Lupin unveils first generic version of Oracea in US

Mumbai: Global pharma major Lupin Limited has announced the
launch of first generic version of Oracea (Doxycycline Capsules, 40 mg), in the United States, after
having received an approval from the United States Food and Drug Administration (U.S. FDA).

Read also: Lupin gets USFDA nod for generic equivalent of Oracea Capsules

Doxycycline Capsules, 40 mg is indicated for the treatment of only inflammatory lesions (papules and
pustules) of rosacea in adult patients.

Rosacea is a chronic skin condition characterized by facial redness, visible blood vessels, and sometimes small, red, pus-filled bumps. It typically affects the central part of the face and can also involve eye irritation. While the exact cause is unknown, factors like genetics, blood vessel abnormalities, and certain bacteria may contribute. 


Doxycycline Capsules had estimated annual sales of USD 128 million in the U.S. (IQVIA MAT February
2024).

Read also: Lupin bags USFDA nod for Eslicarbazepine Acetate Tablets for partial-onset seizures

Lupin is an innovation-led transnational pharmaceutical company headquartered in Mumbai, India. The
Company develops and commercializes a wide range of branded and generic formulations, biotechnology
products, and APIs in over 100 markets in the U.S., India, South Africa, and across the Asia Pacific (APAC), Latin
America (LATAM), Europe, and Middle East regions.

The Company specializes in the cardiovascular, anti-diabetic, and respiratory segments and has
a significant presence in the anti-infective, gastro-intestinal (GI), central nervous system (CNS), and women’s
health areas. The company
invested 7.9% of its revenue in research and development in FY23.
Lupin has 15 manufacturing sites, 7 research centers.

Read also: Lupin names Dr Ranjana Pathak as Chief Quality Officer

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Pioglitazone add-on therapy in patients with type 2 diabetes effective and safe option for better glycemic control: Study

South Korea: Adjunctive pioglitazone therapy in type 2 diabetes mellitus (T2DM) inadequately controlled with dapagliflozin and metformin yielded considerable metabolic benefits, glycemic improvement, and a low hypoglycemia risk, a phase 3 trial showed. The findings were published online in Diabetes, Obesity and Metabolism on February 29, 2024.

The researchers, however, suggest weighing its advantages against the potential for weight gain and increased waist circumference.

“In the randomized, placebo-controlled study, pioglitazone add-on therapy was tied to a significantly reduced fasting plasma glucose (FPG), HbA1c, and postload glucose at 120 min versus placebo in patients with uncontrolled T2DM on metformin and dapagliflozin therapy,” the researchers reported. “This led to greater achievement of the glycaemic target goal of HbA1c < 7.0%: 39.5% vs. 20.5%.”

Additionally, the researchers noted a significant decrease in insulin levels and HOMA-IR and an increase in adiponectin levels in the pioglitazone group, which were not found in the placebo group.

Type 2 diabetes is a complex disease with multiple pathophysiologies. Evidence indicates that only one-third to one-half of diabetes patients achieve their glycemic targets, underscoring the persisting difficulties in ensuring optimal glycemic control. A third agent is commonly needed if the glycemic target is not reached even with two-drug combination therapy.

It has yet to be determined which antidiabetic agent would be best for patients already treated with metformin and a sodium-glucose cotransporter-2 (SGLT2) inhibitor. Sungrae Kim, The Catholic University of Korea, Bucheon, South Korea, and colleagues investigate the safety and efficacy of pioglitazone compared to a placebo when added to metformin plus dapagliflozin, an SGLT2 inhibitor, for patients with type 2 diabetes.

For this purpose, the researchers conducted a multicentre study, with a randomized, double-blind, placebo-controlled design comprising 249 Korean patients with T2DM suboptimally managed on dapagliflozin and metformin. They were assigned to receive either pioglitazone (15 mg daily) or placebo for 24 weeks, followed by an extension of a 24-week pioglitazone.

The study’s primary outcomes were changes in glycated hemoglobin (HbA1c). Secondary outcomes assessed adiponectin levels, insulin resistance, lipid profiles, body weight, liver enzymes, and waist circumference.

The study revealed the following findings:

  • Pioglitazone administration resulted in a significant reduction in HbA1c levels (from 7.80% ± 0.72% to 7.27% ± 0.82%) compared with placebo (from 7.79% ± 0.76% to 7.69% ± 0.86%) at 24 weeks.
  • Additional benefits from pioglitazone treatment included increased adiponectin levels, enhanced insulin sensitivity, raised high-density lipoprotein cholesterol levels, and reduced liver enzyme levels, resulting in improved nonalcoholic fatty liver disease liver fat score.
  • Pioglitazone therapy was modestly but significantly associated with weight gain and increased waist circumference despite no serious adverse events in either group.

“Our study findings suggest that pioglitazone could be a safe and effective option for better glycaemic control in patients with type 2 diabetes treated with metformin and SGLT2 inhibitors,” the researchers concluded.

Reference:

Lim S, Lee SH, Min KW, Lee CB, Kim SY, Yoo HJ, Kim NH, Kim JH, Oh S, Won JC, Kwon HS, Kim MK, Park JH, Jeong IK, Kim S. A multicentre, double-blind, placebo-controlled, randomized, parallel comparison, phase 3 trial to evaluate the efficacy and safety of pioglitazone add-on therapy in type 2 diabetic patients treated with metformin and dapagliflozin. Diabetes Obes Metab. 2024 Feb 29. doi: 10.1111/dom.15526. Epub ahead of print. PMID: 38425186.

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MR Study sheds light on anti-inflammatory effects of SGLT-2 inhibitors and their beneficial impact in reducing HF risk

China: A two-sample Mendelian randomization (MR) study provides genetic evidence supporting the anti-inflammatory effects of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and their beneficial impact in reducing heart failure (HF) risk.

CXCL10 emerged as a potential mediator, offering a novel intervention pathway for the treatment of heart failure. The findings were published online in Cardiovascular Diabetology on April 2, 2024.

“Our findings suggest that SGLT-2 inhibitors may reduce HF risk by modulating inflammatory biomarkers, with CXCL10 potentially playing a mediating role—accounting for approximately 18% of the association between SGLT-2 inhibition and HF risk,” the researchers wrote.

SGLT-2 inhibitors represent a novel class of antihyperglycemic drugs that act by SGLT-2 inhibition in the renal tubules, thereby reducing the reabsorption of filtered glucose and enhancing glycosuria effects. Further research has clarified SGLT-2 inhibitors’ role beyond blood glucose reduction, especially highlighting their potential in HF management. However, the precise mechanisms involved remain to be fully delineated. Evidence points to their potential anti-inflammatory pathway in reducing the risk of HF.

To fill this knowledge gap, Hongbing Yan, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, China, and colleagues employed a two-sample, two-step MR approach to assess the correlation between SGLT-2 inhibition and HF, along with the mediating effects of inflammatory biomarkers in this relationship.

MR is an analytical methodology that leverages single nucleotide polymorphisms as instrumental variables to infer potential causal inferences between exposures and outcomes within observational data frameworks. Using datasets from the Genotype-Tissue Expression project and the eQTLGen consortium, genetic variants correlated with the expression of the SLC5A2 gene and glycated hemoglobin levels (HbA1c) were selected.

Using datasets, the researchers obtained the Genome-wide association study (GWAS) data for 92 inflammatory biomarkers from two datasets comprising 14,824 and 575,531 individuals of European ancestry, respectively.

GWAS data for heart failure was derived from a meta-analysis that combined 26 cohorts, including 47,309 HF cases and 930,014 controls. Odds ratios (ORs) for HF were calculated per 1 unit change of HbA1c.

The study led to the following findings:

· Genetically predicted SGLT-2 inhibition was associated with a reduced risk of heart failure (OR 0.42).

· Of the 92 inflammatory biomarkers studied, two inflammatory biomarkers (C-X-C motif chemokine ligand 10 [CXCL10] and leukemia inhibitory factor) were associated with SGLT-2 inhibition and HF.

· Multivariable MR analysis revealed that CXCL10 was the primary inflammatory cytokine related to HF (MIP = 0.861, MACE = 0.224).

·CXCL10 by 17.85% of the total effect mediated the effect of SGLT-2 inhibition on HF.

In conclusion, the study provides genetic support for the relationship between SGLT-2 inhibition, inflammatory biomarkers, and heart failure. Specifically, CXCL10 appears to mediate the effect of SGLT-2 inhibitors on HF.

Reference:

Guo, W., Zhao, L., Huang, W. et al. Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study. Cardiovasc Diabetol 23, 118 (2024). https://doi.org/10.1186/s12933-024-02210-5

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Stopping aspirin one month after PCI significantly reduces bleeding complications in patients with MI: Lancet

Withdrawing aspirin one month after percutaneous coronary intervention (PCI) in high-risk heart patients and keeping them on ticagrelor alone safely improves outcomes and reduces major bleeding by more than half when compared to patients taking aspirin and ticagrelor combined (also known as dual antiplatelet therapy or DAPT), which is the current standard of care.

These are the results from the ULTIMATE-DAPT study announced during a late-breaking trial presentation at the American College of Cardiology Scientific Sessions on Sunday, April 7, and published in The Lancet.

This is the first and only trial to test high-risk patients with recent or threatened heart attack (acute coronary artery syndromes, or ACS) taking ticagrelor with a placebo starting one month after PCI, and compare them with ACS patients taking ticagrelor with aspirin over the same period. The significant findings could change the current guidelines for standard of care worldwide.

“Our study has demonstrated that withdrawing aspirin in patients with recent ACS one month after PCI is beneficial by reducing major and minor bleeding through one year by more than 50 percent. Moreover, there was no increase in adverse ischemic events, meaning continuing aspirin was causing harm without providing any benefit,” says Gregg W. Stone, MD, the study co-chair of ULTIMATE-DAPT, who presented the trial results.

“It is my belief that it’s time to change the guidelines and standard clinical practice such that we no longer treat most ACS patients with dual antiplatelet therapy beyond one month after a successful PCI procedure. Treating these high-risk patients with a single potent platelet inhibitor such as ticagrelor will improve prognosis,” adds Dr. Stone, who is Director of Academic Affairs for the Mount Sinai Health System and Professor of Medicine (Cardiology), and Population Health Science and Policy, at the Icahn School of Medicine at Mount Sinai.

The study analyzed 3,400 patients with ACS at 58 centers in four countries between August 2019 and October 2022. All of the patients had undergone PCI, a non-surgical procedure in which interventional cardiologists use a catheter to place stents in the blocked coronary arteries to restore blood flow. The patients were stable one month after PCI and were on ticagrelor and aspirin. Researchers randomized the patients after one month, withdrawing aspirin in 1,700 patients and putting them on ticagrelor and a placebo, while leaving the other 1,700 patients on ticagrelor and aspirin. All patients were evaluated between 1 and 12 months after the procedure.

During the study period, 35 patients in the ticagrelor-placebo group had a major or minor bleeding event, compared to 78 patients in the ticagrelor-aspirin group, meaning that the incidence of overall bleeding incidents was reduced by 55 percent by withdrawing aspirin. The study also analyzed major adverse cardiac and cerebrovascular events including death, heart attack, stroke, bypass graft surgery, or repeat PCI. These events occurred in 61 patients in the ticagrelor-placebo group compared to 63 patients in the ticagrelor-aspirin group, and were not statistically significant – further demonstrating that removing aspirin did no harm and improved outcomes.

“It was previously believed that discontinuing dual antiplatelet therapy within one year after PCI in patients with ACS would increase the risk of heart attack and other ischemic complications, but the present study shows that is not the case, with contemporary drug-eluting stents now used in all PCI procedures. Discontinuing aspirin in patients with a recent or threatened heart attack who are stable one month after PCI is safe and, by decreasing serious bleeding, improves outcomes,” Dr. Stone adds. “This study extends the results of prior work that showed similar results but without the quality of using a placebo, which eliminates bias from the study.”

Reference:

Zhen Ge, Jing Kan, Xiaofei Gao, Afsar Raza, Jun-Jie Zhang, Bilal S Mohydin, Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomised, placebo-controlled, double-blind clinical trial, The Lancet, https://doi.org/10.1016/S0140-6736(24)00473-2.

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Adjuvant HBOT is beneficial in treating patients with pyoderma gangrenosum: Study

Brazil: A recent study has revealed that adjuvant hyperbaric oxygen therapy (HBOT) may provide some benefits in treating pyoderma gangrenosum patients, particularly those with multiple comorbidities precluding them from receiving more traditional treatments.

The study findings were published online in the Journal of the European Academy of Dermatology and Venereology on March 20, 2024

“After HBOT sessions initiation, 58.4% of the patients achieved complete lesion healing, and 20.8% showed an “improved lesion status,” the researchers reported. However, 20.8% of the patients did not experience improvement with HBOT.

Pyoderma gangrenosum is a painful, rare, and difficult-to-treat neutrophilic dermatosis often linked with underlying medical conditions such as hematologic malignancies or inflammatory bowel disease. It is often a challenging condition for diagnosis and treatment. First, the diagnosis can be delayed. Pyoderma gangrenosum patients do not always present to dermatologists and can go through rounds of broad-spectrum systemic antibiotics, local wound care, and even surgical debridement before making a correct diagnosis. Second, even with the correct diagnosis, treatment is challenging.

Treatment of Pyoderma gangrenosum mainly has two main goals — first, cessation of the neutrophilic inflammation, and, second, healing the chronic wound.

Against the above background, Gisele Viana de Oliveira, Medical Sciences School of Minas Gerais, Belo Horizonte, Brazil, and colleagues conducted a literature review of case reports and series to evaluate the outcomes of using HBOT as an adjuvant treatment in pyoderma gangrenosum patients.

The study is a review of 32 case reports and two case series comprising 48 patients with pyoderma gangrenosum treated with HBOT. In the review, about 60% of the patients experienced complete healing of lesions.

The key findings of the study were as follows:

  • Hyperbaric oxygen therapy was utilized as an adjuvant therapy in 93.7% of the patients and as solo therapy in 6.3% of the patients.
  • After HBOT session initiation, 58.4% of the patients achieved complete lesion healing, and 20.8% showed an “improved lesion status.”
  • 20.8% of the patients did not experience improvement with HBOT.

The researchers suggest it to be an excellent idea and fit within the already established indications for HBOT, as these are chronic wounds. Additionally, based on the small retrospective data set, indicates that the intervention is helpful in many cases.

The article’s authors were careful to note that most patients had received adjuvant therapy. “This is expected as the proposed mechanism of action of HBOT in chronic is angiogenesis and increased tissue oxygenation. These effects are likely more relevant to chronic wound healing versus the underlying neutrophilic inflammation seen in pyoderma gangrenosum,” Jonathan Jeter, a dermatologist in the US Army and is currently practicing at the McDonald Army Health Center in Fort Eustis, Virginia, suggested.

He added, “If HBOT is available to you, this would be an excellent treatment option to have in your back pocket for a patient with pyoderma gangrenosum who has stabilized with medical therapy but needs a little help with the healing process.”

Reference:

Xavier, F., Guimarães, N. S., Diniz, R. C., & Canabrava, P. P. Hyperbaric oxygen therapy as an adjuvant treatment in pyoderma gangrenosum: A scoping review. Journal of the European Academy of Dermatology and Venereology. https://doi.org/10.1111/jdv.19943

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Experimental drug Olezarsen may reduce hypertriglyceridemia in high-risk patients: NEJM

Hypertriglyceridemia, or high levels of lipids (fats) in the blood, increases the risk of heart attack, stroke and acute pancreatitis. Currently available medications, including statins, ezetimibe, fibrates and prescription omega 3 fatty acids, typically lower triglyceride levels by anywhere from below 10% to up to 40%. These therapies help, but they are not enough to prevent cardiovascular events in everyone.

An experimental treatment could further lower triglycerides in the blood, according to a placebo-controlled and double-blind trial led by researchers at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. Results were presented at the 2024 American College of Cardiology’s Annual Scientific Session & Expo and simultaneously published in the New England Journal of Medicine.

The trial randomized 154 adults on lipid-lowering therapy with moderate or severe hypertriglyceridemia to receive either 50mg olezarsen, 80mg olezarsen or placebo. Olezarsen is an antisense oligonucleotide that inhibits APOC3, a gene associated with higher levels of triglycerides, by targeting its mRNA. The subcutaneous medication was administered every four weeks, for a period of a year.

Olezarsen reduced triglyceride levels by 49% at the 50mg dose and 53% at the 80mg dose, compared with placebo. The experimental drug also reduced apolipoprotein B and non-HDL cholesterol, which are important in plaque formation, by 18 to 18.5% and 23% to 25%, respectively.

While larger and longer-term studies are needed to further assess the efficacy and safety of olezarsen in preventing heart attacks and strokes, the research opens up new avenues for improving the health of people with high cardiovascular risk. “These findings indicate that targeting APOC3 mRNA is a promising new pathway for lowering triglycerides and potentially reducing the risk of heart attack and stroke,” said corresponding author Brian Bergmark, MD, of the Division of Cardiovascular Medicine at Brigham and Women’s Hospital.

Reference:

Brian A. Bergmark, Nicholas A. Marston, ThoNew England Journal of Medicinemas A. Prohaska, Veronica J. Alexander,  André Zimerman, Filipe A. Moura, Sabina A. Murphy, Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk, New England Journal of Medicine, DOI: 10.1056/NEJMoa2402309.

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Liver transplantation: Normothermic regional perfusion tied to better DCD liver allograft outcome, study reveals

USA: A recent study published in JAMA Surgery reports US liver transplant outcomes after normothermic regional perfusion (NRP) versus standard super rapid recovery.

The findings suggest that NRP improves controlled donation after circulatory death (DCD) liver allograft outcomes and holds the potential to increase DCD organ use.

“The multicenter cohort study comprisng136 livers recovered with super rapid recovery (SRR) and 106 livers recovered with NRP showed comparable patient and graft survival in liver transplant recipients of DCD donors recovered by NRP versus SRR, with reduced ischemic cholangiopathy rates in NRP recipients,” the researchers reported.

Normothermic regional perfusion is an emerging recovery modality for transplantable allografts from controlled donation after circulatory death (cDCD) donors. In the US, only 11.4% of liver recipients transplanted from a deceased donor receive a cDCD liver.

NRP holds the potential to safely expand the US donor pool with improved transplant outcomes versus standard super rapid recovery. Considering this, Aleah L. Brubaker, University of California San Diego, La Jolla, California, and colleagues aimed to assess outcomes of US liver transplants using controlled donation after circulatory death livers recovered with NRP versus standard SRR.

For this purpose, the researchers conducted a retrospective, observational cohort study to compare liver transplant outcomes from cDCD donors recovered by NRP versus SRR. They collated outcomes of cDCD liver transplants from 2017 to 2023 from 17 US transplant centers. The livers recovered by SRR and NRP (thoracoabdominal NRP [TA-NRP] and abdominal NRP [A-NRP]) were included.

Seven transplant centers used NRP, allowing liver allografts to be transplanted at 17 centers; 10 centers imported livers recovered via NRP from other centers.

The study’s primary outcome was ischemic cholangiopathy (IC). Secondary endpoints were early allograft dysfunction (EAD), primary nonfunction (PNF), posttransplant length of stay (LOS), biliary anastomotic strictures, and patient and graft survival.

The study included 242 cDCD livers: 136 recovered by SRR and 106 recovered by NRP (TA-NRP, 79 and A-NRP, 27). Median NRP and SRR donor age was 30.5 years and 36 years, respectively.

The findings of the study were as follows:

  • Median (IQR) posttransplant LOS was significantly shorter in the NRP cohort (7 days vs 10 days).
  • PNF occurred only in the SRR allografts group (n = 2). EAD was more common in the SRR cohort (56.1% versus 36.4%).
  • Biliary anastomotic strictures were increased 2.8-fold in SRR recipients (6.7% vs 22.4%).
  • Only SRR recipients had IC (9.0%); IC-free survival by Kaplan-Meier was significantly improved in NRP recipients.
  • Patient and graft survival were comparable between cohorts.

In conclusion, there was comparable patient and graft survival in liver transplant recipients of cDCD donors recovered by NRP vs SRR, with reduced rates of IC, EAD, and biliary complications in NRP recipients.

The feasibility of TA-NRP and A-NRP implementation across multiple US transplant centers supports increasing NRP adoption to improve organ use, risk of wait-list mortality, and access to transplants.

Reference:

Brubaker AL, Sellers MT, Abt PL, et al. US Liver Transplant Outcomes After Normothermic Regional Perfusion vs Standard Super Rapid Recovery. JAMA Surg. Published online April 03, 2024. doi:10.1001/jamasurg.2024.0520

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MRI imaging in prostate cancer screening reduces number of unnecessary prostate biopsies: JAMA

Austria: Findings from a recent meta-analysis published in JAMA Oncology support the integration of prostate magnetic resonance imaging (MRI) in prostate cancer (PCa) screening to improve the balance of patient harms and benefits.

The systematic review and meta-analysis of 80 114 screened men from 12 studies revealed that MRI-based screening is associated with a reduced number of unnecessary prostate biopsies and detection of clinically insignificant prostate cancer while maintaining the detection of clinically significant prostate cancer versus prostate-specific antigen–only strategies. To balance these benefits and risks, clinical practice guidelines recommend shared decision-making strategies to identify informed candidates who are most likely to benefit from early detection of prostate cancer.

Prostate MRI is increasingly integrated within the prostate cancer early detection pathway. Therefore, Tamás Fazekas, Medical University of Vienna, Vienna, Austria, and colleagues systematically evaluate the existing evidence regarding screening pathways incorporating MRI with targeted biopsy and assess their diagnostic value compared with PSA–based screening with systematic biopsy strategies.

For this purpose, the researchers searched the online databases through May 2023. Randomized clinical trials (RCTs) and prospective cohort studies were eligible if they reported data on prostate MRI’s diagnostic utility in the setting of PCa screening.

The researchers extracted data on biopsy indications, the number of screened individuals, clinically significant PCa (csPCa) defined as International Society of Urological Pathology (ISUP) grade 2 or higher, biopsies performed, and insignificant (ISUP1) prostate cancers detected.

The study’s primary outcome was the detection rate of csPCa. Secondary outcomes included biopsy indication rates, clinically insignificant PCa detection rates, and the positive predictive value for the detection of csPCa.

The MRI-based and PSA-only screening strategies were compared. Based on the timing of MRI (primary/sequential after a PSA test) and cutoff (Prostate Imaging Reporting and Data System [PI-RADS] score ≥3 or ≥4) for biopsy indication, separate analyses were performed.

Data were synthesized from 80 114 men from 12 studies. Based on the analyses, the researchers reported the following findings:

  • Compared with standard PSA-based screening, the MRI pathway (sequential screening, PI-RADS score ≥3 cutoffs for biopsy) was associated with higher odds of csPCa when test results were positive (OR, 4.15), insignificant cancers detected (OR, 0.34), and decreased odds of biopsies (OR, 0.28) without significant differences in the detection of csPCa (OR, 1.02).
  • Implementing a PI-RADS score of 4 or greater threshold for biopsy selection was associated with a further reduction in the odds of detecting insignificant PCa (OR, 0.23) and biopsies performed (OR, 0.19) without differences in csPCa detection (OR, 0.85).

In conclusion, integrating MRI in prostate cancer screening pathways is tied to a reduced number of unnecessary biopsies and overdiagnosis of insignificant PCa while maintaining csPCa detection as compared with PSA-only screening.

“Our results highlight the need to reassess our approach to population-based screening; however, further evaluation is required on the optimal setup of MRI and biopsy scheme in the screening process,” the researchers wrote.

Reference:

Fazekas T, Shim SR, Basile G, et al. Magnetic Resonance Imaging in Prostate Cancer Screening: A Systematic Review and Meta-Analysis. JAMA Oncol. Published online April 05, 2024. doi:10.1001/jamaoncol.2024.0734

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Cannabis use during pregnancy may increase risk of ADHD, autism and intellectual disability in children: Study

A new study presented at the European Psychiatric Association Congress 2024 reveals a significant association between prenatal cannabis use disorder (CUD) and an increased risk of neurodevelopmental disorders in offspring, including attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID).

Cannabis remains by far the most consumed illicit drug in Europe. Around 1.3% of adults in the European Union (3.7 million people) are estimated to be daily or almost daily users of cannabis. Though males have a typically higher prevalence with regards to cannabis use, the latest statistics show that women are catching up with men in drug use, especially in the younger population. There is increasing concern around the increase in cannabis use observed in younger females in the EU, especially among pregnant and breastfeeding women. This concern is amplified by recent studies that have shown that the content of delta9-tetrahidrocannabinol (THC) is currently around 2-fold higher than it was 15-20 years ago, therefore increasing the risk of adverse effects for young women and their offspring following use when pregnant. Additionally, it has been noted that the prevalence of ADHD and ASD in children and adolescents is on the rise with estimates of 5.3% to 5.9% worldwide and 4.6% for Europe for ADHD and 1 in 2000 for ASD across the EU. 

This large-scale study, conducted by researchers at Curtin University in Australia, analysed data from over 222,000 mother-offspring pairs in New South Wales, Australia. The research team utilised an innovative approach, leveraging linked data from health registries, ensuring both the exposure (prenatal CUD) and outcomes (neurodevelopmental disorders) were confirmed using diagnostic tools based on the ICD-10-AM classification system.

Key findings from the study include:

  • Children born to mothers with prenatal CUD displayed a 98% increased risk of ADHD, a 94% increased risk of ASD, and a 46% increased risk of ID compared to offspring without such exposure.
  • The study also identified a significant interaction effect between prenatal CUD and maternal smoking. Children born to mothers with both prenatal CUD and a history of smoking during pregnancy exhibited an even higher risk of developing ADHD, ASD, and ID.
  • Additionally, the research found synergistic effects between prenatal CUD and other pregnancy complications, such as low birth weight and premature birth, further increasing the risk of neurodevelopmental disorders in offspring.

These findings highlight the potential long-term consequences of cannabis use during pregnancy and emphasise the importance of preventive strategies.

Abay Woday Tadesse, lead researcher of the study at the Curtin School of Population Health commented on the findings, stating “The increased risk of neurodevelopmental disorders in children of mothers diagnosed with prenatal cannabis use that we have observed in this study underscores the critical needs for preventive measures, including preconception counselling, to mitigate the potential adverse outcomes.”

Professor Rosa Alati, Head of the Curtin School of Population Health and senior author of the study, added “These findings highlight the need to increase awareness of the risks associated with cannabis use during pregnancy among women planning to become pregnant.”

“This study is unique because it utilises linked data with confirmed diagnoses, providing a more robust picture of the potential risks associated with prenatal cannabis use. The results underscore the need for public health education campaigns and clinical interventions to raise awareness about the potential risks of cannabis use during pregnancy and to support women in making informed decisions regarding their health and the well-being of their children,” explains Dr Julian Beezhold, the Secretary General of the European Psychiatric Association.

Reference:

Cannabis use during pregnancy linked to increased risk of ADHD, autism and intellectual disability in children, European Psychiatric Association, Meeting:32nd European Congress of Psychiatry.

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Plasma Aldosterone levels may not predict ICU mortality in patients treated for COVID-19: Study

Poland: Plasma aldosterone levels do not predict 28-day mortality in patients treated for COVID-19 in the ICU, a recent study published in Scientific Reports has revealed.

Other factors, including the patient’s age, C-reactive protein (CRP), or creatinine contribute to the prognosis and severity of the disease.

In this study, the researchers attempted to find an association between the serum aldosterone levels measured on days 1, 3, 5, and 7 and the overall survival in the intensive care unit (ICU) for 28 days. They found higher mean plasma aldosterone levels in the patients who did not survive for 28 days, however, the results were not statistically significant, suggesting that aldosterone is not associated with ICU mortality.

Aldosterone’s immunotropic effects might play a role in COVID-19, as SARS-CoV-2 reportedly uses angiotensin-converting enzyme 2 receptors as an entry point into cells. The function of aldosterone closely relates to its action on mineralocorticoid receptors in the kidneys; it increases the renal retention of sodium and the excretion of potassium, which raises blood pressure (BP). Despite several studies investigating the effect of Ang-II and its blockers on the course of COVID-19 infection, there is no clarity on the role of aldosterone.

Against the above background, Jarosław Janc, Hospital of the Ministry of the Interior and Administration, Wrocław, Poland, and colleagues aimed to assess the correlation of aldosterone, creatinine, urea, CRP, and procalcitonin (PCT) levels with 28 days of mortality in patients treated for COVID19 in an ICU.

For this purpose, the researchers conducted a cross-selection study comprising 115 adult patients. They were divided into two groups: those who died within 28 days (n = 82) and those who survived (n = 33).

The researchers performed a correlation of urea, aldosterone, PCT, and CRP levels with 28 days of mortality in patients treated for COVID-19. They also analyzed patient’s sex, age, scores from the SAPS II, APACHE II, and SOFA scales, and comorbidities like hypertension (HA), ischemic heart disease (IHD), and diabetes (DM).

The investigation employed univariate and multivariate Cox proportional hazard regression models to explore mortality-related factors.

The study led to the following findings:

  • The individuals who survived for 28 days were of significantly lower mean age and achieved notably lower scores on the APACHE II, SAPS II, and SOFA assessment scales.
  • Statistically significantly higher CRP levels were observed on days 3, 5, and 7 in individuals who survived for 28 days.
  • Creatinine levels in the same group were also statistically significantly lower on days 1, 3, and 5 than those of individuals who died within 28 days.
  • In the univariate analysis, variables with a p-value of less than 0.50 were included in the multivariate model.
  • Age, APACHE II, SAPS II, and SOFA demonstrated significance in univariate analysis and were considered to be associated with mortality.
  • The outcomes of the multivariate analysis indicated that age (HR = 1.03) served as a robust predictor of mortality in the entire study population.

In conclusion, the plasma aldosterone level is not associated with ICU mortality in COVID-19 patients. Other factors, including the age, CRP, and creatinine of the patients’ contribute to the severity and prognosis of the disease.

“More research is needed to reach a definite conclusion,” the researchers wrote.

Reference:

Janc, J., Janc, J. J., Suchański, M., Fidut, M., & Leśnik, P. (2024). Aldosterone levels do not predict 28-day mortality in patients treated for COVID-19 in the intensive care unit. Scientific Reports, 14(1), 1-8. https://doi.org/10.1038/s41598-024-58426-8

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