Medical Bulletin 06/ September/ 2024 - Video

A Danish study published in the The BMJ , has revealed that long term exposure to fine particulate matter (PM2.5) air pollution is linked to a higher risk of infertility in men, whereas road traffic noise is linked to a higher risk of infertility in women over 35.

Infertility is a major global health problem affecting one in seven couples trying to conceive.

Several studies have found negative links between particulate air pollution and sperm quality and success after fertility treatment, but results on fecundability (the likelihood of conceiving) are inconsistent, and no studies have investigated the effects of transport noise on infertility in men and women.

To address this uncertainty, researchers set out to investigate if long term exposure to road traffic noise and fine particulate matter (PM2.5) air pollution was associated with a higher risk of infertility in men and women.

Their findings are based on national registry data for 526,056 men and 377,850 women aged 30-45 years, with fewer than two children, cohabiting or married

Yearly average particulate matter (PM2.5) concentrations and road traffic noise levels at each participant’s address (1995-2017) were calculated, and infertility diagnoses were recorded from the national patient register.

Infertility was diagnosed in 16,172 men and 22,672 women during an 18-year follow-up period (an average of just over 4 years).

After adjusting for several potentially influential factors including income, education level, and occupation, exposure to 2.9 µg/m3 higher average levels of PM2.5 over five years was associated with a 24% increased risk of infertility in men aged 30-45 years. PM2.5 was not associated with infertility in women

Exposure to 10.2 decibels higher average levels of road traffic noise over five years was associated with a 14% increased risk of infertility among women older than 35 years. Noise was not associated with infertility among younger women (30-35 years).

Reference: Sørensen, M., Poulsen, A. H., Nøhr, B., Khan, J., Ketzel, M., Brandt, J., Raaschou-Nielsen, O., & Jensen, A. (2024). Long-term exposure to road traffic noise and air pollution and risk of infertility in men and women: Nationwide Danish cohort study. BMJ (British Medical Journal). https://doi.org/10.1136/bmj-2024-080664

Stroke patients who survive a blood clot in the brain’s blood vessels are prone to developing new blockages during their recovery periods, even if they receive vessel-clearing interventions. In an effort to avoid further clots, doctors at 57 sites around the U.S. tested a possible solution: the addition of anti-coagulant drugs to medicine that dissolves blood clots.

But results from the clinical trial, led by Opeolu Adeoye, MD, head of the Department of Emergency Medicine at Washington University School of Medicine in St. Louis, indicate two such drugs did not improve outcomes.

The findings are published in The New England Journal of Medicine.

“We’re a little disappointed in the results,” said Adeoye, who is also the BJC HealthCare Distinguished Professor of Emergency Medicine. “But it’s meaningful to optimal patient care that we’ve answered the question definitively. Neither of the drugs helps prevent further clots.”

The goal of the Multi-arm Optimization of Stroke Thrombolysis (MOST) clinical trial that Adeoye led was to test the efficacy of adding argatroban, a blood thinner, or eptifibatide, which inhibits blood platelets from sticking together, to the routine intravenous thrombolysis treatment.

The trial closed the chapter on this potential use of these medications, but Peter Panagos, MD, professor of emergency medicine and co-author on the study, said that efforts like these inform future advances in medicine, including potential new anti-coagulant treatments.

“Without negative trials, we would not know how to design new trials,” Panagos said. “Future success is built upon the hard work of previous research effort.”

Physicians do not have a lot of treatment options for patients who experience a stroke. Some patients undergo a procedure to remove the clot. Others receive intravenous thrombolysis to relieve the affected blood vessel through clot-dissolving medication delivered to the bloodstream. A number of patients receive both interventions.

“Even with those treatments, over half of patients still have a significant disability three months after their stroke," said Adeoye, who treats patients at Barnes-Jewish Hospital and Missouri Baptist Medical Center and also provides stroke telemedicine consultation. "After you give the thrombolysis, the clot can re-form, which contributes to the stroke worsening or persisting.”

Preventing these clots with an additional treatment of anti-coagulant drugs seemed like a promising idea, especially as there are FDA-approved medications that earlier studies had suggested could be effective.

In the MOST trial, patients were randomly assigned to receive either argatroban, eptifibatide or placebo. Adeoye explained that the study had checkpoints built in to ensure that treatment outcomes were meeting efficacy thresholds in order to continue. The first checkpoint was set at 500 patients, which the team reached in 2023.

“When we looked at the data, it was readily apparent that neither drug was going to come anywhere close to our threshold,” he said.

In fact, the probability that either drug was helpful was less than 1%. Worse still, argatroban and eptifibatide were linked to greater incidences of disability and mortality within the three-month post-treatment observation window.

This correlation was not necessarily alarming; the safety monitors on the project found that the deaths appeared to have causes unrelated to the medications. The lack of improvement noted with the medications compared with what was noted with the placebo was reason enough to call off the trial.

Reference: Adeoye O, Broderick J, Derdeyn CP, Grotta JC, Barsan W, Bentho O, Berry S., Concha M, Davis I, Demel S, Elm J, Gentile N, Graves T, Hoffman M, Huang J, Ingles J, Janis S, Jasne AS, Khatri P, Levine SR, Majjhoo A, Pancioli A, Panagos P, Pizzella S, Ranasinghe T, Sabagha N, Sivakumar S, Streib C, Vagal A, Wilson A, Wintermark M, Yoo AJ, Barreto AD. Adjunctive intravenous argatroban or eptifibatide for ischemic stroke. The New England Journal of Medicine. Sept. 4, 2024.

Researchers from Michigan State University and South Shore Hospital in Massachusetts have uncovered a connection between two common diabetes drugs injectable insulin and metformin identified in wound exudates of diabetic foot ulcers, which may improve their healing.

Research published in ACS Pharmacology & Translational Science has found that wound exudate the fluid the body sends to an injury site—contains metformin in patients who take the medication orally.

The researchers then explored metformin’s relationship to insulin. They found that for patients who take both insulin injections and oral metformin, the amount of metformin found in wounds significantly increases. It was previously believed that there was no interaction between insulin and metformin.

Diabetic foot ulcers (DFUs) pose a significant challenge in wound care due to their chronic nature and impaired healing processes. This study examines the biogenic amines and small molecule metabolites present in diabetic foot ulcer wound exudates to identify their potential roles in wound healing.

“Until now, pharmacological studies had not found an interaction between insulin and metformin,” said Morteza Mahmoudi, an associate professor in the Department of Radiology and Precision Health Program at the MSU College of Human Medicine.. “Our study shows that there could be at least an indirect role of consuming both insulin and metformin in a way that metformin can end up in a wound area where it enhances the body’s capacity to heal.”

Reference: Gould, L., & Mahmou, M. (2024). Analysis of biogenic amines and small molecule metabolites in human diabetic wound ulcer exudate. ACS Pharmacology & Translational Science.

The heavy metal cadmium, which is found in the air, water, food and soil, is known to cause health problems. A new study published in Neurology examined if thinking and memory skills were associated with cadmium exposure.

They found no association when they looked at the group as a whole. However, when looking at Black and white people separately, it found cadmium may be tied to problems with thinking and memory skills in white people. The study found no such association in Black people. The study does not prove that cadmium causes memory problems in white people; it only shows an association.

Cadmium is a highly toxic heavy metal that enters the body mainly through cigarette smoking, breathing polluted air and food. It is released into the environment through industrial and agricultural activities.

The study involved 2,172 people with an average age of 64 and no problems with thinking or memory skills. Black people made up 39% of the participants and white people made up 61%. Levels of cadmium in the urine were tested at the beginning of the study. Participants took tests of thinking and memory skills every year and were followed for an average of 10 years.

During that time, 195 people developed cognitive impairment. When researchers looked at the overall group, they found no association between cadmium levels and cognitive impairment. However, when they looked at Black and white participants separately, they found that white people with high levels of cadmium were more likely to develop cognitive impairment. They found no association in Black people.

With participants divided into two groups based on cadmium levels, white people with high levels were twice as likely to develop cognitive impairment as those with low levels, even after adjusting for other factors that could affect cognitive impairment, such as physical activity, alcohol use and education. A total of 9.2% of those with high levels developed thinking and memory problems, compared to 6.7% of those with low levels.

The American Journal of Gastroenterology has published a new guideline on the treatment of Helicobacter pylori (H. pylori) infection.

H. pylori is a bacterium that infects over half the people in the world, though most are asymptomatic. It can cause dyspepsia, peptic ulcer disease and gastric cancer.

A previous guideline was published in 2017. It had maintained the recommendation of a proton pump inhibitor-clarithromycin triple therapy as the primary treatment option.

In the new guideline, the number one recommendation for treatment-naïve patients is bismuth quadruple therapy. That treatment typically includes a PPI, tetracycline, bismuth and nitroimidazole for 14 days.

“We were already recommending that healthcare providers move away from PPI triple therapy in 2017 because of increasing problems with chloromycetin resistance amongst H. pylori strains in the United States,” corresponding author of the guideline, William D. Chey said.

“Despite that recommendation, PPI triple therapy still dominates first-line therapy prescriptions for H. pylori patients in the United States. In this newest iteration of the guideline, we are very clear to say that in essentially all circumstances you should not be prescribing PPI triple therapy, and you should be instead using bismuth quadruple therapy or one of the other suggested treatment options.”

A third option consists of a new, highly potent drug which blocks stomach acid production called vonoprazan combined with the antibiotic amoxicillin.

The guideline makes 12 total treatment suggestions for patients in a variety of different situations. The number two recommendation for treatment-naïve patients—after bismuth quadruple therapy—is rifabutin triple therapy (a PPI, rifabutin and amoxicillin.)

Besides the move away from PPI triple therapy, another change from the 2017 guideline is the discussion of increasingly available molecular testing for antibiotic susceptibility.

The guideline also outlines future research priorities, such as identifying which individuals would most benefit from H. pylori testing to prevent gastric cancer and evaluating newly FDA-approved regimens for persistent infections.

Reference: Chey, W. D., Howden, C. W., Moss, S. F., Morgan, D. R., Greer, K. B., Grover, S., & Shah, S. C. (2024). ACG clinical guideline: Treatment of Helicobacter pylori infection. The American Journal of Gastroenterology, 119(9), 1730-1753. https://doi.org/10.14309/ajg.0000000000002968