Category: 8. Health

Faced with a worsening drug crisis, policymakers in recent years have made it much easier for doctors to prescribe the highly effective opioid addiction treatment buprenorphine. However, many patients may still struggle to find pharmacies carrying the treatment, finds new research led by the USC Schaeffer Center for Health Policy & Economics.

Buprenorphine was available at just 39% of U.S. retail pharmacies in 2023, a modest increase from 33% in 2017, according to the study published Sept. 2 in Health Affairs. But disparities in who can access the treatment have persisted. Pharmacies in predominantly Black neighborhoods (18%) and Latino neighborhoods (17%) remain significantly less likely to carry buprenorphine as those in white neighborhoods (46%).

Buprenorphine is one of several medications that can ease opioid cravings and withdrawal, and it is the only one that can be prescribed in primary care settings and dispensed at retail pharmacies. Because these treatments are milder opioids and considered controlled substances, they historically have been subject to tight prescribing and dispensing rules.

Recent efforts to ease prescribing rules include the 2023 elimination of the so-called “X-waiver” that required doctors to receive specialized training and registration to prescribe the treatment. However, dispensing rates have changed little, suggesting that pharmacy regulations aimed at preventing opioid (and buprenorphine) diversion, abuse and misuse continue to discourage pharmacies from carrying the treatment, particularly in minority neighborhoods and some areas hit hardest by the opioid epidemic.

Relaxing buprenorphine prescribing rules was an important step in making this critical treatment more accessible, but too many patients lack a nearby pharmacy that carries it. Federal and state policymakers must reduce barriers that make it difficult for pharmacies to stock buprenorphine, especially in some of the more vulnerable communities.”

Dima Mazen Qato, senior scholar at the Schaeffer Center and the Hygeia Centennial Chair at the USC Mann School of Pharmacy and Pharmaceutical Sciences

Limited access in some hard-hit areas

Researchers analyzed buprenorphine claims from 2017 to 2023 from an IQVIA pharmacy database from covering 93% of U.S. retail prescription claims. Among their key findings:

• Although buprenorphine availability increased in most states, there were significant declines in five states (Florida, Ohio, Tennessee, Washington, Virginia) and Washington, DC.
• In nearly every state, buprenorphine availability was lowest in Black or Latino neighborhoods. In some states (California, Illinois and Pennsylvania), availability in these neighborhoods was about four to five times lower than in white neighborhoods.
• Independent pharmacies in Black and Latino neighborhoods were significantly less likely to stock buprenorphine and were also more likely to stop carrying it over time. But when these pharmacies did stock the treatment, they persistently filled about twice as many prescriptions per month compared with other types of pharmacies.
• Pharmacies in rural counties and those with high rates of opioid-related overdose deaths were persistently more likely to carry buprenorphine. Yet in 73 hard-hit rural counties, less than 25% of pharmacies carried the medication, and another 25 counties lacked a pharmacy.

Areas with fewer dispensing barriers had better access

Researchers said states should consider easing tight controls on buprenorphine dispensing, which can restrict access to the treatment in several ways.

When buprenorphine demand rises, suppliers may delay or pause shipments to pharmacies to avoid scrutiny from the Drug Enforcement Agency (DEA), and pharmacies often refuse to stock buprenorphine out of concern the orders will be flagged to the DEA. Some pharmacies carry the medication but refuse to dispense it for fear of running afoul of the federal Controlled Substances Act and similar state pharmacy regulations and laws, which require pharmacists to ensure that prescriptions for controlled substances are valid.

The researchers found buprenorphine availability was greatest in states with the least restrictive prescription drug monitoring programs, including those that limited how law enforcement could access the electronic databases to investigate suspicious prescribing.

The researchers said state and local governments should consider requiring pharmacies to maintain buprenorphine stock, noting that some have issued similar orders for the overdose reversal treatment naloxone and emergency contraception in an effort to improve access.

“If policymakers fail to introduce policies that increase equitable access to buprenorphine at local pharmacies, existing racial and ethnic disparities in opioid use disorder treatment and recovery will likely worsen,” said first author Jenny S. Guadamuz, an assistant professor at the University of California, Berkeley School of Public Health.

ISLAMABAD – “There was a lot of white vaginal discharge. There was also heavy bleeding — chunks of blood. This would go on for 15 to 20 days at a time and then stop. Come back again after 10 days. I was unable to go out for farm work or carry out household work. My hands and legs would feel weak and tremble. I went to Dr A in the local town. … It cost me more than 5,000 [INR]. There was no change in my condition. Then the same doctor referred me to the medical college hospital. I went there. … Nothing worked. … I went with my son to the cancer hospital in Chennai. … When I returned for the test results, they told me that it was the beginning stage of cervical cancer.”

This story of a cervical cancer survivor and mother of four from India, narrated in a World Health Organisation (WHO) report, is not unique. Cervical cancer is the fourth leading cause of cancer deaths among women around the world, especially in low- and middle-income countries such as India and Pakistan.

But here’s what many people don’t know — the disease is one of the few cancers that can be almost entirely prevented with early screening and vaccination. There are two approved vaccines that can reduce the risk of cancer by protecting against the infections that cause them — the hepatitis B vaccine and the cervical cancer or human papillomavirus (HPV) vaccine.

Pakistan is launching its first-ever cervical cancer prevention vaccine drive this month, and doctors and government officials are pushing to make it a success.

Virtually all cervical cancers are caused by persistent infection with HPV. Two high-risk types, HPV 16 and HPV 18, are responsible for 70 per cent of cases.

In 2006, the United States Food and Drug Administration approved a vaccine to be administered to females nine through 26 years of age. Gardasil, as the vaccine was called, aimed to protect from diseases caused by certain types of HPV, including cervical, vulvar, vaginal, and anal cancers as well as genital warts.

Nearly four years after its licensure, researchers who surveyed vaccinated women aged 14 to 59 found that among vaccinated girls aged 14 to 19 years, vaccine-type HPV prevalence dropped from 11.5pc to 5.1pc — a staggering decline of 56pc. Among other age groups, however, the prevalence didn’t seem to differ significantly.

In 2020, the WHO launched a global strategy aiming to accelerate the elimination of cervical cancer as a public health problem. By 2023, around 140 countries introduced the HPV vaccine into their national immunisation programmes, including those with large populations and cervical cancer burden, such as Bangladesh, Indonesia, and Nigeria.

In August, the WHO announced that it is partnering with the Government of Pakistan to train over 49,000 health workers for the country’s first HPV vaccine drive, planned from September 15 to 27. The campaign is being described as a “historic milestone,” and is set to target 13 million girls aged nine to 14 years across Punjab, Sindh, Islamabad Capital Territory, and Azad Jammu and Kashmir.

The Federal Health Ministry announced that it is launching the campaign in Sindh in collaboration with the provincial health department and urged close coordination with the education department to ensure as many girls as possible are covered in the campaign. Sindh Health Secretary Rehan Iqbal Baloch said the campaign aims to vaccinate about four million girls in the province.

Gavi, a global health alliance that helps lower-income countries access vaccines, is also providing support, he explained. The necessary doses will be available free of charge through the government-led Expanded Programme on Immunisation (EPI).

Why is the drive important?

According to infectious diseases epidemiologist at the Aga Khan University Hospital in Karachi, Dr Muslima Ejaz, the initiative is important because it targets adolescent girls, a group often left out of health interventions. “By reaching them early, before they’re exposed to HPV, we’re literally safeguarding their future health,” she told Images.

She explained that the drive sets a precedent. If Sindh succeeds, it can become a model for scaling up across other provinces. “This campaign is not only about vaccination, it’s about building systems, community trust, and a roadmap for integrating HPV into routine immunisation,” she said. Essentially, it’s a public health breakthrough for women in Pakistan.

Gynaecologist Dr Uzma Chishti said adolescent immunisation is crucial, noting that although cervical cancer has traditionally affected women who are in their 40s to 60s, she has recently seen patients in their 30s.

She pointed out that the WHO now endorses a single-dose schedule, which simplifies delivery and increases the likelihood of uptake. While skepticism towards vaccines in general poses a challenge, she argued that it can be overcome with the right communication.

“Healthcare workers need to build trust, explain the disease, and highlight how vaccination protects girls before they are ever at risk,” she said, adding that counselling on preventive measures such as delaying early marriage and promoting safe practices is equally important.

Beyond vaccination, Dr Chishti highlighted screening as another critical tool. Simple tests such as pap smears or HPV testing can detect precancerous changes years before cervical cancer develops.

The rollout

Dr Sohail Raza Shaikh, additional project director of EPI Sindh, explained that the campaign will use a multi-pronged strategy, including fixed-site services at existing EPI centres, outreach programmes for communities unable to access those sites, and mobile vaccination teams.

Schools are expected to serve as the main vaccination sites, supported by the province’s education department, which has already trained teachers and conducted sensitisation workshops. Dr Shaikh added that around 48.5pc of the target population is enrolled in schools, while the remaining out-of-school girls will be reached through the Lady Health Worker programme and civil society organisations such as HANDS and the Sindh Rural Support Organisation.

He explained that approximately 3,611 vaccinators will take part in the drive, each working in a four-member team with assistants and social mobilisers, bringing the total to over 14,000 field workers. Supervisory structures are also in place, including 1,190 first-level supervisors, mostly doctors trained to handle adverse events following immunisation, and 393 second-level supervisors. A breakdown of the vaccinators includes 490 fixed-site workers, 2,990 outreach workers and 31 mobile teams.

To monitor coverage, the campaign will use the Sindh Electronic Immunisation Record (SEIR) system, with an additional HPV-specific module, along with vaccination cards distributed to recipients.

“Even after the campaign period, there will be a catch-up drive to vaccinate any missed children,” Dr Shaikh told Images. He stressed that the vaccine would become a routine part of the immunisation programme, with the Sindh government already having allocated budgetary resources for the next three years.

He highlighted the key role of teachers and parents in ensuring the success of the campaign. “Teachers, in particular, hold significant influence. If they support the vaccine, parents are more likely to follow,” he said. Districts with higher proportions of out-of-school girls, such as Kashmore, Qambar-Shahdadkot, Shikarpur, Larkana, Umerkot, Tando Muhammad Khan and Badin, are being prioritised for intensified mobilisation efforts.

Potential roadblocks

Epidemiologist Aneela Pasha noted a potential challenge for the drive: while the EPI mainly administers vaccines for infants and toddlers, such as polio, BCG and typhoid, the HPV vaccine is different as it targets adolescent girls, a group that does not routinely visit paediatricians.

She said myths related to the vaccine causing infertility might become a key hesitancy driver. However, she noted that the vaccine actually protects you from infertility because “it’s the HPV infections that could compromise your reproductive system”.

She also highlighted the prevalence of cervical cancer in Pakistan, with more than 5,000 women diagnosed annually and over 3,000 losing their lives to the disease.

Up-to-date figures are difficult to obtain from the Global Cancer Observatory due to the absence of a comprehensive national registry. However, data compiled by Islamabad’s National Institutes of Health from various registries between 2015 and 2019 shows cervical cancer is the fourth most common cancer among women in the country.

While misinformation and vaccine hesitancy are genuine concerns, paediatrician Dr Fyezah Jehan said the vaccine’s relative unfamiliarity might work in its favour. “No information is better than incorrect information,” she said.

Since widespread misconceptions have not yet taken root, health authorities have an opportunity to shape the narrative with accurate messaging. She warned, however, that misinformation could emerge once the campaign begins, making its management, and the timely delivery of correct information, critical to its success.

New research to be presented at this year’s Annual Meeting of the European Association for the Study of Diabetes (EASD) in Vienna, Austria (15-19 September) and published in the journal Diagnostics shows that people with hepatitis B immunity induced by vaccination have a lower risk of developing diabetes of any kind. The study is by Dr Nhu-Quynh Phan, College of Medicine, Taipei Medical University, Taipei, Taiwan, and colleagues, under the supervision of Professor Chiehfeng Chen.

The liver plays an important role in glucose metabolism, specfically maintaining the balance of glucose levels (glucose homeostasis) and it is thought HBV infection may affect liver functions and disrupt these metabolic pathways, increase the risk of abnormal blood sugar profiles and eventually increase the risk of developing diabetes, Thus, HBV vaccination, which provides immunity against HIV infection, may reduce this risk. However the role of HBV immunity in diabetes prevention among individuals without HBV infection is underexplored. In this new study, the authors evaluated whether HBV immunity reduces diabetes risk in individuals without HBV infection.

This retrospective cohort study used deidentified electronic medical records from TriNetX (a global platform that provides access to data on diagnoses, procedures, medications, laboratory results, and genomic information for biomedical and clinical research. At the time of analysis, data were extracted from 131 healthcare organizations within the Global Network, which comprises multiple Local Networks: US, Europe, Middle East, and Africa [EMEA], APAC (Asia Pacific), and LATAM (Latin America).

This study included adults (≥18 years) with HbsAb blood serology results, a marker of hepatitis B immunity, excluding those with prior HBV infection. Participants were classified as HBV-immunized (HBsAb ≥10 mIU/mL) or HBV-unimmunized (HBsAb <10 mIU/mL). Because individuals with prior infection were excluded, HBsAb positivity was attributed to vaccination, whereas negativity indicated either non-vaccination or lack of immune response after vaccination. The study inlcuded 573,785 individuals in the HBV-immunized group (HBsAb ≥ 10 mIU/mL) and 318,684 individuals in the HBV-unimmunized group (HBsAb < 10 mIU/mL). 

Diabetes was defined on the basis of a diabetes diagnosis, diabetes medication use, or glycated haemoglobin (HbA1c – a measure of blood sugar control) of 6.5% or higher. The data was adjusted for demographics and comorbidities.

The authors found that the HBV-immunized group had a 15% lower diabetes risk than the HBV-unimmunized group. A dose-response effect was observed, with higher diabetes protection at higher hepatitis B antibody (HBsAb) levels. HBsAb levels of 100 mIU/mL and above and 1000 mIU/mL and above were associated with 19% and 43% reductions in diabetes risk, respectively, compared with HBsAb lower than 10 mIU/mL.

The diabetes protective effect was also associated with age. Overall, immunised individuals aged 18 to 44 years, 45 to 64 years, and 65 years and older had 20%, 11%, and 12% lower diabetes risks, respectively, compared with unimmunised individuals.

The authors discuss other important findings from the study, namely the geographical variation in the association, saying “stratified analysis revealed significant geographical differences in the protective effects of HBV immunity against diabetes. Notably, the United States-despite its wealth and advanced healthcare system, showed the least benefit in diabetes prevention associated with HBV immunity.” The authors say that other studies are needed to clarify possible reasons for this.

Regarding the effect of aging, the authors comment: “The association between HBV immunity and reduced diabetes risk was stronger in younger individuals compared to middle-aged and older individuals. This finding may be attributed to the natural aging of the immune system, also known as immunosenescence, which leads to diminished vaccine-induced immune responses in older adults.”

On health behavior, they observe: “From a behavioral perspective, individuals who complete vaccination schedules may be more health-conscious and more likely to engage in healthier behaviors, such as maintaining a better diet or exercising regularly. This raises the possibility that health behavior may act as a confounder in the observed association.” 

The authors conclude: “The potential for the HBV vaccine to prevent both hepatitis B and diabetes suggests that the HBV vaccine is a unique dual-benefit intervention. Traditional diabetes prevention requires lifestyle changes, dietary adjustments, exercise, or medication, which require long-term commitment and can be costly. By contrast, the HBV vaccine is accessible and cost-effective, especially in regions with a high prevalence of both HBV and diabetes, such as the Asia-Pacific region and Africa. Further studies are needed to confirm these effects and investigate the underlying mechanisms. If validated, the HBV vaccine could become a key tool for the prevention of both infectious and chronic diseases.”

A father’s exposure to passive smoking as a child may impair the lifelong lung function of his children, putting them at risk of COPD-a risk that is heightened further if they are childhood passive smokers themselves-finds research published online in the respiratory journal Thorax.

The findings highlight the intergenerational harms of smoking, say the researchers, who urge fathers to intercept this harmful legacy by avoiding smoking around their children.

Chronic obstructive pulmonary disease, more usually known by its acronym of COPD, includes chronic bronchitis and emphysema. Now the third leading cause of death around the world, COPD kills around 3 million people every year, say the researchers.

Several factors throughout the lifespan may increase the risk of poor lung function and subsequent COPD, and attention is now beginning to focus on the potential role of intergenerational factors, they explain.

While previously published research showed that passive smoking during a father’s childhood may be linked to a heightened risk of asthma in his children by the time they are 7, it’s not clear if compromised lung function may extend into middle age and beyond, they add. 

To explore this further, the researchers drew on 8022 child participants in the Tasmanian Longitudinal Health Study (TAHS), all of whom had tests to assess their lung function (spirometry).

Their parents completed an initial comprehensive survey on their and their children’s respiratory health. Further check-ups ensued when those children were 13, 18, 43, 50 and 53. These included spirometry to assess 2 measures of lung function (FEV1 and FVC) as well as questionnaires on demographics and respiratory symptoms/disease. 

Of the 7243 parents who were alive and could be traced in 2010, 5111 were re-surveyed about whether either of their own parents had smoked when they were under the age of 5 and/or up to when they were 15.

Among the 5097 respondents with complete data, 2096 were fathers. The final analysis included 890 father-child pairs with data on the father’s passive smoke exposure before puberty and lung function data for their children up to the age of 53.

More than two thirds of the fathers (nearly 69%) and more than half of their children (56.5%) had been exposed to passive smoking during their childhoods.

Around half of the children (49%) had a history of active smoking by middle age, and just over 5% of them had developed COPD by this time point, as assessed by spirometry.

After adjusting for potentially influential factors, including the father’s lifetime history of asthma/wheeze and his age, his passive smoke exposure as a child was associated with 56% higher odds of below average FEV1, but not FVC, across the lifespan of his children. 

Similarly, fathers’ childhood passive smoke exposure was also associated with a doubling in the odds of an early low-rapid decline in FEV1/FVC in their children. This was statistically significant even after adjusting for potentially influential factors.

And paternal exposure to passive smoking as a child was also associated with a doubling in the risk of COPD by the age of 53 in his children, although this was no longer statistically significant after adjusting for potentially influential factors. 

But children whose fathers had been exposed to passive smoking as a child were twice as likely to have below average FEV1 if they, too, had been exposed to passive smoking during their childhood.

The observed associations were only partly mediated through smoking and respiratory illnesses in fathers and their children (each contributing less than 15%).

This is an observational study, and as such, no firm conclusions can be drawn about cause and effect. And the researchers acknowledge that TAHS lacks data on paternal lung function and genetics, preventing assessment of familial aggregation as a potential mechanism. 

And their children’s childhood passive smoke exposure was defined as at least one parent smoking 6 days a week, which might have misclassified moderate/light smokers as non-smokers, they add.

But the period before puberty is especially critical for boys, when exposure to harmful substances may change gene expression and modify repair mechanisms, which may then become heritable, say the researchers by way of an explanation for their findings. 

“Our findings are novel as this is the first study to investigate and provide evidence for an adverse association of paternal prepubertal passive smoke exposure, rather than just active smoking, on impaired lung function of offspring by middle age,” they write. 

“This is of importance from a public health perspective, as passive smoke exposure affects about 63% of adolescents, which is significantly higher than the approximately 7% affected by active smoking.” 

They conclude: “These findings suggest that smoking may adversely affect lung function not only in smokers but also in their children and grandchildren…Fathers exposed to tobacco smoke during prepuberty may still reduce risk for future generations by avoiding smoking around their children.” 

Also Read | Cardiologist says ‘gut health impacts your heart health’; shares simple lifestyle habits to avoid post-meal bloating

In an Instagram post shared on April 10, Dr Robert Ostfeld, MD, MSc (cardiology), busted one of these myths that if you have smoked for years, you can’t reduce your risk of heart disease by quitting. Let’s find out what the cardiologist said.

Does quitting smoking not help your heart?

According to the cardiologist, the benefits of quitting smoking start the minute you quit, no matter your age, no matter how long you have smoked.

He also revealed the benefits of quitting after 1 year and 15 years. He highlighted, “Only one year after quitting, your heart attack risk will drop by about 50 percent. In 15 years, it will be the same as if you never smoked. It’s never too late to quit and put your health first.

What happens to the body when smoking?

According to the Department of Health, disability and Ageing, smoking is a major cause of cardiovascular disease, such as heart disease and stroke, and cardiovascular disease is one of the major causes of death for both men and women. Smoking increases the risk of blood clots, which block blood flow to the heart, brain or legs.

It can also cause type 2 diabetes. The risk of developing diabetes is 30 to 40% higher for active smokers compared to non-smokers. Smoking can also worsen some of the health conditions related to type 1 diabetes, such as kidney disease, eye disease and poor circulation, which can lead to gangrene.

Note to readers: This article is for informational purposes only and not a substitute for professional medical advice. Always seek the advice of your doctor with any questions about a medical condition.

A new study shows that beetroot juice can reduce blood pressure in older adults by enhancing nitric oxide pathways through shifts in oral bacteria, pointing to a simple nutritional strategy for healthier aging.

Study: Ageing modifies the oral microbiome, nitric oxide bioavailability and vascular responses to dietary nitrate supplementation. Image Credit: Liudmyla Chuhunova / Shutterstock

In a recent study published in the journal Free Radical Biology and Medicine, researchers investigated whether nitric oxide (NO) deficiencies, a common aspect of human aging, could be mitigated by consuming nitrate-rich beetroot juice. The study leveraged data from a randomized crossover trial comparing the impacts of beetroot juice consumption on young and older adults.

Study findings revealed that beetroot juice consumption substantially lowered blood pressure (BP) scores in older adults, while having no statistically significant impact on their younger counterparts. Furthermore, the study found that this BP improvement was associated with higher plasma nitrite levels and correlated with decreases in a Prevotella-dominated bacterial module, rather than directly with increases in nitrate-reducing genera. The Prevotella-dominated group included taxa capable of dissimilatory nitrate reduction to ammonia (DNRA), which may divert nitrite away from NO production. These findings support the notion that dietary nitrate may enhance blood pressure regulation in older adults, with microbiome shifts potentially mediating this effect. However, endothelial function and arterial stiffness were unchanged.

Background

Decades of research have elucidated some of the routine processes associated with aging, with the body’s deteriorating ability to produce nitric oxide (NO), a key molecule for cardiovascular health, well-documented. Conventional interventions often involve the use of pharmacological supplements; however, a significant number of patients respond poorly to these interventions, prompting the search for newer, naturally derived, and physiologically safe alternatives.

Recent research has also established robust links between oral health and systemic disease. However, the biological mechanisms governing these benefits remain largely unknown. One of the few well-documented pathways involves the conversion of dietary nitrate, abundant in green leafy vegetables and beetroot, into nitric oxide (NO). Studies have shown that this process entirely depends on specific oral bacteria (living on human tongues) that process the machinery to convert (enzymatically reduce) nitrate to nitrite. This nitrite is then converted to NO, a vital signaling molecule that relaxes blood vessels and lowers blood pressure.

Unfortunately, aging substantially hinders this process, as the body’s primary mechanism for producing NO, via the enzyme nitric oxide synthase (NOS), becomes less efficient. This age-related decline has been observed to contribute to hypertension and increased cardiovascular risk. However, the oral microbiome and vascular system responses to the aging process remain unknown. Elucidating these interactions may allow for a new “backup” means to mitigate NO deficiency, thereby contributing to healthier aging. In this study cohort, however, baseline NO biomarkers were similar across age groups, suggesting that NO availability may be maintained during healthy aging, and thus, age-related NO decline should be framed cautiously.

About the study

The present study aimed to address the knowledge gaps by conducting a placebo-controlled, double-masked crossover trial involving 39 young adults (aged 18–30) and 36 older adults (aged 67–79), to investigate the impacts of different oral solutions (beetroot juice and mouthwash) on participants’ oral microbiome and vascular responses.

Individuals with known medical histories of pulmonary, metabolic, or cardiovascular diseases were excluded from the sample cohort. Exclusion criteria also included oral diseases, smoking, high BP (> 140/90 mmHg) at baseline, and recent (<3 months) antibiotic use.

The study intervention lasted two weeks (each treatment), separated by additional two-week ‘washout’ periods. The interventions included:

• Nitrate-rich beetroot juice (BR): 2 × 70 ml shots/day, each containing ~595 mg nitrate.
• Placebo beetroot juice (PL): An identical juice with the nitrate removed. This served as the experimental control.
• Antiseptic mouthwash (MW): To observe the impacts of externally disrupting oral bacteria.

Data collection involved the collection of tongue swabs (before and after each period) for oral microbiome analysis via high-throughput 16S rRNA gene sequencing. Additionally, participants’ key cardiovascular health markers (brachial and central BP) and endothelial function (using flow-mediated dilation [FMD]) were recorded at the same frequency. Finally, Plasma nitrate and nitrite levels were measured as proxy biomarkers of NO bioavailability.

Study findings

The study demonstrated a surprising contrast in how young and older participants responded to the dietary nitrate. The latter cohort had higher baseline BP (mean arterial pressure of 95 vs. 87 mmHg, P < 0.001), but when provided the nitrate-rich beetroot juice, demonstrated a significant reduction in brachial mean arterial pressure (4 ± 4 mmHg [P = 0.003]). Young, healthy adults, however, did not see any such change. Post-nitrate BP was lower than after mouthwash, but not lower than after placebo beetroot juice, which itself increased plasma nitrate and nitrite and had a modest effect on BP in older adults.

Further analyses revealed that the nitrate intervention directly correlated with the decrease in a co-occurring module of bacteria dominated by the genus Prevotella. Prevotella concentrations, in turn, were strongly associated with both the increase in plasma nitrite (r = -0.72, P = 0.001) and decreased BP.

The use of antiseptic mouthwash was also associated with reduced oral microbial diversity (Shannon index, P = 0.004) and impaired vascular function in the young group. Conversely, nitrate supplementation altered the oral microbiome in older adults, leading to increases in specific nitrate-reducing genera, including Neisseria and Rothia. Notably, Neisseria exhibited a proportionally greater increase in older adults compared to the young group.

Conclusions

The present study reveals that dietary nitrate may serve as a potent tool for enhancing cardiovascular health, particularly in older adults. The findings demonstrate, for the first time, that a shift in the oral microbiome associated with higher plasma nitrite levels may contribute to the blood-pressure-lowering effect of nitrate, rather than proving direct causation. This research opens a new frontier for targeted nutritional and probiotic strategies to support cardiovascular health, especially in our aging global population.

Researchers at the Johns Hopkins Kimmel Cancer Center, Johns Hopkins All Children’s Hospital and four other institutions have devised a novel method to test for prostate cancer using biomarkers present in urine, funded in part by the National Institutes of Health. This approach could significantly reduce the need for invasive, often painful biopsies, they say.

By analyzing urine samples from prostate cancer patients before and after prostate-removal surgery, as well as from healthy individuals, researchers identified a panel of three biomarkers – TTC3, H4C5 and EPCAM – that robustly detected the presence of prostate cancer. These biomarkers were detectable in patients prior to surgery but were nearly absent post-surgery, confirming that they originated in prostate tissue.

Researchers tested the three-biomarker panel in a development and validation group. The test had an area under the curve (AUC) of 0.92 (1.0 is a perfect performance). It accurately identified prostate cancer 91% of the time and accurately ruled out people without prostate cancer 84% of the time in the validation study. It also determined that the panel could better than PCA3 distinguish patients with prostate cancer from those with BPH.

The panel maintained diagnostic accuracy in 78.6% (development study) and 85.7% (validation study) of prostate-specific antigen (PSA)-negative prostate cancer cases and distinguished prostate cancer from benign prostate conditions with an AUC of 0.89. These results were published Sept. 2 in eBioMedicine.

TTC3 (tetratricopeptide repeat domain 3) plays a role in asymmetric cell division in cancer cells, H4C5 (H4 clustered histone 5) plays a role in modulating the structure of chromatin (a complex of DNA and proteins found in cells), and EPCAM (epithelial cell adhesion molecule) is a protein highly overexpressed in many human cancers that originate in the epithelial tissue lining the surface of organs and structures throughout the body.

Prostate cancer, one of the leading causes of death in men in the United States, is typically detected by blood tests to measure PSA, a protein produced by cancerous and noncancerous tissue in the prostate. In most men, a PSA level above 4.0 nanograms per milliliter is considered abnormal and may result in a recommendation for prostate biopsy, in which multiple samples of tissue are collected through small needles.

However, the PSA test is not very specific, meaning prostate biopsies are often needed to confirm a diagnosis of cancer, says senior study author Ranjan Perera, Ph.D., director of the Center for RNA Biology at Johns Hopkins All Children’s Hospital in St. Petersburg, Florida, and a professor of oncology and neurosurgery at the Johns Hopkins University School of Medicine. In many cases, these biopsies are negative and can result in unintended complications, Perera says. PSA tests also can lead to unnecessary treatment for very low-grade prostate cancers that are very unlikely to grow and spread over a short period of time.

“This new biomarker panel offers a promising, sensitive and specific, noninvasive diagnostic test for prostate cancer,” says Perera. “It has the potential to accurately detect prostate cancer, reduce unnecessary biopsies, improve diagnostic accuracy in PSA-negative patients, and serve as the foundation for both laboratory-developed and in vitro diagnostic assays.”

The panel was found to be able to detect prostate cancer even when PSA was in the normal range and could distinguish prostate cancer from conditions like prostatitis (inflammation of the prostate) and an enlarged prostate, a condition known as benign prostatic hyperplasia (BPH).

There is a real need for non-PSA-based biomarkers for prostate cancer, and urine is quite easy to collect in the clinic. Most urologists feel that an accurate urinary biomarker would be a valuable addition to our current diagnostic armamentarium.”

Christian Pavlovich, M.D., study co-author, the Bernard L. Schwartz Distinguished Professor of Urologic Oncology at Johns Hopkins and program director for the Prostate Cancer Active Surveillance Program

During the study, investigators studied biomarkers in urine samples from healthy individuals as well as from patients with biopsy-proven prostate cancer undergoing prostate-removal surgeries at The Johns Hopkins Hospital, Johns Hopkins Bayview Medical Center or AdventHealth Global Robotics Institute in Celebration, Florida. They studied 341 urine specimens (107 from healthy individuals, 136 from patients with prostate cancer before surgery and 98 after surgery) during the development of their urine test and an additional 1,055 specimens (162 from healthy individuals, 484 from patients with prostate cancer before surgery and 409 after surgery) to validate the test.

During the performance evaluation phase of testing, the scientists also studied samples from patients with BPH or prostatitis, and healthy controls, from The Johns Hopkins Hospital from 2022–25.

Investigators extracted RNA from prostate cells shed in 50-ml urine samples and analyzed them using RNA sequencing and also real-time quantitative polymerase chain reaction (qPCR) to study gene expression. They also used immunohistochemistry to study biomarkers in samples from cancerous prostate tissue and healthy adjacent tissue, and statistical analyses to compare biomarkers found in the urine and tissue samples.

From an initial 815 prostate-specific genes identified in urine from men with prostate cancers, the investigators prioritized the top 50 genes, then the top nine, and from there selected the three top performers: TTC3, H4C5 and EPCAM for further analysis.

Overall, expression levels of the three biomarkers were significantly higher in urine samples from individuals with prostate cancers than in urine from the healthy controls. The expression of each biomarker diminished to low or undetectable levels in samples taken after surgery. A greater proportion of patients with prostate cancer tested positive for the three biomarkers than for PCA3, another biomarker associated with prostate cancers, in both the development study and the validation study.

“This test has the potential to help physicians improve diagnostic accuracy of prostate cancer, reducing unnecessary interventions while allowing early treatment for those who need it,” says study co-author Vipul Patel, M.D., director of urologic oncology at AdventHealth Cancer Institute in Celebration, Florida. Patel also is medical director of global robotics for AdventHealth’s Global Robotics Institute, and founder of the International Prostate Cancer Foundation. “On behalf of physicians and patient globally, I advocate for further study and progress for these biomarkers.”

Investigators are considering how the biomarker panel could be used alone or combined with a PSA test to make a “super PSA,” Perera says. The next steps for the research are to have an independent trial of the test at another institution and to further develop the test for laboratory use in clinical settings, he says. The investigators have filed a patent, and Johns Hopkins Technology Ventures is helping the team to spin off a company.

The study co-authors were Menglang Yuan, Kandarp Joshi, Yohei Sanada, Bongyong Lee, Rudramani Pokhrel, Alexandra Miller, Ernest K. Amankwah, Ignacio Gonzalez-Gomez, Naren Nimmagadda, Ezra Baraban, Anant Jaiswal and Chetan Bettegowda of Johns Hopkins. Additional co-authors were from Charles University in Prague; the University of Kansas; Orlando Health Medical Group Urology-Winter Park in Orlando, Florida; and AdventHealth Cancer Institute.

The work was supported by the International Prostate Cancer Foundation, the Johns Hopkins Kimmel Cancer Center (NIH grant # P30CA006973), the Bankhead-Coley Cancer Research Program (grant # 24B16) to Perera, and by the Maryland Innovation Initiative Grant to Pavlovich and Perera.

Bettegowda is a consultant for Haystack Oncology, Privo Technologies and Bionaut Labs. He is a co-founder of OrisDx and Belay Diagnostics.