Smoking Duration and Log Cig-Years Outperform Pack-Years in Predicting Survival in HNSCC: Study Finds

Canada: A recent cohort study published in JAMA Otolaryngology-Head & Neck Surgery evaluated the effectiveness of different smoking metrics in predicting overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC). The study identified smoking duration (aHR: 1.11) and log cig-years (aHR: 1.11) as the most reliable predictors of overall survival, demonstrating a strong linear correlation with OS and surpassing pack-years in predictive accuracy.

“Their effectiveness remained consistent across different patient subgroups and tumor sites, reinforcing their potential as superior metrics for assessing the impact of smoking on survival outcomes,” the researchers wrote.

Cigarette smoking plays a critical role in the development and prognosis of head and neck squamous cell carcinoma, significantly impacting patient survival. While smoking is a well-established risk factor, there is limited evidence on the most effective metric for accurately modeling its association with survival outcomes. Existing survival models often rely on smoking status or pack years to quantify exposure, but these measures may not fully capture the long-term effects of smoking.

To address this limitation, Andrew C. L. Lam, Department of Medicine, University of Toronto, Toronto, Ontario, Canada, and colleagues have explored alternative metrics that provide a more precise evaluation of smoking impact on survival in HNSCC patients.

For this purpose, the researchers conducted a retrospective multicenter cohort study across six clinical epidemiological studies, including five from the Human Papillomavirus, Oral and Oropharyngeal Cancer Genomic Research (VOYAGER) consortium. The study analyzed data from patients aged 18 and older with pathologically confirmed HNSCC, collected between January 2002 and December 2019 and evaluated between January 2022 and November 2024.

The primary outcome was overall survival (OS), assessed using eight smoking metrics, including pack-years, duration, and log cig-years. These metrics were compared based on their association strength in Cox proportional hazard models, linear trend significance, Akaike information criterion (AIC), and spline curve assessments. Secondary analyses explored OS across clinicodemographic subgroups and tumor subsites, while exploratory outcomes included cancer-specific and noncancer survival.

The following were the key findings:

  • The study included 8,875 patients with HNSCC, with a median age of 61 years and 24% female participants.
  • Among the eight smoking metrics evaluated, smoking duration (aHR: 1.11) and log cig-years (aHR: 1.11) had the highest adjusted hazard ratios (aHRs).
  • Both smoking duration and log cig-years showed a statistically significant linear association with overall survival.
  • Log cig-years demonstrated the best model fit, with the lowest Akaike information criterion (AIC) linear value and the most visually linear spline curve for OS modeling.
  • Smoking duration and log cig-years outperformed pack-years in predicting OS across all age groups, smoking statuses, and cancer stages.
  • Both metrics performed well in lip and oral cavity cancers, while duration alone showed significance in laryngeal cancer and human papillomavirus (HPV)-negative oropharyngeal cancers.
  • In an exploratory analysis, smoking duration had the highest aHR (1.15) for noncancer survival, while log cig-years had the lowest AIC linear value in modeling noncancer survival.

The researchers found that smoking duration and log cig-years demonstrated the strongest linear association with overall survival in patients with HNSCC, maintaining consistent predictive performance across various clinicodemographic subgroups and tumor subsites.

“While conventional survival models often rely on smoking status or pack-years to quantify smoking exposure, these findings suggest that duration and log cig-years may serve as superior metrics for assessing the impact of smoking on survival. Their robustness in modeling survival outcomes highlights their potential for both clinical decision-making and future research applications in HNSCC,” the researchers concluded.

Reference:

Lam ACL, Hueniken K, Pienkowski M, et al. Performance of 8 Smoking Metrics for Modeling Survival in Head and Neck Squamous Cell Carcinoma. JAMA Otolaryngol Head Neck Surg. Published online February 20, 2025. doi:10.1001/jamaoto.2024.5392

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Selumetinib shows Limited Efficacy in Treatment of cutaneous neurofibromatosis: JAMA

Researchers have found in a nonrandomised pilot trial that selumetinib showed a reduction in cutaneous neurofibromatosis volume, but it did not lead to sustained improvements in patient-reported outcomes.

Cutaneous neurofibromas (cNFs) can cause itching, disfigurement, pain, and emotional difficulties in people with neurofibromatosis type 1 (NF1). A study was done to determine the impact of the mitogen-activated protein kinase kinase inhibitor selumetinib on cNF including change in tumor volume and patient-reported outcome measures. Adults with NF1 and 9 or more measurable cNFs were enrolled in this nonrandomized pilot trial at the National Cancer Institute and the University of Alabama at Birmingham, which spanned from August 26, 2017, to August 21, 2023. Participants received selumetinib for up to 24 cycles (1 cycle = 28 days) with restaging visits after every 4 cycles. Photography and volumetric measurements of cNFs using calipers were used to evaluate the number and volume of tumors. Participants completed the Skindex-29 Quality of Life assessment to quantify the effect of treatment on symptoms, functioning, emotions, itching, and pain. Results Among the 11 participants who enrolled, the median (range) age was 54 (28-75) years, and 6 were female. The median (IQR) best response across all participants and tumors was a −28.5% (−40.9% to −12.5%) decrease in cNF volume from baseline. Some participants showed a visible improvement in cNF burden while receiving treatment in standardized photographs. The median (range) duration of treatment was 9 cycles (1-24), with only 4 participants completing the full 24 cycles of treatment. Two of these participants continued treatment beyond the original 24 cycles due to perceived clinical benefit. All participants experienced at least 1 reversible drug-related adverse event (AE), with cutaneous AEs such as dry skin and rash being the most common. Two participants were removed from treatment due to concern for drug reaction with eosinophilia and systemic symptoms. While the Skindex-29 assessment showed improvement in emotion scores after cycle 1, there were no other significant or durable changes in scores. In this nonrandomized pilot trial, selumetinib resulted in some decrease in cNF volume; however, there was no sustained improvement in patient-reported outcome measures. Study enrollment was incomplete, in part due to the COVID-19 pandemic, and highlights the challenges of treating patients with cNF with a drug that often leads to dermatologic AEs. Future larger studies using other measurement techniques, such as 3-dimensional photography, could help to yield results that are more generalizable to the phenotypically diverse NF1 population.

Reference:

Gross AM, Reid OH, Baldwin LA, et al. Treatment of Cutaneous Neurofibromas in Neurofibromatosis Type 1 With MEK Inhibitor Selumetinib: A Nonrandomized Clinical Trial. JAMA Dermatol. Published online February 26, 2025. doi:10.1001/jamadermatol.2024.6574

Keywords:

Selumetinib, shows, Limited, Efficacy, Treatment, cutaneous, neurofibromatosis, JAMA, Gross AM, Reid OH, Baldwin LA, JAMA Dermatology

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Lactation Consultant Interventions effective for promoting and supporting breastfeeding: JAMA

Researchers have found in a new study that Lactation consultant interventions significantly improve both exclusive breastfeeding and overall breastfeeding rates. The findings of the study have been published in JAMA.

By providing education, hands-on support, and problem-solving strategies, lactation consultants help mothers overcome challenges such as latching difficulties, low milk supply, and breastfeeding pain. Their guidance leads to increased breastfeeding duration and adherence to exclusive breastfeeding recommendations, benefiting both maternal and infant health.Breast milk offers numerous health benefits, yet breastfeeding recommendations are met less than half of the time in high-income countries. A study was done to evaluate the effect of lactation consultant (LC) interventions on breastfeeding, maternal breastfeeding self-efficacy, and infant growth compared to usual care. Data extracted included study design, participant and intervention characteristics, and outcome data. To account for studies that reported outcomes at multiple time points, effect estimates were pooled with 3-level correlated and hierarchical effects models. Meta-regression was performed for clinically important characteristics, such as the time point when the outcome was measured, intervention intensity, and participant income. The primary outcome was stopping exclusive breastfeeding. Secondary outcomes included stopping any breastfeeding, exclusive breastfeeding and any breastfeeding duration, maternal breastfeeding self-efficacy, infant overweight and obesity, and infant growth. Results The search yielded 6476 records, of which 40 studies were included involving 8582 participants. Studies were published between 1992 and 2024, and most studies (n = 22) were conducted in the US. Compared to usual care, LC interventions reduced the risk of stopping exclusive breastfeeding (risk ratio [RR], 0.96; 95% CI, 0.94-0.99) and any breastfeeding (RR, 0.92; 95% CI, 0.87-0.96) and increased any breastfeeding duration by 3.63 weeks (95% CI, 0.13-7.12). There was weak evidence that LC interventions increased exclusive breastfeeding duration (mean difference [MD], 1.44 weeks; 95% CI, −2.73 to 5.60), maternal breastfeeding self-efficacy (MD, 2.83; 95% CI, −1.23 to 6.90), or the risk of infant overweight and obesity (RR, 1.52; 95% CI, 0.94-2.46). Meta-regression showed that LC interventions were more effective at reducing the risk for stopping exclusive breastfeeding (P = .01) and any breastfeeding (P < .001) the earlier that breastfeeding was measured in the postpartum period. LC interventions with a higher intensity (ie, number of LC visits) were more effective at reducing the risk for stopping any breastfeeding (P = .04). According to the results of this systematic review and meta-analysis, LC interventions are a promising intervention for improving exclusive breastfeeding and any breastfeeding in high-income countries.

Reference:

D’Hollander CJ, McCredie VA, Uleryk EM, et al. Breastfeeding Support Provided by Lactation Consultants: A Systematic Review and Meta-Analysis. JAMA Pediatr. Published online March 03, 2025. doi:10.1001/jamapediatrics.2024.6810

Keywords:

Lactation, Consultant, Interventions, effective, promoting, supporting, breastfeeding, JAMA, D’Hollander CJ, McCredie VA, Uleryk EM, JAMA Pediatrics

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Promising new class of antimalarial drugs discovered

Innovative research approaches are therefore urgently needed to achieve long-term progress in prevention and treatment.

Malaria is caused by parasites of the genus Plasmodium, which is transmitted to humans through the bite of infected mosquitoes.

Plasmodium falciparum, the deadliest of the malaria species, has a highly complex life cycle controlled by precise gene regulation.

Understanding these regulatory processes is crucial in order to specifically combat the pathogen at different stages of development.

The team identified the chromatin remodeler PfSnf2L (a protein complex that regulates the accessibility of DNA for transcription) as a key regulator of genes that play an important role in various stages of the pathogen’s development.

“Our research shows that PfSnf2L is essential for P. falciparum to dynamically adjust gene expression,” explains Maria Theresia Watzlowik, lead author of the study.

“The unique sequence and functional properties of PfSnf2L led to the identification of a highly specific inhibitor that only kills Plasmodium falciparum,” explains Gernot Längst, Professor of Biochemistry at the University of Regensburg.

“This inhibitor represents a new class of antimalarials, potentially targeting all life cycle stages,” adds Professor Markus Meißner, Chair Professor of Experimental Parasitology at LMU’s Faculty of Veterinary Medicine.

“Malaria is one of the most adaptive diseases we face,” observes Längst.

Targeting its epigenetic regulation could pave the way for increasing the effectiveness of existing drugs, for example, or preventing the development of resistant parasites.

“The study underscores the importance of integrating epigenetics into malaria research. Future work will focus on testing small molecules that inhibit the parasite’s epigenetic machinery and exploring their effectiveness in preclinical models,” concludes Meißner.

In addition to scientists from LMU and the University of Regensburg, researchers from the University of Zurich (Switzerland), Pennsylvania State University (United States), and the University of Glasgow (United Kingdom) were involved in the study, which was supported by the German Research Foundation (DFG).

 Reference: Maria Theresia Watzlowik, Elisabeth Silberhorn, Sujaan Das, Ritwik Singhal, Kannan Venugopal, Simon Holzinger, Barbara Stokes, Ella Schadt, Lauriane Sollelis, Victoria A. Bonnell, Matthew Gow, Andreas Klingl, Matthias Marti, Manuel Llinás, Markus Meissner, Gernot Längst. Plasmodium blood stage development requires the chromatin remodeller Snf2L. Nature, 2025; DOI: 10.1038/s41586-025-08595-x

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Common gynaecological disorders linked to raised heart and cerebrovascular disease risk: Study

Having one or more common gynaecological disorders, such as endometriosis or heavy or irregular periods, may be linked to a heightened risk of heart disease and conditions that affect blood flow to the brain (cerebrovascular disease), finds a pooled data analysis of the available evidence published online in the journal Heart.

Although the quality of the studies included in the analysis was variable, the researchers nevertheless conclude that clinicians and the public need to be more aware of these associations to potentially mitigate the risks.

Long term non-cancerous gynaecological disorders are common and include polycystic ovary syndrome (PCOS), endometriosis (where tissue similar to the womb lining grows outside of the womb), adenomyosis (where the womb lining grows into the muscular wall), uterine fibroids, primary dysmenorrhoea (painful menstrual cramps), chronic pelvic pain, irregular and/or very heavy periods, and abnormal uterine bleeding, explain the researchers.

These disorders significantly affect women’s health and wellbeing. And previously published research indicates that they may be associated with cardiovascular or cerebrovascular disease, they add.

To explore this further, the researchers scoured research databases looking for relevant studies published up to April 2024. From an initial haul of 59 studies, 28, involving 3,271,242 women, were eligible for systematic review and inclusion in the pooled data analysis.

Only endometriosis, polycystic ovary syndrome, heavy periods, and irregular menstrual cycles featured in the studies included in the analysis.

Overall, the pooled data analysis of the study results showed that compared with people without one of these conditions, those who had at least one had a significantly (28%) higher risk of cardiovascular and cerebrovascular disease.

Specifically, their risk of ischaemic heart disease was 41% higher, while their risk of cerebrovascular disease alone was 33% higher.

Further analysis indicated that the overall risk of cardiovascular and cerebrovascular disease and each of its components was higher among those with a history of endometriosis or polycystic ovary syndrome.

The researchers caution that the design and methodology of the included studies varied considerably, and over half (53.5%) of the studies were scored as having a very high risk of bias, largely because of the lack of adequate consideration of potentially influential factors.

And several aspects of cardiovascular disease weren’t covered by the included studies, such as atrial fibrillation (abnormal heart rhythm).

But the researchers nevertheless suggest that there may be plausible biological pathways linking cardiovascular and cerebrovascular disease and common gynaecological disorders, including systemic inflammation and oestrogen production.

There may also be an overlap between gynaecological risk factors and cardiovascular risk factors, they suggest, pointing out that metabolic syndrome is often present in people with polycystic ovary syndrome, for example.

“The association between [cardiovascular and cerebrovascular disease] and [common gynaecological disorders] requires further exploration with high-quality longitudinal studies adjusted for confounders to establish temporal relationships and causality,” they emphasise.

But they nevertheless conclude: “Although the extent of this association is still to be explored, and causality has not been established, the findings suggest that it is important to raise awareness of the potential association…. both in the general public and healthcare professionals.

“Awareness of this association would allow healthcare professionals to advise patients regarding risk-reducing behavioural changes and interventions, to potentially prevent or delay the onset of, or reduce the severity of cardiovascular and cerebrovascular disease.”

Reference:

Non-malignant gynaecological disease and risk of cardiovascular or cerebrovascular disease: a systematic review and meta-analysis. Heart. DOI: 10.1136/heartjnl-2024-324765

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Brain plays central role in development of obesity, suggests research

The number of obese persons has grown significantly in recent decades, which presents significant difficulties for those who are impacted, healthcare systems, and those who provide treatment. The hormone insulin plays a key role in the development of obesity. Up until recently, there have been numerous signs indicating insulin causes neurodegenerative and metabolic disorders, especially in the brain. A recent study by the University Hospital of Tübingen, the German Center for Diabetes Research (DZD), and Helmholtz Munich offers intriguing new insights into the origins of type 2 diabetes and obesity as well as the brain’s function as a critical control center.

Obesity has only been officially recognized as a disease in Germany since 2020, despite the fact that it has long been known to cause a number of illnesses, including diabetes, heart attacks, and even cancer. The World Health Organization has already declared obesity to be an epidemic, affecting over one billion individuals globally and almost 16 million in Germany alone. A body mass index of 30 or more is considered obese, and a poor diet and insufficient exercise are frequently cited as the causes of this chronic illness. However, the mechanisms in the body that lead to obesity and cause the disease are more complex.

Obesity and the role of insulin in the brain

Unhealthy body fat distribution and chronic weight gain are linked to the brain’s sensitivity to insulin. What specific functions does insulin perform in the brain, and how does it affect individuals of normal weight? In their study, Prof. Dr. Stephanie Kullmann and her colleagues at the Tübingen University Hospital for Diabetology, Endocrinology, and Nephrology found the answer to this query. “Our findings demonstrate for the first time that even a brief consumption of highly processed, unhealthy foods (such as chocolate bars and potato chips) causes a significant alteration in the brain of healthy individuals, which may be the initial cause of obesity and type 2 diabetes,” says Prof. Kullmann, the study’s leader. In a healthy state, insulin has an appetite-suppressing effect in the brain. However, in people with obesity in particular, insulin no longer regulates eating behavior properly, resulting in insulin resistance. “Interestingly, in our healthy study participants, the brain shows a similar decrease in sensitivity to insulin after a short-term high calorie intake as in people with obesity,” says Ms. Kullmann. “This effect can even be observed one week after returning to a balanced diet,” she adds. She is also deputy head of the Metabolic Neuroimaging department at the DZD partner Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of Tübingen.

Focus on the brain

Prof. Dr. Andreas Birkenfeld, Medical Director of Internal Medicine IV, Director of the IDM and DZD Board Member, and the study’s final author, concludes, “We assume that the brain’s insulin response adapts to short-term changes in diet before any weight gain occurs and thus promotes the development of obesity and other secondary diseases.” He urges more research on how the brain contributes to the development of obesity and other metabolic illnesses in light of the current findings.

Short period with far-reaching effects

29 male volunteers of average weight participated in the study and were split into two groups. For five days in a row, the first group had to supplement their regular diet with 1500 kcal from highly processed, high-calorie snacks. The extra calories were not consumed by the control group. Both groups underwent two separate examinations following an initial evaluation. One examination was conducted immediately following the five-day period, and another was conducted seven days after the first group had resumed their regular diet. The researchers used magnetic resonance imaging (MRI) to look at the liver’s fat content and the brain’s insulin sensitivity. Not only did the fat content of the liver of the first group increase significantly after five days of increased calorie intake. Surprisingly, the significantly lower insulin sensitivity in the brain compared to the control group also persisted one week after returning to a normal diet. This effect had previously only been observed in obese people.

Reference:

Stephanie Kullmann, Lore Wagner, Robert Hauffe, Anne Kühnel, Leontine Sandforth, Ralf Veit, Corinna Dannecker, Jürgen Machann, Andreas Fritsche, Nobert Stefan, Hubert Preissl, Nils B. Kroemer, Martin Heni, André Kleinridders, Andreas L. Birkenfeld. A short-term, high-caloric diet has prolonged effects on brain insulin action in men. Nature Metabolism, 2025; DOI: 10.1038/s42255-025-01226-9

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Screening & treating maternal psychological health key to improving cardiovascular health: Study

Integrating routine psychological health screening and treatment during and after pregnancy may reduce the risk of adverse pregnancy outcomes and improve maternal cardiovascular health, according to a new scientific statement published today in a Go Red for Women spotlight issue of the Journal of the American Heart Association, an open cess, peer-reviewed journal of the American Heart Association.

This spotlight issue focuses on research about sex differences in cardiovascular disease and their implications for care.

The new scientific statement, “Optimizing Psychological Health Across the Perinatal Period: An Update on Maternal Cardiovascular Health,” highlights the need to support maternal cardiovascular health by including comprehensive screening of psychological health during the perinatal period (pregnancy through one year postpartum). Cardiovascular issues are the No. 1 cause of maternal death.

The new statement summarizes the evidence associating psychological health concerns and adverse cardiovascular outcomes; highlights effective management strategies and integrated care delivery models; and identifies current challenges and future directions for improving maternal health outcomes.

“It’s critical that we redefine maternal cardiovascular health to include psychological health because there is robust evidence on the association of psychological health with cardiovascular outcomes,” said writing group Chair Garima Sharma, M.D., FAHA, director of preventive cardiology and women’s cardiovascular health at Inova Schar Heart and Vascular in Fairfax, Virginia. “We also recognize the importance of providing guidance to clinicians on how to integrate psychological health screening into the perinatal period and focus on providing a holistic approach with the mind and heart interconnection.”

Maternal Psychological and Cardiovascular Health Linked

The maternal mortality rate in the United States is two to three times higher than estimates from other high-income countries and has worsened since the COVID-19 pandemic, with significant disparities among people in underrepresented races and ethnicities. The mortality rate for non-Hispanic Black birthing women is 2.6 times higher than for non-Hispanic white women.

Perinatal psychological health conditions such as depression and anxiety are among the leading causes of maternal mortality in the U.S. and are associated with adverse pregnancy outcomes and long-term cardiovascular outcomes. Psychological health, often used interchangeably with mental health, encompasses emotional, social and functional well-being and is affected by factors such as living conditions, traumatic events and daily stressors.

An estimated 52% of women of reproductive age report having a history of a psychological health condition, and 40% of those from underrepresented races and ethnicities experience anxiety or depression in the perinatal period.

People with suboptimal mental health may engage in negative health behaviors (such as poor diet, irregular sleep, low physical activity, tobacco, alcohol and/or illicit substance use and/or difficulty adhering to medical recommendations), which can negatively affect their cardiovascular health. Maternal psychological health can also affect the child’s neurodevelopment and well-being.

Screening for Risk Factors for Psychological Health

“Pregnancy is an important time of life from a health perspective. However, it is not known how many health care professionals understand the connection between the mind and heart and routinely screen and optimize psychological health during the perinatal period. Screening for psychological health before, during and after pregnancy should be used alongside screening for high blood pressure, Type 2 diabetes and other modifiable risk factors for cardiovascular disease,” said Sharma.

Risk factors for psychological concerns include domestic violence, sleep disorders, personal or family history of psychological conditions, incarceration, active-duty military service, Veteran status, lack of partner support, unemployment, and racism and discrimination. Adverse outcomes in prior pregnancies, including miscarriage, ectopic pregnancy and high blood pressure during pregnancy, are also risk factors for perinatal anxiety and depression.

Incorporating regular psychological health screening into perinatal care involves training health care professionals to use screening tools effectively and establishing protocols for follow-up care, including comprehensive assessment and appropriate interventions. For example, the Patient Health Questionnaire (PHQ-9) can be used by health care professionals to screen for symptoms of depression and anxiety. This universal screening tool has been effective at increasing awareness of and decreasing stigma associated with psychological health challenges.

Initial prenatal mental health screening should take place as early as practical in pregnancy and should be repeated at least once. During the initial obstetric visit, it is essential to review the patient’s psychological history and use of psychopharmacotherapies or other treatments to identify risk factors for mental health conditions.

“During pregnancy and postpartum, identifying and intervening on modifiable risk factors that increase the risk of depression, such as social isolation, no or inadequate partner support, depression before pregnancy and poor sleep quality, may improve maternal psychological health as well as future cardiovascular health,” Sharma said.

Since psychological symptoms may fluctuate over time, inquiring about emotional well-being (and the well-being of their partner, if appropriate) should ideally be part of every prenatal or postpartum visit.

Considerations for Managing Maternal Psychological Health

Whatever the setting and circumstances, perinatal psychological care should be culturally responsive, language-appropriate and family-centered. It should involve shared decision-making with the patient (and their significant other(s), if the patient agrees), including a full discussion of the potential risks and benefits of any treatments offered to the mother and the fetus or newborn.

When considering pharmacologic treatment for depression or anxiety, the choice of medication should be based on efficacy in pregnancy, safety in pregnancy, safety during breastfeeding (if applicable) and consideration of interactions with other medications.

As medications carry potential side effects to both mother and child, there is significant interest in non-pharmacological strategies to both prevent and treat depression and anxiety symptoms during and after pregnancy. Counseling, cognitive behavioral therapies, exercise, stress management strategies and other treatment methods may be preferred.

Health professionals providing care, such as psychologists, clinical social workers, psychiatrists, general internal medicine specialists and obstetricians, should work as a team and have appropriate training and skills and work collaboratively to provide continuity of care for patients and their families during pregnancy and postpartum.

Opportunities for Improvement and Future Research Needs

Barriers to integrating perinatal psychological health care into cardiovascular health care exist at individual, health system, community level and government and policy levels along the perinatal care continuum. Known barriers to addressing perinatal mental health concerns include stigma, fears of Child Protective Services removing the child, clinician time constraints, clinician inexperience, workforce issues and reimbursement related concerns.

There is a need to create health care delivery models to incentivize health systems and clinicians to adopt evidence-based, accessible models of care focused on awareness, screening and optimization of psychological health with partnerships with community-based organizations. Initiatives that could potentially improve outcomes and reduce racial and socioeconomically-mediated inequities include expanding reimbursement for doulas, midwives and community health workers.

Additionally, there is a critical need for long-term research on perinatal psychological health because it influences cardiovascular health and other chronic disease outcomes across the individual’s lifespan. Considering the known disparities in maternal health based on race, ethnicity and social drivers of health, more people of underrepresented races and ethnicities need to be included in studies on maternal psychological and cardiovascular health. Increased research is also needed related to other psychological factors besides depression, such as anxiety, adverse childhood experiences, post-traumatic stress disorder and psychosocial stressors that disproportionately or differentially affect women.

This scientific statement was prepared by the volunteer writing group on behalf of the American Heart Association’s Cardiovascular Disease & Stroke in Women and Underrepresented Populations Committee of the Council on Clinical Cardiology; the Council on Cardiovascular and Stroke Nursing; the Council on Cardiovascular Radiology and Intervention; the Council on Cardiovascular Surgery and Anesthesia; the Council on Lifelong Congenital Heart

Disease and Heart Health in the Young; the Council on Lifestyle and Cardiometabolic Health; the Council on Quality of Care and Outcomes Research; and the Stroke Council.

American Heart Association scientific statements promote greater awareness about cardiovascular diseases and stroke issues and help facilitate informed health care decisions. Scientific statements outline what is currently known about a topic and what areas need additional research. While scientific statements inform the development of guidelines, they do not make treatment recommendations. American Heart Association guidelines provide the Association’s official clinical practice recommendations.           

References: Garima Sharma, MD, FAHA, Chair, Allison E. Gaffey, PhD, FAHA, Afshan Hameed, MD, Nadine A. Kasparian, PhD, Rina Mauricio, MD, Elisabeth Breese Marsh, MD, Dana Beck, PhD, MS, MSN, Jenna Skowronski, MD, Diana Wolfe, MD, and Glenn N. Levine, MD, FAHA, Vice Chair the American Heart Association Women’s Health Science Committee of the Council on Clinical Cardiology and the Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Surgery and Anesthesia; Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Lifestyle and Cardiometabolic Health; and Council on Quality of Care and Outcomes ResearchAuthor Info & Affiliations Journal of the American Heart Association New online https://doi.org/10.1161/JAHA.125.041369                   

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Propranolol effectively reduced sedative need in critically ill patients during the pandemic

A new study published in the journal of Critical Care Medicine showed that in severely sick patients treated during the COVID-19 epidemic, propranolol successfully reduced the requirement for sedatives.

Guidelines suggest dexmedetomidine and propofol as first-line sedatives for critically sick patients who frequently need sedation to tolerate mechanical breathing. Propofol shortages occurred in Canada, the US, and other countries as a result of increases in demand for mechanical ventilation during the COVID-19 pandemic.

Because of its expensive cost, dexmedetomidine is not frequently used for profound sedation. Since neurotransmitters like norepinephrine are generated or given to raise blood pressure and heart rate (HR), agitation and delirium in critically ill patients are frequently caused by hyperactivity in the sympathetic nervous system.

Thus, James Downar and colleagues conducted a prospective randomized study to see if the use of propranolol could significantly reduce the sedative needs of patients receiving mechanical ventilation. This was done because pandemic-related surges in mechanical ventilation could deplete our supply of sedatives.

3 university hospitals participated in this open-label randomized controlled experiment. The primary participants were any nonparalyzed patient on mechanical ventilation who needed high-dose sedatives. All individuals received protocol-titrated sedation with either propofol or midazolam as part of the primary intervention, which involved enteral propranolol 20 mg to 60 mg every 6 hours titrated to effect in the intervention group.

The percentage of sedation ratings that fall within the desired range, the incidence rate of adverse events, and the mean change in the 24-hour sedative dosage from baseline to day 3. A total of 72 patients were enrolled between January 2021 and October 2022. With a mean (sd) age of 54 years (15.91 years), 69% of the participants were male. The majority were hospitalized with either non-COVID or COVID pneumonia.

Propranolol (mean daily dose: 90 mg) was administered to intervention participants for an average of 10 days. When compared to controls, the intervention group saw a considerably greater reduction in sedative dosage from baseline and more sedation evaluations within the target range. There were no variations in adverse events or death. Overall, patients on mechanical breathing needed a much lower amount of sedative when propranolol was used as a sedative-sparing technique.

Reference:

Downar, J., Lapenskie, J., Kanji, S., Watpool, I., Haines, J., Saeed, U., Porteous, R., Polskaia, N., Burry, L., Himed, S., Anderson, K., & Fox-Robichaud, A. (2025). Propranolol as an anxiolytic to reduce the use of sedatives for critically ill adults receiving mechanical ventilation (PROACTIVE): An open-label randomized controlled trial. Critical Care Medicine, 53(2), e257–e268. https://doi.org/10.1097/ccm.0000000000006534

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Metabolic Surgery Reduces Liver Disease Risk in Patients with MASH-Related Cirrhosis: Study

A recent study found metabolic surgery to demonstrate significant benefits in lowering the risk of major adverse liver outcomes (MALO) for cirrhosis patients due to metabolic dysfunction-associated steatohepatitis (MASH). The findings published in the recent issue of Nature Medicine journal suggest that surgical intervention could provide a safer and more effective treatment option when compared to traditional nonsurgical management.

Cirrhosis is marked by scarring and impaired function of liver which often progresses without clear therapeutic solutions. The patients with obesity and histologically confirmed MASH-related cirrhosis face elevated risks of liver failure and related complications. Despite advancements in research, no medical therapy has proven effective at reducing these risks so far.

The Surgical Procedures Eliminate Compensated Cirrhosis In Advancing Long-term (SPECCIAL) study tracked 62 patients who underwent metabolic surgery and compared their outcomes to 106 nonsurgical controls over an average follow-up period of 10 years. The surgery group was predominantly female (68%), as was the control group (71%). The study employed robust estimation methods to balance key baseline characteristics between the two groups by ensuring reliable results.

The cumulative incidence of MALO was 20.9% in the surgical group versus 46.4% in the nonsurgical group. This translates to a 72% lower risk of MALO among patients who underwent metabolic surgery (adjusted hazard ratio 0.28, P=0.003).

The incidence of decompensated cirrhosis where the liver can no longer maintain normal function, was 15.6% in the surgical group when compared to 30.7% in the nonsurgical group. This reflected an 80% lower risk (adjusted hazard ratio 0.20, P=0.01). The findings illuminate the potential role of metabolic surgery in altering the long-term trajectory of cirrhosis in patients with obesity and compensated MASH.

These data suggest that metabolic surgery is not just a weight-loss tool but also a potent therapeutic option for improving liver health. In addition, this has major implications for the future care of patients with cirrhosis linked to metabolic dysfunction. Overall, this study highlights the transformative potential of metabolic surgery as a safe and impactful option.

Source:

Aminian, A., Aljabri, A., Wang, S., Bena, J., Allende, D. S., Rosen, H., Arnold, E., Wilson, R., Milinovich, A., Loomba, R., Sanyal, A. J., Alkhouri, N., Wakim-Fleming, J., Laique, S. N., Dasarathy, S., McCullough, A. J., & Nissen, S. E. (2025). Long-term liver outcomes after metabolic surgery in compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis. Nature Medicine. https://doi.org/10.1038/s41591-024-03480-y

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PCOS and Mental Health: Study Reveals Higher Risk of Depression, Bipolar Disorder

Korea: A recent retrospective cohort study based on a Korean nationwide population database has highlighted a significant association between polycystic ovary syndrome (PCOS) and an increased risk of mental health disorders.

The study, published in the International Journal of Women’s Health, revealed that women with polycystic ovary syndrome faced an increased risk of mental health conditions, with a 50% higher likelihood of developing bipolar disorder (HR 1.50), a 24% greater risk of depression (HR 1.24), a 23% higher risk of sleep disorders (HR 1.23), and a 15% increased risk of anxiety (HR 1.15). In contrast, schizophrenia prevalence was lower in this group.

“These findings reinforce the need for regular mental health screening in PCOS patients to facilitate early intervention and comprehensive care,” the researchers wrote.

The researchers note that PCOS is a common endocrine disorder affecting reproductive-age women, characterized by hormonal imbalances, irregular menstrual cycles, and metabolic complications. While PCOS has been linked to various mental health disorders, research on this association in Korean populations remains limited. To address this gap, Youngjin Kim, Department of Preventive Medicine and Public Health, College of Medicine, The Catholic University of Korea, Seoul, Korea, and colleagues explore the risk of mental disorders among PCOS patients in Korea, providing valuable insights into their psychological well-being.

For this purpose, the researchers analyzed health insurance billing data from the National Health Insurance Corporation to assess the risk of five mental disorders in PCOS patients. They identified 188,973 individuals with PCOS and compared them with 412,022 control participants. The study examined the prevalence and cumulative incidence of these mental disorders, calculating hazard ratios (HR) for each condition to determine the extent of the association.

The study revealed the following findings:

  • PCOS patients had a higher prevalence of depressive disorders (OR 1.208), bipolar disorders (OR 1.403), and anxiety disorders (OR 1.089).
  • In contrast, schizophrenia (OR 0.686) and sleep disorders (OR 0.911) were less common in individuals with PCOS.
  • The risk of developing depressive disorders (adjusted HR 1.244), bipolar disorders (adjusted HR 1.502), anxiety disorders (adjusted HR 1.147), and sleep disorders (adjusted HR 1.228) was significantly higher in PCOS patients.

The researchers found that PCOS patients face a higher risk of depressive disorders, bipolar disorders, anxiety disorders, and sleep disorders. Their findings align with international PCOS guidelines that recommend mental health screening for these patients. The study highlights the importance of early identification and intervention.

“While the database had certain limitations, the results emphasize the need for active mental health screening in Korean PCOS patients, considering individual factors like age and obesity to ensure timely and personalized care,” the researchers concluded.

Reference:

Kim Y, Chae K, Kim S, Kang S, Yoon H, Namkung J. Risk of Mental Disorders in Polycystic Ovary Syndrome: Retrospective Cohort Study of a Korean Nationwide Population-Based Cohort. Int J Womens Health. 2025;17:627-638. https://doi.org/10.2147/IJWH.S490673

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