, the Hermit, the Crow, and the Monk.”

N Engl J Med 2013;369:1115-23Background: The COURAGE trial was published in 2007. It compared up-front PCI to medical therapy alone in patients with stable CAD. Preventive PCI did not reduce the chance of dying or having a heart attack over a median follow up time of 5 years. The results rocked the cardiology world because for years prior to the publication of COURAGE, the standard of care called for revascularization of obstructive coronary stenosis. Despite what we would consider minor criticisms of COURAGE, the results have held over time as a preventive PCI strategy has failed repeatedly to reduce death or MI compared to medicine alone in subsequent large trials (BARI 2D, FAME 2, ISCHEMIA and ISCHEMIA-CKD) involving patients with stable CAD. But what about patients with acute coronary syndromes who have, a clearly defined “culprit” lesion and stable coronary stenosis of a non-infarct vessel? On the surface, the answer might seem simple - treat the “culprit” lesion with PCI and leave the stable disease alone. Continue optimal medical treatment of stable CAD indefinitely with consideration of revascularization only if new symptoms arise. But what if a stable coronary stenosis behaves differently in a patient with an acute coronary syndrome than in patients without it? Are these patients predisposed or particularly susceptible to acute plaque rupture and thrombogenesis to such an extent that they would benefit from a preventive revascularization strategy? The Primary Angioplasty in Myocardial Infarction (PRAMI) trial sought to test the hypothesis that immediate preventive PCI of non-culprit vessels plus the culprit vessel compared to culprit vessel only PCI would improve outcomes in patients with a STEMI and coronary stenosis of a non-infarct related artery.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients: From 2008 through 2013, patients were enrolled from 5 coronary care centers in the United Kingdom. Patients could be any age with acute STEMI and multivessel CAD detected at the time of emergency PCI. The trial was limited to patients with STEMI because ST-segment elevation, unlike ST-segment depression, localizes the area of ischemia in the myocardium and an “infarct-artery” is usually easy to distinguish. Clinically stable patients were considered for eligibility after undergoing PCI of the infarct artery while they were in the catheterization lab. They were eligible if successful PCI of infarct artery was performed and there was stenosis of 50% or more in one or more non-infarct arteries. Exclusion criteria included cardiogenic shock, previous CABG, had left main or significant disease in the ostia of both the LAD and circumflex vessels, or if the only non-infarct stenosis was a chronic total occlusion.Baseline characteristics: The trial screened 2,428 patients and randomized 465 patients (19%) with 234 to preventive PCI and 231 to no preventive-PCI. The majority of patients were excluded for single vessel disease (1122/1922 [58%]). The average age of patients was 62 years and more than 75% were men. Close to 50% were current smokers. The infarct artery was anterior in 35%, inferior in 60% and lateral in 5%. Approximately 65% of patients had 2 vessel disease and 35% had 3 vessel disease.Procedures: After completion of PCI in the infarct artery, eligible patients were randomized and those assigned to the preventive-PCI group underwent the procedure immediately in all non-infarct arteries with a coronary stenosis >50%. PCI was discouraged at a later date (sometimes this strategy is referred to as “staged PCI”) in the no preventive-PCI group unless it was symptom driven. Any patient in the trial with subsequent symptoms of angina that were not controlled with medicine was required to undergo objective assessment of ischemia to secure a diagnosis of refractory angina. Follow-up information was collected at 6 weeks and then yearly thereafter.Endpoints: The primary endpoint was a composite of death from cardiac causes, nonfatal MI, or refractory angina. Secondary outcomes included the individual components of the composite endpoint along with noncardiac death and repeat revascularization. Myocardial infarction was defined as symptoms of cardiac ischemia and a troponin level >99% URL. However, within 14 days after randomization, MI diagnosis also required ECG evidence of new STE or left bundle branch block and angiographic evidence of coronary artery occlusion (essentially this makes it so only in-stent thrombosis or spontaneous STEMI count and other causes of peri-procedural MI do not - this would bias the trial in favor of the preventive-PCI group).Refractory angina was defined as angina despite medical therapy and objective evidence of myocardial ischemia (i.e., ischemia on ECG during spontaneous episode of pain or abnormal results on functional testing).It was determined that 600 patients would be needed to achieve 80% power to detect a 30% relative reduction in the preventive-PCI group, at a 5% level of significance, assuming an annual rate of the primary outcome of 20% in the control group. Stopping criteria were prespecified if the results from the trial showed a primary outcome difference at the 0.001 level of significance. Results: The trial was stopped early based on a significant difference (P50%, preventive PCI significantly reduced a primary composite outcome of cardiac death, nonfatal MI and refractory angina in the PRAMI trial with an estimated NNT of 7 patients over 2 years. Individual components of the primary endpoint that were significantly reduced included nonfatal MI and refractory angina by similarly large margins. These results may seem impressive at first glance but we urge extreme caution in their interpretation. First, this is a relatively small trial with a historically large effect size, especially when considering hard endpoints like cardiac death and nonfatal MI were included. Such results are often later found to be falsely positive when larger, confirmatory studies are conducted. Second, the trial was stopped early and early stopping is prone to yield false positive and/or exaggerated results. Third, inclusion of refractory angina in the primary endpoint, an endpoint susceptible to bias in an unblinded study (see earlier discussion of “faith healing” and “subtraction anxiety” in FAME 2; consideration also must be given to nocebo effects in patients who know they have “untreated blockages”), clouds the main findings by inflating the effect size and making the trial susceptible to large differences in underpowered endpoints before sufficient data can be accumulated on hard outcomes. For example, if the trial had sought to detect a conservative difference of 30% in a primary composite endpoint that only included cardiac death or nonfatal MI, based on an event rate of 12% in the control group (the actual event rate in the trial), over 2,200 patients would be needed for 80% power at a 5% level of significance. The estimated number of actual events would be around 230. However, only 47 events occurred in PRAMI making the results highly susceptible to noise.While results of PRAMI suggest a beneficial role for preventive-PCI in patients with STEMI, more evidence is needed to confirm the results.Thanks for reading Cardiology Trial's Substack! This post is public so feel free to share it. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Back at cha with another one!  This week Ahri tries to get Casey to move into the apartment above his and shockingly, she's not oppossed to it! Casey also vents about what really grinds her gears and how making food for a toddler everyday is a certain level of hell. Please send help! ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/

Hi and hello from your best friends Ahri and Casey!  This week, Casey threatens to go to New Jersey and punch Ahri in the face for suggesting she could pass for a grandma (rude). Email the pod if you think Casey should punch Ahri in the face nevernottiredpod@gmail.com. Besides violence, these crazy kids talk about a disturbing news story about cyber bullying, and how to prepare your children for birthday parties when they have never met the other friends of the birthday kid.  Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/  

Back in person. this dynamic duo tackles all of lifes important issues this ep - life insurance, and staying healthy as we age.  Have we done a good job of it so far? Negative.  But there's always time to stretch and perhaps get into jazz.  Ahri also talks being ex-communicated by a parent in his childs friend group and Casey suggests pettiness as a way to get back.  ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/

Sorry sorry sorry to leave you hanging after our New Years announcement!  You will hear all about why in todays ep. (Spoiler alert - it's because of puke lots and lots of puke) Casey gives all the deets about her transfer, the nightmare of a first trimester she's having and what sex the baby is. And we get deep discussing the LA wild fires tragedy and how hard it is to parent when tragedy after tragedy just seems to keep on coming.    ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/

Dr. Resa E. Lewiss takes a look back at a year of transformative conversations and storytelling on The Visible Voices Podcast. In this episode she reflects on a few conversations highlighting healthcare leadership, healthcare design, equity, innovation, and action.  You'll hear excerpts from:Wendy Dean (Episode 170): Physician, host of 43cc podcast, Moral Matters podcast, author of If I Betray These Words: Moral Injury in Medicine and Why It's So Hard for Clinicians to Put Patients First and founder of Moral Injury in Healthcare.  Wendy Schiller (Episode 160): Brown University's Interim Director of the Watson Institute for International and Public Affairs, Director of the Taubman Center for American Politics and Policy, and co-author of Inequality Across State Lines  Joanna McClinton (Episode 164): Attorney, politician and 143rd Speaker of the House of Representatives for the State of Pennsylvania Rob Gore (Episode 173): Physician, author ofTreating Violence: An Emergency Room Doctor Takes on a Deadly American Epidemic, and founder of KAVI the Kings Against Violence Initiative Thea James (Episode 133): Physician, Vice President of Mission and Associate Chief Medical Officer at Boston Medical Center, featured in Faces of Medicine docuseries by Khama Ennis. Pooja Kumar (Episode 169): Physician and senior partner McKinsey & Company and leader in the McKinsey Health Institute.   Joe Saul-Sehy (Episode 141): Personal finance expert, co-author of Stacked: Your Super-Serious Guide to Modern Money Management, and host of Stacking Benjamins Show Valerie Jarrett (Episode 136): CEO of The Obama Foundation, and author of Finding My Voice: My Journey to the West Wing and the Path Forward.  Graham Walker (Episode 175): Physician, HealthTech visionary, co founder of MDCalc, the NNT, the Physicians' Charter for Responsible AI, and OffCall, and host of How I Doctor podcast Here's to amplifying voices and creating meaningful change in 2025! If you enjoy the show, please leave a ⭐⭐⭐⭐⭐ rating or review on Apple or YouTube and subscribe via the Website.

Yoo hoo! We are back this week and we are all over the place!  With both Ahri and Casey's families recovering from illnesses, these two dingbats discuss STD's, when Ahri thought he cheated on his wife before thay had ever gone on a date, and Casey slips in some exciting news towards the end of the pod. What happens in the middle of the pod?  No one knows. If you listen can you tell us? ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/

As Casey recovers from norovirus, guest host comedian Liz Glazer is back to chop it up with Ahri! These two parental wonders get into being a great house guest, being someone's "step 9", and being able to apologize. And of course it wouldn't be the holiday season without covering hand, foot and mouth disease - the gift that keeps on giving!   ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/              

N Engl J Med 2010;362:1663-74.Background: The RAVEL and TAXUS-IV trials compared the sirolimus- and paclitaxel-eluting 2nd generation stents to 1st generation bare metal stents. Both trials reported improvements in surrogate endpoints - “in-stent luminal loss” was the primary endpoint of RAVEL and “ischemia-driven target-vessel revascularization” was the primary endpoint of TAXUS-IV. Neither trial showed differences in hard endpoints like death or MI but were not powered for such events.The observation that restenosis still occurred with 2nd generation stents drove interest in developing newer stent technology with improved bioavailability and drug delivery. The 3rd generation everolimus-eluting stent was felt to represent such a development but like its predecessors had only been tested in experiments using surrogate endpoints that were not driven by clinical symptoms. Thus, the SPIRIT IV trial sought to test the hypothesis that 3rd generation everolimus-eluting stents would reduce patient-driven clinical outcomes compared 2nd generation paclitaxel-eluting stents. Furthermore, it was designed to be large enough to provide data on important subgroups, especially patients with diabetes.Patients: Limited details are provided about inclusion and exclusion criteria in the main manuscript and readers are directed to a previous publication and supplemental appendix. Lesion characteristics had to be less than 28 mm in length with a reference-vessel diameter between 2.5 to 3.75 mm. Patients were excluded if they had features making them complex from either a clinical or angiographic standpoint. *Note to learners: Be especially skeptical of trials that do not include at least an abridged version of important inclusion and exclusion criteria in the main publication manuscript. This often indicates that the criteria are complex and that patients are highly selected, which limits the generalizability of the findings to routine practice. Baseline characteristics: The average age of patients was 63 years and 68% were men. Approximately 32% of patients had diabetes with about one quarter being insulin-dependent. Over 20%of patients smoked and a similar percentage had a previous heart attack.Three quarters of patients had 1 target lesion, 22% had 2 target lesions and 3% had 3 and 11% of patients had 1 or more complex lesions. The average lesion length was 15 mm, reference-vessel diameter was 2.75 mm, minimal luminal diameter was 0.75 mm, and average % stenosis was 72%.Procedures: Patients were randomized in a 2:1 ratio to receive an everolimus- or paclitaxel-eluting stent. They were stratified based on having diabetes or not, whether they had a single or complex lesion, and study site. Operators were not blind to the stent being used. At least 300 mg of aspirin was administered before catheterization and at least 300 mg of clopidogrel was recommended before the procedure and was required within 1 hour after stent implantation. Patients took at least 80 mg of aspirin daily for an indefinite period and 75 mg of clopidogrel for at least 12 months. Clinical follow-up visits were scheduled at 30, 180, 270, and 365 days and yearly through 5 years.Endpoints: The primary end point was ischemia-driven target lesion failure at 1 year defined by the composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization. As was the case in the TAXUS-IV trial, “ischemia-driven” did not necessarily mean “symptom-driven”. Two major secondary endpoints were also prespecified which included ischemia-driven target-lesion revascularization and the composite of death or target-vessel MI.The trial was powered for sequential testing of noninferiority and superiority for both the primary and 2 major secondary endpoints. The criteria for noninferiority would be met if the upper limit of the 97.5% confidence interval was not more than 3.1%. This was based on an assumed 1 year target-lesion failure rate of 8.2% for both groups. The trial had 90% power to show non-inferiority. Superiority testing was prespecified if the criterion for noninferiority was met. It was estimated that 3690 patients would have 90% power to detect a 2.9% absolute reduction in the primary end point, at a two-sided alpha of 0.05. The trial also had 90% power to test noninferiority for ischemia-driven target-lesion revascularization and the composite of cardiac death or target-vessel MI at a 2.1% margin. It had 90% and 91% power to test for superiority of these endpoints if noninferiority was met.*Note to learners: The statistical analysis plan for this trial demonstrates 2 important concepts in hypothesis testing. First, trials can be powered in a prespecified manner for non-inferiority and superiority testing. Second, trials can be powered for prespecified hypothesis testing of more than just a single endpoint.Results: Patients were enrolled over a 2 year period from 66 U.S. sites. There were a total of 3,687 patients included in the final analysis with 2,458 in the everolimus-eluting stent group and 1,229 in the paclitaxel-eluting stent group. There were some significant differences for patients receiving everolimus-eluting stents that included the number of stents per lesion, total stent length per lesion, the ratio of stent length to lesion length and the maximum pressure used.At 1 year, everolimus-eluting stents met non-inferiority for the primary and major secondary endpoints and met superiority for 2 of 3. Everolimus-eluting stents reduced the primary endpoint of target-lesion failure (4.2% vs 6.8%; RR 0.62; 95% CI 0.46 to 0.82) and the major secondary endpoint of ischemia-driven target lesion revascularization (2.5 vs 4.6%; RR 0.55; 95% CI 0.38 to 0.78) but not the other major secondary endpoint of cardiac death or target-vessel MI (2.2% vs 3.2%; RR 0.69; 95% CI 0.46 to 1.04). Differences in target-lesion failure were driven by statistically significant reductions in target-lesion revascularization (2.5% vs 4.6%) as well as MI (1.9% vs 3.1%) but not all-cause (1.0% vs 1.3%) or cardiac death (0.4% vs 0.4%). Stent thrombosis was also significantly reduced but rates were very low in both groups and the trial was not powered for this endpoint.Interestingly, subgroup analysis of the primary endpoint revealed a statistically significant interaction for treatment efficacy in patients with diabetes such that diabetics did not appear to benefit from everolimus-eluting stents (6.4% vs 6.9%) compared to non-diabetics (3.3% vs 6.7%; p for interaction = 0.02).Conclusions: In patients with stable CAD who underwent generally non-complex PCI procedures, 3rd generation everolimus-eluting stents compared to 2nd generation paclitaxel-eluting stents reduced a composite endpoint of ischemia-driven target-lesion failure by 38% with a number needed to treat of approximately 40 patients. This was associated with statistically significant reductions in nonfatal MI with a NNT of approximately 100 patients and ischemia-driven target lesion revascularization with a NNT of approximately 50 patients. Everolimus-eluting stents did not reduce death.There was an interaction noted for diabetic patients who did not appear to significantly benefit from everolimus-eluting stents. Notably, diabetics exhibited more severe angiographic disease with a higher prevalence of multivessel disease, diffuse plaque burden, and a greater likelihood of left main coronary artery involvement. This subgroup finding along with the highly selected nature of the study cohort reduces our confidence that the 3rd generation everolimus-eluting stent confers significant advantages over 2nd generation stents for many patients who receive them in clinical practice.One final consideration is that the trial was single blinded and operators were aware of stent type which could have biased their performance and the study results.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

This week Casey and Ahri discuss how hard it would be to home school. Like what do you even do???? We both could never. These dodo's also get into Ahri changing his babies schedule, a fun game at 5 Below and Casey's parenting pet peeve - saying "you're ok" to your kid when they fall.  There's opinions in this ep!! ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/

Live and in person Casey and Ahri are back and they definitely say some questionable things! There is the normal dilly dallying in the beginning of the episode, this time it's about WICKED. Go see it right now. Then we have some sad stuff, but end with some happy stuff. Casey also rants about Urban Outfiters and scares Ahri a bit. So in short - it's a classic ep of NNT.  ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/  

Happy Thanksgiving week from your two best friends that never call! This week as the holidays approach we talk about a Christmas themed restaurant in NYC that's a rip off, childrens "theater" performances, microplastics, and how terrifying it is if your kid has to go into an MRI machine. Eat a ton of Turkey and tell a friend about NNT! ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/  

In today's episode I speak with Graham Walker, MD, the co-founder of MDCalc.  In this conversation we talk about leadership, HealthTech and Graham's visionary HealthTech innovations including  MDCalc, the NNT, the Physicians' Charter for Responsible AI, and OffCall.  Graham is an emergency medicine physician in San Francisco and holds leadership positions with The Permanente Medical Group. He is trained in medical simulation and focuses on clinical informatics and AI in medicine. Graham created, edited, and co-authored the Physicians' Charter for Responsible AI, a practical guide for how AI should be adopted in medical care.  If you enjoy the show, please leave a ⭐⭐⭐⭐⭐ rating or review on Apple or YouTube and subscribe via the Website.

Hello from sunny New York City! Ahri and Casey are reunited and catch up on a smattering of topics. We touch on adult naps, smoking cigs (so cool), what Casey is doing while her husband and child are away and a discovery that Ahri makes while on the road. It is definitely what you think it is!   ********RATE AND REVIEW******** Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/    

After taking last week off, Ahri is back with guest comedian Deric Cahill! Deric kept the co-host seat warm while Casey was away by telling Ahri about being a "liberal" in texas, having a huge wake up call after an arrest and growing up with drug addicts for parents. He also talks about being a parent of 3 kids! That's so many kids! Have a listen and tell a friend. ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/ Follow Deric!  https://www.instagram.com/deric_cahill/?hl=en          

Ahri is back this week and he recounts his once in a lifetime parents night out! Did it make him cry? It wouldn't be Ahri if tears weren't shed. We also talk about how flight delays without kids are actually quite nice, wearing mens shapewear, and how Casey got Botox for the first time. Check it out!  AND PLEASE REVIEW! !!!!!!!AND DON'T FORGET TO VOTE!!!!!!! ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/

N Engl J Med 2012;367:2375-2384Background: The first large trial to compare PCI vs CABG was SYNTAX. In the subgroup of patients with diabetes, which made up approximately 25% of the trial population, PCI was associated with a higher rate of adverse events compared to CABG, primarily driven by higher rates of repeat revascularization in the PCI group.The Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) trial sought to assess the optimal revascularization strategy for patients with diabetes and multivessel coronary artery disease.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients: Eligible patients had diabetes and multivessel coronary artery disease defined as a stenosis of 70% or more in two or more major coronary arteries supplying at least two separate territories.Patients with left main stenosis of 50% or more were excluded as well as patients with severe congestive heart failure, prior CABG or valve surgery, stroke within 6 months, significant bleeding within 6 months, 2 or more chronic total occlusions in major coronary territories that are targets for revascularization, and patients with STEMI within 72 hours.Baseline characteristics: The trial randomized 1,900 patients – 953 randomized to PCI and 947 to CABG.The average age of patients was 63 years and 71% were men. The average HbA1c was 7.8 and 32% were using insulin. Approximately 26% had prior myocardial infarction and 16% were current smokers. The average left ventricular ejection fraction was 66%.Approximately 83% had three vessel disease and 6% of the lesions were classified as chronic total occlusions. The SYNTAX score was low (22 or less) in 35% of the patients, intermediate (23 - 32) in 45% and high (33 or more) in 20%.Procedures: Patients were randomized in a 1:1 ratio to undergo CABG or PCI using drug-eluting stents. The use of arterial conduits was encouraged for patients undergoing CABG.Dual antiplatelet therapy with aspirin and clopidogrel was recommended for at least 12 months following PCI.Endpoints: The primary endpoint was a composite of death from any cause, nonfatal myocardial infarction, and nonfatal stroke. Secondary analysis was performed based on the SYNTAX score and study center location; north America vs not.Analysis was performed based on the intention-to-treat principle. The estimated sample size was 1,900 patients to be followed up for at least 2 years. This sample size would provide 80% power to detect a 27% relative risk reduction in one treatment group based on an estimated event rate of 21.5% in the arm with higher event rate.It's important to note that the initial sample size was 2,400 patients but this was amended twice due to slow recruitment.Authors performed 3 interim analyses and therefore, the p value to indicate statistical significance for the primary outcome was adjusted to be 0.044.Results: Among 32,966 patients who were screened for inclusion, 3,309 (10%) were found eligible. Among eligible patients, 1,900 consented to the trial and were randomized. The breakdown for excluding patients was not provided. The median follow up time was 3.8 years (interquartile range: 2.5 - 4.9). In the PCI arm, the average number of lesions stented per patient was 3.5 and 34% underwent a staged procedure. In the CABG arm, the average number of vessels grafted was 2.9 and 94% had a left internal mammary artery graft.At 5-years, the primary outcome was lower in the CABG arm (18.7% vs 26.6%, absolute difference 7.9%, 95% CI: 3.3 – 12.5; p= 0.005). All-cause death was lower with CABG (10.9% vs 16.3%; p= 0.049) as well as myocardial infarction (6.0% vs 13.9%; p< 0.001). When examining the Kaplan-Meier curves for the primary endpoint as well as death (figure 1 of the manuscript), the curves start to diverge, in favor of surgery, at approximately 2-years of follow up.Stroke was higher with CABG (5.2% vs 2.4%; p= 0.03). Excess stroke in the CABG arm was largely within 30-days after the procedure (1.8% vs 0.3%).Major bleeding within 30-days after revascularization was not significantly different between both treatment groups (3.6% with CABG vs 2.4% with PCI; p= 0.13). Acute renal failure requiring dialysis within 30-days after revascularization was higher with CABG (0.8% vs 0.1%; p= 0.02).There were no significant subgroup interactions that included the SYNTAX score, sex, 2- or 3-vessel disease and study center location; north America vs not.Conclusion: In patients with diabetes and multi-vessel stable coronary artery disease, CABG was superior to PCI in reducing the primary endpoint that consisted of death from any cause, nonfatal myocardial infarction, and nonfatal stroke with a number need to treat (NNT) of approximately 13 patients over an average follow-up period of 3.8 years. All-cause death and myocardial infraction were significantly lower with CABG with a NNT of approximately 19 and 13, respectively. Stroke was higher with CABG with a number needed to harm (NNH) of 36 patients. CABG also increased the risk of acute renal failure requiring dialysis within 30-days after revascularization with a NNH of approximately 143.A key difference between this trial and the early CABG trials is the frequent use of internal mammary grafts in FREEDOM (94% vs 10%). Internal mammary grafts are resistant to atherosclerosis and have high patency rates. One possible explanation for the divergent results between this trial and SYNTAX, which also used arterial grafts frequently, is the follow up time. In SYNTAX, patients were followed for 1 year while FREEDOM followed patients up to 5 years and the curves for the primary outcome and death favoring CABG started to diverge at approximately 2 years.When deciding between CABG and PCI for patients meeting the trial's eligibility criteria, it's important to consider the early risks associated with surgery, with the benefits of CABG becoming more apparent after 2 years. Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

As Ahri recovers from a wedding and a Taylor Swift concert, Casey takes the reigns with guest comedian Megan Gailey! These loose moms discuss birthing big babies, calling Santa to cancel Christmas and how we feel about the new rule that we aren't allowed to tell children we are proud of them anymore.  Spoiler! We both hate it. Listen and for the love of God rate and review! ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/  

This week the dynamic duo of Casey and Ahri decide to lean into positivity and asking for favors! We gotta shoot our shots and reach for the stars or at least read some books that have inspirational quotes that can worm their way into our brains and make us belive we can do it. Heck this is a good old fashioned pep talk of an episode. ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/  

While Casey is out with covid, Ahri interviews his father! We hear from the grandparents side about becoming a grandparent and what parenting styles were like back in the day. He also tells us about being the child of immigrants, dealing with bullies and shares some sad Holocaust stories and one really fun one! ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/  

This weeks episode we are joined by Nicole Gorman AKA @thehungryclementine to talk all thigs diet culture! Nicole is a registered dietician who specializes in intuitive eating and explains the differences between intuitive eating and dieting. Casey and Ahri also decide to do her three week course but will they follow through???? Find out in 3 weeks!!! We answer an email from a listener all about food curiousity with kids as well.  ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/

Well folks after a 15 minute interlude about how Ahri sits down to pee, he shares an insane story about his babies new daycare! Casey also has thoughts on the daycare centers in her area after watching some of the care givers out and about. Should they be on their phones? Was it just a bad moment?  Should they be putting kids in time out or letting parents know if they do time out at the day care???? There are so many questions!!! We answer none of them. But come see us Friday in Chester New York. ***PLEASE REVIEW THE POD SO WE CAN KEEP DOING IT!*** Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/      

It wouldn't be NNT if our two leads didn't start the episode with a soft argument! Casey thinks Ahri ghosted her on a playdate, Ahri says Casey never follwed through either.  Who's the big winner? Ding ding! No one! But the real guts of the episode comes when discussing overly sensitive children - how do you parent them? What's the best approach for diffusing big emotions? We also answer an email about politics! It's a good one folks. ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/  

Our pod picks up this week with Casey and Ahri both in good moods after stellar weekends. We dish on a toddler birthday party that went off without a hitch, and a trip to the Finger Lakes with friends. Then Casey really darkens the mood with a story about one woman's idea of appropriate punishment for a child. We then discuss what is appropriate punishment for kids?     ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/

Episode 69 baby! Our two hero's are back this week and tackling back to school week! As Ahri preps his daughter to return to school, Casey recounts her favorite things about the first day of school and they asnswer an email from a listener who is also feeling the first day jitters. If this sounds like a pretty put together episode just wait till Casey computer dies and all hell breaks loose! Some other highlights include how to step in when one kids is being aggressive with their sibling, and Casey and Ahri clear the air about whether or not they hate each other.  ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/

This week Casey and Ahri are joined by comedian and fellow parent Mike Feeney! After this trio gets into a talk about MMA that prompts Feeney to ask, "what is this podcast about?", they get back on track to dish about sleep training and all the things they never thought they would do as a parent but definitely do as a parent!  Also, what happens that makes Casey and Ahri leave Mike alone to host the pod solo? ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/

Ahri and Casey Are back... This week, Casey genriously allows Ahri to share about his trip and Ahri discusses his recent run in with the Police!!!!!!! AND our hosts play the Newlyed game and let's just say it DID NOT turn how how they thought it would.      ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/  

While Casey was off galavanting in Italy, Ahri called in married comedians Emily and Chris! They discussed being diagnosed with a gene mutation, dating through grief, and what happens when you get your fallopian tubes removed and then immediately host a game night. Don't miss this one! ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/

This piece looks at the DanGer Shock Trial which examines the efficacy of the Impella device in reducing mortality in patients with acute myocardial infarction and cardiogenic shock. We explain how the device works, its implantation process, and the significant findings from the trial, including a notable reduction in six-month mortality with a number needed to treat (NNT) of eight. Despite higher rates of bleeding and renal filtration therapy in the Impella group, the trial provides strong evidence supporting its use in high-volume centers with trained personnel, emphasizing the importance of careful patient selection and timely intervention. Presented by Andy Cumpstey and Joff Lacey with their guest Vasileios Panneudales, an interventional cardiologist at Brompton and Harefield Hospitals.

Casey and Ahri reveal their deepest Darkest Secrets. Casey is a Thief and Ahri might be a serial killer! Ahri shows casey his artwork and she does everything in her power to diminish him. becuase friendship is not about support...ts about breaking each other down until there is nothing left! If anyone is still reading this, im so deeply lonely! ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/

Alrighty we are back and in person! In this weeks episode Ahri finds himself in hot water after he fed his newborn outside of the feeding schedule! Naughty naughty. We discuss why the schedule is so important to moms, and Ahri pitches Casey another terrible business idea. We pepper in chat about movie theater snacks and M Night Shyamalan as well. Get your ears ready for a dang party! ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/ Episode 63 sponsored by Luna Park  https://www.instagram.com/golunapark/ Book a game today at golunapark.com!

It's back - your favorite podcast that you haven't told anyone about (please start telling people)! This week Casey and Ahri tackle how to implement structure, what that means and if people will think your a bad parent if you don't have enough of it. We also talk about Casey's new haircut, our first memories as people and what are go to "moves" are. It's a banger.  ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/ Episode 62 sponsored by Luna Park  https://www.instagram.com/golunapark/ Book a game today at golunapark.com!

Well are you? Casey isn't. Ahri may have cheated. This episode brings the laughs and the drama as tweedle dee and tweedle dum do what they do - argue and get off topic. But also, they take an are you smarter than a 5th grader quiz and Ahri defends wearing a bathing suit for shorts. After all that hulabaloo, Casey discusses the process of having a second child via IVF and where she stands with that.  ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/ Episode 61 sponsored by Luna Park  https://www.instagram.com/golunapark/ Book a game today at golunapark.com!

Episode 60! Casey and Ahri are back live and in person!  Ahri recounts his first weekend away from his newborn and Casey is dealing with the internet comments on a viral video. This leads her on a rant about people working at the bank. It's a wild one folks!  Also email us darnit! ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/ Episode 60 sponsored by Luna Park  https://www.instagram.com/golunapark/ Book a game today at golunapark.com!  

This week we cover a topic that has become controversial - sleepovers! Are we having them, are we not having them? Sleepovers used to be so common and yet many parents are opting out of this old tradition. Ahri also pitches Casey his Shark Tank idea and spoiler alert! She did not invest.    ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/ Episode 59 sponsored by Luna Park  https://www.instagram.com/golunapark/ Book a game today at golunapark.com!  

The JournalFeed podcast for the week of June 10-14, 2024.These are summaries from just 2 of the 5 articles we cover every week! For access to more, please visit JournalFeed.org for details about becoming a member.Monday Spoon Feed:This was a validation study for the recently published American College of Cardiology (ACC) Expert Consensus Decision Pathway for chest pain. Results suggest this pathway is safe and efficacious for use in patients without known CAD; however, performance was not as good for patients with known CAD.Friday Spoon Feed:Noninvasive ventilation (NIV) was superior to standard non-rebreather (NRB) oxygen mask for preoxygenation of critically ill, adult ED or ICU patients requiring intubation, with a NNT of 11 to prevent 1 episode of hypoxemia

Ello! Casey and Ahri are reunited and they immediately cross the line! But good news - Casey successfully stopped breastfeeding after her third attempt! But now she's struggling with a whole other set of emotions and feeling disconnected now that she's no longer physically connected to her baby. Ahri is struggling with emotions as well as he heads back into society after spending the last three weeks holed up with a newborn. Also we talk about buttholes.  ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/ Episode 58 sponsored by Luna Park  https://www.instagram.com/golunapark/ Book a game today at golunapark.com!

Yo ho ho! Ahri is joined this week by his brother, comedian Noah Findling and his wife comedian Sydney Steinberg while Casey is out with a mysterious illness. These bros talk becoming aunts and uncles, having parents in their 80's and completely changing your mind about having kids. It can happen!! And check out Noah and Sydneys podcast - @thebedtimepod ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/ Episode 57 sponsored by Luna Park  https://www.instagram.com/golunapark/ Book a game today at golunapark.com!

The Filtrate:Joel TopfSwapnil HiremathJosh WaitzmanNayan AroraSophia AmbrusoWith Special Guest:Brendon Neuen Super smart guy and clinical trialistVlado Perkovic Lead author of FLOW and friend of NephJCEditor Joel TopfShow NotesThe manuscript (NEJM): Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 DiabetesThe acronym FLOW from the title: evaluate renal Function with semagLutide Once Weekly (Twitter)Joel wrote a blog post prior to the FLOW publication to try to set the table: Peeking Inside Schrödinger's BoxBrendon's Neuen's tweet about total versus chronic slope (X | Twitter)Modification of Association of Cystatin C With Kidney and Cardiovascular Outcomes by Obesity (Science Direct)Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials (PubMed)The Efficacy and Safety of the Combination Therapy With GLP-1 Receptor Agonists and SGLT-2 Inhibitors in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis (Frontiers in Pharmacology)Statistical considerations for testing multiple endpoints in group sequential or adaptive clinical trials (PubMed)Proteinuria Thresholds Are Irrational: A Call for Proteinuria Indexing (Nephron Clinical Practice)Frank Harrel on why the NNT sucks (data methods)Regulation of Na+/H+ exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells (PubMed)Switching Between Glucagon-Like Peptide-1 Receptor Agonists: Rationale and Practical Guidance (PubMed)Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial (PubMed)Doctors are like the pyromaniac fireman (PBFluids)Suggest topics for NephMadness (Twitter)Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint study (CONFIDENCE) (PubMed)Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and Their Combination in Patients with Chronic Kidney Disease: A Randomized Crossover Clinical Trial (PubMed)Spitzer's involvement in revolutionizing nephrology is part of this lecture I did at the University of Nebraska Diabetes Symposium. (Dropbox: Start on slide 29)Spitzer Resigns, Citing Personal Failings (New York Times)Tubular Secretions Swap: Dumb Money on NetFlix (Wikipedia)Josh: Hiking Zion National Park (National Park Service)Sophia: Lost in Space 2018 TV series on NetFlix (Wikipedia)Nayan: Pelican Hill resort (Website)Joel: BodkinNephJC Summer Book Club: Covenant of Water by Abraham Verghese (Amazon)

And baby makes 4! This week we discuss the arrival of Ahri's new baby and how he almost passed out in the delivery room. Men amirite? He tells us how they spent their last few hours as a family of three and what Real Housewife they spotted in Homegoods.  ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/ Episode  sponsored by Luna Park  https://www.instagram.com/golunapark/ Book a game today at golunapark.com!

Casey is joined this week by her husband Robby who is filling in for Ahri as he enjoys his new baby!! These two lovebirds discuss attachment parenting and being a parent not a friend to your child which are both considered hot topics in the parenting sphere. What side are you on? We also discuss our favorite snacks growing up and how Robby spent their babies money. ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/ Episode 55 sponsored by Luna Park  https://www.instagram.com/golunapark/ Book a game today at golunapark.com!

Folks we have a very special ep for you today! Casey forced Ahri to participate in her old podcast Shady Shit's format where she picks a topic that's shady and they discuss it. Todays topic is the mommy blogger turned jail bird Ruby Franke. What happened to this Utah mom who had 2.5 million youtube subscribers that led her to  recieve 4 consecutive jail sentences??? Trigger warning - it's something very bad.  ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/ Episode 54 sponsored by Luna Park  https://www.instagram.com/golunapark/ Book a game today at golunapark.com!  

What happens when you try and record a podcast with a sick baby and two people with no attention span? You're about to find out! Ahri comes to Casey's house to pick up stuff for the new baby and madness ensues. Honestly no idea what we talk about. Should be fun! ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/ Episode 53 sponsored by Luna Park  https://www.instagram.com/golunapark/ Book a game today at golunapark.com!

In todays ep we have a discussion about toys! Can you have too many? Do you rotate? Hide them? Regift them? Only have a few? Or do you say f it and buy every toy on the market and surround your child in toys from all angles? Before we tackle this, we talk about embarassing wedding behavior and our favorite american idol audition videos to watch and end with a listener email about bargaining toddlers. 10/10 ep. ++RATE AND REVIEW++ Need advice? Have a funny story?  Email us at nevernottiredpod@gmail.com Follow Casey and Ahri for all NNT updates! https://www.instagram.com/casefaceb/ https://www.instagram.com/theycallmeahri/ Episode 52 sponsored by Luna Park  https://www.instagram.com/golunapark/ Book a game today at golunapark.com!