Archive for category: News

Iron plays a vital role in the growth and development of young children. In low- and middle-income countries, anaemia is a significant health issue, and young children are vulnerable to iron deficiency anaemia. Previous research studies have shown the association between low iron and poor development outcomes in children.

University of New Mexico researchers have found that even low to moderate alcohol use by pregnant patients may contribute to subtle changes in their babies’ prenatal development, including lower birth length and a shorter duration of gestation.

In a new paper published in the journal Alcohol Clinical & Experimental Research, a team led by Ludmila Bakhireva, MD, PhD, MPH, professor and assistant dean for Clinical and Translational Research in the UNM College of Pharmacy, also reported some sex-related differences in the effects of drinking during pregnancy on the developing baby.

“In exploratory analyses, the effect on gestational age was more pronounced in male infants, and for birth length it actually was stronger in females,” Bakhireva said. She cautioned that these effects should be interpreted with caution because of the study’s limited statistical power to conduct sex-specific analyses and the challenges of accounting for other contributing factors.

The paper reported on three prospective studies conducted at UNM over the course of 10 years that followed 281 participants, most of whom were recruited in the second trimester of their pregnancies and then followed, along with their children, for some time afterward, she said.

There is a good deal of research on the prenatal effects of heavy alcohol use, usually defined as 14 drinks per week, or binge drinking, defined as four drinks or more per occasion, Bakhireva said.

“We know quite a bit from these earlier studies of heavy alcohol use about the effect on prenatal outcomes, especially preterm delivery and growth restriction, as well as neurodevelopmental outcomes, but we specifically focused on more moderate alcohol exposure because it’s much more prevalent,” she said.

Early pregnancy is a critical period for the formation of organs in the developing fetus, making it a particularly vulnerable window for alcohol exposure, Bakhireva said.

“Almost everybody drinks before they know they are pregnant, and risky drinking before pregnancy is predictive of drinking later on,” she said. “That’s a unique aspect of the study. We carefully looked at the patterns of drinking around conception and early pregnancy.”

Most of the participants substantially reduced their drinking or stopped altogether once they learned they were pregnant, Bakhireva said. Even with reduced alcohol there were some deficits seen in both male and female infants, however.

She emphasizes that larger studies that combine samples across the country are needed to replicate the findings and examine sex-specific effects further.

Bakhireva is the principal investigator of the HEALthy Brain and Child Development study at UNM, part of a national initiative that will recruit 7,500 parent-child pairs and follow them for up to 10 years. “With that type of multi-site study, we’ll have sufficient power to look at the effects of different patterns and timing of alcohol use in even a more nuanced way,” she said.

The paper underscores messaging from the National Institute of Alcohol Abuse and Alcoholism-that no amount of drinking during pregnancy is safe, she said.

“I think this study, as well as prior preclinical studies, show that even moderate alcohol use might have negative effects. The degree of negative effects might vary, and it is important to address alcohol use without the stigma often associated with it, but overall, if we try to encourage abstinence from alcohol during pregnancy, we will maximize positive health and developmental outcomes for the children.”

Reference:

Ludmila N. Bakhireva, Xingya Ma, Alexandria Wiesel, Fiona E. Wohrer, Jared DiDomenico, Sandra W. Jacobson, Melissa H. Roberts, Dose–response effect of prenatal alcohol exposure on perinatal outcomes, Alcohol Clinical and Experimental Research, https://doi.org/10.1111/acer.15284.

The US Food and Drug Administration (FDA) has granted approval to iloperidone (Fanapt) for acute treatment of bipolar I disorder.

Fanapt is an atypical antipsychotic agent that has been used for the acute treatment of patients with schizophrenia since its FDA approval in 2009.

“Manic or mixed episodes associated with bipolar I disorder are highly complex conditions, which require a host of trusted options to meet individual patient needs. With over 100,000 patient years of experience, Fanapt is a familiar therapeutic agent that offers flexible dosing with a well-known safety profile. This FDA approval gives patients and service providers a new treatment option for managing bipolar I disorder,” said Mihael H. Polymeropoulos M.D., Vanda’s President, CEO and Chairman of the Board.

Bipolar disorder is a serious, highly prevalent psychiatric chronic condition affecting approximately 2.8% of the U.S. adult population, with 83% of them classified as severe1. Bipolar disorder is a group of disorders that are characterized by periods of elevated mood alternating with periods of depressed mood. For the diagnosis of bipolar I disorder, people must have experienced one or more episodes of mania and most would have episodes of both mania and depression. Patients with bipolar I disorder with manic or mixed episodes are a subset of those approximately 10 million Americans with bipolar disorder1. The marketing approval of Fanapt in bipolar I disorder with manic and mixed episodes significantly increases the commercial opportunity for Fanapt.

Stephen Stahl, MD, PhD, Professor of Psychiatry at the University of California San Diego, said, “Many patients today are still unable to find suitable treatment options for effectively managing bipolar disorder. Tailoring the right treatment for the right patient is critical for effective care, and the approval of Fanapt represents an important milestone. Fanapt possesses a well-studied safety profile, and its approval will provide patients with a new and effective option for treating a highly complex disorder.”

The approval of Fanapt for the acute treatment of adults with manic or mixed episodes associated with bipolar I disorder was based on a pivotal study randomizing approximately 400 patients. The primary endpoint measured in Week 4 of treatment was assessed by the Young Mania Rating Scale (YMRS), a rating scale of clinical severity in the core symptoms of mania. At the end of the study (Week 4), Fanapt treated patients showed a larger improvement than placebo treated patients, and this difference was highly statistically significant (p=0.000008). YMRS was assessed at the end of Weeks 1, 2, 3 and 4. Statistically significant benefit in the Fanapt treated group over placebo was observed as early as the Week 2 assessment. The safety profile of Fanapt in this study was similar to that seen in Fanapt studies previously conducted for the treatment of schizophrenia in adults.

Dr. Polymeropoulos continued, “Today’s announcement marks a significant step forward for one of Vanda’s leading franchises and underscores the effectiveness of our strategy in pursuing innovative therapies that address high unmet medical needs to improve the lives of patients. With this as our foundation, we have established a resilient business, with a diverse product pipeline, a history of revenue growth and strong financial position. We remain focused on providing critical medicines to patients across the world while creating sustainable, long-term value.”

ChatGPT-4, an artificial intelligence program designed to understand and generate human-like text, outperformed internal medicine residents and attending physicians at two academic medical centers at processing medical data and demonstrating clinical reasoning. In a research letter published in JAMA Internal Medicine, physician-scientists at Beth Israel Deaconess Medical Center (BIDMC) compared a large language model’s (LLM) reasoning abilities directly against human performance using standards developed to assess physicians.

“It became clear very early on that LLMs can make diagnoses, but anybody who practices medicine knows there’s a lot more to medicine than that,” said Adam Rodman MD, an internal medicine physician and investigator in the department of medicine at BIDMC. “There are multiple steps behind a diagnosis, so we wanted to evaluate whether LLMs are as good as physicians at doing that kind of clinical reasoning. It’s a surprising finding that these things are capable of showing the equivalent or better reasoning than people throughout the evolution of clinical case.”

Rodman and colleagues used a previously validated tool developed to assess physicians’ clinical reasoning called the revised-IDEA (r-IDEA) score. The investigators recruited 21 attending physicians and 18 residents who each worked through one of 20 selected clinical cases comprised of four sequential stages of diagnostic reasoning. The authors instructed physicians to write out and justify their differential diagnoses at each stage. The chatbot GPT-4 was given a prompt with identical instructions and ran all 20 clinical cases. Their answers were then scored for clinical reasoning (r-IDEA score) and several other measures of reasoning.

“The first stage is the triage data, when the patient tells you what’s bothering them and you obtain vital signs,” said lead author Stephanie Cabral, MD, a third-year internal medicine resident at BIDMC. “The second stage is the system review, when you obtain additional information from the patient. The third stage is the physical exam, and the fourth is diagnostic testing and imaging.”

Rodman, Cabral and their colleagues found that the chatbot earned the highest r-IDEA scores, with a median score of 10 out of 10 for the LLM, 9 for attending physicians and 8 for residents. It was more of a draw between the humans and the bot when it came to diagnostic accuracy—how high up the correct diagnosis was on the list of diagnosis they provided—and correct clinical reasoning. But the bots were also “just plain wrong” – had more instances of incorrect reasoning in their answers – significantly more often than residents, the researchers found. The finding underscores the notion that AI will likely be most useful as a tool to augment, not replace, the human reasoning process.

“Further studies are needed to determine how LLMs can best be integrated into clinical practice, but even now, they could be useful as a checkpoint, helping us make sure we don’t miss something,” Cabral said. “My ultimate hope is that AI will improve the patient-physician interaction by reducing some of the inefficiencies we currently have and allow us to focus more on the conversation we’re having with our patients.

“Early studies suggested AI could makes diagnoses, if all the information was handed to it,” Rodman said. “What our study shows is that AI demonstrates real reasoning-maybe better reasoning than people through multiple steps of the process. We have a unique chance to improve the quality and experience of healthcare for patients.”

Reference:

Stephanie Cabral, Daniel Restrepo, Zahir Kanjee, Philip Wilson, Byron Crowe, Raja-Elie Abdulnour, Adam Rodman. Clinical Reasoning of a Generative Artificial Intelligence Model Compared With Physicians. JAMA Internal Medicine, 2024; DOI: 10.1001/jamainternmed.2024.0295.

South Korea: A recent study has shown an association between tuberculosis (TB) and cancer, with those with current or previous TB more likely to have a diagnosis of a variety of cancers, including blood, lung, colorectal, and gynecological cancers.

The findings from the population-wide observational study were presented at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024) in Barcelona, Spain (27-30 April). The study is by Dr Jiwon Kim, National Health Insurance Service, Ilsan Hospital, Goyang, South Korea, and Dr Jinnam Kim, Hanyang University College of Medicine, Seoul, South Korea, and colleagues.

Despite a successful cure of TB being possible, complications can occur at various anatomical sites due to structural or vascular damage, metabolic abnormalities and host inflammatory response. These complications may include an increased risk of cancer, which may be influenced by host tissue and DNA damage, and/or interruption of normal gene repair processes and growth factors present in the blood. In this study, the authors investigated the association between cancer incidence and TB compared with the general population.

They retrospectively reviewed data from the National Health Insurance Service-National Health Information Database of South Korea between 2010 and 2017. Patients with TB were defined as a those with a disease code for TB entered into the system, or treated with two or more TB drugs for more than 28 days. The control group from the general population was randomly selected in a 1:5 ratios and matched for sex, age, income level, residence, and index year. The authors analysed the incidence of newly diagnosed cancer patients after enrolment (post-TB diagnosis). The primary outcome was the incidence of cancer in patients diagnosed with TB infection in the period 2010-2017 compared with the matched cohort. The secondary outcomes were to investigate the risk factors for cancer incidence in TB patients.

The final analysis included total of 72,542 patients with TB and 72,542 matched controls. The mean follow-up duration was 67 months (around five-and-a-half years), and the mean age in patients with TB was 62 years.

Compared with the general population, the incidence of cancer was significantly higher in TB patients: 80% higher for all cancers combined; 3.6 times higher for lung cancer, 2.4 times higher for blood (haematological) cancers); 2.2 times higher for gynaecological cancer; 57% higher for colorectal cancer; 56% higher for thyroid cancer and 55% higher for oesophagus and stomach cancer.

After adjustment, current smoking (40% increased risk versus non-smokers), heavy alcohol consumption (15% increased risk versus regular alcohol consumption) chronic liver disease (42% increased risk versus no liver diseases) and chronic obstructive pulmonary disease (COPD) (8% increased risk) were also identified as independent risk factors for cancer in people with TB.

The authors say: “TB is an independent risk factor for cancer, not only lung cancer, but also various site-specific cancers, after adjusting for confounders. Screening and management for cancer should be warranted in patients with TB.”

Reference:

Study finds association between TB infection and increased risk of various cancers, European Society of Clinical Microbiology and Infectious Diseases, Meeting: The European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024).