Insulin Resistance Linked to Lung Abnormalities and Disease Risk: Insights From Framingham Study

USA: A recent study from the Framingham Offspring Study has revealed a significant association between insulin resistance (IR), radiographic lung abnormalities, and the incidence of lung disease.

The research published in Diabetes Care found that insulin resistance is associated with radiographic lung abnormalities and an increased risk of incident lung disease. These findings suggest a potential link between metabolic dysfunction and lung health, emphasizing the need for deeper phenotyping to understand better the mechanisms driving IR-associated lung injury.

Insulin resistance has been suggested as a potential risk factor for lung disease, though objective evidence remains limited. To address this gap, Tianshi David Wu, Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, and colleagues investigated the relationship between longitudinal IR levels, radiographic imaging findings, and examiner-confirmed incident lung disease within the Framingham Offspring Study cohort.

For this purpose, the researchers analyzed data from participants without baseline lung disease, who underwent repeated measurements of fasting insulin and glucose levels over an average of 13.6 years. From these measurements, time-weighted average HOMA-IR values were calculated. Each participant then received a cardiac-gated whole-lung computed tomography (CT) scan, which was evaluated for emphysema, interstitial lung abnormalities (ILAs), and quantitative airway features.

A study examiner identified incident lung disease. To estimate the relationship between HOMA-IR and these outcomes, researchers used models adjusted for factors such as demographics, BMI, and lifetime smoking history.

The following were the key findings of the study:

  • Researchers analyzed data from 875 participants with longitudinal IR data and outcomes.
  • The participants had a mean age of 51.5 years and an average BMI of 26.7 kg/m².
  • HOMA-IR values showed temporal instability, with a within-person standard deviation (SD) of approximately two-thirds of the between-person SD.
  • In adjusted models, a 1 SD increase in log(HOMA-IR) z score was linked to higher odds of qualitative emphysema (odds ratio [OR] 1.33).
  • The same increase was associated with higher odds of interstitial lung abnormalities (ILAs) (OR 1.35).
  • Modest increases in airway wall thickness and wall area percentage were also observed with higher HOMA-IR levels.
  • A positive association between HOMA-IR and the incidence of lung disease supported these radiographic findings.

The findings also stress the broader implications of managing insulin resistance. Early detection and intervention could not only improve metabolic outcomes but also potentially reduce the risk of lung disease. As rates of metabolic disorders continue to climb, these insights could guide strategies to improve systemic and lung health.

“The Framingham Offspring Study sheds light on a previously underexplored link between insulin resistance and lung disease. The evidence underscores the importance of continued research to uncover the mechanisms of IR-associated lung injury and develop targeted interventions to mitigate its impact on respiratory health,” the researchers concluded.

Reference: Sarath Raju, Paula Sierra, Vickram Tejwani, Kristen A. Staggers, Meredith McCormack, Dennis T. Villareal, Ivan O. Rosas, Nicola A. Hanania, Tianshi David Wu; Association of Insulin Resistance With Radiographic Lung Abnormalities and Incident Lung Disease: The Framingham Offspring Study. Diabetes Care 2024; dc241754. https://doi.org/10.2337/dc24-1754

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CABG Offers Superior Outcomes Over PCI in High-Risk NSTEMI Patients, reveals research

Researchers have reported better long-term results of coronary artery bypass grafting (CABG) than of percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation myocardial infarction (NSTEMI) and multivessel disease, especially in the high-risk subgroups. A recent study was conducted by Elmir O. and colleagues which was published in the European Heart Journal.

The participants were NSTEMI patients treated with multivessel disease from January 2005 and June 2022. Of the 57,097 participants, 42,190 (73.9%) were subjected to PCI, and 14,907 (26.1%) were given CABG. All-cause mortality was evaluated as the first and secondary endpoint and included outcomes such as MI, stroke, new revascularization, and heart failure. Controlling confounding variables used multilevel logistic regression and instrumental variable methods in the analysis.

Patients who underwent PCI were older and had a history of more prior cardiovascular events, whereas CABG patients were more likely to have diabetes, hypertension, left main or three-vessel disease, and reduced ejection fraction.

Key Findings

  • Mortality Risk: PCI was associated with a 67% higher risk of death compared to CABG (adjusted odds ratio [aOR] 1.67; 95% confidence interval [CI] 1.54–1.81).

  • Myocardial Infarction: Patients who underwent PCI had a 51% increased risk of MI (aOR 1.51; 95% CI 1.41–1.62).

  • Stroke: No significant difference in stroke risk was observed between PCI and CABG.

  • Repeat Revascularization: Patients who underwent PCI were three times more likely to require repeat revascularization (aOR 3.01; 95% CI 2.57–3.51).

  • Heart Failure: CABG was associated with a 15% reduced risk of heart failure (aOR 1.15; 95% CI 1.07–1.25).

  • Survival Benefit: CABG conferred longer survival, especially in patients under 70 years of age, or in the presence of left main disease, or with left ventricular dysfunction. This survival benefit was abated in patients with poorer survival probabilities.

Although a superior long-term outcome exists for CABG compared to PCI in patients with multivessel disease and NSTEMI, this comes at the expense of losing the survival advantage in severely ill or high-risk subjects with reduced life expectancy and thus should be used carefully in clinical practice.

Reference:

Omerovic, E., Råmunddal, T., Petursson, P., Angerås, O., Rawshani, A., Jha, S., Skoglund, K., Mohammad, M. A., Persson, J., Alfredsson, J., Hofmann, R., Jernberg, T., Fröbert, O., Jeppsson, A., Hansson, E. C., Dellgren, G., Erlinge, D., & Redfors, B. (2024). Percutaneous vs. surgical revascularization of non-ST-segment elevation myocardial infarction with multivessel disease: the SWEDEHEART registry. European Heart Journal, ehae700. https://doi.org/10.1093/eurheartj/ehae700

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Acupuncture can significantly improve symptoms in Meniere’s disease, Study finds

A study published in Frontiers in
Medicine found that acupuncture can effectively treat Meniere’s disease (MD), a
chronic inner ear disease.

Meniere’s disease (MD) is an
idiopathic chronic inner ear disease characterized by vertigo, nausea,
vomiting, hearing loss, tinnitus, or aural fullness. It affects the quality of
life due to its impact on the patients’ physical and mental health. There is a
lot of ambiguity on the etiopathogenesis and the management of MD. Despite the
efficacy of medications, additional and alternative treatment modalities are
necessary for the management of MD. Hence, researchers from the Nanjing
University of Chinese Medicine, Nanjing, China, conducted a systematic review of
the efficacy of acupuncture treatment for MD.

Also Read: Higher Risk of Meniere’s Disease found in Atopic Dermatitis Patients, Especially Among Older Adults and Women: Study

The systematic review collected
data from eight databases and focused on studies evaluating the efficacy of
acupuncture on MD. Researchers used the Cochrane Risk of Bias 2.0 tool to
assess the risk of bias in the randomized controlled trials. RevMan 5.4 and
Stata 16.0 software were used to conduct the meta-analysis.

Findings:

  • The review included six studies in total.
  • There were two groups: the treatment group and the
    control group.
  • The treatment group received acupuncture alone or
    a combination of acupuncture with Western medicine.
  • The control group was treated with Western
    medicine alone.
  • The treatment group was significantly better
    than the control group in terms of efficacy rate
  • The treatment group was found to have significantly
    improved scores on the dizziness handicap inventory (DHI), tinnitus handicap
    inventory (THI), stuffy ear visual analog scale (VAS), and pure tone audiometry
    score.
Also Read: Using 100 Hz Sound Stimulation promising for Treatment of Saccular Dysfunction in Meniere’s Disease, Study Shows

Limitations:

Despite these significant
improvements, certain limitations remained, such as inadequate blinding
procedures, inconsistent outcome measures, and variations in clinical
interventions. The variations were a selection of acupoints, acupuncture
sessions, and therapist techniques.

The study concluded that
acupuncture can effectively reduce MD and its symptoms of vertigo, tinnitus,
ear fullness, and hearing loss. However, the researchers highlighted the
necessity of rigorous and long-term studies that can address the methodological
shortcomings of the present studies. Further well-designed trials with
long-term follow-ups have to be carried out to evaluate the efficacy and safety
of acupuncture in MD.

Further reading: Efficacy and
safety of acupuncture in the treatment of Meniere’s disease: A systematic
review and meta-analysis. Frontiers in Medicine. doi: 10.3389/fmed.2024.1463821

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Aortic stenosis linked to insulin resistance in large national study

A large new population study of men over 45 indicates insulin resistance may be an important risk factor for the development of the world’s most common heart valve disease – aortic stenosis (AS).

Published today in the peer-reviewed journal Annals of Medicine, the findings are believed to be the first to highlight this previously unrecognised risk factor for the disease.

It is hoped that by demonstrating this link between AS and insulin resistance-when cells fail to respond effectively to insulin and the body makes more than necessary to maintain normal glucose levels – new avenues for the prevention of the disease could open.

Aortic stenosis is a debilitating heart condition. It causes a narrowing of the aortic valve, restricting blood flow out of the heart. Over time, the valve thickens and stiffens, making the heart work harder to pump blood effectively around the body. If not addressed, this can gradually cause damage that can lead to life-threatening complications, such as heart failure.

People living with AS can take years to develop symptoms, which include chest pain, tiredness, shortness of breath and heart palpitations. Some may never experience symptoms, but may still be at risk of heart failure and death. Previously identified risk factors for AS include age, male sex, high blood pressure, smoking and diabetes.

Insulin resistance, which often develops years before the onset of type 2 diabetes, occurs when cells fail to respond effectively to insulin, the hormone responsible for regulating blood glucose levels. In response, the body makes more insulin to maintain normal glucose levels – leading to elevated blood insulin levels (hyperinsulinemia).

In the current study, researchers analysed data from 10,144 Finnish men aged 45 to 73 years old, all initially free of AS, participating in the Metabolic Syndrome in Men (METSIM) Study. At the start of the study, the researchers measured several biomarkers, including those related to hyperinsulinemia and/or insulin resistance. After an average follow-up period of 10.8 years, 116 men (1.1%) were diagnosed with AS.

The team identified several biomarkers related to insulin resistance – such as fasting insulin, insulin at 30 minutes and 120 minutes, proinsulin, and serum C-peptide – that were associated with increased AS risk. These biomarkers remained significant predictors of AS, even after adjusting for other known risk factors, such as body mass index (BMI) and high blood pressure, or excluding participants with diabetes or an aortic valve malformation.

The researchers then used advanced statistical techniques to isolate key biomarker profiles, identifying two distinct patterns that indicate insulin resistance as a predictor of AS, independent of other cardiovascular risk factors, such as age, blood pressure, diabetes, and obesity.

“This novel finding highlights that insulin resistance may be a significant and modifiable risk factor for AS,” says lead author Dr Johanna Kuusisto, from the Kuopio University Hospital, in Finland.

“As insulin resistance is common in Western populations, managing metabolic health could be a new approach to reduce the risk of AS and improve cardiovascular health in aging populations. Future studies are now warranted to determine whether improving insulin sensitivity through measures such as weight control and exercise can help prevent the condition.”

The major strengths of this study include its large population-based cohort and long follow-up period. However, its limitations include the sole focus on male subjects and the relatively small number of AS cases, which may limit the generalisability of the findings to other populations.

Reference:

Maija Sohlman, Raimo Jauhiainen, Biomarkers reflecting insulin resistance increase the risk of aortic stenosis in a population-based study of 10,144 Finnish men, Annals of Medicine, https://doi.org/10.1080/07853890.2024.2419996

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Iodine povacrylex tied to fewer surgical-site infections than chlorhexidine gluconate in closed extremity fractures: study

Skin antisepsis with iodine povacrylex in alcohol resulted in fewer surgical-site infections than with chlorhexidine gluconate in alcohol in closed extremity fractures: study

Studies evaluating surgical-site infection have had conflicting results with respect to the use of alcohol solutions containing iodine povacrylex or chlorhexidine gluconate as skin antisepsis before surgery to repair a fractured limb (i.e., an extremity fracture).

In a cluster-randomized, crossover trial at 25 hospitals in the United States and Canada, the authors randomly assigned hospitals to use a solution of 0.7% iodine povacrylex in 74% isopropyl alcohol (iodine group) or 2% chlorhexidine gluconate in 70% isopropyl alcohol (chlorhexidine group) as preoperative antisepsis for surgical procedures to repair extremity fractures. Every 2 months, the hospitals alternated interventions. Separate populations of patients with either open or closed fractures were enrolled and included in the analysis. The primary outcome was surgical-site infection, which included superficial incisional infection within 30 days or deep incisional or organ-space infection within 90 days. The secondary outcome was unplanned reoperation for fracture-healing complications.

The study has been published in ‘The new england journal of medicine’

Key findings of the study were:

• A total of 6785 patients with a closed fracture and 1700 patients with an open fracture were included in the trial.

• In the closed-fracture population, surgical-site infection occurred in 77 patients (2.4%) in the iodine group and in 108 patients (3.3%) in the chlorhexidine group (odds ratio, 0.74; 95% confidence interval [CI],

• 0.55 to 1.00; P = 0.049).

• In the open-fracture population, surgical-site infection occurred in 54 patients (6.5%) in the iodine group and in 60 patients (7.3%) in the chlorhexidine group (odd ratio, 0.86; 95% CI, 0.58 to 1.27; P = 0.45).

• The frequencies of unplanned reoperation, 1-year outcomes, and serious adverse events were similar in the two groups.

The authors concluded that – ‘Among patients with closed extremity fractures, skin antisepsis with iodine povacrylex in alcohol resulted in fewer surgical-site infections than antisepsis with chlorhexidine gluconate in alcohol. In patients with open fractures, the results were similar in the two groups. Nevertheless, the possibility that patients will have an allergic reaction to an ingredient in either solution means that hospitals will need to continue to stock both interventions.’

Further reading:

Skin Antisepsis before Surgical Fixation of Extremity Fractures

Sprague and Slobogean et al

N Engl J Med 2024;390:409-20.

DOI: 10.1056/NEJMoa2307679

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Congenital cataract with persistent fetal vasculature without anterior segment pathology associated with best postoperative visual acuity: Study

Congenital cataract with persistent fetal vasculature (PFV)
represents a complex and challenging condition in paediatric ophthalmology.
PFV, formerly known as persistent hyperplastic primary vitreous, is a rare
developmental anomaly characterized by incomplete regression of the primary
vitreous and embryonal hyaloid vasculature, leading to a spectrum of ocular
abnormalities, including cataract and retinal detachment. In the worst case,
the persistent hyaloidal stalk is integrated anteriorly into the posterior lens
capsule and posteriorly to the vascular bundle of the optic nerve head (ONH)
and exerts tractional forces radially in all directions. Ultimately, tractional
retinal detachment (TRD) may occur due to retrolental fibrovascular tissue
proliferation and contraction. In PFV eyes, concomitant retrolental stalk,
avascular peripheral retina, and regional capillary dropout have been observed
with fluorescein angiography examination.

The management of unilateral congenital cataract with PFV
poses unique therapeutic challenges. Surgical intervention is often required to
address the congenital cataract and associated PFV-related anterior and/or
posterior segment complications, with techniques such as lensectomy,
vitrectomy, membranectomy, and retinal detachment repair. And in many cases
multiple surgical interventions are needed. However, in cases with advanced
pathology, including ONH hypoplasia, severe tractional retinal detachment, or
microphthalmia, surgery is generally not a preferred choice since post-operative
vision is often modest. Postoperatively, achieving optimal visual outcomes in
the PFV cases can be hindered by factors including amblyopia, nystagmus,
glaucoma, proliferative vitreoretinopathy (PVR), and refractive errors. Case
selection for surgical treatment is of great importance, since long-standing
complications such as sympathetic ophthalmia, ie, bilateral granulomatous
panuveitis, may occur postoperatively and need to be considered.

Authors carried out a real-world single-centre study with
the aim to provide a comprehensive overview of the clinical features,
management strategies and final visual outcomes for eyes with unilateral
congenital cataract and PFV. By elucidating the complexity of this rare
paediatric condition, clinicians could enhance their understanding and improve
the individually tailored management of affected children, ultimately
optimizing visual outcomes and quality of life

Retrospective observational single-center study was
conducted between January 1, 2009, and December 31, 2019, at Helsinki
University Hospital. The national cohort encompassed 82 children aged from
birth to 15 years who underwent lensectomy, 3-port vitrectomy, or a combined
procedure, with the objective of achieving visual rehabilitation. Among the
surgical cohort, paediatric cases with International Classification of Disease
(ICD-10) codes Q14.0 for PFV and Q12.0 for congenital cataract were identified
and analyzed. Data were collected through a comprehensive review of medical
records, encompassing clinical history (birth weight), gender distribution,
ocular parameters (laterality, intraocular pressure [IOP], visual acuity [VA]),
details of cataract and vitreoretinal surgical interventions, indications for
surgery, postoperative ophthalmic complications, as well as evaluations of
functional and anatomical outcomes.

The cohort consisted of 11 children, ranging in age from 6
months to 12 years. Surgical intervention resulted in the attainment of at
least light perception vision in nine of the operated eyes, representing 81.8%
of cases. Among these, two eyes (18.2%) achieved hand motion vision, while 5
eyes (55.6%) achieved vision of finger counting or better. Additionally, two
eyes (18.2%) achieved visual acuity measurable on the Snellen chart. However,
one eye (9.1%) experienced complete vision loss, while the contralateral eye
developed sympathetic ophthalmia.

Congenital cataract with PFV devoid of anterior segment
pathology tends to correlate with the most favorable postoperative visual
outcomes. Conversely, eyes presenting with anterior segment pathology, such as
microphthalmia, or exhibiting complex posterior segment pathologies like macular
TRD, optic nerve hypoplasia, or foveal hypoplasia, are associated with a less
promising visual prognosis. Most children undergoing surgical intervention
achieve only modest improvements in vision. Given the potential occurrence of
sympathetic ophthalmia following surgery, meticulous case selection for
surgical management is paramount. Furthermore, delving deeper into the
pathogenesis of PFV is imperative to enhance our understanding of this
condition.

Source: Loukovaara; Clinical Ophthalmology 2024:18

https://doi.org/10.2147/OPTH.S472028

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Younger age, lower income and higher stress levels linked to increased risk of PCOS, suggests study

Recent study aimed to investigate the associations of polycystic ovarian syndrome (PCOS) risk with various factors among women in Saudi Arabia. The research was a cross-sectional study conducted across different regions in Saudi Arabia. Data were collected using anonymous, self-administered questionnaires distributed through social media platforms. The study found that factors associated with PCOS risk included age, region of residence, income, weight status, smoking status, presence of chronic conditions, medication and herbal remedy use, and perceived stress. Younger age, lower income, and higher stress levels were linked to an increased risk of PCOS. Additionally, chronic conditions were significantly associated with PCOS diagnosis rates.

Participants’ Profile and PCOS Risk Analysis

The participants’ profile revealed that most were younger than 30 years, single, urban residents, educated, employed or students, and non-smokers. A significant portion had no chronic illnesses, with an average stress level of 19.71. Regarding PCOS risk, 41.3% were at low risk, 33.3% at suspected risk, 2.9% at high risk, and 22.5% diagnosed with PCOS. The study highlighted the impact of PCOS on women’s health, with potential complications like metabolic syndromes, gestational diabetes, and cardiovascular diseases.

Factors Influencing PCOS Risk and Necessary Interventions

Sociodemographic factors like age, region of residence, and income status were significantly associated with PCOS risk. Health behaviors such as smoking were linked to PCOS risk. Furthermore, the presence of chronic physical and psychological conditions, medication use, herbal remedy use, and perceived stress were also associated with PCOS risk. The study emphasized the need for tailored interventions addressing lifestyle, stress, and comorbid disease management to reduce the risk of PCOS and enhance women’s health outcomes.

Study Sample Size, Limitations, and Implications

The study had a large and robust sample size of 1,068 women with a high response rate of 95.9%. Limitations included the convenience sample and reliance on self-reported diagnoses for chronic illnesses. The findings highlight the importance of understanding the multifactorial nature of PCOS risk in Saudi women, providing valuable insights for healthcare professionals and policymakers to develop targeted interventions and support strategies for improving women’s health and well-being.

Key Points

1. Factors associated with PCOS risk in Saudi women included age, region of residence, income, weight status, smoking status, chronic conditions, medication and herbal remedy use, and perceived stress. Younger age, lower income, and higher stress levels were linked to an increased risk of PCOS, while chronic conditions were significantly associated with PCOS diagnosis rates.

2. Participants in the study were mostly younger than 30 years, single, urban residents, educated, employed or students, and non-smokers. A significant portion had no chronic illnesses, with an average stress level of 19.71. The distribution of PCOS risk among participants was categorized as 41.3% low risk, 33.3% suspected risk, 2.9% high risk, and 22.5% diagnosed with PCOS.

3. Significant sociodemographic factors influencing PCOS risk included age, region of residence, and income status, while health behaviors like smoking were also associated with increased PCOS risk. Chronic physical and psychological conditions, medication use, herbal remedy use, and perceived stress played a role in PCOS risk, indicating the complex interplay of various factors in PCOS development.

4. The study emphasized the importance of tailored interventions addressing lifestyle modifications, stress management, and comorbid disease management to reduce PCOS risk and improve women’s health outcomes. This highlights the need for comprehensive approaches to address the multifactorial nature of PCOS and its potential complications like metabolic syndromes, gestational diabetes, and cardiovascular diseases.

5. The research had a robust sample size of 1,068 women with a high response rate of 95.9%, providing valuable insights into the factors influencing PCOS risk among Saudi women. Limitations included the convenience sample and reliance on self-reported diagnoses for chronic illnesses, indicating potential bias in the findings.

6. The study’s findings have implications for healthcare professionals and policymakers in Saudi Arabia, suggesting the need for targeted interventions and support strategies to mitigate PCOS risk and enhance women’s overall health and well-being. Understanding the multifaceted nature of PCOS risk is crucial for developing effective public health initiatives and personalized healthcare interventions for Saudi women.

Reference –

E. Alenzi et al. (2024). Risk Of Polycystic Ovary Syndrome: A Population-Based Analysis Of Sociodemographic Factors, Healthcare Access, Health Behaviors, And Health Status. *BMC Women’S Health*, 24. https://doi.org/10.1186/s12905-024-03446-9.

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Antibiotics alone to treat children with appendicitis cost-effective and safe alternative to surgery, study shows

Using antibiotics alone to treat children with uncomplicated appendicitis is a cost-saving alternative to surgery, according to a study published in the Journal of the American College of Surgeons (JACS).

Appendicitis is the fifth most common reason for hospitalization among children in the U.S., and appendectomy is the most common surgical procedure performed during inpatient hospitalizations in children, according to theNational Institutes of Health.

Appendectomy is also one of the costliest surgical procedures performed during hospital stays; however, treating appendicitis with intravenous antibiotics alone, known as nonoperative management, has been shown to be a safe and effective alternative in previous studies.

“We know that nonoperative management of appendicitis is safe and effective, so what surgeons want to know is whether nonoperative management is cost-effective. Our study helps answer that question,” said study coauthor Peter C. Minneci, MD, FACS, chair of the department of surgery at Nemours Children’s Health in Wilmington, Delaware. “This cost analysis demonstrates that nonoperative management for pediatric uncomplicated acute appendicitis is the most cost-effective management strategy over one year, compared to upfront surgery.”

Antibiotics vs. Urgent Surgery

The analysis was based on a review of data from more than 1,000 patients, age 7 to 17, who were treated for uncomplicated acute appendicitis at several hospitals throughout the Midwest region between 2015 and 2018. Parents were given the choice of two treatment strategies — antibiotics alone or urgent laparoscopic appendectomy. Nonoperative management consisted of at least 24 hours of intravenous antibiotics. Patients whose symptoms did not resolve underwent laparoscopic appendectomy during the same hospital admission.

Ratio of costs-to-charges-based data (cost divided by the charges) for the initial hospitalization, readmissions, and unplanned emergency department visits were extracted from the Pediatric Health Information System, which captures data from approximately 50 children’s hospitals. Patient-reported health-related quality-of-life scores and disability days (a measure of time off from school and pain) were determined at 30 days and 1 year after treatment respectively. Using a standardized survey, children were asked how they were doing in daily life and how they felt about their quality of life.

For these analyses, researchers looked at quality-of-life scores after 30 days and converted them to datapoints. Quality-adjusted life year scores ranged from zero to one, with one being perfect health and no issues and lower scores reflecting worsening health and dysfunction, with a zero score reflecting death. A quality-adjusted life year score indicating normal health without issues would be about .95. Quality-adjusted life year scores were evaluated for each patient and compared. Patients were followed for one year, and total average costs for each strategy were calculated in 2023 dollars.

Key Findings

  • Of 1,068 patients, 370 chose antibiotics alone and 698 opted for urgent laparoscopic appendectomy.
  • The results show an average cost of $9,791 and 0.884 quality-adjusted life years per patient for laparoscopic appendectomy and $8,044 and 0.895 quality-adjusted life years per patient for nonoperative management.
  • Nonoperative management was both less costly and more effective in three analyses, including an analysis using disability days and alternative methods of calculating quality of life and cost over one year.

“Our study findings add an additional benefit to the antibiotics-only approach being safe and effective for children in that this strategy is shown to be cost effective,” Dr. Minneci said. “In short, nonoperative management is a safe and cost-effective initial therapy and a reasonable alternative to surgery.”

Study authors said the next step is to investigate rates of treatment failure and cost-effectiveness of outpatient nonoperative management and laparoscopic appendectomy with same-day discharge.

Some limitations of the study are the one-year follow-up period and the fact that the analysis only includes patients treated at children’s hospitals across the Midwest region. As a result, these findings may not apply to other patient populations, the authors said.

Reference:

Gil, Lindsay A MD, MPHa,b; Asti, Lindsey MPH, PhDa,c; Chen, Huey-Fen MHA, PhDa; Saito, Jacqueline M MD, FACS, MSCI, MBAd; Pattisapu, Prasanth MD, MPHa,e; Deans, Katherine J MD, FACS, MHScc; Minneci, Peter C MD, FACS, MHScc; for the Midwest Pediatric Surgery Consortium. Cost-Effectiveness of Nonoperative Management vs Upfront Laparoscopic Appendectomy for Pediatric Uncomplicated Appendicitis Over 1 Year. Journal of the American College of Surgeons ():10.1097/XCS.0000000000001232, November 19, 2024. | DOI: 10.1097/XCS.0000000000001232

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Xanomeline-trospium found efficacious among schizophrenia patients experiencing acute psychosis: JAMA

Researchers discovered that xanomeline-trospium, a new-generation antipsychotic devoid of D2 dopamine receptor blocking activity, has shown potency and tolerance in patients with schizophrenia who present with acute psychosis. A recent study was conducted by Inder Kaul and colleagues. This study was published in JAMA Psychiatry.

Schizophrenia affects millions of people worldwide, with current treatments often limited by side effects, including weight gain, sedation, and movement disorders due to D2 dopamine receptor blockade. Xanomeline-trospium combines xanomeline, a dual M1/M4 muscarinic receptor agonist, with trospium chloride, a peripheral muscarinic receptor antagonist, to enhance tolerability.

The EMERGENT-3 clinical trial was a 5-week, multicenter, double-blind, randomized, placebo-controlled study performed at 30 inpatient sites in the US and Ukraine. A total of 256 adults with schizophrenia and acute psychosis were randomized 1:1 to xanomeline-trospium (maximum dose: 125 mg/30 mg) or placebo. The main measure of outcome was the change in Positive and Negative Syndrome Scale (PANSS) total score at week 5 compared with baseline. Secondary measures were changes in PANSS subscale scores and Clinical Global Impression–Severity (CGI-S) scores.

Key findings of the study were:

Primary Outcome:

  • PANSS total score change at week 5 compared with baseline was reduced by 20.6 points with Xanomeline-trospium, and by a reduction of 12.2 points with placebo.

  • The least squares mean difference was −8.4 (95% CI: −12.4 to −4.3; P < .001).

Secondary Outcomes:

  • Both PANSS positive and negative subscale scores and PANSS Marder negative factor scores improved significantly.

  • More participants in the xanomeline-trospium group than in the placebo group showed a reduction of at least 30% in PANSS total score.

Safety Profile:

  • Treatment-emergent adverse events (TEAEs) prompted discontinuation in 6.4% of the xanomeline-trospium and 5.5% of the placebo participants

  • Common TEAEs were nausea in 19.2% vs 1.6%, dyspepsia in 16.0% vs 1.6%, vomiting in 16.0% vs 0.8%, and constipation in 12.8% vs 3.9%

  • No between-group differences were observed for extrapyramidal symptoms, weight gain, or somnolence.

Xanomeline-trospium has been shown to be effective and well tolerated in the treatment of acute psychosis associated with schizophrenia with minimal D2 dopamine receptor blockade. This new therapy provides hope to transform the treatment landscape for schizophrenia, overcomes the limitations of current drugs, and brings about new possibilities for millions of patients around the world.

Reference:

Kaul, I., Sawchak, S., Walling, D. P., Tamminga, C. A., Breier, A., Zhu, H., Miller, A. C., Paul, S. M., & Brannan, S. K. (2024). Efficacy and safety of xanomeline-trospium chloride in schizophrenia: A randomized clinical trial. JAMA Psychiatry (Chicago, Ill.), 81(8), 749. https://doi.org/10.1001/jamapsychiatry.2024.0785

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Older Adults with Celiac Disease Have Increased Risk of Frailty: Study

A new Swedish study published in the American Journal of Gastroenterology revealed that older adults diagnosed with celiac disease (CeD) are significantly more prone to frailty when compared to their peers without the condition. The nationwide cohort study examined individuals aged 60 and older diagnosed with CeD between 2004 and 2017 and matched them with non-CeD controls of similar age, sex, and location. The findings illuminate the heightened vulnerability faced by older adults with CeD by raising concerns about the long-term health impacts of the disease.

This research analyzed frailty levels within 3 years prior to diagnosis using the Hospital Frailty Risk Score, a tool that stratifies individuals into low, intermediate, and high frailty risk categories. Of the 4,646 CeD patients included, 54.4% were classified as frail at baseline when compared to 29.7% of the 21,944 matched controls. Also, frailty was more prevalent across all categories for CeD patients where 43.4% were at low-risk when compared to 23.8% of controls, 10.3% were at intermediate-risk when compared to 5.4%, and 0.8% were at high-risk versus 0.6% among controls.

For individuals without baseline frailty, this study found a stark 66% increased likelihood of developing frailty over the subsequent 5 years for the individuals with CeD. This translated to a significantly higher risk of functional decline and potential complications in this population.

This study also explored the role of mucosal healing where follow-up biopsies that indicated mucosal healing did not correlate with a reduced risk of frailty by suggesting that frailty in older CeD patients may be driven by broader systemic effects of the disease rather than localized gut damage alone. The study suggests that frailty, characterized by decreased resilience and increased susceptibility to adverse health outcomes, poses challenges ranging from reduced mobility to higher risks of hospitalization and mortality.

Overall, this study highlights the need for further research into the mechanisms linking CeD and frailty, as well as interventions tailored to the unique needs of older patients. Proactive measures such as comprehensive care plans and targeted therapies may help manage frailty risk and improve the quality of life for this patient popult.

Source:

Zylberberg, H. M., Lebwohl, B., Söderling, J., Kochar, B., Jylhävä, J., Green, P. H. R., & Ludvigsson, J. F. (2024). Older Adults with Celiac Disease Are At Increased Risk of Frailty:A Nationwide Cohort Study. In American Journal of Gastroenterology. Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.14309/ajg.0000000000003217

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