Drug-induced dystonia after sacubitril/valsartan combination therapy in a 19-year-old female student: Case study

India: A recent case study published in Annals of Internal Medicine: Clinical Cases reports the case of classical dystonia in a young girl who presented with reduced systolic left ventricular function, had cardiac surgery, and was prescribed sacubitril/valsartan combination for reversal of heart remodelling.

After the stoppage of this combination in the patient, dystonia did not reoccur. Although being an effective drug for heart failure with reduced ejection fraction, “newer indications will need further assessment for the different dose regimen and adverse drug reactions,” Prabhat Tewari, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India, and colleagues wrote.

The fixed-dose combination of sacubitril (neprilysin inhibitor) and valsartan has revealed a significant benefit in cardiovascular death and hospitalization for heart failure with reduced ejection fraction (HFrEF) as compared with other commonly used single-drug regimens in the PARADIGM-HF trial. Newer indications for its use may include postoperative cardiovascular patients with HFrEF who may require early reverse remodelling of the left ventricle.

Usual adverse drug reactions with this combination include renal impairment and symptomatic hypotension. Adverse drug reaction by definition can be an unpleasant response due to a drug use that can adversely impact a person and may call for either treatment or withdrawal of the medication.

Dr. Tewari and the team shared the recent complication of abnormal muscular movements that started shortly after administering sacubitril/valsartan combination therapy in a young female patient during the postoperative period after cardiac surgery.

This case report may result in the further reevaluation of the sacubitril/valsartan combination for its dose regimen adjustment in newer therapeutic indications where this therapy may prove to be helpful.

The case concerns a 19-year-old female student with a height of 159 cm and weight of 35 kg who was admitted with grade III dyspnea. Upon detailed echocardiographic evaluation, she was diagnosed with severe aortic regurgitation due to the right coronary cusp prolapse, subpulmonic ventricular septal defect, and dilated left ventricle with reduced ejection fraction (40%). She was managed in the intensive care unit and was weaned off the ventilator support after 12 hours. She did well in the postoperative period and was prescribed diuretics (spironolactone–torsemide combination) and aspirin.

She was also started on low-dose sacubitril/valsartan combination therapy (total 25 mg per day), divided into 2 equal doses given twice daily for two days after her consent as she had a dilated left ventricle with moderate ejection fraction.

She was discharged from the hospital on the fifth postoperative day with a good activity level but was readmitted in the same evening with the symptoms of bouts of an extremely stiff, nonpainful neck that tilted her head involuntarily leftwards, upwards, and backwards in hyperextension. This involuntary movement resolved by itself in an hour, only to reoccur after some time and stay for a longer duration. A neurology consultation adjudged this as drug-induced acute dystonia.

Being the new drug used in this particular postoperative setting, the Sacubitril/valsartan combination was stopped and replaced with carvedilol, a beta-blocker. She responded well to this change, and the dystonic movements never occurred afterwards in the follow-up.

In conclusion, the Sacubitril/valsartan combination is an effective therapy for HFrEF patients to improve their quality of life. Its use in postoperative settings underlies the fact that this kind of adverse reaction of this beneficial drug may need close monitoring, and studies may be required to determine the mechanism of such an adverse reaction in humans. It is also important that healthcare providers are well versed with these new side effects, and reporting of these incidences is to be encouraged.

“Although being an effective drug for heart failure with reduced ejection fraction, newer indications will need further assessment for the different dose regimen and adverse drug reactions,” the research team concluded.

Reference:

DOI: https://doi.org/10.7326/aimcc.2023.0131

Powered by WPeMatico

Maternal Prescription Opioid Use linked to Spontaneous Preterm Birth: JAMA

A recent study highlighted the potential risks that are associated with prescription opioid use during pregnancy. The findings of this study were published in the Journal of American Medical Association.

This research examined data from pregnant individuals enrolled in Tennessee Medicaid which spanned over a decade, from 2007 to 2019 and involved over 250,000 patients. Olivia Bosworth and colleagues investigated the association between prescription opioid use during pregnancy and the occurrence of spontaneous preterm birth, which is a significant concern for maternal and child health. 

The findings found that among the group studied, over 7% of patients had filled an opioid prescription in the 60 days preceding childbirth. Also, for each doubling of opioid dosage, there was a 4% increase in the risk of spontaneous preterm birth. This explores a dose-dependent relationship between opioid exposure and the risk of preterm delivery.

The study emphasized the importance of these findings in guiding clinical practice. These results support existing recommendations to minimize opioid exposure during pregnancy and to prescribe the lowest effective dose only when necessary. While opioids can be important to manage pain in certain medical conditions, their potential impact on pregnancy outcomes warrants close consideration.

The rigorous methodology of this study utilized a large retrospective cohort that adds strength to its conclusions. Further research may be required to explore the underlying mechanisms that drive this association and to develop targeted interventions for populations at-risk. Overall, the outcomes serve as a crucial addition to the body of evidence linking prescription opioid use during pregnancy to adverse birth outcomes. 

Reference:

Bosworth, O. M., Padilla-Azain, M. C., Adgent, M. A., Spieker, A. J., Wiese, A. D., Pham, A., Leech, A. A., Grijalva, C. G., & Osmundson, S. S. (2024). Prescription Opioid Exposure During Pregnancy and Risk of Spontaneous Preterm Delivery. In JAMA Network Open (Vol. 7, Issue 2, p. e2355990). American Medical Association (AMA). https://doi.org/10.1001/jamanetworkopen.2023.55990

Powered by WPeMatico

Age when periods first start and early menopause linked to heightened COPD risk

A range of reproductive factors, including age when periods first start and an early menopause, are all linked to a heightened risk of COPD-the umbrella term for progressive lung conditions that cause breathing difficulties-finds research published online in the journal Thorax.

Miscarriage, stillbirth, infertility, and having 3 or more children are also associated with a heightened risk of COPD, which includes emphysema and chronic bronchitis, the findings show.

Recent evidence indicates substantial gender differences in susceptibility to, and severity of, COPD, note the researchers. Women seem to develop severe COPD at younger ages than men. And while smoking is a major risk factor, non-smokers with COPD are more likely to be women, they add.

Previously published studies looking at the potential influence of female hormones on COPD risk have been hampered by methodological flaws, note the researchers. To try and get round these issues, they drew on the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) consortium.

This is a collection of 27 observational studies, pooling individual level data from more than 850,000 women in 12 countries.

For the purposes of the current study, the researchers included three groups of women (283,070; average age 54) with data on reproductive factors and COPD: the Australian Longitudinal Study on Women’s Health 1946–51 (ALSWH-mid); the UK Biobank; and the Swedish Women’s Lifestyle and Health Study (WLH).

In the ALSWH-mid and UK Biobank groups, women were tracked until the end of December 2019. Women in WLH were tracked up to the end of 2010.

Information on reproductive factors was collected at study entry or at subsequent data collection points, along with potentially influential factors: birth year (before or after 1950), ethnicity, educational level, duration of smoking, asthma (never and ever), and weight (BMI).

COPD was retrospectively and prospectively identified through self-report and medical records, which included prescriptions, hospital admissions, emergency care visits, and death registry data.

The women’s health was monitored for an average of 11 years. During this time, 10,737 (4%) women developed COPD at an average age of 63.

Women with COPD were more likely to be older when recruited to their studies, to have fewer than 10 years of formal education, to be obese, to have smoked for at least 10 years, and to have asthma–all risk factors for the condition. Some 53, 205 (16%) women were excluded because of missing data.

Several reproductive factors were associated with the risk of COPD, including age when periods first started; number of children; a history of infertility, miscarriage or stillbirth, especially multiple miscarriages or stillbirths; and age at menopause.

A U-shaped pattern emerged for the age at which periods first started. Those who began menstruating before or at the age of 11 were 17% more likely to develop COPD than those who did so at the age of 13; after the age of 16, the risk was 24% higher.

Women with children were at higher risk of COPD than childless women. Compared with having 2 children, more than 3 was associated with a 34% higher risk, while women with one child were at 18% higher risk.

Women who experienced infertility also had a 13% higher risk of COPD than women who were fertile.

And among those who had ever been pregnant, a history of miscarriage was associated with a 15% higher risk of COPD, with the risk rising in tandem with the number of miscarriages: 28% higher for 2; and 36% higher for 3 or more.

Similarly, stillbirth was associated with a 42% overall higher risk of COPD, with the risk rising in tandem with the number of stillbirths.

Menopause before the age of 40 was associated with a 69% higher risk, compared with those experiencing it naturally at the age of 50-51, while the risk was 21% lower for those who went through it at or after the age of 54.

This is an observational study, so can’t establish cause, and the researchers acknowledge various limitations to their findings, including potentially influential factors.

For example, they had no detailed information on hormonal contraception and HRT use, and data on parental history of COPD, childhood respiratory infections, secondhand smoking or occupational exposures, weren’t available for all 3 of the groups.

But by way of an explanation for their findings, they suggest that the female hormone oestrogen is likely to have a key role in COPD risk in women, because of its various effects on the lung.

“The overall effect of oestrogen might differ depending on the timing,” they suggest. “In the early or middle reproductive stage, long or higher accumulated exposure to oestrogen would be detrimental to the lung, leading to a higher risk of COPD among women with early menarche or multiple live births.

“In the later stage, oestrogen may be protective, since earlier age at menopause or [ovary removal] (indicates shorter exposure to oestrogen) were associated with a higher risk of COPD.”

Other factors, including autoimmune disease, such as type 1 diabetes, and social and environmental factors, such as air pollution, underweight, and socioeconomic deprivation, might also be influential, they add.

Reference:

Liang C, Chung H, Dobson A, et alFemale reproductive histories and the risk of chronic obstructive pulmonary diseaseThorax Published Online First: 13 February 2024. doi: 10.1136/thorax-2023-220388.

Powered by WPeMatico

FDA approves device for treatment of paediatric patients with kidney injury due to sepsis

The US Food and Drug Administration has approved a new device for treating children weighing 10 kg or more with acute kidney injury (AKI) due to sepsis or a septic condition who require kidney replacement therapy. The approval is granted to company SeaStar which is currently testing the device in critically ill patients with AKI and looking at other applications.

This is the first product in the Company’s newly branded Quelimmune product family, and the Quelimmune pediatric device can now be commercially marketed as a Humanitarian Use Device (HUD).

“This first regulatory approval is a major accomplishment for our company and, most importantly, it provides critically ill children with AKI access to a much-needed new therapy,” said Eric Schlorff, SeaStar Medical CEO. “Only about one-half of the children in the ICU with AKI requiring CKRT survive, and those who do are at increased risk of long-term conditions such as chronic kidney disease. In clinical studies, Quelimmune for pediatric AKI has been shown to reduce mortality rates and dialysis dependency in clinical studies.

“We appreciate the FDA’s willingness to work collaboratively with SeaStar Medical and our advisors to grant HDE approval to Quelimmune for pediatric use,” Mr. Schlorff added. “We believe the HDE for children weighing as little as 10 kilograms – or roughly 22 pounds – acknowledges the proven life-saving capabilities of our device and addresses a critical unmet need for patients. We are working to make Quelimmune therapy the new standard of care for AKI requiring CKRT in the ICU and to demonstrate its benefit in the many indications where hyperinflammation and dysregulated inflammatory processes are involved.”

The initial commercial launch of Quelimmune for pediatric AKI is expected in the coming weeks by SeaStar Medical’s U.S. license and distribution partner Nuwellis, with a full commercial program to follow. Nuwellis has established strong relationships with pediatric nephrology and intensive care key opinion leaders across the U.S.

“The unique technology behind Quelimmune has demonstrated great promise in making a positive impact on children with potentially deadly hyperinflammation,” said Nestor Jaramillo, Jr., Nuwellis President and CEO. “The pediatric segment of our business has gained significant traction over the past several years, and we are excited to add the Quelimmune pediatric device to our product offering.”

The FDA granted HDE approval to the Quelimmune pediatric device for AKI based upon clinical results showing safety and probable clinical benefit to critically ill children with AKI who have few treatment options. Pooled analysis from two non-controlled studies, SCD-PED-01 (funded by the FDA Office of Orphan Products Development) and SCD-PED-02 showed that pediatric patients ≥10kg with AKI requiring CKRT treated with the Quelimmune pediatric device had no device-related serious adverse events or device-related infections, a 77% reduction in mortality rate, and no dialysis dependency at Day 60. The SCD-PED-01 (weight range ≥15 kg) and PED-02 (weight range ≥10 kg) studies demonstrated 75% and 83% reductions in mortality, respectively. These data were recently published in the journal Kidney Medicine. SeaStar Medical is currently focused on its NEUTRALIZE-AKI pivotal clinical trial to evaluate Quelimmune therapy in the larger adult AKI population, while exploring other applications for this device.

About Hyperinflammation

Hyperinflammation is the overproduction or overactivity of inflammatory cells that can lead to damage of vital organs. It occurs when the body overproduces inflammatory effector cells and other molecules that can be toxic, damaging to vital organs and result in multi-organ failure and even death. This is known as the cytokine storm.

About Quelimmune

Quelimmune is a patented cell-directed extracorporeal device that employs immunomodulating technology to selectively target proinflammatory neutrophils and monocytes during CKRT and reduces the hyperinflammatory milieu including the cytokine storm that causes inflammation, organ failure and possible death in critically ill patients. Unlike pathogen removal and other blood-purification tools, the device is integrated with CKRT hemofiltration systems to selectively target and transition proinflammatory monocytes to a reparative state and promote activated neutrophils to be less inflammatory. Quelimmune selectively targets the most highly activated proinflammatory neutrophils and monocytes. These cells are then returned back into the body through the blood, and the body is signaled to lower its inflammatory environment and focus on repair. This unique immunomodulation approach may promote long-term organ recovery and eliminate the need for future KRT, including dialysis.

Powered by WPeMatico

Eating too much protein bad for your arteries and this amino acid is to blame

University of Pittsburgh School of Medicine researchers discovered a molecular mechanism by which excessive dietary protein could increase atherosclerosis risk. The findings were published in Nature Metabolism today.

The study, which combined small human trials with experiments in mice and cells in a Petri dish, showed that consuming over 22% of dietary calories from protein can lead to increased activation of immune cells that play a role in atherosclerotic plaque formation, driving the disease risk. Furthermore, the scientists showed that one amino acid-leucine-seems to have a disproportionate role in driving the pathological pathways linked to atherosclerosis, or stiff, hardened arteries.

“Our study shows that dialing up your protein intake in pursuit of better metabolic health is not a panacea. You could be doing real damage to your arteries,” said senior and co-corresponding author Babak Razani, M.D., Ph.D., professor of cardiology at Pitt. “Our hope is that this research starts a conversation about ways of modifying diets in a precise manner that can influence body function at a molecular level and dampen disease risks.”

According to a survey of an average American diet over the last decade, Americans generally consume a lot of protein, mostly from animal sources. Further, nearly a quarter of the population receives over 22% of all daily calories from protein alone.

That trend is likely driven by the popular idea that dietary protein is essential to healthy living, says Razani. But his and other groups have shown that overreliance on protein may not be such a good thing for long-term health.

Following their 2020 research, in which Razani’s laboratory first showed that excess dietary protein increases atherosclerosis risk in mice, his next study in collaboration with Bettina Mittendorfer, Ph.D., a metabolism expert at the University of Missouri, Columbia, delved deeper into the potential mechanism and its relevance to the human body.

To arrive at the answer, Razani’s laboratory, led by first-authors Xiangyu Zhang, Ph.D., and Divya Kapoor, M.D., teamed up with Mittendorfer’s group to combine their expertise in cellular biology and metabolism and perform a series of experiments across various models – from cells to mice to humans.

“We have shown in our mechanistic studies that amino acids, which are really the building blocks of the protein, can trigger disease through specific signaling mechanisms and then also alter the metabolism of these cells,” Mittendorfer said. “For instance, small immune cells in the vasculature called macrophages can trigger the development of atherosclerosis.”

Based on initial experiments in healthy human subjects to determine the timeline of immune cell activation following ingestion of protein-enriched meals, the researchers simulated similar conditions in mice and in human macrophages, immune cells that are shown to be particularly sensitive to amino acids derived from protein.

Their work showed that consuming more than 22% of daily dietary calories through protein can negatively affect macrophages that are responsible for clearing out cellular debris, leading to the accumulation of a “graveyard” of those cells inside the vessel walls and worsening of atherosclerotic plaques overtime. Interestingly, the analysis of circulating amino acids showed that leucine – an amino acid enriched in animal-derived foods like beef, eggs and milk – is primarily responsible for abnormal macrophage activation and atherosclerosis risk, suggesting a potential avenue for further research on personalized diet modification, or “precision nutrition.”

Razani is careful to note that many questions remain to be answered, mainly: What happens when a person consumes between 15% of daily calories from protein as recommended by the USDA and 22% of daily calories from protein, and if there is a ‘sweet spot’ for maximizing the benefits of protein – such as muscle gain – while avoiding kick-starting a molecular cascade of damaging events leading to cardiovascular disease.

The findings are particularly relevant in hospital settings, where nutritionists often recommend protein-rich foods for the sickest patients to preserve muscle mass and strength.

“Perhaps blindly increasing protein load is wrong,” Razani said. “Instead, it’s important to look at the diet as a whole and suggest balanced meals that won’t inadvertently exacerbate cardiovascular conditions, especially in people at risk of heart disease and vessel disorders.”

Razani also notes that these findings suggest differences in leucine levels between diets enriched in plant and animal protein might explain the differences in their effect on cardiovascular and metabolic health. “The potential for this type of mechanistic research to inform future dietary guidelines is quite exciting,” he said.

Reference:

Zhang, X., Kapoor, D., Jeong, SJ. et al. Identification of a leucine-mediated threshold effect governing macrophage mTOR signalling and cardiovascular risk. Nat Metab 6, 359–377 (2024). https://doi.org/10.1038/s42255-024-00984-2.

Powered by WPeMatico

EEP using thulium fiber laser equally effective as high-power holmium laser in large prostates in terms of complications: Study

Singapore: A recent real-world study published in Prostate International reaffirmed that high-power holmium laser (HPHL) thulium fiber laser (TFL) in large prostates is equally efficacious concerning 30-day complications.

The researchers also found that thulium fiber laser with the en-bloc technique has a shorter operative time which significantly and positively impacts short- and medium-term functional outcomes.

Endoscopic enucleation of the prostate (EEP) has gained acceptance as an equitable alternative to transurethral resection of the prostate for benign prostate hyperplasia (BPH), primarily due to the use of lasers and bipolar energy and the introduction of morcellators. EEP and holmium laser (HL) enucleation of the prostate, in particular, has demonstrated lower rates of hospital stay and postoperative catheterization, and complications with excellent functional outcomes versus open simple prostatectomy.

With the recent introduction of TFL for EEP which is gaining increasing popularity, there is an urgent to compare with HPHL. Therefore, Ee Jean Lim, Department of Urology, Singapore General Hospital, Singapore, and colleagues aimed to compare perioperative outcomes of EEP between TFL and HPHL for large prostates (≥80 ml in volume), using data from experienced surgeons. Secondary outcomes were to assess complications within one year of follow-up.

For this purpose, they retrospectively reviewed patients with benign prostatic hyperplasia who underwent EEP with TFL or HPHL in 13 centres. Patients with prostate volume ≥80 ml were included, while those with previous prostate/urethral surgery, concomitant prostate cancer, and pelvic radiotherapy were excluded.

The study led to the following findings:

  • Of 1,929 included patients, HPHL was utilized in 1,459 and TFL in 470.
  • After propensity score matching (PSM) for baseline characteristics, 247 patients from each group were analyzed.
  • Overall operative time (90 vs. 52.5 min) and enucleation time (90 vs. 38 min) were longer in the TFL group, with comparable morcellation time (13 vs. 13 min).
  • In terms of postoperative outcomes, there were no differences in 30-day complications such as acute urinary retention, urinary tract infection or sepsis.
  • In the PSM cohort, univariable analyses showed that higher age, lower preoperative Qmax, higher preoperative PVRU, and longer operation time were associated with higher odds of postoperative incontinence, while 2-lobe enucleation had lower odds of incontinence compared to 3-lobe enucleation.

The researchers caution that attention to hemostasis in EEP of large prostates with any laser is quintessential to minimize morcellation-related as well as post-operative morbidity.

“Our study successfully shows how EEP is confidently being adopted with different lasers by different techniques even in large prostates,” the research team concluded.

Reference:

Lim, E. J., Castellani, D., Somani, B. K., Gökce, M. I., Fong, K. Y., Sancha, F. G., Herrmann, T. R., Biligere, S., Tursunkulov, A. N., Dellabella, M., Sofer, M., Enikeev, D., Petov, V., Gadzhiev, N., Elterman, D., Mahajan, A., Socarras, M. R., Yunusov, D. S., Nasirov, F., . . . Gauhar, V. (2023). High-power holmium laser versus thulium fiber laser for endoscopic enucleation of the prostate in patients with glands larger than 80 ml: Results from the Prostate Endoscopic EnucLeation study group. Prostate International. https://doi.org/10.1016/j.prnil.2023.12.001

Powered by WPeMatico

Avocado Consumption Positively Linked to Improved Cardiometabolic Health in Adults, unveils Australian Study

In a promising revelation, a recent cross-sectional analysis of
the Australian Health Survey 2011-2013 has uncovered positive associations
between avocado consumption and enhanced cardiometabolic health in Australian
adults. Avocados have long been recognized for their potential health benefits.

The study results were published in the Nutrition Journal.

Also Read: Daily avocados consumption may improve diet quality, lower cholesterol levels

Avocados, recognized for their nutrient-rich profile, are a
source of monounsaturated fats, dietary fiber, and phytochemicals. Studies have
associated higher avocado intake with enhanced dietary quality. To delve deeper
into this relationship, a cross-sectional analysis was conducted on a
representative sample of Australian adults using data from the Australian
Health Survey 2011-2013.


The study, involving 2,736 observations, utilized day 1 24-hour
recall data to assess avocado consumption and its potential impact on
cardiometabolic risk measures. Avocado intake, both whole avocados, and
products excluding avocado oil, was examined alongside markers such as LDL,
HDL, total cholesterol, triglycerides, apolipoprotein B, HbA1c, plasma glucose,
systolic and diastolic blood pressure.


Results:


  • Key findings revealed that 14.7% of Australians were classified
    as ‘avocado consumers.’

  • The mean avocado intake for this group was 24.63 (95% CI: 20.11,
    29.15) grams per day, with a median intake of 10.40 (IQR: 4.49–26.00) grams per
    day.

  • Avocado consumers exhibited lower BMI and waist circumference
    (p ≤ 0.001), along with a significant decrease in plasma glucose levels
    (p = 0.03) and higher HDL cholesterol (p ≤ 0.001) compared to non-consumers.


  • Further analysis between high and low consumers of avocado
    revealed a notable trend: high consumers showcased lower plasma glucose and
    HbA1c (each, p = 0.04) and a higher dietary fiber intake (p = 0.05).

  • These findings suggest a positive association between avocado
    intake and improved cardiometabolic characteristics.

Also Read: Flaxseeds, almonds, avocados, tomatoes, turmeric and green tea distinctly bring down LDL cholesterol


While the study establishes a correlation, it emphasizes the
need for future research, particularly clinical trials, to explore the
potential causative relationships between avocado consumption and
cardiometabolic risk factors, especially in the realm of glucose homeostasis.
The study underscores the potential benefits of incorporating avocados into the
diet for improved metabolic health, urging further exploration into the
mechanisms behind these observed positive outcomes.

Further reading: Probst Y, Guan V, Neale E. Avocado intake and cardiometabolic risk factors in a representative survey of Australians: a secondary analysis of the 2011-2012 national nutrition and physical activity survey. Nutr J. 2024 Jan 25;23(1):12. doi: 10.1186/s12937-024-00915-7. 

Powered by WPeMatico

Apitegromab improves motor function of patients with spinal muscular atrophy, reveals study

Spinal muscular atrophy (SMA) is a debilitating genetic disorder characterized by muscle weakness and degeneration that often leading to severe disability and shortened lifespan. A new therapy called apitegromab for patients revealed promising results in a recent phase 2 clinical trial published in the Neurology Journal.

Apitegromab is an investigational fully human monoclonal antibody that works by inhibiting myostatin that regulates skeletal muscle growth. Unlike the currently approved therapies for SMA that mainly focus on reversing degeneration, apitegromab targets the preservation of muscle mass to address the underlying impairment caused by neurodegeneration.

The phase 2 TOPAZ trial evaluated the safety and efficacy of apitegromab in individuals with later-onset type 2 and type 3 SMA. The study explored potential eligibility criteria and treatment regimens for future research that involved three cohorts of participants aged from 2 to 21 years. The trial was conducted across 16 sites in the United States and Europe that revealed promising results. 58 participants received apitegromab infusions every four weeks for 12 months. The primary efficacy measure using the Hammersmith Functional Motor Scale demonstrated improved motor function in participants across all cohorts.

The participants in cohort 3, who received apitegromab in combination with nusinersen showed the most significant improvement. At 12 months, the mean scores increased by 5.3 points for the 2-mg/kg arm and 7.1 points for the 20-mg/kg arm. Also, this therapy demonstrated a favorable safety profile with no deaths or serious adverse reactions reported.

These encouraging outcomes support the advancement of apitegromab into a randomized, placebo-controlled phase 3 trial for SMA patients. If successful, apitegromab could offer the much-needed treatment option that halts disease progression and further improves motor function by enhancing the quality of life for individuals living with SMA.

Source:

Crawford, T. O., Darras, B. T., Day, J. W., Dunaway Young, S., Duong, T., Nelson, L. L., Barrett, D., Song, G., Bilic, S., Cote, S., Sadanowicz, M., Iarrobino, R., Xu, T. J., O’Neil, J., Rossello, J., Place, A., Kertesz, N., Nomikos, G., & Chyung, Y. (2024). Safety and Efficacy of Apitegromab in Patients With Spinal Muscular Atrophy Types 2 and 3. In Neurology (Vol. 102, Issue 5). Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1212/wnl.0000000000209151

Powered by WPeMatico

Biologic and Targeted Synthetic DMARDs may Improve Work Productivity in Psoriatic Arthritis: Study

Psoriatic arthritis (PsA) not only affects joint health but also significantly impacts work productivity and leisure activities. Previous studies have highlighted the substantial burden of PsA on patients’ ability to work and engage in daily activities. PsA is associated with reduced health-related quality of life and various comorbidities, leading to impaired social participation and functional limitations.

A recent study has found that targeted DMARD therapy improves the quality and ability to work regularly in PsA patients. This study was published in the journal Arthritis Research Therapy by Gossec L and colleagues.

A systematic literature review and meta-analysis were conducted to evaluate the impact of b/tsDMARD treatment on work productivity in PsA patients. Studies published between January 2010 and October 2021 were included, focusing on outcomes related to absenteeism, presenteeism, and activity impairment using the Work Productivity and Activity Impairment Questionnaire (WPAI).

The key findings were:

  • Twelve studies, comprising 10 randomized controlled trials and 2 observational studies, were analyzed.

  • Among employed PsA patients (n = 3741), baseline scores indicated significant impairment in work productivity and activity participation.

  • After 24 weeks of b/tsDMARD treatment, substantial improvements were observed across all WPAI domains, with absolute mean improvements of 2.4 percentage points for absenteeism, 17.8% for presenteeism, 17.6% for total work productivity impairment, and 19.3% for activity impairment.

  • These findings corresponded to a 41% relative improvement in total work productivity.

The study underscores the significant impact of PsA on work productivity and highlights the effectiveness of b/tsDMARDs in mitigating these effects. Despite limitations, including the exclusive use of WPAI and variations in cost estimation methods, the results provide valuable insights into the economic benefits of b/tsDMARD treatment in PsA.

Measurement of work impact is essential for assessing the economic burden and value of therapies in PsA. The study demonstrates meaningful improvements in work productivity following 24 weeks of b/tsDMARD treatment, emphasizing the importance of early and effective management strategies for PsA patients to enhance their overall well-being and economic outcomes.

Reference:

Gossec L, Humphries B, Rutherford M, Taieb V, Willems D, Tillett W. Improvement in work productivity among psoriatic arthritis patients treated with biologic or targeted synthetic drugs: a systematic literature review and meta-analysis. Arthritis Res Ther. 2024;26(1):50. Published 2024 Feb 15. doi:10.1186/s13075-024-03282-0

Powered by WPeMatico

High-sensitivity CRP and monocyte to HDL ratio associated with Increased Type 2 Diabetes Risk: BMC study

A recent study published in the Journal of Translational Medicine explored the intricate relationship between monocytic inflammation, C-reactive protein (CRP) and the onset of type 2 diabetes (T2D). The investigation looked into the association between systemic inflammation that assessed by joint cumulative high-sensitivity C-reactive protein (CumCRP), monocyte to high-density lipoprotein ratio (CumMHR)and the incidence of T2D within the general population.

Over 40,000 nondiabetic individuals participated in this prospective real-life cohort study, with biennial follow-ups that spanned from 2010/2011 to December 31, 2020. Through rigorous multivariable Cox regression analyses, the team evaluated adjusted hazard ratios (aHRs) of incident diabetes.

The findings revealed that over a median follow-up of nearly eight years, 4848 cases of T2D emerged. CumMHR and CumCRP was found to be significant predictors of T2D, both independently and in conjunction. The elevated CumMHR levels were found to increase the risk of developing diabetes across all CumCRP strata by indicating a relationship between these markers. The observation that individuals with concurrent elevations in CumMHR and CumCRP underwent the highest risk of T2D by emphasizing the importance of considering multiple markers in assessing diabetes risk was striking.

This study highlighted the influence of demographic and clinical factors such as age, sex, hypertension, dyslipidemia and prediabetes status on the observed risk. This precise understanding underlines the complexity of T2D development and the need for personalized risk assessment strategies. The addition of CumMHR and CumCRP to established risk factors significantly enhanced risk prediction and reclassification of diabetes by improvements in C-statistics and net reclassification improvement.

Reference:

Wu, D., Chen, G., Lan, Y., Chen, S., Ding, X., Wei, C., Balmer, L., Wang, W., Wu, S., & Xu, W. (2024). Measurement of cumulative high-sensitivity C-reactive protein and monocyte to high-density lipoprotein ratio in the risk prediction of type 2 diabetes: a prospective cohort study. In Journal of Translational Medicine (Vol. 22, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1186/s12967-024-04895-4

Powered by WPeMatico