Medical Bulletin 20/ September/ 2024

A comparison of three surgical techniques in patients with trachomatous trichiasis showed that bilamellar tarsal rotation (BLTR) at 3mm incision height and posterior lamellar tarsal rotation (PLTR) are equally effective in treating the condition with no difference in postoperative trichiasis. The study, published in PLOS Neglected Tropical Diseases, was supported by the National Eye Institute (NEI), part of NIH.

Trachomatous trichiasis, a potentially blinding condition where inward-turned eyelashes scratch the front of the eye, can successfully be treated by either of the two most common types of eyelid surgery, according to findings from a large comparison trial funded by the National Institutes of Health.

“Some studies have reported post-operative trichiasis rates of 30% or higher for patients with trachomatous trichiasis following surgery, and repeat surgeries are more difficult,” said Emily Gower, Ph.D., University of North Carolina at Chapel Hill. “This trial sought to determine if we could decrease the risk of post-operative trichiasis by modifying the surgical procedure. We found that existing approaches result in better outcomes.”

Trachomatous trichiasis affects approximately 1.7 million people worldwide, mostly in poor and rural areas of Africa. The condition arises after repeated or chronic eye infections with the bacteria Chlamydia trachomatis, which is spread by person-to-person contact. Trachoma is very common in hot, dry areas of the world, and repeat infections can eventually lead to scarring and malformation of the eyelid. This malformation causes the edge of the eyelid to draw inward, so that eyelashes scratch the eye. If left untreated, trichiasis can result in corneal clouding, and eventually blindness.

The study, which took place in southern Ethiopia, enrolled 4,914 patients with trichiasis in one or both eyes (6,940 eligible eyes). The participants were randomized to receive bilamellar tarsal rotation at 3 mm incision height, bilamellar tarsal rotation at 5 mm incision height, or posterior lamellar tarsal rotation. Researchers rechecked the patients for post-operative trichiasis at six weeks and again at 12-18 months. On average, approximately 17% of eyelids had post-operative trichiasis. There was no difference in risk of post-operative trichiasis between the two methods with a 3 mm incision height, while those who received the 5 mm incision height bilamellar tarsal rotation were significantly more likely to have post-operative trichiasis. The results indicate that the current standard surgeries – either method at 3 mm – are better options for trichiasis treatment than the 5 mm method.

Reference: Emily W. Gower, Alemayehu Sisay, Belay Bayissasse, Dawit Seyum, Jerusha Weaver, Beatriz Munoz, Alexander P. Keil, Andrea Bankoski, Kristin M. Sullivan, Hashiya Kana, Fisseha Admassu, Demissie Tadesse, Shannath L. Merbs. The impact of modified incision height and surgical procedure on trichiasis surgery outcomes: Results of the maximizing trichiasis surgery success (MTSS) randomized trial. PLOS Neglected Tropical Diseases, 2024; 18 (9): e0012034 DOI: 10.1371/journal.pntd.0012034

Study Finds Casual Blood Glucose test misses 70% of Gestational Diabetes Cases

A study conducted at the Kobe university reveals that 70% of the cases get unnoticed when casual blood sugar levels were measured to evaluate gestational diabetes. The authors suggest that a more reliable test like Glucose tolerance test should be used for screening the same.

The results, published in the Journal of Diabetes Investigation, showed that out of the 99 women who in the end were diagnosed with gestational diabetes mellitus, 71.7% had blood sugar levels in their first blood sample that would have resulted in a negative (no diabetes) diagnosis. Tomimoto explains, “Although there have been studies showing that the casual blood glucose test is less sensitive than others, no studies have directly compared the results in the same individuals. Our study confirmed that this screening method, which is widely used in practice, frequently misses the condition it is meant to detect.”

To see how widespread this issue is, the team also conducted a survey amongst health care facilities in Hyogo Prefecture, where Kobe University is based. They found that 43% of the respondents who used blood glucose tests relied only on the casual screening. “In Japan, where about half of all deliveries take place in obstetric clinics rather than in hospitals, the more accurate but complicated and time-consuming tests are not widely used,” says TOMIMOTO Masako, graduate student at Kobe University. However, this is not a problem unique to Japan, as similar surveys showed that in the UK, 48% of clinics also rely on only the casual blood glucose test for the first screening.

Kobe University obstetrician TANIMURA Kenji says about the implications of their study: “We would like to educate healthcare professionals and patients about this danger and encourage them to promote the use of the more accurate glucose tolerance screening method. We hope that our data can contribute to improvements in the management system and to the revision of the guidelines for gestational diabetes mellitus screenings. The goal is to protect more mothers and babies from gestational and childbirth issues caused by this form of diabetes, and in general reduce the risk of developing the disease in the future.”

Reference: Tomimoto, M., Tanimura, K., Masuko, N., Uchida, A., Imafuku, H., Deguchi, M., Yamamoto, A., Hirota, Y., Ogawa, W., & Terai, Y. (2024). Problems in screening for gestational diabetes mellitus by measurement of casual blood glucose levels at 24–28 gestational weeks. Journal of Diabetes Investigation. https://doi.org/10.1111/jdi.14310

Administering IV iron found Effective in Pregnant Females with Iron Deficiency Anaemia than Oral Iron Intake: Randomised trial Finds

Researchers found that a medicine called ferric carboxymaltose given in drip through the vein works faster and better than an iron tablet taken by mouth for the treatment of anaemia – and it is as safe as the tablet. The findings were published in Lancet Global Health.

A team of researchers in a recently concluded clinical trial, called the IVON TRIAL, tested a medicine for treating anaemia (low blood level), called ferric carboxymaltose. They compared the effectiveness and safety of this medicine with that of a popular tablet, called ferrous sulphate, which is currently being used to treat anaemia in Nigeria. They found that this new medicine given in drip (continuous fluid) through the vein works faster and better than iron tablets taken by mouth for treatment of anaemia; and it is as safe as the tablet.

The study enrolled 1,056 pregnant women, aged 15 – 49 years, who were between five and seven-and-half months pregnant and had anaemia with haemoglobin (red blood level) measurement less than 10 g/dl.

“We used a web-based platform to assign them to treatment groups. Half of the women were treated with one dose of iron given in drip through the vein while half took iron tablets three times a day till they gave birth”, says Ochuwa A. Babah, a doctoral student at Department of Global Public Health, Karolinska Institute and one of the authors of the paper.

Their haemoglobin levels and iron levels were checked, and they were screened for depression at specific time points. They were followed-up until six weeks after delivery to collect more data from mother and baby. Blood was collected from the baby’s cord at delivery to know if the medicine affected the baby’s phosphate level.

Only one dose of iron (ferric carboxymaltose) given by drip through a vein during pregnancy causes a faster rise in blood level after four weeks compared to iron tablet taken by mouth three times every day. The drip iron also corrects low body iron better than iron tablets. The side effects of the drip iron are comparable to that with iron tablets, with no adverse effect on the babies.

“These findings are reassuring because pregnant women often reject new medicines because of fear of harm to their babies. We now have evidence that implementing the use of this new drip iron (ferric carboxymaltose) in regions where many pregnant women suffer anaemia like Africa, will be a valuable step towards reducing the proportion of pregnant women who suffer from this condition and its complications”, says Ochuwa A. Babah and continues:

“The pregnant women were willing to accept the drip iron during pregnancy, supported by their families. The healthcare workers were ready to administer drip iron but identified a need to increase staff strength and possibly medicine subsidy. We know from the clinical trial that the drip iron is effective and safe, so we are already liaising with the Federal Ministry of Health, Nigeria to add it to the essential drug list.”

Reference: Afolabi, B. B., Babah, O. A., Adeyemo, T. A., Balogun, M., Banke-Thomas, A., & Abioye, A. I. (2024). Intravenous versus oral iron for anaemia among pregnant women in Nigeria (IVON): An open-label, randomised controlled trial. The Lancet Global Health. https://doi.org/10.1016/S2214-109X(24)00239-0

Systematic Review Finds Triptans Outperforms Newer Expensive Migraine Drugs

Some triptans are a more effective treatment for acute migraines than newer, more expensive drugs, finds an analysis of the latest evidence published by The BMJ.

The findings show that four triptans - eletriptan, rizatriptan, sumatriptan, and zolmitriptan - were better at relieving migraine pain than the recently marketed and more expensive drugs lasmiditan, rimegepant, and ubrogepant, which were comparable to paracetamol and most anti-inflammatory painkillers (NSAIDs).

The researchers argue that triptans are currently widely underused, and say access to the most effective triptans should be promoted globally and international guidelines updated accordingly.

The researchers trawled scientific databases to identify randomised controlled trials published up to 24 June 2023 that compared licensed oral drugs for treatment of acute migraine in adults.

A total of 137 randomised controlled trials comprising 89,445 participants (average age 40, 86% women) allocated to one of 17 individual drugs or placebo were included. The trials were of varying quality, but the researchers were able to assess the certainty of evidence using a recognised tool.

The results show that all drugs were more effective than placebo at relieving pain after two hours and most were effective for sustained pain relief up to 24 hours, except paracetamol and naratriptan.

When drugs were compared with each other, eletriptan was the most effective drug for pain relief at two hours, followed by rizatriptan, sumatriptan, and zolmitriptan. For sustained pain relief up to 24 hours, the most effective drugs were eletriptan and ibuprofen.

The researchers point out that the best performing triptans should be considered the treatment of choice for migraine episodes and should be included into the WHO Model List of Essential Medicines to promote global accessibility and uniform standards of care.

They acknowledge that some people can’t take triptans due to heart problems or unpleasant side effects.

Nevertheless, they say these results, even if limited to average treatment effects due to the lack of individual patient data, “offer the best available evidence to guide the choice of acute oral drug interventions for migraine episodes” and “should be used to guide treatment choices, promoting shared, informed decision making between patients and clinicians.”

Reference: Karlsson, W. K., Ostinelli, E. G., Zhuang, Z. A., Kokoti, L., Christensen, R. H., Al-Khazali, H. M., Deligianni, C. I., Tomlinson, A., Ashina, H., Ruiz de la Torre, E., Diener, H.-C., Cipriani, A., & Ashina, M. (2024). Comparative effects of drug interventions for the acute management of migraine episodes in adults: Systematic review and network meta-analysis. BMJ, 386, e080107. https://doi.org/10.1136/bmj-2024-080107

Clinical Trial Finds Bone Marrow Cancer Drugs Effective in Managing Rare Blood Disorder

A clinical trial supported by the National Institutes of Health (NIH) was stopped early after researchers found sufficient evidence that a drug used to treat bone marrow cancer and Kaposi sarcoma is safe and effective in treating hereditary hemorrhagic telangiectasia (HHT), a rare bleeding disorder that affects 1 in 5,000 people worldwide.

The trial results, which were published in the New England Journal of Medicine, detail how patients with hereditary hemorrhagic telangiectasia given the drug, called pomalidomide, experienced a significant reduction in the severity of nosebleeds, needed fewer of the blood transfusions and iron infusions that HHT often demands, and showed improved quality of life.

“Finding a therapeutic agent that works in a rare disorder is highly uncommon, so this is a real success story,” said Andrei Kindzelski, M.D., Ph.D., of NIH’s National Heart, Lung, and Blood Institute. “Before our trial, there was no reliable therapeutic to treat people with hereditary hemorrhagic telangiectasia. This discovery will give people who suffer with this disease a positive outlook and better quality of life.”

Current options to treat hereditary hemorrhagic telangiectasia involve closing off the malformed blood vessels in the nose and gastrointestinal tract or prescribing off-label medications that temporarily stabilize blood clotting at sites of bleeding vessels, which in turn reduces bleeding. There are currently no Food and Drug Administration-approved medications for long-term management of hereditary hemorrhagic telangiectasia.

Researchers speculated that pomalidomide worked by blocking the growth of abnormal blood vessels. It may cause the blood vessels to have a more normal structure or thicker walls so they are less fragile. However, the research team, led by Keith McCrae, M.D., professor of molecular medicine at the Cleveland Clinic, says further study will be needed.

Researchers enrolled 144 adults with hereditary hemorrhagic telangiectasia at 11 U.S. medical centers between Nov. 5, 2019, and June 27, 2023. All participants had moderate to severe nosebleeds requiring iron infusions or blood transfusions. Researchers gave 95 of the participants 4 mg of pomalidomide daily, though the dosage was reduced to 3 mg or 2 mg daily in patients with adverse reactions – mostly constipation, rashes, and lower than average white blood cell counts. The remaining 49 patients received a daily sugar pill designed to look exactly like the pomalidomide pill, in addition to their usual care

At the start of the trial, researchers used a validated hereditary hemorrhagic telangiectasia -specific bleeding assessment tool to score each patient’s nosebleed severity. To establish a baseline in other areas, participants self-reported other data throughout the trial, particularly the severity of their nosebleeds and the effect of their hereditary hemorrhagic telangiectasia symptoms on everyday activities using a special scoring system. The number of units of red blood cells transfused or iron infused was also recorded.

In June 2023, 43 months into the scheduled four-year trial, an interim analysis found pomalidomide had met a prespecified threshold for efficacy, and the trial was closed to further enrollment.

“These findings have broader implications for people with more severe forms of hereditary hemorrhagic telangiectasia,” said Kindzelski. “In those cases, malformed blood vessels can develop in organs such as the lung, liver, and brain, which can lead to hemorrhagic stroke, bleeding in the lungs, or heart failure. A treatment like this could be lifesaving for such patients.”

Reference: Al-Samkari, H., Kasthuri, R. S., Iyer, V. N., Pishko, A. M., Decker, J. E., Weiss, C. R., Whitehead, K. J., & McCrae, K. R. (2024). Pomalidomide for epistaxis in hereditary hemorrhagic telangiectasia. New England Journal of Medicine, 391(12), 1015-1027. https://doi.org/10.1056/NEJMoa2312749