General Interest
Pseudo-Endocrine Disorders: Clinical Realities and Responsible Management
20 Jan, 2025 | 11:42h | UTCIntroduction:
This summary outlines key points from a review discussing “pseudo-endocrine disorders”—conditions that lack scientific proof but gain popularity through misinformation. The text focuses on recognizing such disorders, understanding their purported mechanisms, and guiding clinicians on how to approach patients who have received these unvalidated diagnoses. The review emphasizes evidence-based evaluation, patient education, and compassionate care.
Key Recommendations:
- Recognize the Lack of Scientific Validation: Adrenal fatigue, Wilson’s syndrome, and reverse T3 syndrome lack credible evidence. Testing methods (such as salivary cortisol profiles or axillary temperature measurements) are not scientifically validated.
- Avoid Non-Evidence-Based Treatments: Preparations like raw adrenal extracts, high-dose liothyronine, or unverified testosterone treatments may harm patients. Such interventions can induce secondary adrenal insufficiency or suppress endogenous hormone production. Similarly, while not strictly an endocrine issue, the use of Low-Dose Naltrexone (LDN) for autoimmune and other disorders lacks sufficient evidence to support its efficacy and should be approached with caution.
- Thorough Diagnostic Evaluation: Use established endocrine tests (e.g., ACTH stimulation tests for adrenal function, morning testosterone levels for hypogonadism). It is paramount to differentiate between pseudo-endocrine disorders and actual endocrine conditions. Rule out genuine disorders—such as true adrenal insufficiency, primary vs. secondary hypogonadism, or autoimmune thyroid disease—before attributing symptoms to a pseudo-condition.
- Investigate Confounding Factors: Biotin supplements, opioid use, and other medications can invalidate hormone assays or temporarily suppress hormone levels. Conditions like depression, fibromyalgia, or chronic fatigue may underlie nonspecific symptoms but can be overlooked when pseudo-endocrine labels are hastily applied.
- Educate and Empower Patients: Counter internet-driven misinformation by explaining the importance of validated testing and proven treatments. Encourage lifestyle measures (healthy diet, exercise, sufficient sleep) while respecting patients’ concerns and emotional distress.
- Promote Public Awareness and Professional Advocacy: Physicians can inform the public through media appearances, local or national medical organizations, and educational campaigns. Reporting harmful or fraudulent practices to medical boards can protect the public and uphold standards of care.
Conclusion: Adopting an evidence-based strategy and a patient-centered approach is vital when confronted with “pseudo-endocrine” diagnoses. Valid laboratory testing, careful clinical evaluation, and thoughtful follow-up can rule out legitimate endocrine disorders or detect root causes such as sleep apnea or depression. Honest communication and empathy foster trust, counter misinformation, and safeguard patients from unnecessary or dangerous interventions. Ultimately, a commitment to evidence-based medicine and patient-centered care is the most effective strategy in addressing the challenges posed by pseudo-endocrine disorders.
Reference: McDermott MT. “Pseudo-endocrine Disorders: Recognition, Management, and Action.” Journal of the Endocrine Society, Volume 9, Issue 1, January 2025, bvae226. https://doi.org/10.1210/jendso/bvae226
Avian Influenza A(H5N1) Outbreak Among US Farm Exposures: Clinical Findings and Early Treatment Outcomes
2 Jan, 2025 | 17:01h | UTCBackground: Highly pathogenic avian influenza A(H5N1) has reemerged in the United States with documented infections in poultry and dairy cows since 2021. From March through October 2024, 46 human cases were identified, most of whom were workers engaged in poultry depopulation or dairy-farm activities where infected or presumably infected animals were present.
Objective: To characterize the clinical presentations, exposure settings, and outcomes of individuals with laboratory-confirmed H5N1 infection and to investigate potential routes of transmission, disease severity, and risk to public health.
Methods: Using a standardized case-report form, data were collected on exposure history, symptom onset, and use of personal protective equipment (PPE). Respiratory and conjunctival swabs from symptomatic persons underwent real-time RT-PCR for H5 subtyping at both state laboratories and the Centers for Disease Control and Prevention (CDC). Genetic sequencing was performed on available samples. Investigators also monitored close household contacts to evaluate the risk of secondary transmission. An additional hospitalized patient with no identifiable exposure source was detected through routine influenza surveillance.
Results: Of the 46 adult case patients, 20 were exposed to infected poultry, 25 to infected or presumably infected dairy cows, and 1 had unknown exposure. Among the 45 occupationally exposed patients, illness was mild, with no hospitalizations or deaths. Conjunctivitis was present in 93% of cases; 49% reported fever, and 36% had respiratory symptoms. Fifteen patients had only conjunctivitis, highlighting the utility of conjunctival specimens for detection. Early antiviral therapy with oseltamivir was common, initiated at a median of two days after symptom onset. No additional cases were found among 97 closely monitored household contacts, indicating no evidence of sustained human-to-human transmission. Genetic analyses revealed clade 2.3.4.4b viruses, with some genotypic differences between poultry-related (D1.1 genotype) and cow-related (B3.13 genotype) infections.
Conclusions: In this observational study, H5N1 infections in US adults were generally mild, self-limited, and predominantly associated with conjunctivitis. The absence of critical illness or fatalities contrasts with historical reports of more severe H5N1 disease. Although no ongoing person-to-person transmission was documented, continued vigilance is warranted, given the virus’s potential for rapid adaptation.
Implications for Practice: Occupational health measures, such as consistent PPE use (especially eye protection), timely surveillance, and prompt antiviral treatment, may reduce the impact of H5N1 infections among exposed workers. Clinicians should consider conjunctival sampling for symptomatic patients with relevant animal contact. Policy efforts should focus on improving biosecurity practices in both poultry and dairy settings.
Study Strengths and Limitations: Strengths include systematic surveillance, robust laboratory testing of both respiratory and conjunctival specimens, and early antiviral administration. Limitations involve possible underreporting of mild or asymptomatic cases, incomplete details on exposure duration, and limited data on specific routes of cow-to-human transmission.
Future Research: Further studies should explore viral evolution in cows, the significance of raw milk as a transmission vehicle, and the potential for more severe infections, as highlighted by sporadic reports of severe H5N1 illness worldwide.
Reference: Garg S, Reinhart K, Couture A, Kniss K, Davis CT, Kirby MK, Murray EL, et al. Highly Pathogenic Avian Influenza A(H5N1) Virus Infections in Humans. New England Journal of Medicine. Published December 31, 2024. Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2414610
- Editorial: Ison MG, Marrazzo J. The Emerging Threat of H5N1 to Human Health. New England Journal of Medicine. Published December 31, 2024. Link: https://www.nejm.org/doi/full/10.1056/NEJMe2416323
Cohort study: Higher Telehealth Use Linked to Lower Rates of Select Low-Value Services in Medicare
3 Jan, 2025 | 09:30h | UTCBackground: Telehealth has rapidly expanded in recent years, potentially transforming how primary care is delivered. However, questions remain regarding its impact on low-value services—tests or procedures that confer minimal benefit and might be wasteful. Previous research raised concerns that virtual encounters could either reduce or increase unnecessary care, but rigorous data on this matter have been limited.
Objective: To assess whether a primary care practice’s adoption of telehealth is associated with changes in the rate of eight established low-value services, comprising office-based procedures, laboratory tests, imaging studies, and mixed-modality interventions.
Methods: This retrospective cohort study used Medicare fee-for-service claims from 2019 through 2022 for 577,928 beneficiaries attributed to 2,552 primary care practices in Michigan. Practices were grouped into low, medium, or high tertiles of telehealth volume in 2022. A difference-in-differences approach was performed, comparing annualized low-value service rate changes between the prepandemic (2019) and postpandemic (2022) periods.
Results: Overall, high-telehealth practices demonstrated reduced rates of certain office-based low-value services, specifically cervical cancer screening (−2.9 services per 1000 beneficiaries, 95% CI −5.3 to −0.4) among older women. Additionally, high-telehealth practices showed lower rates of select low-value thyroid tests (−40 per 1000 beneficiaries, 95% CI −70 to −9). For five other measures—including imaging for low back pain, imaging for uncomplicated headache, and PSA tests in older men—no significant association was observed between greater telehealth use and low-value service rates. Notably, telehealth volume increased markedly from 2019 to 2022, while in-person visits generally decreased.
Conclusions: These findings suggest that widespread telehealth adoption in Michigan primary care was not associated with elevated low-value service use. In fact, certain office-based low-value tests appeared to decline, possibly owing to fewer face-to-face opportunities to perform unnecessary interventions. Nonetheless, caution is warranted in generalizing these findings, as telehealth’s effects may vary across different clinical contexts.
Implications for Practice: Health care systems should consider structured telehealth protocols that encourage judicious testing and minimize overuse. While telehealth can broaden access, clinicians must remain vigilant to avoid missing necessary care. Clear guidelines, effective triage, and patient education might help balance convenience with quality.
Study Strengths and Limitations: Strengths include a large Medicare population and established low-value service metrics, enhancing the study’s validity. Limitations include a single-state focus (Michigan) and reliance on claims data without detailed clinical information, restricting the scope of outcomes assessed.
Future Research: Further investigation is needed to verify whether these trends extend to other states, different insurance models, and additional low-value services (including medications). Evaluations of telehealth’s role in both low-value and high-value care could offer deeper insights into its broader effects on cost and quality.
Reference: Liu T, Zhu Z, Thompson MP, et al. Primary Care Practice Telehealth Use and Low-Value Care Services. JAMA Network Open. 2024;7(11):e2445436. DOI: http://doi.org/10.1001/jamanetworkopen.2024.45436
Dose-Response Meta-Analysis: At Least 150 Weekly Minutes of Aerobic Exercise Needed for Significant Waist and Fat Reduction
2 Jan, 2025 | 09:30h | UTCBackground: Elevated body weight and adiposity remain major public health concerns worldwide, with overweight and obesity affecting nearly half of the adult population. Although various guidelines advocate for aerobic exercise as a core strategy in weight management, robust meta-analyses exploring dose-response relationships are scarce.
Objective: To clarify how different doses and intensities of supervised aerobic exercise affect body weight, waist circumference, and body fat in adults with overweight or obesity.
Methods: This systematic review and meta-analysis encompassed 116 randomized clinical trials (RCTs) including a total of 6880 participants (mean [SD] age, 46 [13] years). All studies involved supervised continuous aerobic interventions (e.g., walking or running) for at least 8 weeks. Comparisons were made against sedentary or usual-activity controls. Frequency, duration (minutes per week), and intensity (moderate, vigorous, or combined) of aerobic sessions were extracted.
Results: Across all trials, each additional 30 minutes per week of aerobic exercise was linked to a mean reduction of 0.52 kg in body weight (95% CI, −0.61 to −0.44), 0.56 cm in waist circumference, and 0.37 percentage points in body fat. Body weight and waist circumference showed largely linear decreases with increasing weekly exercise, whereas body fat percentage displayed a pattern suggesting that at least 150 minutes per week may be required to achieve clinically meaningful reductions (>2% reduction in body fat). Aerobic training was generally well tolerated, although a modest increase in mild musculoskeletal complaints was noted (risk difference, 2 more events per 100 participants).
Conclusions: Engaging in up to 300 minutes per week of aerobic exercise was associated with progressively greater benefits for weight control, waist circumference, and body fat. While even small doses yielded modest improvements, these findings suggest that an intensity of at least moderate level and a duration of at least 150 minutes per week may be necessary to achieve clinically important reductions in central obesity and fat percentage.
Implications for Practice: Clinicians managing patients with overweight or obesity can recommend a minimum of 150 minutes per week of moderate-to-vigorous aerobic training to achieve significant anthropometric changes. Gradual progression is essential to balance effectiveness and safety, especially in individuals with musculoskeletal constraints.
Study Strengths and Limitations: Strengths include the large number of RCTs, robust dose-response analyses, and consistent directions of effects. However, high heterogeneity, publication bias for certain fat measures, and limited data on medication use and health-related quality of life in longer trials were noted.
Future Research: Further trials should explore additional subgroup analyses (e.g., older adults, individuals with chronic comorbidities), longer durations of follow-up, and the integration of resistance training to optimize cardiometabolic outcomes.
Reference: Jayedi A, Soltani S, Emadi A, et al. Aerobic Exercise and Weight Loss in Adults: A Systematic Review and Dose-Response Meta-Analysis. JAMA Network Open. 2024;7(12):e2452185. DOI: http://doi.org/10.1001/jamanetworkopen.2024.52185
VisionFM: A Generalist AI Surpasses Single-Modality Models in Ophthalmic Diagnostics
25 Dec, 2024 | 13:41h | UTCBackground: Ophthalmic AI models typically address single diseases or modalities. Their limited generalizability restricts broad clinical application. This study introduces VisionFM, a novel foundation model trained on 3.4 million images from over 500,000 individuals. It covers eight distinct ophthalmic imaging modalities (e.g., fundus photography, OCT, slit-lamp, ultrasound, MRI) and encompasses multiple diseases. Compared with prior single-task or single-modality approaches, VisionFM’s architecture and large-scale pretraining enable diverse tasks such as disease screening, lesion segmentation, prognosis, and prediction of systemic markers.
Objective: To develop and validate a generalist ophthalmic AI framework that can handle multiple imaging modalities, recognize multiple diseases, and adapt to new clinical tasks through efficient fine-tuning, potentially easing the global burden of vision impairment.
Methods: VisionFM employs individual Vision Transformer–based encoders for each of the eight imaging modalities, pretrained with self-supervised learning (iBOT) focused on masked image modeling. After pretraining, various task-specific decoders were fine-tuned for classification, segmentation, and prediction tasks. The model was evaluated on 53 public and 12 private datasets, covering eight disease categories (e.g., diabetic retinopathy, glaucoma, cataract), five imaging modalities (fundus photographs, OCT, etc.), plus additional tasks (e.g., MRI-based orbital tumor segmentation). Performance metrics included AUROCs, Dice similarity coefficients, F1 scores, and comparisons with ophthalmologists of varying clinical experience.
Results: VisionFM achieved an average AUROC of 0.950 (95% CI, 0.941–0.959) across eight disease categories in internal validation. External validation showed AUROCs of 0.945 (95% CI, 0.934–0.956) for diabetic retinopathy and 0.974 (95% CI, 0.966–0.983) for AMD, surpassing baseline deep learning approaches. In a 12-disease classification test involving 38 ophthalmologists, VisionFM’s accuracy matched intermediate-level specialists. It successfully handled modality shifts (e.g., grading diabetic retinopathy on previously unseen OCTA), with an AUROC of 0.935 (95% CI, 0.902–0.964). VisionFM also predicted glaucoma progression (F1, 72.3%; 95% CI, 55.0–86.3) and flagged possible intracranial tumors (AUROC, 0.986; 95% CI, 0.960–1.00) from fundus images.
Conclusions: VisionFM offers a versatile, scalable platform for comprehensive ophthalmic tasks. Through self-supervised learning and efficient fine-tuning, it extends specialist-level performance to multiple clinical scenarios and imaging modalities. The study demonstrates that large-scale, multimodal pretraining can enable robust generalization to unseen data, potentially reducing data annotation burdens and accelerating AI adoption worldwide.
Implications for Practice: VisionFM may help address global shortages of qualified ophthalmologists and expand care in low-resource settings, though clinical decision-making still requires appropriate human oversight. Further multicenter studies are needed before widespread implementation, especially for higher-risk use cases such as tumor detection.
Study Strengths and Limitations: Strengths include its unique multimodal design, large-scale pretraining, and extensive external validation. Limitations involve demographic bias toward Chinese datasets, the need for larger cohorts in certain applications (e.g., intracranial tumor detection), and the challenges of matching real-world clinical complexity when only image-based data are used.
Future Research: Further validation in diverse populations, integration of new imaging modalities (e.g., widefield imaging, ultrasound variants), and expansion to additional diseases are planned. Hybridization with large language models could facilitate automatic generation of clinical reports.
Reference: Qiu J, Wu J, Wei H, et al. Development and Validation of a Multimodal Multitask Vision Foundation Model for Generalist Ophthalmic Artificial Intelligence. NEJM AI 2024;1(12). DOI: http://doi.org/10.1056/AIoa2300221
Review: Enhancing Interpretability and Accuracy of AI Models in Healthcare
16 Dec, 2024 | 11:06h | UTCIntroduction: Artificial intelligence (AI) has shown remarkable potential in healthcare for improving diagnostics, predictive modeling, and treatment planning. However, the “black-box” nature of many high-performing AI models limits their trustworthiness and clinical utility. Challenges such as limited generalizability, variable performance across populations, and difficulty in explaining model decisions remain critical barriers to widespread adoption. This review synthesizes current evidence on AI models in healthcare, focusing on the interplay between model accuracy and interpretability. By highlighting these issues, we aim to guide healthcare professionals and researchers toward strategies that balance performance with transparency and reliability.
Key Recommendations:
- Adopt Interpretable Models: Incorporate interpretable frameworks (e.g., LIME, SHAP, Grad-CAM) that allow clinicians to understand model outputs. Such techniques facilitate better acceptance of AI-driven diagnostics, reducing the risk of misinterpretations and erroneous clinical decisions.
- Balance Accuracy and Transparency: Consider hybrid models that achieve high accuracy while maintaining a degree of explainability. Techniques that blend deep learning with simpler statistical or machine learning approaches can offer clinical insights into AI-derived predictions without substantially sacrificing performance.
- Integrate Uncertainty Quantification: Employ methods that estimate uncertainty in AI predictions, providing clinicians with confidence intervals or probability distributions. This approach helps manage expectations, enabling safer decision-making in critical clinical scenarios.
- Use Multimodal Data and Diverse Populations: Encourage the integration of multiple data sources—imaging, clinical notes, genomics—to improve model generalizability. Validate models on diverse patient cohorts to ensure robust performance across various healthcare environments and patient demographics.
- Collaborative, User-Centered Development: Engage healthcare professionals in the model development process to ensure clinical relevance and usability. User-centered design can guide AI solutions that seamlessly fit into existing workflows and foster greater trust among end-users.
Conclusion: The path to fully leveraging AI in healthcare involves overcoming interpretability challenges while maintaining accuracy. Implementing interpretable, uncertainty-aware models validated on diverse datasets will enhance trust, foster responsible adoption, and ultimately improve patient outcomes. By focusing on both technological innovation and user-centered development, we can drive AI models toward safer, more transparent, and clinically beneficial applications.
Cohort Study: Oral Hormone Therapy and Tibolone Increase Cardiovascular Risk in Menopausal Women
28 Nov, 2024 | 18:42h | UTCBackground: Cardiovascular disease is the leading cause of mortality worldwide, with incidence in women increasing notably during the menopausal transition. Menopausal hormone therapy (MHT) effectively alleviates menopausal symptoms but has been associated with cardiovascular risks in previous studies. The impact of contemporary MHT formulations and administration routes on cardiovascular disease risk in women aged 50–58 remains unclear.
Objective: To assess the effect of different types of contemporary MHT on the risk of cardiovascular disease, focusing on various hormone combinations and administration methods.
Methods: This nationwide register-based emulated target trial included 919,614 Swedish women aged 50–58 years between 2007 and 2020 who had not used MHT in the previous two years. Participants were assigned to one of eight treatment groups—including oral and transdermal therapies—or to a non-initiator group. The primary outcomes were hazard ratios (HRs) for venous thromboembolism (VTE), ischemic heart disease (IHD), cerebral infarction, and myocardial infarction, analyzed separately and as a composite cardiovascular disease outcome.
Results: Among the participants, 77,512 were MHT initiators and 842,102 were non-initiators. During follow-up, 24,089 cardiovascular events occurred. In intention-to-treat analyses, tibolone was associated with an increased risk of cardiovascular disease (HR 1.52, 95% CI 1.11 to 2.08) compared with non-initiators. Initiation of tibolone or oral estrogen-progestin therapy was linked to a higher risk of IHD (HRs 1.46 and 1.21, respectively). A higher risk of VTE was observed with oral continuous estrogen-progestin therapy (HR 1.61), sequential therapy (HR 2.00), and estrogen-only therapy (HR 1.57). Per protocol analyses showed that tibolone use was associated with increased risks of cerebral infarction (HR 1.97) and myocardial infarction (HR 1.94).
Conclusions: Use of oral estrogen-progestin therapy was associated with increased risks of IHD and VTE, while tibolone was linked to higher risks of IHD, cerebral infarction, and myocardial infarction but not VTE. These findings underscore the varying cardiovascular risks associated with different MHT types and administration methods.
Implications for Practice: Clinicians should exercise caution when prescribing oral estrogen-progestin therapy or tibolone for menopausal symptom relief, considering the elevated cardiovascular risks. Alternative MHT options, such as transdermal therapies, may offer a safer profile and should be considered.
Study Strengths and Limitations: Strengths include the large, nationwide cohort and the emulated target trial design, which reduces selection bias and confounding. Limitations involve the lack of data on menopausal status, smoking, and body mass index, which may affect cardiovascular risk. Potential misclassification of exposure and adherence could also impact results.
Future Research: Further studies should investigate the cardiovascular effects of specific progestins within MHT formulations and explore the impact of different doses and durations of therapy.
Review: Chronic Low-Level Lead Poisoning
3 Nov, 2024 | 01:15h | UTCIntroduction: Lead poisoning, historically known as plumbism, remains a significant health concern despite reductions in lead use. Chronic low-level lead exposure has been identified as a critical risk factor for cardiovascular disease in adults and cognitive deficits in children, even at blood lead concentrations previously deemed safe. This review by Lanphear et al. explores the multifaceted effects of chronic, low-level lead poisoning, emphasizing its impact on neurodevelopment, kidney function, and cardiovascular health, and underscores the urgent need for effective prevention strategies.
Key Findings:
- Exposure and Absorption: Lead exposure occurs primarily through ingestion and inhalation, with children absorbing lead more readily than adults. Absorption is enhanced in the presence of iron or calcium deficiency. Once absorbed, lead is predominantly stored in the skeleton, and factors altering bone metabolism can mobilize lead back into the bloodstream.
- Neurodevelopmental Effects: Lead exposure is linked to preterm birth, cognitive deficits, attention deficit–hyperactivity disorder (ADHD), and behavioral disorders in children. Notably, cognitive deficits are proportionately larger at lower blood lead levels, with significant IQ reductions observed even at the lowest measurable concentrations.
- Kidney Disease: Chronic lead exposure is a risk factor for chronic kidney disease. Higher blood lead levels are associated with reduced glomerular filtration rates and an increased risk of developing chronic kidney conditions.
- Cardiovascular Disease: Lead induces hypertension and atherosclerosis through mechanisms such as oxidative stress and endothelial dysfunction. It is a leading risk factor for mortality from cardiovascular disease, with substantial risk increases even at low blood lead concentrations. Studies indicate that lead exposure may have contributed to historical trends in coronary heart disease mortality.
- Global Burden: In 2019, lead exposure accounted for approximately 5.5 million deaths from cardiovascular disease and the loss of 765 million IQ points in children globally. The economic cost associated with lead-related health outcomes is estimated at $6 trillion annually, representing about 7% of the global gross domestic product.
- Screening and Treatment: Screening high-risk populations is recommended, including children in older housing and workers in certain industries. While chelation therapy can reduce body lead burden, its effects on health outcomes are inconsistent, highlighting the importance of primary prevention.
- Prevention Strategies: Eliminating environmental sources of lead through government-funded population strategies is essential. This includes replacing lead-containing infrastructure like water service lines, banning leaded aviation fuel, reducing lead in consumer products, and remediating contaminated soils and older housing with lead-based paints.
Conclusion: Chronic low-level lead poisoning continues to pose a significant global health threat, contributing to cardiovascular disease and neurodevelopmental deficits. The disproportionate effects at even the lowest exposure levels underscore the necessity for robust, population-wide prevention strategies. Implementing stringent regulatory actions to eliminate sources of lead exposure is imperative to reduce the substantial morbidity, mortality, and economic burdens associated with lead poisoning.
Cohort Study: GIP/GLP-1 Receptor Agonist Prescriptions Linked to Reduced Opioid Overdose and Alcohol Intoxication
20 Oct, 2024 | 18:36h | UTCBackground: Opioid use disorder (OUD) and alcohol use disorder (AUD) are prevalent conditions leading to significant morbidity and mortality, including overdose and intoxication. Current pharmacotherapies for OUD and AUD are underutilized due to barriers like access and stigma. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), used for type 2 diabetes and obesity, have shown potential in modulating reward pathways associated with substance use, suggesting a possible role in reducing substance-related harms.
Objective: To estimate the association between prescriptions of glucose-dependent insulinotropic polypeptide (GIP) and/or GLP-1 receptor agonists and the incidence of opioid overdose and alcohol intoxication in patients with OUD and AUD, respectively, and to assess this association among patients with comorbid type 2 diabetes and obesity.
Methods: This retrospective cohort study analyzed de-identified electronic health record data from 136 U.S. health systems in the Oracle Cerner Real-World Data, covering over 100 million patients from January 2014 to September 2022. Adults aged 18 years or older with a history of OUD (n = 503,747) or AUD (n = 817,309) were included. The exposure was defined as having one or more prescriptions of GIP/GLP-1 RAs after the first OUD or AUD diagnosis. The primary outcomes were the incidence rates of opioid overdose in the OUD cohort and alcohol intoxication in the AUD cohort.
Results: Patients with GIP/GLP-1 RA prescriptions had significantly lower rates of opioid overdose (aIRR in OUD patients: 0.60; 95% CI, 0.43–0.83) and alcohol intoxication (aIRR in AUD patients: 0.50; 95% CI, 0.40–0.63) compared to those without such prescriptions. The protective association remained significant among patients with comorbid type 2 diabetes and obesity.
Conclusions: Prescriptions of GIP and/or GLP-1 receptor agonists are associated with lower rates of opioid overdose and alcohol intoxication in patients with OUD and AUD. These protective effects persist across various subgroups, including those with comorbid type 2 diabetes and obesity.
Implications for Practice: GLP-1 RAs show promise for reducing substance-related harms in patients with OUD and AUD. Clinicians may consider the potential benefits of GIP/GLP-1 RA prescriptions in this population, while recognizing the need for further research to establish causality and understand underlying mechanisms.
Study Strengths and Limitations: Strengths include a large, diverse patient population and adjustment for multiple confounders. Limitations involve the retrospective observational design limiting causal inference and reliance on data from Cerner-affiliated health systems, which may affect generalizability.
Future Research: Prospective clinical trials are needed to validate these findings, elucidate underlying mechanisms, and assess the efficacy and safety of GIP/GLP-1 RAs as treatments for substance use disorders.
Psychedelic-Assisted Therapy May Reduce Anxiety and Depression in Patients with Life-Threatening Diseases
20 Oct, 2024 | 18:02h | UTCBackground: Anxiety, depression, and existential distress are prevalent among individuals facing life-threatening illnesses, significantly impacting their quality of life. Traditional treatments often have limited efficacy in this population. Psychedelic-assisted therapy, involving substances like psilocybin and LSD under professional supervision, has been proposed as a potential intervention. However, these substances are illegal in most countries and pose potential risks.
Objective: To assess the benefits and harms of psychedelic-assisted therapy compared to placebo or active comparators in treating anxiety, depression, and existential distress in people with life-threatening diseases.
Methods: This Cochrane systematic review included six randomized controlled trials conducted in the USA and Switzerland between 2011 and 2022. A total of 149 participants (140 analyzed), aged 36 to 64 years with life-threatening illnesses (e.g., cancer), were randomized to receive psychedelic-assisted therapy using classical psychedelics (psilocybin or LSD) or MDMA. Interventions included preparatory sessions, the psychedelic experience, and integration sessions. Comparators were active placebos (e.g., low-dose psychedelic or niacin) or placebo. Primary outcomes were anxiety, depression, and existential distress measured 1 to 12 weeks post-intervention.
Results: Psychedelic-assisted therapy with classical psychedelics may reduce anxiety and depression compared to active placebo:
- Anxiety: Mean difference (MD) of −8.41 points on the STAI-Trait scale (20–80 range; 95% CI, −12.92 to −3.89; 5 studies, 122 participants; low-certainty evidence).
- Depression: MD of −4.92 points on the Beck Depression Inventory (0–63 range; 95% CI, −8.97 to −0.87; 4 studies, 112 participants; low-certainty evidence).
The effect on existential distress was mixed and very uncertain. No treatment-related serious adverse events or grade 3/4 adverse events were reported. Common mild to moderate adverse events included elevated blood pressure, nausea, anxiety, and transient psychotic-like symptoms, which resolved shortly after the sessions.
Conclusions: Psychedelic-assisted therapy with classical psychedelics may reduce symptoms of anxiety and depression in patients with life-threatening diseases, but the evidence is of low certainty due to methodological limitations and small sample sizes. The effects of MDMA-assisted therapy are very uncertain.
Implications for Practice: While findings are promising, clinicians should exercise caution due to the low certainty of evidence and legal restrictions surrounding psychedelic substances.
Study Strengths and Limitations: Strengths include randomized designs and standardized therapeutic protocols involving preparation and integration sessions. Limitations are high risk of bias due to unblinding, small sample sizes, potential expectation bias, and cross-over designs with carry-over effects.
Future Research: Larger, well-designed RCTs with rigorous blinding are needed to confirm these findings. Future studies should explore long-term outcomes, diverse patient populations, and strategies to mitigate bias, such as using active placebos and measuring expectancy effects.
Meta-Analysis: Effects of Psychological, Psychosocial, Pharmacological, Physical and Combined Treatments for Adults with a New Episode of Depression – eClinicalMedicine
17 Aug, 2024 | 19:49h | UTCStudy Design and Population: This systematic review and network meta-analysis examined 676 randomized controlled trials (RCTs) involving 105,477 participants, comparing psychological, psychosocial, pharmacological, physical, and combined treatments for adults with a new episode of unipolar depression. The study stratified interventions based on depressive symptom severity (less severe and more severe).
Main Findings: For less severe depression, group cognitive behavioral therapy (CBT) was the only treatment class that significantly improved depressive symptoms compared to treatment as usual (TAU). For more severe depression, effective interventions included combined individual CBT with antidepressants, individual behavioral therapies, and combined treatments like acupuncture or exercise with antidepressants. Notably, antidepressants alone did not show significant effects in less severe depression.
Implications for Practice: These findings suggest that group CBT may be an effective first-line treatment for less severe depression, while combined therapies, particularly those involving antidepressants and individual psychological interventions, are more effective in treating more severe depression. This evidence could guide clinical decision-making and inform updates to treatment guidelines.
Deep Learning Model Noninferior to Radiologists in Detecting Clinically Significant Prostate Cancer at MRI – Radiology
10 Aug, 2024 | 21:31h | UTCStudy Design and Population: This retrospective study evaluated the performance of a deep learning (DL) model for detecting clinically significant prostate cancer (csPCa) using multiparametric MRI (mpMRI) images from 5215 patients (5735 examinations) with a mean age of 66 years. The study included patients who underwent prostate MRI between January 2017 and December 2019 at a single academic institution. The DL model was trained on T2-weighted, diffusion-weighted, and contrast-enhanced MRI sequences, with pathologic diagnosis as the reference standard.
Main Findings: The DL model achieved an area under the receiver operating characteristic curve (AUC) of 0.89 on the internal test set and 0.86 on an external test set, demonstrating noninferiority to radiologists, who had AUCs of 0.89 and 0.84, respectively. Additionally, the combination of the DL model and radiologists improved diagnostic performance (AUC of 0.89). Gradient-weighted class activation maps (Grad-CAMs) effectively localized csPCa lesions, overlapping with true-positive cases in 92% of internal test set and 97% of external test set cases.
Implications for Practice: The DL model showed comparable performance to experienced radiologists in detecting csPCa at MRI, suggesting its potential to assist radiologists in improving diagnostic accuracy and reducing interobserver variability. Future research should focus on integrating the model into clinical workflows and assessing its impact on biopsy targeting.
Cross-Sectional Study: AI Model Accurately Detects Myopia, Strabismus, and Ptosis in Children Using Smartphone Photos – JAMA Netw Open
10 Aug, 2024 | 21:21h | UTCStudy Design and Population: This cross-sectional study was conducted at Shanghai Ninth People’s Hospital from October 2022 to September 2023, including 476 children diagnosed with myopia, strabismus, or ptosis. A total of 1,419 images were used to develop an AI model to detect these conditions based on mobile phone photographs.
Main Findings: The AI model demonstrated strong performance with a sensitivity of 0.84 for myopia, 0.73 for strabismus, and 0.85 for ptosis. The model achieved overall accuracies exceeding 0.80 for myopia and strabismus and 0.92 for ptosis, indicating its effectiveness in early detection of these pediatric eye conditions using only smartphone images.
Implications for Practice: The findings suggest that AI-based screening tools could enable early detection of common pediatric eye diseases at home, reducing the reliance on hospital-based screenings. This approach could facilitate timely intervention, improving visual outcomes and reducing the burden on healthcare systems.
Erythritol Ingestion Increases Platelet Reactivity and Thrombosis Potential in Healthy Adults – Arterioscler Thromb Vasc Biol
10 Aug, 2024 | 21:11h | UTCStudy Design and Population: This interventional study evaluated the effects of erythritol versus glucose on platelet reactivity and thrombosis potential in 20 healthy volunteers, with 10 participants in each group. Researchers measured erythritol plasma levels and assessed platelet function through aggregometry and granule marker analysis both before and after ingestion of 30 g of erythritol or glucose.
Main Findings: Erythritol ingestion resulted in a more than 1000-fold increase in plasma erythritol concentration and significantly enhanced stimulus-dependent platelet aggregation and release of serotonin and CXCL4, markers of platelet activation. In contrast, glucose ingestion did not significantly alter platelet reactivity or granule marker release, highlighting erythritol’s unique pro-thrombotic effects.
Implications for Practice: These findings raise concerns regarding the safety of erythritol as a non-nutritive sweetener, particularly its potential to enhance thrombosis risk. The results suggest a need to reevaluate erythritol’s safety status and consider its impact on cardiovascular health in regulatory guidelines.
New Guidelines Recommend Against Routine Vitamin D Testing and Treatment for Healthy Adults – J Clin Endocrinol Metab
4 Aug, 2024 | 19:19h | UTCIntroduction: The Endocrine Society has developed new clinical practice guidelines focused on the use of vitamin D for the prevention of various diseases. These guidelines were created by a multidisciplinary panel, including experts in adult and pediatric endocrinology, internal medicine, obstetrics and gynecology, nutrition, and epidemiology.
Key Points:
1 – Empiric Vitamin D Supplementation in Children and Adolescents:
– Recommended to prevent nutritional rickets.
– May lower the risk of respiratory tract infections.
– Dosage in trials ranged from 300 to 2000 IU daily, with an average of about 1200 IU per day.
2 – Empiric Vitamin D Supplementation or Testing in Adults Under 75:
– Not recommended for generally healthy adults without specific indications.
3 – Empiric Vitamin D Supplementation in Adults Over 75:
– Suggested due to its potential to lower the risk of mortality.
– Treatment should be empirical, no testing recommended if there are no established indications for testing (e.g., hypocalcemia).
– Recommended daily rather than intermittent high doses. Dosage in clinical trials ranged from 400 to 3333 IU daily equivalent.
4 – Vitamin D Supplementation During Pregnancy:
– Suggested to lower the risk of preeclampsia, intrauterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality.
– Empiric supplementation recommended without routine 25(OH)D testing unless there are established indications for testing.
– Dosages in trials ranged from 600 to 5000 IU daily equivalent, with an average of about 2500 IU per day.
5 – Vitamin D and High-Risk Prediabetes:
– Suggested to reduce the progression to diabetes.
– In clinical trials, vitamin D dosages ranged from 842 to 7543 IU daily. The estimated weighted average was approximately 3500 IU per day.
6 – Routine 25(OH)D Testing:
– Not recommended for the general population, including those with obesity or dark complexion.
– No clear evidence defining optimal target levels for disease prevention.
Conclusion: These guidelines emphasize the importance of targeted vitamin D supplementation for specific age groups and conditions, while advising against routine testing for vitamin D levels in the general population. Empiric supplementation is considered beneficial, particularly in children, pregnant women, and older adults, and is feasible, cost-effective, and generally acceptable.
RCT: Impact of single PSA screening invitation on 15-year prostate cancer mortality – JAMA
25 May, 2024 | 19:01h | UTCStudy Design and Population: This study is a secondary analysis of the Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP), which focused on the long-term effects of prostate-specific antigen (PSA) screening on prostate cancer mortality. It involved 415,357 men aged 50 to 69 years from 573 primary care practices across England and Wales. Participants were randomized to either receive a single invitation for a PSA screening or to a control group receiving standard practice without invitation. The follow-up period concluded on March 31, 2021, after a median duration of 15 years.
Main Findings: The intervention group, which received one PSA screening invitation, showed a prostate cancer mortality rate of 0.69% compared to 0.78% in the control group, translating to a rate ratio of 0.92 and demonstrating a statistically significant but modest reduction in death from prostate cancer. Additionally, the screening led to increased detection rates of low-grade and localized prostate cancer. However, there were no significant differences in detection of more advanced cancer stages between the two groups. All-cause mortality rates were similar across both groups.
Implications for Practice: While the introduction of a single PSA screening invitation was associated with a slight decrease in prostate cancer mortality over 15 years, the absolute reduction was small. These findings suggest that while PSA screening can detect cancer earlier, its impact on long-term survival is limited and should be weighed against the potential for overdiagnosis and overtreatment. Future strategies in prostate cancer screening might need to focus more on risk stratification and personalized screening approaches to maximize benefits and minimize unnecessary interventions.
Reference (link to abstract – $ for full-text):
M-A: Psilocybin significantly reduces depression symptoms across diverse populations – The BMJ
4 May, 2024 | 12:51h | UTCStudy Design and Population:
This systematic review and meta-analysis synthesized data from randomized trials assessing the efficacy of psilocybin as a treatment for depression in adults. Researchers utilized five electronic databases for published literature and four databases for unpublished and international studies. The analysis included 436 participants, aged 36 to 60 years, from seven randomized trials, with both genders represented and varying comorbidities such as cancer.
Main Findings:
The meta-analysis revealed a significant reduction in depression scores among participants treated with psilocybin, with a Hedges’ g value of 1.64, indicating a large effect size. Notably, the improvement was more pronounced among those with secondary depression and those assessed using self-report depression scales. Subgroup analyses and metaregression also highlighted that older age and previous use of psychedelics correlated with greater symptom improvement. Despite the robust findings, high heterogeneity and a risk of small study bias led to a low certainty of evidence.
Implications for Practice:
The findings support psilocybin’s potential as an effective antidepressant, particularly among specific subgroups such as those with secondary depression. However, the presence of high heterogeneity and small study biases suggests that further research is needed to explore the impact of expectancy effects, moderating factors, and treatment modalities. Clinicians should consider these elements when discussing psilocybin as a treatment option with patients, and further high-quality studies are necessary to solidify its role in clinical practice.
Reference (link to free full-text):
Review: Key findings from the Women’s Health Initiative studies on postmenopausal interventions – JAMA
3 May, 2024 | 13:34h | UTCThe Women’s Health Initiative (WHI) studied the impact of various interventions on postmenopausal women aged 50-79, using data from 161,808 participants between 1993 and 2018. The findings suggest that hormone therapy, specifically with conjugated equine estrogens and medroxyprogesterone acetate, does not reduce the risk of cardiovascular diseases, dementia, or other chronic conditions in postmenopausal women. It is, however, effective for managing severe menopausal symptoms when initiated before age 60 in women without contraindications. The trials also concluded that universal supplementation of calcium and vitamin D does not effectively prevent fractures and should be limited to those not meeting dietary intake recommendations. Furthermore, a low-fat diet rich in fruits, vegetables, and grains did not reduce the incidence of breast or colorectal cancer, though it may decrease breast cancer mortality rates, indicating the need for further investigation.
Reference (link to free full-text for a limited period):
USPSTF Guideline: Biennial screening mammography recommended for women aged 40-74 to reduce breast cancer morbidity and mortality
1 May, 2024 | 21:45h | UTCStudy Design and Population:
The US Preventive Services Task Force (USPSTF) performed a systematic review and collaborated on modeling studies to evaluate the effectiveness of various mammography-based breast cancer screening strategies. This assessment included factors such as age of initiation and cessation of screening, screening intervals, modalities, and the use of supplemental imaging. The population studied consisted of cisgender women and all other persons assigned female at birth who are 40 years or older and at average risk of breast cancer.
Main Findings:
The USPSTF concludes with moderate certainty that biennial screening mammography for women aged 40 to 74 years provides a moderate net benefit in reducing the incidence of and progression to advanced breast cancer, as well as in decreasing breast cancer morbidity and mortality. However, the evidence is insufficient to assess the benefits and harms of mammography screening in women aged 75 and older, as well as the use of supplemental screening with ultrasound or MRI in women with dense breasts.
Implications for Practice:
Based on these findings, the USPSTF recommends biennial screening mammography for women aged 40 to 74 years. This recommendation aims to optimize breast cancer outcomes while considering the balance of benefits and harms of screening. There is a need for further research to clarify the benefits and risks associated with mammography in women older than 75 and for those with dense breasts considering supplemental screening.
Commentary on X (thread – click for more)
🧵 Just published: USPSTF recommends all women undergo routine #breastcancer screening every other year beginning at age 40, an update from the 2016 recommendation to start at age 50.
https://t.co/xDPK4qu7JH pic.twitter.com/3zVBMWeuKb— JAMA (@JAMA_current) April 30, 2024
Reference (link to free full-text):
Pooled Analysis: Changes in prevalence of underweight and obesity from 1990 to 2022 in 200 countries
27 Apr, 2024 | 16:02h | UTCStudy Design and Population:
This pooled analysis utilized data from 3,663 population-representative studies involving 222 million participants to assess trends in underweight, thinness, and obesity. The study separated its analysis between adults (aged ≥20 years) and school-aged children and adolescents (aged 5–19 years) across 200 countries from 1990 to 2022. Bayesian hierarchical models were employed to estimate trends in different BMI categories.
Main Findings:
The findings indicate significant geographical and demographic variations in the prevalence of underweight and obesity. While the combined prevalence of underweight and obesity decreased in a minority of countries, it increased significantly in the majority, particularly in island nations, the Middle East, and North Africa. The study also found that obesity rates have surpassed underweight rates in the vast majority of countries by 2022.
Implications for Practice:
The increasing prevalence of obesity alongside persistent underweight and thinness issues underscores the need for a dual-focused public health approach. Strategies should prioritize not only the reduction of obesity through healthy eating and physical activity but also address undernutrition by improving access to nutritious foods, especially in regions like south Asia and parts of Africa where underweight remains prevalent.
RCT: Lack of significant effect of Paxlovid (nirmatrelvir–ritonavir) on symptom alleviation in Covid-19
26 Apr, 2024 | 11:49h | UTCStudy Design and Population:
This phase 2–3 randomized clinical trial investigated the efficacy of nirmatrelvir in combination with ritonavir for treating mild-to-moderate Covid-19 in adults. Participants, both vaccinated and unvaccinated, were enrolled based on their risk factors for severe Covid-19. The study included 1296 adults who had confirmed Covid-19 with symptom onset within the past 5 days. They were randomly assigned to receive either nirmatrelvir–ritonavir or placebo every 12 hours for 5 days.
Main Findings:
The primary endpoint was the time to sustained alleviation of all targeted Covid-19 signs and symptoms. Results showed that the median time to alleviation was 12 days for the treatment group and 13 days for the placebo group, a difference that was not statistically significant (P=0.60). Hospitalizations and deaths were slightly lower in the treatment group (0.8%) compared to the placebo group (1.6%), but this difference was also not statistically significant. Adverse events were similar across both groups, with dysgeusia and diarrhea being the most common in the treatment group.
Implications for Practice:
The findings indicate that nirmatrelvir–ritonavir treatment does not significantly reduce the time to symptom alleviation for Covid-19 compared to placebo among vaccinated or unvaccinated adults. These results suggest that further research is needed to explore the potential benefits of this treatment in specific subpopulations or in combination with other interventions.
Reference (free full-text):
Systematic Analysis: Global Burden and Trends of Nervous System Disorders, 1990–2021
21 Mar, 2024 | 11:10h | UTCStudy Design and Population
This study, a systematic analysis conducted by the Global Burden of Disease Study 2021, aimed to estimate the global, regional, and national health loss attributable to 37 unique nervous system conditions from 1990 to 2021. The researchers estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs) across 204 countries. The analysis included morbidity and deaths directly resulting from damage to the central or peripheral nervous system, as well as neurological health loss from conditions where nervous system morbidity is a secondary outcome.
Main Findings
The collective global burden of these nervous system conditions emerged as the leading cause of DALYs in 2021, affecting approximately 3.40 billion individuals (43.1% of the global population) and resulting in 443 million DALYs. Although global DALY counts for these conditions increased by 18.2% from 1990 to 2021, there was a notable decrease in the age-standardised rates of deaths and DALYs by 33.6% and 27.0%, respectively. The conditions contributing most significantly to the age-standardised DALYs were stroke, neonatal encephalopathy, migraine, and Alzheimer’s disease among others.
Implications for Practice
This analysis underscores the critical need for effective prevention, treatment, and rehabilitation strategies for nervous system disorders, which now lead the global disease burden. Highlighting an 18.2% increase in DALY counts over the study period, it calls for heightened public health attention and resource allocation towards these conditions. The findings support the prioritization of nervous system health on the global health agenda and stress the importance of further research into modifiable risk factors and equitable access to care.
Reference
GBD 2021 Nervous System Disorders Collaborators (2024). Systematic Analysis: Global Burden and Trends of Nervous System Disorders, 1990–2021. The Lancet Neurology, Volume(issue), Pages. DOI: https://doi.org/10.1016/S1474-4422(24)00038-3. Access the study here: Link
Meta-Analysis: Efficacy of exercise modalities in major depressive disorder treatment
20 Mar, 2024 | 17:54h | UTCStudy Design and Population: This article presents a systematic review and network meta-analysis of randomized controlled trials to assess the optimal dose and modality of exercise for treating major depressive disorder, comparing its effects to psychotherapy, antidepressants, and control conditions such as usual care or placebo. The review included 218 unique studies encompassing 495 arms with a total of 14,170 participants who met the clinical cutoffs for major depression.
Main Findings: The findings revealed moderate reductions in depression symptoms for several exercise modalities when compared to active controls. Notably, walking or jogging, yoga, and strength training demonstrated the most significant effects. The effectiveness of exercise was found to be proportional to the intensity of the activity prescribed. Among these, yoga and strength training were identified as the most acceptable modalities for participants. However, the overall confidence in these results is low due to the high risk of bias in the included studies, with only one study meeting the criteria for a low risk of bias.
Implications for Practice: The study concludes that exercise, particularly walking or jogging, yoga, and strength training at sufficient intensities, can be an effective treatment for major depressive disorder. These modalities could be recommended alongside traditional treatments such as psychotherapy and antidepressants. Future research should focus on blinding participants and staff to mitigate expectancy effects and improve the reliability of findings. The inclusivity of exercise as a core treatment for depression could significantly impact treatment strategies and patient outcomes.
Reference: Noetel, M., et al. (2024). Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials. BMJ, 384, e075847. DOI: https://doi.org/10.1136/bmj-2023-075847. Access the study here: [Link]
Perspective | Clinicians debate the usefulness of NAFLD name change
11 Aug, 2023 | 15:39h | UTCClinicians debate the usefulness of NAFLD name change – MDedge
Original article: From NAFLD to MASLD | New consensus changes fatty liver disease terminology to avoid stigmatization
Study | The high financial and human cost of quality metric reporting in hospitals
11 Aug, 2023 | 15:36h | UTCThe Volume and Cost of Quality Metric Reporting – JAMA (link to abstract – $ for full-text)
Author Interview: The Costs of Quality Reporting – JAMA
Commentaries:
The Cost of “Quality” – Emergency Medicine Literature of Note
How John Hopkins spent $5m and 108,478 hours on quality reporting in one year – HealthLeaders
The cost of quality metric reporting – Becker’s Hospital Review