The Dr Louise Newson Podcast - 183 - Urinary tract infections in women with Professor Chris Harding

Episode Date: December 20, 2022

Professor Chris Harding is a Consultant Urologist working at the Freeman Hospital in Newcastle upon Tyne and at Newcastle University. He has a particular interest in bladder dysfunction, continence and urinary tract infections (UTIs). In recent years, his research has focused on non-antibiotic treatments for recurrent UTIs and developing targeted treatments for specific patient groups. In this episode, Professor Chris talks to Dr Louise about the challenges of diagnosing UTIs accurately, the severe impact recurrent UTIs can have on your life, how antibiotics can be used appropriately, and how to prevent UTIs occurring. The experts share some of their plans to study the effects of systemic HRT and vaginal hormone treatments on UTIs in women. Chris’s advice if you have recurrent UTIs: You don’t need to put up with UTIs in the perimenopause and menopause; there are many proven treatments available Acknowledge that current tests for UTIs are not 100% accurate. If you think you have a UTI, you probably have, even if your test was negative - the diagnosis can always be questioned Discuss with your doctor how you can prevent infections if you have had 2 episodes within 6 months, or 3 within a year Hormone replacement, particularly vaginal treatments, are significantly protective and preventative against UTIs. Follow Prof Chris Harding on social media at @chrisharding123

Hello, I'm Dr Louise Newsome and welcome to my podcast. I'm a GP and menopause specialist and I run the Newsome Health Menopause and Wellbeing Centre here in Stratford-Bron-Avon. I'm also the founder of the Menopause charity and the menopause support app called Balance. On the podcast, I will be joined each week by an exciting guest to help provide evidence-based, information and advice about both the perimenopause and the menopause. So today on the podcast, I'm very excited and delighted to introduce to you, someone that I've been stalking for quite a long time without him realising actually. So someone called Professor Chris Harding, who I was first

introduced to or about really from my husband, Paul, who's a urologist, and he kept saying, you need to read this guy's work. So I have been reading a lot of his work and kept saying, to Paul, I'm going to try and reach out to him and he said, don't, you're a menopause specialist. He's not going to be interested in you, Louise. But now, here, I have him in the studio. So thanks, Chris, for coming today. Oh, it's a pleasure to join you. So you're obviously a urologist, like my husband, but you're different to my husband because you specialize differently and you're very academic and you have the most amazing past record of research as well. So do you mind telling me a bit about why you do what you do and how you got here?

So I'm a consult neurologist, as you say, and I work in Newcastle. And for about a third of my working week, I work in Newcastle University with an absolutely amazing team of very clever scientists who do most of the hard work for me. And our research program is centred around urinary tract infection and looking at various different factors, the microbes themselves, the host response. and we've kind of over the last five to seven years concentrated our efforts on non-antibiotic treatments for recurrent unit tract infections and we're now really thinking about different patient groups and how we might target treatments, particularly some novel treatments, because of course the issue with antibiotics is the emerging problem with antimicrobial resistance.

So that's in essence what we do. if anything is UTI related, I'm interested in it. Brilliant. And how did you get into that? Why did you decide urology in the first place, then, Chris? By accident, really. I did a job on the King's College rotation in London, and I was originally on a pathway to doing neurosurgery.

But I did a six-month training scheme in neurosurgery, didn't really fall in love with it, and then did a urology job, which I absolutely adored. And I thought that urology sort of gave me the ability, to do a little bit of academic work, a bit of operative surgery, and it was just the perfect balance, really. And what about, there's lots of areas of research in neurology, isn't there? So why did you decide to do urinary tract infections?

Well, I like a challenge. Unretract infections are a big problem. It affects a lot of people. And I think with regards to the impact you can have with research, Uri-Tract infection is such a massive area, it's probably one of the few bits of urology that every single urologist gets involved with, and not just every single urologist, but every medical practitioner will probably as part of their usual work pattern have to treat UTIs. So if you do make any kind of significant contribution in that field, then, you know,

the size of the impact is potentially massive. Bit like the menopause really, isn't it? Indeed. It is huge and almost overwhelmingly huge. And we always talk about how common they are, especially in women, but are there many women that have never had a urinary tract infection, do you think? Yeah, no, I do. I think if you look at the statistics, 50% of women will have a urinary tract infection,

at least one episode in their lifetime. But that means 50% won't. And of course, that leads you to thinking many different things. You know, is there some kind of genetic predisposition? And there are a few abnormalities that have been explored in previous research, but there's nothing really too concrete. But I think the thing with urinary tract infections, it sounds fairly trivial.

It's an infection. You get antibiotics and you move on. But actually, when you talk to these women in particular, the impact of UTI on their daily living, their quality of life is enormous. And especially if they start to develop recurrenti tract infections, that can almost govern their lives. And therefore, as I said before,

the amount of impact you could potentially have with some research that might change clinical pathways enormous. And when you say recurrent urinary tract infections, can you just explain what that is, Chris? Do you mind? Yeah, so I think we've been arguing for many years about what recurrent human contract infection actually means, but over the last few years, we've settled on a standardized definition, which is either two episodes in six months or three in a year. I think in reality, sufferers of recurrent UTI will have many more episodes.

A recent clinical trial that we've published, the average number of UTI suffered per year by the trial participants was around seven. So, you know, you can imagine seven episodes of UTI in one year is going to have a significant effect on your life, every aspect of it. Yeah, absolutely. And it's can be quite hard sometimes to diagnose you and you tract infections. So when I was in general practice, we'd have lots of women, and thinking about they were usually menopoles or women actually,

who would queue outside the surgery at 8 o'clock in the morning waiting for it to open with their urine pots that they'd filled because they were having horrendous symptoms, especially over the weekend. And then the receptors would usually dip them. And if the dipstick was negative, they'd say, well, you haven't got a urinary tract infection. And there'd be others that would be sent off to the labs saying, well, we'll get your result in three or four days' time. We'll contact you if it shows anything.

And looking back, I think, well, was that good practice? Because these women were still suffering. So it was almost like they couldn't have an appointment unless they had a proven urinary tract infection, but they were having symptoms. And there are some problems, aren't there, with dipping the urine or doing an actual test where it goes off to the hospital laboratory?

Yeah, I mean, there are so many problems with UTI diagnostics. You know, this is one of the reasons why Nice have recently made this a priority and have decided to set up a task force with regards to UTI diagnostics. I think the main thing is that I can remember when I was a medical student, the classical teaching was that the bladder was a sterile environment. Now, of course, we know with sophisticated techniques like PCR that can amplify up even the smallest amount of DNA,

that the bladder actually has a bacterial environment, a microbiome, as we call it, all of its own. And therefore, tests that are really, requiring some kind of demonstration of the isolation of a bacteria, they may well be flawed because it may well be that you can regularly demonstrate bacteria in patients' urine, but whether or not that's the causal bacteria for their symptoms is another question. Now, of course, on the other side of the spectrum, there are many, many women who undoubtedly have urinary tract infections. They have symptoms which suggest they have infection. They have a reliable response to

to antibiotics, and yet their urine tests will always, you know, come back negative as the phrase goes. And this may be just a function of the fact that most women, when they get UTI symptoms, do what we would all do, which is increase our fluid intake, dilute the urine, and that includes dilute in the amount of bacteria that's in the urine. I think we've got to really look at UTI diagnostics in the next sort of five to ten years and really try and come up with something that is a little bit more accurate, a bit more reliable, and maybe that doesn't solely rely on the demonstration of a bacteria in the urine. And the tests we use now that, you know, they're decades and decades old.

They've not really been refined enormously in the last, I would say, 20 to 30 years. Now, the research we've just published didn't rely on the demonstration of bacteria in urine. And that's why I think it was so novel. We called a UTI a UTI if the women had suggestive symptoms and if an independent healthcare practitioner assessed those symptoms and thought they were, you know, enough to merit a course of antibiotics targeted for youropathogenic bacteria. And I think research has now got to move towards

that kind of clinical definition of unretract infection. Which is very interesting, isn't it? Because I think, I know I've done women. a disservice in the past because sometimes if the clinical diagnosis and the biochemical diagnosis or the microbiological diagnosis is different, in the past, especially I suppose as a more junior doctor, you look at the numbers or you look at the results and you try and sometimes fit the symptoms into that result. And then if you've got a result saying this woman, you know, doesn't have a proven UTI from her results, then sometimes you can almost not believe the

women who are sitting there saying, but I've got these symptoms and it's so horrendous and and and then I think that that can be really disparaging to, I'm talking women, obviously, because it's more common in women, but even to men as well. And I think it's really important and amazing that you're moving the agenda and changing the way that we diagnose because it is really important to get the diagnosis right. Of course it is. But it's also really important to look at the right treatment options for these women because it can cause, like you say, a lot of distress and a lot of other symptoms can occur as well, can't they? It's not just that people need to we a bit more often. People can be in pain

and it can really ruin people's lives, can't it, having recurrent UTIs? No, absolutely. I mean, there's a couple of things to pick up on there. Firstly, it's the severity of symptoms associated with these episodes. So, you know, you can have a patient who is usually fully continent have really, really debilitating urinary incontinence. You know, you can have a patient who sleeps through the night, usually getting up five, six, seven, ten times to avoid pain whenever they pass water, generalised symptoms, you know, an infection in anybody tissue can cause generalized symptoms. And that has sort of, you know, knock on effect. They don't want to, you know, they can't go to work, they can't do the jobs that they normally would do,

you know, and obviously relationships. They find intimacy with their partner is impossible because everything is so sore. I think the second thing to pick up on there is the almost belief that we've got to break, which is that a negative urine culture means there's no infection present. I really think that's the single most important thing to pass on to other healthcare professionals, you know, I mean, I hear stories all the time. You may have a woman who's several episodes of urinary tract infection in their lifetime, all responded to antibiotics, presents with the exact same symptom set, and yet this time the urine comes back negative and is denied antibiotic treatment. Now, a lot of the time, the urinary infection, you can clear with your own

immune system, but a lot of the time you can't. And yet denying these people treatment, I think, You know, you talk about doing patients a disservice. I think that's a really good example of that. And I think the third thing to bring up is that in urology, there's just a finite number of symptoms. So, you know, pain passing water, urinary frequency, peeing a bit of blood. You know, they could have so many different causes. You know, an urinary tract infection would be the most common, a bladder stone, you know, a tumour in the bladder. And they could, all of those three very different diagnoses could contribute to that symptom complex.

So, you know, I think we've just got to listen to the patients a little bit more. And, you know, I find if a woman tells me she's got a urinary tract infection, 99% of the time she'd be right. Yeah, I think that is so important. But I think it's also looking at ways we can reduce urinary tract infections as well. And I think certainly when I was younger as a sort of more junior GP, I would, you treat the problem and then you wouldn't think ahead. And certainly now a lot of my time is thinking ahead to prevent a condition. But if someone has it, how can we reduce the risk of it happening again?

And I think that's really important. And actually, I have learned quite a lot from my husband, believe it or not. Even little things like some women who have urinary tract infections after having penetrative sex, just them emptying their bland. after having sex and some people have a prophylactic antibiotic which can actually be better than having a course of antibiotics frequently if they are prone to it but looking at some of their intimate hygiene as well because there's so many products now that are available over the counter that are sort of intimate washes and scented goodness only knows what and some of those can cause a lot of irritation can't they to the vulva the vagina the or the or

threat. And so some women can get a lot of irritation and then if they have a urine infection or just urinary symptoms that might not be an infection, looking at any triggers that can cause this pain are really important actually to consider, aren't they? Yeah, I mean, I think UTI prevention is the key really for a number of reasons. You know, we're living in a world where, you know, not to be overdramatic, we are running out of antibiotics. And at some stage, we may be faced with a patient who you don't have an antibiotic option for and it will be over to the patient and their immune system to clear this infection or not. And that's like a throwback to kind of, you know, pre-penicillin times. So it is really important to look at UTI prevention. And, you know,

there's good evidence for a range of different agents that you can use for UTI prevention. You know, there's even a randomized controlled trial which looks at drinking more water, which is a real common sense. thing to do, but you know, you can see several different reports and recommendations with regards to prevention. And as you say, you know, sometimes even using antibiotics as a preventative measure, for instance, the example you gave which was post-coitally, you know, that can actually result in your overall antibiotic consumption going down. If you're avoiding infection, which may require a three, five, seven-day course of antibiotics, then taking a small dose of an antibiotic each time you have intercourse, your overall antibiotic consumption can be less. So I think it, you know,

it is vital to look at UTI prevention. You know, we talked about diagnostics a few moments ago, but actually I think, you know, the prevention of unutracted infections is really, really important. And, you know, you can actually prevent them with non-antibartic agents, which is, you know, That's the best, isn't it? Because you don't use any antibiotics at all. You save the antibiotics for the times when they get breakthroughs. I think it's important that women realize when they're on a preventative therapy that this is not going to be the end of all their UTIs forever.

They will get the occasional UTI. And it's important to realize that that is probably best treated with antibiotics. But, you know, the other times when they're not having UTIs, prevention and reducing the frequency of these episodes is absolutely key. Absolutely, and that's one of the reasons, obviously, that I wanted to reach out to you many years ago and I was forbidden by my husband, because certainly in the past, actually, when I was at medical school and probably you as well, we used to call the vaginal and vulvaal symptoms related to the menopause, VBA or vulvo vaginal atrophy. And actually looking up the word atrophy in the dictionary just means withering and wasting away. And as a menopausal woman, I don't want to think that I'm withering and wasting away. So quite rightly, the terminology was changed to GSM, which stands for genitone-e-eunary

syndrome of the menopause. And that was good for two reasons. Firstly, it doesn't define us as being atrophic, but also more importantly, it encompasses urinary symptoms of the menopause. And a lot of people, myself included, don't always or didn't always think about it. And of course, we've got estrogen and testosterone receptors in our urinary system and our pelvic floor. And so a lot of women, and we know from studies, the majority of women actually have symptoms related to GSM, and we know the minority of women receive treatment, but the majority of women will have symptoms,

which can include urinary symptoms, and women are more prone to have urinary tract infections when they're menopausal. So looking at giving localised plus or minus systemic hormones is likely to really reduce the need for antibiotics, and that's where I sort of finally approached you, in time and say, can we look at this a bit more closely? Because it's so common, and antibiotic prescribing in women is so common, especially postmenopausal women. And so I'm delighted that you've

actually listened, Chris, because it's a huge unmet need, isn't it really, for women? Yeah, so this is what really attracted me to the project that we've been planning, which is the need. There is really a problem. You know, you start any kind of research by thinking, well, what's the size of the problem. The hormonal influence on urinary tract infections is really under-researched. I think we don't know anywhere near enough about this. So I think when you look at the studies, I think we've established that using estrogen topically inside the vagina will reduce the frequency of urine utract infection episodes. But I think the conception that systemic HRT doesn't help is probably something that you can challenge given how, you know,

systemic HRT has changed of the last couple of decades. When we look at the evidence, when we collate the evidence for, you know, a hormonal effect with regards to your retract infections, a lot of the papers are two, three decades old and there's been nothing new since. So it's really interesting to have a look and see how the modern methods of systemic hormone replacement might affect the urinary tract infection frequency. And I think one thing I've noticed since we started talking is that the urinary symptoms as part of the complex that is menopause, perimenopause,

it seems a bit underplayed to me. And I think that's something that perhaps we can change in terms of just getting it out there. And some women just think that having a urinary tract infection is just, oh, it's just part and parcel of being a woman. women, isn't it? Well, you know, like I said at the start, for 50% of the female population, it will never have a urinary tract infection, it's not. So in those who are getting the current episodes, perhaps we can look for reasons why that is? I think you're absolutely right. I mean,

I was reading a study recently, and it takes about a third of women five years or more to actually consult with a healthcare practitioner if they've got urinary symptoms related to their menopause. And that isn't a surprise, really, but it's really sad because the treatment is very easy for a lot of women. And a lot of women tell me that they can't run. They're not exercising or they even coughing or sneezing because they get a bit of leakage. And they think, oh, it's just because I'm getting old. I'm now 56 or I'm 62. Well, that's not old at all.

And they've never seen anyone. They've never thought of any treatment at all. And often when you say to them, do you have any symptoms related to vaginal dryness? And it doesn't have to be dryness. It could just be some irritation or some itchiness or some soreness or to discomfort. or some people have more discharge actually. And they say, oh, yeah, that's just part of getting old as well. And never think that the two could be associated.

And so it's really important. But also I think it's important that us as healthcare practitioners ask the questions because the symptom questionnaire, as you've seen it, the one we use in our clinic, about three or four months into opening my clinic, I actually added two symptoms to the questionnaire. One was urinary symptoms and the other was vagina. dryness because they weren't on the questionnaire and women weren't coming forward with those symptoms but every time I directly asked they always said yes so I thought right I'm going to add the question so then I don't forget to ask in the consultation and the women will be primed

and actually then the women seem very grateful that it's a way into talking about it because we're all very good as women talking about our symptoms but we're not so good talking about our vaginas or even urinary symptoms and I think it might be Chris because we just think we just think that's just part of being a woman and it's wrong isn't it no absolutely i couldn't agree more with that i think you know just accepting these as part and parcel of aging is just incorrect but you know the medical profession has got a role to play here in that we can educate and shine a spotlight on these symptoms and you know it doesn't take much to explain in very simple terms to any patient why vaginal dryness and utis are linked and you know you've got to highlight that

the change in the bacteria in the vagina is probably the chief cause. And, you know, I think a change in the hormonal states in the vagina will, I mean, I just use very simple terms. I say, you know, the hormonal states of the vaginal tissues changes. The good bacteria are outcompeted by the bad bacteria and the bad bacteria migrate from vagina to urethra and then into the bladder. And before you know it, there's a urinary tract infection. And, you know, that little spiel there took about 20 seconds.

and you'll be amazed that, well, you wouldn't be, but a lot of people would be amazed at how many women don't know this. And I think shining a spotlight on the symptoms by asking about them further reinforces, as you say, the relative ease with which we can do things to help. I think it's so right. I mean, I reached out to Cepsy, UK a few years ago, and I was trying to work out the incidence of Eurosepsis in women because sepsis secondary to urinary to urinary tract infection is not insignificant.

and it's a lot more common in older women, especially women in nursing homes. And we know that a lot of older women are not receiving any vaginal hormones at all. And vaginal hormones are very safe even for women who've had breast cancer because they just work locally. They don't get systemically absorbed. So it's almost, I think we should be thinking, why are women not using vaginal estrogen rather than, you know, how bad do they have to be before we start it? Because certainly in patients that I've seen,

and I have seen thousands of women, that the earlier they started, the less likely they're going to have more severe symptoms. Whereas those women that have recurrent new tract infections, sometimes interstitial cystitis, really having a lot of problems, it can take sometimes a year, 18 months, to reverse that pathology and improve their symptoms.

So it's always better to start almost too early than weight, I think. Yeah, so that raises a couple of issues that I'm glad you brought. up. The first one is you talked about the early treatment which is sufficient to eradicate infections. That's so important. I've seen a lot of patients who've ended up with lifelong unilary tract symptoms and a lot of them remember an initial episode and perhaps that wasn't completely resolved by the medical treatment they were given. And there's some sort of fairly novel thinking now in the UTI community and beyond that there may be a concept of chronic

urinary tract infection. So this is where perhaps the bacteria from the first infection or one of the initial episodes would kind of attempt to hide from the immune system by embedding themselves within the wall of the bladder. And that leads to sort of unremitting symptoms that are sometimes incorrectly called interstitial cystitis. And interstitial cystitis really is a kind of diagnosis of exclusion. Once you've excluded every other cause, and this again goes back to the small number of urinary tract symptoms that are in existence that I alluded to earlier.

And I just wonder whether or not, you know, there are more of these women than we appreciate with chronic embedded urinary tract infections. And that might be a separate entity, and it would be brilliant, wouldn't it, to avoid the development of these kind of chronic infections. You know, you can get a chronic infection in almost any body tissue or cavity. And I'm sure the ural tract is no different at all.

And I think the prevention, you know, the aspect of prevention is absolutely vital here. You know, and this is where we can start the conversation about the safety and efficacy of these preventative agents. you talk about topical vaginal estrogen, well, it's virtually risk-free. You know, even if, you know, I have oncology colleagues now who are, they're really, really not at all concerned about using vaginal estrogen in estrogen receptor positive breast cancer patients, which highlights just the complete zero absorption from vaginal tissues. This is having a local effect.

You know, we've done some work in the lab in Newcastle, which shows actually what this is doing is this is activating part of your immune response, but your initial, what we call your innate immune response. And so we have grown up kind of vaginal tissue cultures in the lab, treated them with estrogen, and shown that these vaginas, they release these things called antimicrobial peptides, which are small proteins, which just hammer holes into the cell wall of E. coli. So, you know, this effect is almost certainly a local effect,

because there's just no systemic absorption. And maybe this is why the old HRTs, systemic HRTs, were not effective against urinary tract infection, and it remains to be seen whether the newer preparations, whether or not they can be. But this is why, you know, we've always got to keep researching this, because, you know, reliance on data that's 20, 30 years old

is just not good enough in today's society. Yeah, I think it's very interesting. So we know that about a fifth of women who use systemic HRCTS, still need to use local vaginal HRT. You know, and I think you're right. I think the way that it works is different. We know that systemic hormones, the systemic eustodal,

can improve the immune system. But actually, there are different ways of our immune system working. And I think for some women, they need a higher concentration in the vagina that will obviously go into urinary system. But I think you're right, you can have a different way of action. And then for some women, you can give them all the vaginal estrogen in the world, but it doesn't work well enough until they've got systemic too. So it's very important that even women who have systemic HRT, they might think,

oh, I don't need a small dose of localized vaginal estrogen, but often it can make a huge difference, especially for people who have a lot of urinary symptoms. We certainly find that using both can really be very life-changing, actually, for a lot of women, because there is, as you say, so much suffering. and people really can reach the end of a road because of the way that they're feeling, which sounds very dramatic, but for any of you of listening who've had severe unretracted infections, and especially when they're recurrent, then it can just really disable people in all sorts of ways. No, I think that's a point that deserves underlining the potential need for both systemic and local hormone replacement.

I can't stress that enough. But yet you still do get patients who, who have concerns about exogenous hormones. And in the field of UV tract infection, you know, there are other options. There are other well-proven preventative options if patients didn't want to use, you know, systemic and local hormone replacement. You can talk about urea antiseptics. You can talk about sugars such as de-manos that are protective.

There are a range of different non-antibiotic treatments that will work. And I think I use the phrase quite often. show you the menu, but I won't tell you what to pick. And I just show patients the evidence for and against these treatments. But when it comes down to showing them the evidence, you've got to explore efficacy, how good are they at preventing your tract infections, but also safety. You know, there's now a widespread acceptance of the safety profile of local vaginal estrogen. And I think we can be much more definite than we were in the past about the lack of absorption, the lack of side effects from this particular treatment because, you know, not just the research

we've done, but the experience I have as a clinician leads me to conclude that really these are very, very safe preparations. Yeah, absolutely. And I think that's the most important thing is choice and knowing that if one treatment doesn't work, you can add in something else or you could substitute it. So it's really important that people do get help advice. And I'm really excited with the work that we're doing together, Chris, and I look forward to seeing how it goes from there not forward because we're really hoping it will make a big difference. So before I finish though, Chris, I'd really like to just ask three take-home tips, if I may. So I'd be really keen for you just to summarize three things that if women are listening to this podcast and they are one of these women that have

had recurrent or are still having recurrent urinary tract infections, what are the three things that you would recommend that they should do to help? I think. three take-home messages would be one, urinary tract infections in the peri and postmenopausal face are not just part and parcel and something you need to just get on with and suffer with. I think there is a lot of hope out there in terms of research that's going on in the field of urinary tract infections. And, you know, as we sit here today, there are many, many proven treatments which we

can discuss, my three bits of advice for women with recurrent episodes of urinary tract infection or indeed urinary symptoms associated with the peri or menopausal phase would be, I wouldn't be reliant on the current diagnostics. I think if they think they've got a ure tract infection, they almost certainly have. And, you know, one thing that I put a lot of stock by is their previous response to short causes of antibiotics. I think they should discuss with their doctor's means of preventing infections. If they are classified as recurrent, they should realize that the bar for recurrent uti is not high. It's two episodes in six months or three in a year.

And I think that they should realize that the use of hormonal manipulation, particularly for and estrogen, is significantly protective and preventative against unutract infections. something that can be taken alongside systemic HRT for the local effects I was pointing out. Perfect. That was about six take-home measures. That's okay. You're allowed that. That's fine.

I'm still a multiple of three, so I'll give you that. So thanks very so much for your time, Chris, because I know how busy you are. I'm really grateful for you sharing and imparting some of your wonderful knowledge to others. So thank you very much. That has been an absolute pleasure. Thanks for inviting me. For more information about the perimenopause and menopause, please visit my website, balance hyphen menopause.com, or you can download the free balance app, which is available to download from the App Store or from Google Play.