Category: Urogenital

Treatment for Women with Frequent UTIs Found Wanting

Photo by Sora Shimazaki from Pexels

Women with frequent urinary tract infections report being unhappy at perceived overuse of antibiotics by their doctors and with the limited treatment options available to them, according to a new study.

The study highlights the need to get to the cause of women’s recurrent UTIs, to come up with prevention and to avoid unnecessary antibiotics use, which can eventually lead to resistance.

“Since there’s already a common treatment for UTIs – antibiotics – many doctors don’t see a need to do anything differently,” said senior author Dr Ja-Hong Kim, an associate professor at UCLA Health. “This study really gave us insight into the patient perspective and showed us those with recurrent UTIs are dissatisfied with the current management of the condition. Continued episodes can have a major impact on their quality of life.”

More than half of women will develop a UTI at some point, and roughly 1 in 4 will have repeat infections that can last for years. Many with recurrent infections will be prescribed antibiotics frequently over their lifetime.

The researchers conducted focus groups with 29 women with recurrent UTIs, which were defined as two infections in six months or three in a year. Participants were asked about their knowledge of UTIs and prevention strategies and about treatment impact on their quality of life. Two common themes were revealed: fear and frustration.

Participants were concerned foremost about antibiotic use, with a fear of unnecessary antibiotic prescriptions and developing resistance. Some also reported antibiotic treatment for symptoms which may have signified other genitourinary conditions, like an overactive bladder.

“Other bladder diseases can cause symptoms similar to recurrent UTIs, such as urination frequency and urgency, pain with urination and blood in the urine,” Dr Kim said. “These could be signs of an overactive bladder, interstitial cystitis, kidney or bladder stones, or something more serious, like bladder cancer. As physicians, we really need to be careful about not just giving patients with these symptoms antibiotics without verifying a UTI through a positive urine culture.”

SInce diagnoses take 48 hours, women can wait days for the correct prescription. This shows the need for better diagnostic tools, Dr Kim said.

Frustration and resentment toward their medical providers for “throwing antibiotics” at them without presenting alternative options for treatment and prevention, and for not understanding their experience with UTIs. In addition, many said their physicians did not properly educate them on the potential negative impacts of antibiotics; the women instead had to rely on information from the internet, magazines and TV.

Beyond improved diagnostics, treatment approaches and guidelines, better patient education is key, Dr Kim said. “We need to do a better job of letting patients know when antibiotics are necessary and when to consider alternative therapy for bladder conditions other than UTIs.”

Dr Kim and her colleagues are currently working to improve UTI diagnosis and management, including developing comprehensive patient-care pathways through which primary care physicians and general gynecologists and urologists will provide initial UTI patient education and management. They are also pursuing studies examining the relationship of the vaginal microbiome to lower urinary tract symptoms and are working to incorporate novel diagnostic methods to allow for point-of-care treatment for UTIs.

Source: UCLA

Geology Helps Medicine to Understand Kidney Stones

Image by photochur from Pixabay
Geologists with the tools of their trade. Image by photochur from Pixabay 

Geology studies stones to help find minerals, predict earthquakes and more, but now their expertise has been tapped to understand kidney stones — how they form, why are some people more susceptible to them and can they be prevented?

In a new paper published in the journal Nature Reviews Urology, researchers described the geological nature of kidney stones, outlined the arc of their formation, introduced a new classification scheme and suggested possible clinical interventions.

“The process of kidney stone formation is part of the natural process of the stone formation seen throughout nature,” Illinois geology professor Bruce Fouke said. “We are bringing together geology, biology and medicine to map the entire process of kidney stone formation, step by step. With this road map in hand, more effective and targeted clinical interventions and therapies can now be developed.”

Kidney stones affect in 10 adults in their lifetime and send half a million people in the United States to emergency rooms annually, according to the National Kidney Foundation. Yet little is understood about the geology behind how kidney stones form, Fouke said.

The team’s previous  research found that kidney stones form in the same way as regular stones do: they don’t crystallise all at once, instead going through cycles of partial dissolution and reformation. Doctors had previously believed that they form suddenly and intact.

The research team described in detail the multiple phases kidney stones go through in forming, dissolving and re-forming, using high-resolution imaging technologies. Their findings defy the typical classification schemes doctors use, which are based on bulk analyses of the type of mineral and the presumed location of formation in the kidney. Instead, the researchers drew up a new classification scheme based on the phase of formation the stone is in, and the chemical processes it is undergoing.

“If we can identify these phase transformations, what makes one step to go to another and how it progresses, then perhaps we can intervene in that progression and break the chain of chemical reactions happening inside the kidney tissues before a stone becomes problematic,” said lead author Mayandi Sivaguru, assistant director of core facilities at the Carl R Woese Institute for Genomic Biology at Illinois.

One particularly revelatory finding was in the very beginnings of kidney stone formation. The stones start off as microspherules, tiny droplets of mineral, which merge to form larger crystals throughout kidney tissues. They are normally flushed out, but when they merge together and form larger stones that continue to grow, they can become excruciatingly painful and even deadly in some cases, Fouke said.

“Stone formation is part of a natural, healthy process within kidneys where these tiny mineral deposits are shuttled away and excreted from the body,” Fouke explained. “But then there is a tipping point when those same mineral deposits start to grow together too rapidly and are physically unable to leave the kidney.”

Image source: Leon Macapagal on Unsplash
An example of agate, which shows similar formation characteristics to kidney stones. Image source: Leon Macapagal on Unsplash

As the stone goes through the formation process, more microspherules merge, lose their rounded shape and transform into much larger, perfectly geometric crystals. Stones go through multiple cycles of partially dissolving—shedding up to 50% of their volume—and then growing again, creating a signature pattern of layered crystals much like those of agates, coral skeletons and hot-spring deposits seen around the world.

“Looking at a cross-section of a kidney stone, you would never guess that each of the layers was originally a bunch of little balls that lined up and coalesced. These are revolutionary new ways for us to understand how these minerals grow within the kidney and provide specific targets for stone growth prevention,” Fouke said.

The researchers listed a number of possible clinical interventions and treatment targets derived from this extra knowledge on kidney stone formation. They hope that these options can be tried out, from drug targets to changes in diet or supplements that could disrupt the cascade of kidney stone formation, Sivaguru said.

To aid in this testing, Fouke’s group developed the GeoBioCell, a microfluidic cartridge that mimics the intricate internal structures of the kidney. The team hopes the device can contribute to research as well as clinical diagnostic testing and the evaluation of potential therapies, particularly for the more than 70% of kidney stone patients with recurring stones.

“Ultimately, our vision is that every operating room would have a small geology lab attached. In that lab, you could do a very rapid diagnostic on a stone or stone fragment in a matter of minutes, and have informed and individualized treatment targets,” Fouke said.

Source: University of Illinois

Journal information: Mayandi Sivaguru et al, Human kidney stones: a natural record of universal biomineralization, Nature Reviews Urology (2021). DOI: 10.1038/s41585-021-00469-x

New Vaccine for UTIs Developed With a Localised Approach

Urinary tract infections (UTIs) are a common complaint, affecting women more than men, with a lifetime prevalence of 50% in women, but so far an effective vaccine has proved elusive. Now, researchers from Duke University have come up with an approach that could result in an workable vaccine.

UTIs are caused by a wide range of Gram-negative and positive bacteria, such as Escherichia coli, and antibiotic resistance coupled with common recurrence makes it a growing health burden. It is thought that the immune response to bladder infections sends more repair cells to deal with the bacterial infection than cells to kill the invading bacteria. Because of this, there are often surviving bacteria that reproduce to cause a subsequent infection.

“Although several vaccines against UTIs have been investigated in clinical trials, they have so far had limited success,” said senior author Professor Soman Abraham at Duke University.

“There are currently no effective UTI vaccines available for use in the U.S. in spite of the high prevalence of bladder infections,” Prof Abraham said. “Our study describes the potential for a highly effective bladder vaccine that can not only eradicate residual bladder bacteria, but also prevent future infections.”

According to lead author Jianxuan Wu, PhD, “the new vaccine strategy attempts to ‘teach’ the bladder to more effectively fight off the attacking bacteria. By administering the vaccine directly into the bladder where the residual bacteria harbour, the highly effective vaccine antigen, in combination with an adjuvant known to boost the recruitment of bacterial clearing cells, performed better than traditional intramuscular vaccination.”

The study found that mice immunised in this way effectively fought off infecting E. coli, eliminating all residual bladder bacteria. This suggests that the site of administration could be important for determining vaccine effectiveness.

“We are encouraged by these findings, and since the individual components of the vaccine have previously been shown to be safe for human use, undertaking clinical studies to validate these findings could be done relatively quickly,” Prof Abraham said.

Source: Medical Xpress

Journal information: Jianxuan Wu el al., “Local induction of bladder Th1 responses to combat urinary tract infections,” PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.2026461118

Dialysis Crisis from Texas Ice Storm

Widespread power outages and water supply issues have created a dialysis crisis in Texas, following an onslaught of snow, ice, and sub-freezing temperatures.

“To say we’re stressed is an understatement. Almost all outpatient dialysis units closed due to power outages. Trying desperately to do as many as we can inpatient. To make matters worse some of our hospitals lost water today (so no HD [haemodialysis]). Truly a nightmare,” tweeted Tessa Novick, MD, a nephrologist at the University of Texas at Austin.
Half of Texas’ dialysis centres, serving 54 000 people, were unable to operate in the wake of the severe ice storm that has caused widespread damage in Texas and other parts of the US. Some patients had been without dialysis for four to five days, causing risk of potentially life-threatening potassium and fluid problems.

The large storm system, unofficially called Winter Storm Uri, dropped snow and ice over Texas on February 14 and 15, resulting in widespread power failures as lines were damaged. Few clinics have generators. Water pipes have also frozen, and this is a further problem as dialysis needs clean water to prepare concentrates and dialysate, and to reprocess the machines for following patients.

Fresenius Kidney Care said that around half of its Houston area centres have been impacted by a lack of water, “with the other centres either fully operational or operating on generators.” Water truck deliveries will allow other centres to reopen.

Tiffany Jones-Smith, CEO of the Texas Kidney Foundation, pointed out that there were some bright spots, such as eight clinics in San Antonio that brought water in and have been day and night to dialyse patients from any closed clinic regardless of affiliation. Other clinics were following suit, and Jones-Smith said patients were being given Uber and Lyft coupons to reach their dialysis centres. “We’re just kind of banding together and figuring out what needs to be done,” she said.

Looking ahead to when the crisis had cleared, Jones-Smith said, “We can’t let this go, because we need to be prepared for the next time, not just reacting to chaos, which is what we’re doing right now. … There’s no getting around we’ve had an epic failure.”

Climate change is predicted to increase the frequency and severity of such extreme events in the future, requiring better preparation.

Source: MedPage Today

Relugolix Combination Therapy is Promising for Fibroid Symptom Relief

A pair of clinical trials showed that combination therapy with relugolix reduced heavy bleeding and pain from uterine fibroids without the risk of side effects from low oestrogen levels.

Relugolix is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, currently approved for men with advanced prostate cancer.  Uterine fibroids are common in women, and a quarter of those who are affected by them experience symptoms such as heavy menstrual bleeding and pain.

Injectable long-acting GnRH agonists are effective treatments for uterine fibroids, but cause BMD loss and thus are not generally eligible for long term use.  
In the two trials done in North and South America, Africa, and Europe, 71% and 73% of patients, respectively, who received relugolix together with estradiol and norethindrone acetate had significantly lower blood loss, compared with 19% and 15% in the placebo group.
Similar bone mineral density (BMD) measures were seen in the placebo and relugolix combination therapy groups; but MD decreased among patients who received relugolix monotherapy.

“For the first time, we have an oral treatment that can effectively and safely improve the symptoms of uterine fibroids, particularly heavy menstrual bleeding,” Ayman Al-Hendy, MD, PhD, of the University of Chicago Medicine, stated in an interview. and added that relugolix may be a viable, long-term alternative to the current surgical treatments available for fibroids patients.

“The goal of this program from the beginning was to develop an effective and long-term treatment as a viable alternative to hysterectomy,” Dr Al-Hendy said. “Any patient with uterine fibroids would be a good candidate for this non-surgical treatment.”

Lauren Schiff, MD, associate professor of minimally invasive gynecologic surgery at the school of medicine at the University of North Carolina at Chapel Hill, said that relugolix seems to be a good option for non-surgical treatment of fibroids.

Dr Schiff, who was not involved with the study, said that understanding bone mineral density (BMD) is key for using relugolix past six months. “If the bone density safety measure is maintained for long-term use, then this would be really ideal medication,” she told MedPage Today.

The trial’s primary endpoint was less than 80 ml blood loss, and >50% reduction in total blood loss from trial start. The investigators assessed several secondary outcomes, including amenorrhea, volume of menstrual blood loss, distress, pain, anaemia, fibroid volume, and uterine volume.

Around 388 participants were randomised in the first trial, and 382 in the second.

Around three-quarters of patients who received relugolix combination therapy reached the primary endpoint, with the treatment effects appearing similar baseline characteristics.

Amenorrhea over the last 35 days of the trial occurred in 52% and 50% of participants who received relugolix combination therapy in each trial, respectively. Pain was also reduced in the treatment groups.

Patients who received the combination therapy also had improvements in pain, distress from bleeding and pelvic discomfort, anaemia, and experienced reduced uterine volume. However, significant shrinkage in fibroid volume was not observed.

The prevalence of side effects was similar in the relugolix combination therapy group and the placebo cohort, with hot flashes being the most commonly reported side effect in the trial.

Strict assessment criteria for patients meant generalisability was limited. Additionally, study duration was only six months. The researchers plan to release data from a 28-week extension study, as well as a 52-week randomised-withdrawal trial, and these may shed more light on safety and efficacy in the long term.

Source: MedPage Today

Journal information: Al-Hendy A, et al “Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy” N Engl Med 2021; DOI: 10.1056/NEJMoa2008283.

New Research Links Bladder Pain Flare-ups to Pollen

High pollen counts have long been associated with allergic rhinitis with its well known symptoms such as itching eyes, running nose and sneezing, but now new research suggests that it may be aggravating a completely unexpected condition: chronic bladder pain.

In the United States, more than 10 million people are believed to suffer from urologic chronic pelvic pain syndrome (UCPPS) – a mysterious cluster of problems which include bladder pain syndrome and interstitial cystitis in women, chronic pelvic pain syndrome, and in men, chronic prostatitis.

Researchers regard it as “one of the most frustrating urologic conditions to understand and manage”, requiring a multidisciplinary and multimodal approach to management. However, it has been known to be associated with flare-ups of allergies, prompting Washington University epidemiologist Siobhan Sutcliffe to lead a team to investigate a possible connection. Their study recruited 290 participants diagnosed with UCPPS, and tracked pollen levels from three days before and on the day against UCPPS symptoms. Daily pollen counts did not correlate with UCPPS symptoms, but in participants with when pollen count was medium or high, there was a significant association with symptoms. The mast cell activation involved in pollen allergies release histamines which may be a contributing factor in UCPPS. Evidence for this comes from animal studies which have shown that exposure to histamine makes the bladder hypersensitive. Histamines also stays resident in the bladder longer than in the bloodstream as they are excreted via urine.

Sutcliffe said: “Our study provides evidence to suggest increased pollen counts may trigger symptom flares in people living with UCPPS.”This research may bring an avenue for some now forms of relief to UCPPS sufferers, but further research is needed to eliminate confounding factors, such as environmental factors associated with high pollen counts – strong levels of wind and thunderstorms may trigger pollen allergies but also exert some other kind of separate influence.

“Patients may benefit from taking antihistamines on days with high pollen levels, or from allergy testing and immunotherapy,” concluded Sutcliffe.

Source: Science Alert

Journal information: Javed I, Yu T, Li J et al. Does Pollen Trigger Urologic Chronic Pelvic Pain Syndrome Flares? A Case-Crossover Analysis in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network. Journal of Urology. 2020. doi:10.1097/ju.0000000000001482