Primary Care Guidelines

My name is Fernando Florido and I am a GP in the United Kingdom. In today’s episode I look at a new random case to see how the guidelines could apply to it. By way of disclaimer, I am not giving medical advice; this video is intended for health care professionals and remember that guidelines are there to be interpreted and applied using your clinical judgement. What I am doing here is sharing with you what my interpretation would be in this case. It does not mean that it is the only way, or indeed the best way to treat any individual patient.

There is a YouTube version of this and other videos that you can access here:

·      The NICE GP YouTube Channel: NICE GP - YouTube

This podcast also appears in:

Diabetes in Primary Care podcast:

·      Redcircle: https://redcircle.com/shows/diabetes-in-primary-care

·      Spotify: https://open.spotify.com/show/5BmqS0Ol16oQ7Kr1WYzupK

·      Apple podcasts: https://podcasts.apple.com/us/podcast/diabetes-in-primary-care/id1562910252

Prescribing information links: 

·      Website: DPP-4 inhibitors | Prescribing information | Diabetes - type 2 | CKS | NICE or

·      Download PDF: DPP-4 inhibitors- Prescribing information- Diabetes- type 2- NICE.pdf

·      Website: GLP-1 receptor agonists | Prescribing information | Diabetes - type 2 | CKS | NICE or

·      Download PDF: GLP-1 receptor agonists- Prescribing information- Diabetes- type 2- NICE.pdf

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Music provided by Audio Library Plus

Watch: https://youtu.be/aBGk6aJM3IU

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Transcript

Hello everyone and welcome. My name is Fernando Florido and I am a GP in the United Kingdom.

In today’s episode I look at a new random diabetic case to see how the guidelines could apply to it. By way of disclaimer, I am not giving medical advice; see the description for full information about this:

·     NOT medical advice

·     Intended for health care professionals

·     Only my interpretation of the guideline

·     Use your clinical judgement

And as you know, we are focusing only on the pharmacological treatment.

Remember that there is also a podcast version of these videos so have a look in the description below.

Remember that there is also a Youtube version of these episodes so have a look in the episode description.

Right, so let’s generate our random patient. So, we have 45-year-old woman with poorly controlled T2DM with an HbA1c of 60 mmols/mol/7.6%, who has CKD stage 3a with an eGFR of 45 and who is also at high risk of CVD. She is also on triple therapy with Metformin 500 mg BD, Dapagliflozin 10 mg OD and Saxagliptin 2.5mg OD. And finally, she is severely obese with a BMI of 43

So, let’s have a look at the guidelines. As usual I will focus on the NICE guidelines but at the end I will tell you what my interpretation would have been following the EASD / ADA consensus guideline.

Firstly NICE says that we need to consider if rescue therapy is necessary for symptomatic hyperglycaemia with insulin or a sulfonylurea.

And for the clinical presentation we will say that she has no symptoms of diabetes, her obesity is long-standing and being managed with diet, lifestyle advice and bariatric referral. We have excluded other causes of Obesity e.g. hypothyroidism or Cushing’s disease and, because of her age, other causes of CKD such as glomerulonephritis or obstructive nephropathy have also been excluded and she has the diagnosis of diabetic nephropathy.

Right, so what are my thoughts? Firstly, that she is relatively young and she already has a degree of diabetic nephropathy. So we should manage her fairly aggressively to try and improve her diabetic control and improve long term outcomes.

Secondly, it seems quite clear that her main problem is her weight. She is severely obese and already being managed for that. I am very pleased to see that she is not on any medication that promotes weight gain. Both metformin and SGLT2 inhibitors promote weight loss and DPP4 inhibitors are weight neutral. So Dr Spinning Wheel has done very well indeed.

The first step is always metformin which would be helpful for her weight too. So I would be interested to see why she is only on 500mg BD instead of the full dose, double that, 1000mg BD.

I would first look if it has been kept at that dose because of safety reasons, for example because of her renal function. You can prescribe metformin 1000 mg BD to anyone with an eGFR of 45 or above. Her eGFR is exactly that, 45. Because of being right on the limit, I would want to be sure and I would look back and see what her previous renal function tests have been. If previously the eGFR has been bumping along the high 40s or 50s that I would definitely increase the dose because the drop to 45 could be just a temporary “blip”, although, of course, we would watch her renal function closely. If on the other hand her previous eGFR readings have been in the high 30s or low 40s, then I would not increase the dose because I would want to see a stable eGFR above 45 before increasing it. 

If she is suitable for a dose increase, I would also like to look at previous records and see if she has not tolerated higher doses. And if that is the case, I would also want to make sure that she has been managed appropriately. NICE says that metformin should be increased gradually over several weeks to minimise the risk of gastrointestinal side effects. So, if the previous increase in dose was abrupt, I would want to revisit it. Also I would make sure that the patient is counselled and advised that for many patients the side effects are temporary and get better over a number of weeks. So, I would advise her that, if the side effects are not severe, to try and work through them to see if the short term inconvenience of the side effects can translate into a long term therapeutic benefit. And finally, if she has not been able to tolerate it despite these efforts. NICE says that we should consider a trial of modified‑release metformin, so I would offer this to her too. So I am really emphasizing that we should leave no stone unturned before giving up of the benefits of a full dose of metformin, especially in a person with such an obesity problem.

So, let’s assume that she is keen and able to increase the dose, so we do that. Would I try to add or increase other medication in this consultation too?

Because I want to manage her aggressively and all her medication has a very low risk of hypoglycaemia, I would say yes. True, we may advise her to delay the addition or the increase of other drugs for a few days or weeks to make sure that if side effects develop, we know which medication is the culprit. But as soon as that patient is sure that the increased dose of metformin is not causing any issues, I would add or increase the other medication. I would not want to leave her for, say, 3 months before further action is taken.

So as a next step, NICE says that, for patients at high risk of CVD, we need to consider an SGLT2 inhibitor with proven cardiovascular benefit. And she is on the full dose of dapagliflozin, which is one of them. The cardiovascular benefit of SGLT2 inhibitors is a drug class effect so there isn’t necessarily any need to consider other types if there is no concern with the use of dapagliflozin. Dapagliflozin can be initiated as long as the eGFR is above 15 so her eGFR of 45 is not a problem.

So, we now look at the third drug, which is a DPP4 inhibitor, saxagliptin 25mg OD. NICE says that for patients who are not controlled with dual therapy with metformin and an SGLT2 inhibitor, we should consider either:

u triple therapy, including combinations with either a sulphonylurea or a DPP‑4 inhibitor or,

u going directly from dual therapy to starting insulin

I am definitely going to exclude insulin and a sulphonylurea at this stage because they can be associated with weight gain, which is the last thing that we want for this patient. As we have seen, DPP4 inhibitors are acceptable and saxagliptin is already prescribed. NICE says that the recommended dose of saxagliptin is 5 mg OD and the patient is only on 2.5mg OD. However, the dose of saxaglitpin has to be reduced to 2.5 mg OD if the eGFR is below 45. So, we are in the same situation as the metformin earlier. If her eGFR has consistently been above 45 you can increase the dose but not otherwise.

There are many other considerations when choosing which DPPG4 inhibitor you are going to use and they all have different thresholds for renal impairment, and also other conditions like hepatic impairment, heart failure and for the elderly. So I would encourage you to look at your formulary carefully before making the decision. I will put in the episode description the link for the NICE guidance on DPP4 inhibitor prescribing in case that you are interested.

DPP-4 inhibitors | Prescribing information | Diabetes - type 2 | CKS | NICE

It is worth saying that linagliptin is the only DPP4 inhibitor that does not require dose adjustment for renal or hepatic impairment so if there is any doubt, you can always give linagliptin at the full recommended dose of 5 mg OD.

So this is my interpretation for this patient following the NICE guidelines:

1- increase metformin if at all possible,

2- continue dapagliflozin at the full dose and

3- increase the dose of saxagliptin to 5 mg OD if renal function allows or switch it to linagliptin 5mg OD if there are concerns

What would I do if I were following the EASD / ADA consensus guideline?

Well, I would still try to increase metformin if at all possible and then, because this patient has a high CVD risk, she would be started on a GLP1 receptor agonist for their cardiovascular benefit, independently of the HbA1c level. This would also have the benefit of their added weight loss so that would be great for this patient too.

The difference is that NICE is more restrictive when it comes to GLP1 receptor agonists and they would only be considered if the initial suggestion that I said earlier failed to control the patient.

You can prescribe all of the GLP1 receptor agonists, as long as the eGFR is above 30, so not a real issue for this patient. I will put in the episode description a link to the guidance for the prescribing of GLP1 agonist so have a look if you are interested.

GLP-1 receptor agonists | Prescribing information | Diabetes - type 2 | CKS | NICE

Acceptable options would be:

• exenatide
• liraglutide
• lixisenatide
• dulaglutide or
• semaglutide

The next step after Metformin and GLP1 receptor agonist according to EASD and ADA is an SGLT2 inhibitor.

So my interpretation for this patient following the EASD /ADA guidelines is:

1- increase metformin, if at all possible,

2- stop saxagliptin and start a daily preparation of a GLP1 receptor agonist and

3- continue dapagliflozin at the full dose

We have come to the end of this episode. I hope that you have found it useful. Thank you for listening and good-bye

My name is Fernando Florido and I am a GP in the United Kingdom. With this episode I am starting a new series on Diabetes Guidelines in Practice, looking at how the guidelines could apply to randomly selected clinical cases. By way of disclaimer, remember that guidelines are there to be interpreted and applied using your clinical judgement. What I am doing here is sharing with you what my interpretation would be in this case. It does not mean that it is the only way, or indeed the best way to treat any individual patient. 

This episode also appears in the Diabetes in Primary Care podcast: 

·      Redcircle: https://redcircle.com/shows/diabetes-in-primary-care

·      Spotify: https://open.spotify.com/show/5BmqS0Ol16oQ7Kr1WYzupK

·      Apple podcasts: https://podcasts.apple.com/us/podcast/diabetes-in-primary-care/id1562910252

 There is a YouTube version of this and other videos that you can access here: 

·      The NICE GP YouTube Channel: NICE GP - YouTube 

Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release]

Music provided by Audio Library Plus

Watch: https://youtu.be/aBGk6aJM3IU

Free Download / Stream: https://alplus.io/halfway-through 

Transcript

Hello everyone and welcome. My name is Fernando Florido and I am a GP in the United Kingdom.

With today’s episode I am starting a new series on Diabetes Guidelines in Practice, looking at how the guidelines could apply to randomly selected clinical cases. By way of disclaimer, remember that guidelines are there to be interpreted and applied using your clinical judgement. I am not giving medical advice here and what I am only doing is sharing with you what my interpretation of the guideline would be in this case. It does not mean that it is the only way, or indeed the best way to treat any individual patient. So, you must always apply your clinical judgement at all times.

 I will also say that I will only focus on the pharmacological treatment of type 2 diabetes. By all means, we will need to advise about diet, exercise, lifestyle etc, but this will not be addressed in these episodes.

Remember that there is also a podcast version of these videos so have a look in the description below.

Remember that there is also a Youtube version of these episodes so have a look in the episode description.

Right, so let’s get started and let’s generate our random patient. For that we are going to spin a random wheel: 

Right, so we have an 85-year-old man, newly diagnosed with type 2 diabetes who is poorly controlled with an HbA1c of 65 mmols or 8.1%, who also has heart failure and CKD stage 3b with an eGFR of 32. In addition, he is underweight, even possibly malnourished to some degree. 

Right, we are going to look at the guidelines and how to apply them. Although I will focus on the NICE guideline, in this case my interpretation and the outcome would be exactly the same if you follow the EASD recommendations or the ADA guideline.

So, what does NICE say that we should do? Firstly, we need to consider if rescue therapy is necessary because, for symptomatic hyperglycaemia, we will need to consider insulin or a sulfonylurea and review when blood glucose control has been achieved. 

So, we are going to assume that he is well and that he has no symptoms of diabetes. He is underweight, but this has been like this for a few years. There hasn’t been rapid weight loss indicating an urgent need for insulin and his urinary ketones are negative. Other causes of unintentional weight loss such as cancer have also been excluded.

So, we are just focusing on the diabetes. His HbA1c is high and has not improved with diet and lifestyle advice, so we should do something. However, given his age, we are not going to manage him too aggressively because, at 85, we are probably more concerned about harmful hypoglycaemia. But he does need treatment and certain diabetic agents could also help his co-morbidities. 

So, next, we must look at his medical history. He has both CKD and heart failure and we know that SGLT2 inhibitors can be beneficial for both these conditions.

However, because of the benefits of metformin, NICE says that first, we should consider starting metformin alone to assess tolerability and once this has been confirmed, we could add an SGLT2 inhibitor.

Arguments against using metformin at all in this patient are that his eGFR is fairly low and at 32 he is quite close to CKD stage 4.

Also, because he is underweight with possible low muscle mass, we need to remember how the estimated GFR is calculated and consider that, as a result of the low muscle mass, his eGFR may be overestimated and that his actual GFR could be below 30. We know that we can use metformin quite normally if the eGFR is above 45, we need to review the dose and prescribe it cautiously if the eGFR is between 30 and 45 and then stop it completely when the eGFR falls below 30.

The manufacturer of metformin also advises caution in chronic stable heart failure with the advice to monitor cardiac function closely.

We also know that metformin can have potential gastrointestinal side effects and promote weight loss, which we would not want in this patient.

And finally, the mode of action of metformin is primarily by reducing insulin resistance. But in an 85-year-old underweight patient, it is more likely that his diabetes is due to insufficient insulin secretion by the ageing pancreas.

On the other hand, we also know that metformin has proved to have cardiovascular benefits.

So, a controversial decision. You could justify both giving and not giving metformin based on this patient’s individual circumstances.

Right, time to decide. What would I do?

I would probably err on the side of caution and not give metformin. It can always be introduced later if his weight goes up and his renal and heart failure are stable or improve with other medication.

If you really wanted to prescribe metformin, it would be best to start a very cautious introduction, maybe at 500 mg OD and then monitoring this patient very closely. Generally, the maximum accepted dose of metformin for patients with an eGFR between 30 and 45 is 500 mg twice daily but I would be quite nervous about it and I would not increase the dose above 500mg OD for this patient unless the circumstances really changed.

So, we are not giving metformin but we still need to prescribe something for this patient. And NICE says that if there is a history of heart failure, we should give an SGLT2 inhibitor with proven cardiovascular benefit. NICE says that the benefits in reduction of hospitalisations for heart failure and cardiovascular mortality can be attributed to SGLT2 inhibitors as a drug class, although at present ertuglifozin has not consistently shown these cardiovascular benefits in clinical trials. So, we are likely to choose either dapaglifozin, canaglifozin or empaglifozin for this patient.

Remember that SGLT2 inhibitors are also associated with possible weight loss, so along with this prescription there should be appropriate nutritional advice.

We also know that there may be an increased risk of DKA associated with SGLT2 inhibitors so NICE advises us that before prescribing, we should check the patient’s individual risk of DKA, for example if, they have had a previous episode of DKA, they are unwell with intercurrent illness or they are following a very low carbohydrate or ketogenic diet. In particular, I would be very keen to make sure that this patient does not continue to lose weight as this is also likely to put him at greater risk of DKA once the SGLT2 inhibitor is started.

Also remember that we will need to check our formulary or BNF if you are in the UK because each drug has its own recommendations and eGFR thresholds for dose reduction, caution or avoid. Acceptable options would be:

·     dapaglifozin maybe starting cautiously at 5 mg OD possibly increasing to 10 mg OD if no issues develop.

·     canaglifozin starting at 100mg OD, which is the starting dose and also the maximum daily dose for anyone with eGFR <60 or

·     empaglifozin starting at 10 mg OD, which is also the starting dose and the maximum daily dose for anyone with eGFR <60

So that would probably be my first pharmacological action for this patient, but by no means is necessarily the only or best one.

Remember that we need to keep monitoring the patient and consider other treatments as and when the situation changes. 

We have come to the end of this episode. I hope that you have found it useful. Thank you for listening and good-bye

My name is Fernando Florido and I am a GP in the United Kingdom. With this episode I continue with the series on the monthly “NICE News” bulletin, which includes new guidance published in that month as well as any updates, also in that particular month, to already published guidelines. However, I will only address guidance which is relevant to Primary Care.

In today’s episode, I go through the NICE Guidance and advice published in February 2023.  

There is a YouTube version of this and other episodes that you can access here: 

NICEGP YouTube channel:  

·      NICE GP - YouTube

The Full NICE News bulleting for February 2023 can be found at:  

·      https://www.nice.org.uk/guidance/published?from=2023-02-01&to=2023-02-28

Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release]

Music provided by Audio Library Plus

Watch: https://youtu.be/aBGk6aJM3IU

Free Download / Stream: https://alplus.io/halfway-through

Transcript

Hello everyone and welcome. My name is Fernando Florido and I am a GP in the United Kingdom.

With today’s episode I am continuing with the series on the monthly “NICE News” bulletin, which includes any new guidance published in that month as well as any updates, also in that particular month, to already published guidelines, also updated in that month. However, I will only address guidance which is relevant to Primary Care. In today’s episode, I go through the NICE Guidance and advice published in February 2023. 

Remember that there is also a Youtube version of these episodes so have a look in the episode description.

The first guideline update that we are looking at refers to Urinary tract infections in adults 

And the new quality statements are:

Statement 1 Women aged under 65 years are diagnosed with a urinary tract infection (UTI) if they have 2 or more key urinary symptoms and no other excluding causes or warning signs.

This means that according to the updated quality standard on urinary tract infections (UTI) in adults, healthcare professionals should diagnose women under 65 with a UTI if they have 2 or more key urinary symptoms. Therefore, women who present with 2 or more key symptoms should not require a dipstick test. Professionals should however exclude any other causes of urinary symptoms and consider warning signs of other conditions such as sepsis and cancer when diagnosing a UTI. We also need to ensure that vaginal and urethral causes of urinary symptoms are excluded by asking about vaginal discharge and irritation, and other possible urethral causes of urinary symptoms.  

Statement 2 Adult patients with indwelling urinary catheters do not have dipstick testing to diagnose UTIs. Therefore, instead, we need to assess signs and symptoms to diagnose a UTI and use urine culture and sensitivity testing to support the diagnosis. 

Statement 3 Men and non-pregnant women are not prescribed antibiotics to treat asymptomatic bacteriuria. Instead, we need to assess symptoms to determine if a urine sample should be sent for culture and if antibiotics should be prescribed when a urine culture identifies bacteriuria. 

Statement 4 non-pregnant women with an uncomplicated lower UTI are prescribed a 3-day course of antibiotics, and men and pregnant women with an uncomplicated lower UTI are prescribed a 7-day course of antibiotics. We also need to reassess if a person's symptoms worsen or do not start to improve within 48 hours of taking the antibiotic.

Statement 5 Men with a recurrent UTI, and women with a recurrent lower UTI where the cause is unknown or a recurrent upper UTI are referred for specialist advice.

The next section refers to an update to the antenatal care guidelines.

The new quality statements are:

Statement 1 Pregnant women are seen by antenatal care by 10 weeks of pregnancy.

Statement 2 Pregnant women have a risk assessment at routine antenatal appointments.

Statement 3 Pregnant women have coordinated care from a small team of midwives.

Statement 4 Pregnant women are offered vaccinations at routine antenatal appointments, including flu, pertussis and COVID-19 vaccinations. 

Statement 5 Pregnant women and partners who smoke are referred for stop-smoking support and treatment at routine antenatal appointments.  

The next guideline update refers to cardiovascular disease: risk assessment and reduction, including lipid modification 

And in February 2023, a new recommendation on aspirin for primary prevention of CVD has been added. This is based on a 2023 surveillance decision. The results of this evidence strongly suggests that the benefit from aspirin for primary prevention is very closely balanced or outweighed by the increased risk of bleeds. So, the overall decision is that we should not routinely offer the use aspirin for primary prevention of CVD. 

And finally, there was a brand-new guideline published for the first time this month in respect of the monitoring and management of Barrett's oesophagus and stage 1 oesophageal adenocarcinoma.

The recommendations are that:  

1.   We will Follow the recommendations for gastro-oesophageal reflux disease to achieve symptom control 

2.   We will not offer aspirin to patients with Barrett's oesophagus to prevent progression to oesophageal dysplasia and cancer. 

3.   We will discuss the benefits and risks of endoscopic surveillance with the person diagnosed with Barrett's oesophagus. 

4.   We will offer endoscopic surveillance with Seattle protocol biopsies:

a.   every 2 to 3 years to people with long-segment (3 cm or longer) Barrett's oesophagus

b.   every 3 to 5 years to people with short-segment (less than 3 cm) Barrett's oesophagus with intestinal metaplasia.  

5.   We will assess a person's risk of cancer based on their age, sex, family history of oesophageal cancer and smoking history and tailor the frequency of endoscopic surveillance accordingly.

6.   We will not offer endoscopic surveillance to people with short-segment (less than 3 cm) Barrett's oesophagus without intestinal metaplasia provided the diagnosis has been confirmed at 2 endoscopies

7.   We will not offer anti-reflux surgery to people with Barrett's oesophagus to prevent progression to dysplasia or cancer.

The rest of the guideline refers to the management of Barrett's oesophagus with dysplasia and management of oesophageal adenocarcinoma, which I will not go into because it is a specialist area.

We have come to the end of this episode. I hope that you have found it useful. Thank you for listening and good-bye

Podcast description

My name is Fernando Florido and I am a GP in the United Kingdom. With this episode I am starting a new series on the monthly “NICE News” bulletin, which will include any new guidance published in that month as well as any updates, also in that particular month, to already published guidelines. However, I will only address guidance which is relevant to Primary Care.

 In today’s episode, I go through the NICE Guidance and advice published in January 2023. 

There is a YouTube version of this and other episodes that you can access here: 

NICEGP YouTube channel: 

·      NICE GP - YouTube 

The Full NICE News bulleting for January 2023 can be found at: 

·      https://www.nice.org.uk/guidance/published?from=2023-01-01&to=2023-01-31

Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release]

Music provided by Audio Library Plus

Watch: https://youtu.be/aBGk6aJM3IU

Free Download / Stream: https://alplus.io/halfway-through

Transcript

Hello everyone and welcome. My name is Fernando Florido and I am a GP in the United Kingdom.

With today’s episode I am starting a new series on the monthly “NICE News” bulletin, which will include any new guidance published in that month as well as any updates to already published guidelines, also updated in that month. However, I will only address guidance which is relevant to Primary Care. In today’s episode, I go through the NICE Guidance and advice published in January 2023. 

Remember that there is also a Youtube version of these episodes so have a look in the episode description.

The first update that we are looking at affects the guidance on Diabetes in pregnancy

And the new updated quality statements are as follows: 

Statement 1 Women with diabetes who are of childbearing potential are offered preconception planning advice at diabetes care reviews. So they do not need to be planning a pregnancy to get the advice, just being of childbearing age should prompt us to inform them of the importance of preconception smoking cessation, medication safety, trying to ensure their HbA1c levels are below 48 mmol/mol before pregnancy and taking high-dose folic acid before and for the first 12 weeks of pregnancy. 

Statement 2 Diabetic pregnant women need to be seen in a joint antenatal diabetic clinic as soon as possible after conception, and ideally by 10 weeks' gestation.

Statement 3 Pregnant women with type 1 diabetes are offered continuous glucose monitoring. Remember that that there are two types of continuous glucose monitoring (CGM) systems: real-time CGM (rtCGM) and intermittently scanned (isCGM). Current rtCGM systems automatically transmit a continuous stream of glucose data to the patient, provide alerts and active alarms, and transmit glucose data (trend and numerical) in real time to a receiver, smart watch, or smartphone. The current isCGM system provides the same type of glucose data but requires the user to purposely scan the sensor to obtain information, and it does not have alerts and alarms. Both CGM technologies have significant advantages over self-monitoring of blood glucose; however, differences in the features and capabilities of the two approaches must be considered when guiding patient selection of the system that meets their individual needs.NICE recommends rtCGM (but isCGM can be offered if they prefer it or are unable to use rtCGM). 

Statement 4 Women diagnosed with gestational diabetes are offered postnatal testing of blood glucose levels and referred to the National Diabetes Prevention Programme.

So, women who were diagnosed with gestational diabetes and whose blood glucose levels returned to normal after the birth should be offered:

·      a fasting plasma glucose test ideally between 6 and 13 weeks after the birth to exclude diabetes

·      if this has not been done earlier, a fasting plasma glucose test should be done after 13 weeks, or an HbA1c test if a fasting plasma glucose test is not possible

·      a referral into the National Diabetes Prevention Programme. 

Statement 5 Women diagnosed with gestational diabetes who have negative postnatal testing for diabetes after the birth are offered annual HbA1c testing. 

The next update refers to the guideline on chronic heart failure in adults

And the new quality statements are:

Statement 1 Adult patients with suspected heart failure have their N‑terminal pro‑B‑type natriuretic peptide (NT‑proBNP) measured in Primary Care. 

Statement 2 Adult patients with a very high N‑terminal pro‑B‑type natriuretic peptide (NT‑proBNP) level, that is, over 2,000 ng/litre (236 pmol/litre), should have a transthoracic echocardiography within 2 weeks, or 6 weeks if they have a high NT‑proBNP level, which is defined as between 400 and 2,000 ng/litre (47 to 236 pmol/litre)

Statement 3 Adult patients with chronic heart failure who have reduced ejection fraction receive all appropriate medication at target or optimal tolerated doses. These medications include ACE inhibitors, ARBs, beta-blockers, MRAs, SGLT2i and ARNIs (angiotensin receptor neprilysin inhibitors) and they need to be started and increased in accordance with individual health needs, including monitoring for side effects after each increase in dose.

Statement 4 Adult patients with chronic heart failure have a review within 2 weeks of any change in the dose or type of their heart failure medication. 

Statement 5 Adult patients with chronic heart failure have a review of their condition at least every 6 months. 

Statement 6 Adult patients with chronic heart failure receive a personalised programme of cardiac rehabilitation. 

The next topic is not an update but a completely brand new published guidance on transcutaneous electrical stimulation of the trigeminal nerve for ADHD 

And, although this is fairly specialised, I have included it here because I have found it very interesting and it will help us advice patients accordingly. 

We know that attention deficit hyperactivity disorder (ADHD) is a heterogeneous disorder characterised by the core symptoms of hyperactivity, impulsivity and inattention, which are judged excessive for the person's age or level of overall development. Symptoms are usually evident in childhood and may persist into adulthood. 

We also know that treatment for ADHD may be non-pharmacological, pharmacological or a combination of both. Non-pharmacological treatment includes cognitive behavioural therapy and parent‑training programmes (for parents of children and young people with ADHD). Pharmacological treatment includes central nervous system stimulants such as methylphenidate and amphetamines, and non-stimulants such as atomoxetine. 

The procedure that is being appraised by NICE here is transcutaneous electrical stimulation of the trigeminal nerve for ADHD 

In this procedure, an external trigeminal nerve stimulation device is worn on the clothes and attached by wires to a single-use adhesive patch which is worn overnight. The patch contains 2 electrodes placed over the left and right V1 branches of the trigeminal nerve on the forehead. The stimulator bilaterally stimulates the trigeminal nerve for approximately 8 hours. In a typical treatment course, stimulation is given nightly for approximately 4 weeks. Treatment duration may vary; a clinical response may take longer, and continued therapy may be needed. 

The mechanism of action is not completely understood. The trigeminal nerve connects to regions of the brain that may be associated with selective maintenance of attention and arousal, and it is thought that its stimulation improves the symptoms of ADHD.

Although this seems to be a fairly innocuous treatment, NICE has concluded that the evidence on the safety and efficacy of this procedure is inadequate and therefore they recommend that it should only be used in the context of research.

And finally, the last update refers to the guidance on smoking tobacco

In January 2023, in the section on identifying and referring pregnant women for stop-smoking support, the number of carbon monoxide tests recommended for women with low readings and no history of smoking has been reduced.

So now we will provide routine carbon monoxide testing at the first antenatal appointment and at the 36-week appointment to assess every pregnant woman's exposure to tobacco smoke. We will also provide carbon monoxide testing at all other antenatal appointments if the pregnant woman:

• smokes or
• is quitting or
• used to smoke or
• tested with 4 parts per million (ppm) or above at the first antenatal appointment.

We have come to the end of this episode. I hope that you have found it useful. Thank you for listening and good-bye

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My name is Fernando Florido and I am a GP in the United Kingdom. In this video I have done a summary of the NICE guidance on asthma management. The full guideline also contains advice on asthma diagnosis and, if you are interested in this, please refer to the corresponding episodes on this channel. The NICE guideline “Asthma: diagnosis, monitoring and chronic asthma management” or NG80 was published on 29 November 2017 and it was last updated on 22 March 2021 

There is a Youtube version of this and other videos that you can access here: 

·      @nicegp : https://www.youtube.com/channel/UClrwFDI15W5uH3uRGuzoovw

Full NICE guideline on Asthma: 

·      Website: https://www.nice.org.uk/guidance/ng80 

·      Or download here: Asthma NG80.pdf 

Table of ICS and equivalent doses: 

·      Website: inhaled-corticosteroid-doses-pdf-4731528781 (nice.org.uk)

·      Download: https://1drv.ms/b/s!AiVFJ_Uoigq0lhdkbb2S-N9W_AUw?e=PndeXG

Guidance on how to minimise exposure to air pollution:

·      recommendations on vulnerable groups in the NICE guideline on air pollution: outdoor air quality and health 

·      recommendations on people with asthma, other respiratory conditions or cardiovascular conditions in the NICE guideline on indoor air quality at home 

Short explanation for the change in the recommendation on increasing ICS treatment within a self-management programme in children:

·      see the rationale and impact section on self-management .

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Transcript

Hello everyone and welcome. My name is Fernando Florido and I am a GP in the United Kingdom.

In today’s episode we are looking at a summary of the NICE guidance on asthma management. The full NICE guideline also contains advice on asthma diagnosis and, if you are interested in this, please refer to the corresponding episodes on this channel. 

Remember that there is also a Youtube version of these episodes so have a look in the description.

We will start by saying that we need to consider possible reasons for uncontrolled asthma, before starting or adjusting medicines including:

·      alternative diagnoses

·      lack of adherence

·      poor inhaler technique

·      smoking

·      and occupational exposures amongst others

By the way, we will define uncontrolled asthma as:

• 3 or more days a week with symptoms or
• 3 or more days a week with required use of a SABA for symptomatic relief or
• 1 or more nights a week with awakening due to asthma.

Other pharmacological principles to follow are:

1.   That we will review the treatment after 4 to 8 weeks of initiation or change

2.   If needed, we will offer regular daily ICS rather than intermittent therapy

3.   And that we will adjust ICS doses aiming for the lowest dose required

The pharmacological treatment that is recommended in the guideline is for people with newly diagnosed asthma or asthma that is uncontrolled on their current treatment. So, no need to change people who are stable.

NICE has produced three pathways:

1.   recommendations for adults over the age of 17

2.   recommendations for children aged between 5 and 16 years of age

3.   recommendations for children under 5

But in fact, the recommendations for adults and children between the ages of 5 and 16 are very similar so, in order to avoid excessive repetition, I will amalgamate them together and simply point out the differences between them as and when appropriate.

And, even before we start, I need to point out the difference between ICS adult and paediatric doses. NICE makes recommendations in terms of low dose, moderate dose and high dose of ICS. But this means different things for adults and children.

For adults aged 17 and over:

• up to and including 400 mcg of budesonide or equivalent is a low dose
• more than 400 mcg and up to 800 mcg of budesonide or equivalent is a moderate dose
• more than 800 mcg budesonide or equivalent is a high dose.

However, for children and young people aged 16 and under the thresholds are half of the adults’. That is:

• up to and including 200 mcg budesonide or equivalent is a paediatric low dose
• more than 200 mcg and up to 400 mcg budesonide or equivalent is a paediatric moderate dose
• more than 400 mcg budesonide or equivalent is a paediatric high dose.

And remember that budesonide and beclomethasone have dose equivalence but the potency of fluticasone is roughly double that.

NICE has produced a table of various ICS showing their low, moderate, and high dose thresholds. Please have a look in the episode description if you are interested.

We also need to be aware that at the time of publication, the use of some medicines was off label in children, like the use of some LTRAs, LABAs and MART recommendations.

Asthma management follows a stepwise approach.

In adults and children aged 5 to 16:

1.   Firstly, we will just offer a short-acting beta2 agonist (SABA) as reliever therapy for infrequent, short-lived wheeze. 

2.   Then, if there are symptoms of uncontrolled asthma, we will offer a low dose of an ICS. Remember that uncontrolled asthma would be asthma-related symptoms 3 times a week or more, or causing waking at night.

3.   If asthma remains uncontrolled, we will offer a leukotriene receptor antagonist (LTRA) in addition to the ICS and review in 4 to 8 weeks. 

4.   Then, if symptoms persist, we will offer a long-acting beta2 agonist (LABA) in combination with the ICS, and we will consider stopping the LTRA treatment depending on the response.

5.   If an increase in treatment is still needed, we will offer to change the ICS and LABA maintenance therapy to a MART regimen with a low maintenance ICS dose.

Let us stop here for a second. What is MART? MART stands for Maintenance and reliever therapy and is a form of combined ICS and LABA treatment in which a single inhaler, containing both ICS and a fast-acting LABA, is used for both daily maintenance therapy and the relief of symptoms as required. MART is only available for combinations in which the LABA has a fast-acting component (for example, formoterol). Inhalers with salmeterol, for example, would not be suitable for this.

6.   If asthma is uncontrolled on a MART regimen with a low maintenance ICS dose, with or without an LTRA, we will increase the ICS to a moderate maintenance dose (either continuing on a MART regimen or changing to a fixed dose of an ICS and a LABA, with a SABA as a reliever therapy). 

7.   And finally, if symptoms control remains poor, we will consider one of the following:

·      We will refer to an asthma specialist. And we will do this especially for children as we consider stepping up their treatment.

·      We can also increase the ICS to a high dose as part of a fixed-dose regimen, with a SABA used as a reliever therapy or

·      We could also start a trial of an additional drug (for example, theophylline) 

The pharmacological treatment pathway for children under 5 is slightly different.

It can be difficult to confirm asthma diagnosis in young children, therefore these recommendations apply to children with suspected or confirmed asthma. Asthma diagnosis should be confirmed when the child is able to undergo objective tests.

In terms of pharmacological treatment,

1.   First, we will offer a SABA as reliever therapy

2.   Then, we will consider an 8‑week trial of a paediatric moderate dose of an ICS in children under 5 with asthma-related symptoms 3 times a week or more, or causing waking at night

3.   After 8 weeks, we will stop the ICS treatment and:

·      if symptoms did not resolve during the trial period, we will review whether an alternative diagnosis is likely

·      if symptoms resolved but reoccurred beyond 4 weeks after stopping, we will repeat the 8‑week trial of a paediatric moderate dose of ICS. 

·      if symptoms resolved but then reoccurred within 4 weeks of stopping, we will restart the ICS at a paediatric low dose, not a moderate dose

4.   If the suspected asthma is uncontrolled on a paediatric low dose of ICS we will consider an LTRA in addition to the ICS. 

5.   If the suspected asthma remains uncontrolled on a paediatric low dose of ICS and an LTRA, we will stop the LTRA and refer to an asthma specialist

Now, there is a self-management section that we will address now.

And it says that all patients over the age of 5 should have a written asthma self-management action plan and we will also consider it in the under 5s. In it, we will explain that pollution can trigger or exacerbate asthma, and we will include in the personalised action plan approaches for minimising exposure to indoor and outdoor air pollution.

There is separate guidance on how to minimise exposure to air pollution and I will put details to this in the episode description.

Within a self-management programme, and when asthma control deteriorates, we will offer an increased dose of ICS for 7 days to adults who are using an ICS in a single inhaler. We will clearly outline how and when to do this, and what to do if symptoms do not improve. When increasing ICS treatment:

·      We will consider quadrupling the regular ICS dose

·      But we will not exceed the maximum licensed daily dose. 

For children aged 5 to 16, their self-management plan should include advice on contacting a healthcare professional for a review. If they have not been taking their ICS consistently, we will explain that restarting regular use may help them to regain control of their asthma and that the evidence for increasing ICS doses to self-manage deteriorating asthma is limited in this age group. 

NICE has given a short explanation of why they have changed the recommendation on increasing ICS treatment within a self-management programme in children. I will put details of this in the episode description in case that you are interested.

Also, we will try to identify people with asthma who are at increased risk of poor outcomes (for example, severe exacerbations or hospitalisations), and we will use this information to optimise their care. We will base the risk stratification on factors such as non-adherence to treatment, psychosocial problems and repeated episodes of unscheduled asthma care

When it comes to decreasing maintenance therapy

We will consider doing so when the asthma has been controlled for at least 3 months, updating their asthma action plan and discussing the possible effects and how to monitor them. 

When reducing maintenance therapy, we will only consider stopping ICS treatment completely for those on low dose ICS alone who are symptom free. 

In terms of the ongoing management of asthma

If control is poor, we will at every review:

·      check adherence, inhaler technique and whether the treatment needs to be changed

·      and ask about occupational asthma, if relevant. 

For the monitoring of symptoms in adults we will consider using a validated questionnaire (for example, the Asthma Control Questionnaire or Asthma Control Test). In addition, at each review for everyone aged 5 or over, we will assess control using either spirometry or peak flow variability testing. However, we will not routinely use FeNO or challenge testing for monitoring purposes. 

And finally, we will check the inhaler technique:

·      at every asthma consultation

·      when there is deterioration

·      when the device is changed

·      at every annual review

·      if the person asks for it to be checked. 

We have come to the end of this episode. I hope that you have found it useful. Thank you for listening and good-bye

My name is Fernando Florido and I am a GP in the United Kingdom. In this episode I go through some of the statements made by NICE in the guidelines “Chronic kidney disease: assessment and management” or NG203, published on 25 August 2021, explaining why these statements were made.

There is a Youtube version of this and other videos that you can access here:

·      @nicegp: (1) NICE GP - YouTube

Resources:

Full NICE guideline on CKD:

·      Website: https://www.nice.org.uk/guidance/ng203 or as

·      Or download here: https://1drv.ms/b/s!AiVFJ_Uoigq0lgvjCLLzwi5sLeq7?e=JC2Z0g

CKD visual summaries:

• Websites:
• Identifying CKD: 

https://www.nice.org.uk/guidance/ng203/resources/visual-summary-identifying-chronic-kidney-disease-in-adults-pdf-9206256493

• Managing proteinuria: 

https://www.nice.org.uk/guidance/ng203/resources/visual-summary-chronic-kidney-disease-g15-a13-managing-proteinuria-pdf-9206256495

• Phosphate binders:

https://www.nice.org.uk/guidance/ng203/resources/visual-summary-chronic-kidney-disease-stages-4-and-5-phosphate-binders-pdf-9206256494

·      Or download here:  

o  Identifying CKD: https://1drv.ms/b/s!AiVFJ_Uoigq0lgxMqWAve0P2Uqmw?e=r9Gaj2

o  Managing proteinuria:

https://1drv.ms/b/s!AiVFJ_Uoigq0lg2n86ZBA-LtN8Sx?e=3iUfe7

o  Phosphate binders:

https://1drv.ms/b/s!AiVFJ_Uoigq0lg62GGYNQmkebxqF?e=nG7cm6 

CKD tables- 1&2

·      Download: https://1drv.ms/u/s!AiVFJ_Uoigq0lhN1Hnk7TV08C5lC?e=FaLGZo 

NICE HTA guideline:

·      Full guideline: https://youtu.be/dELO3enIhsI

·      Flowchart: https://youtu.be/Ffa6IYrZWeo

·      Shorts: 

o  https://youtu.be/qmLJtwu677I 

o  https://youtu.be/Izo_eSuECEU 

o  https://youtu.be/BnbcUPriJ9g

SGLT2 inhibitors for adults with CKD and type 2 diabetes, see chronic kidney disease in NICE's guideline on type 2 diabetes in adults.  

·      Summary of guidance: CKD section of diabetes guideline 1.8.17 

For adults with type 2 diabetes and CKD who are taking an ARB or an ACE inhibitor (titrated to the highest licensed dose that they can tolerate), offer an SGLT2 inhibitor (in addition to the ARB or ACE inhibitor) if:

·      ACR is over 30 mg/mmol and

·      they meet the criteria in the marketing authorisation (including relevant estimated glomerular filtration rate [eGFR] thresholds).

·      Website: Diabetes guideline: 

https://www.nice.org.uk/guidance/ng28/chapter/Recommendations#chronic-kidney-disease 

NICE's technology appraisal guidance on dapagliflozin for treating chronic kidney disease.  

·      Website:

https://www.nice.org.uk/guidance/ta775

·      Or download here:

https://1drv.ms/b/s!AiVFJ_Uoigq0lg_O0S-awCfFqpI_?e=rrscuF

NICE's technology appraisals on sodium zirconium cyclosilicate and patiromer.  

·      Website:

o  Zirconium: https://www.nice.org.uk/guidance/ta599

o  Patiromer: https://www.nice.org.uk/guidance/ta623

·      Or download here:

o  Zirconium:

https://1drv.ms/b/s!AiVFJ_Uoigq0lhLUkpx5T4E0mrE_?e=XcfIQt

o  Patiromer: https://1drv.ms/b/s!AiVFJ_Uoigq0lhARwG8vfMNKvISz?e=VEsKLm 

NICE's guideline on cardiovascular disease: risk assessment and reduction, including lipid modification for the use of statins in adults with CKD. 

·      Website: https://www.nice.org.uk/guidance/cg181

·      Or download here:

https://1drv.ms/b/s!AiVFJ_Uoigq0lhEqiQX4EhaMN2A3?e=7u5KIK

MHRA safety advice on recombinant human erythropoietins:

·      Website:

 https://www.gov.uk/drug-safety-update/recombinant-human-erythropoietins-new-advice-for-prescribing

·      Summary of advice: 

Recombinant human erythropoietins: new advice for prescribing:

Over-correction of haemoglobin concentration may increase the risk of death and serious cardiovascular events in patients with chronic kidney disease; it may increase the risk of thrombosis and related complications in patients with cancer.

4-variable Kidney Failure Risk Equation

·      Download:

https://1drv.ms/x/s!AiVFJ_Uoigq0lhS5kRhCr7qSz8vm?e=mDkKEY  

Intro / outro music: Track:

Halfway Through — Broke In Summer [Audio Library Release]  

Music provided by Audio Library Plus  

Watch: https://youtu.be/aBGk6aJM3IU (https://www.youtube.com/watch?t=0s&v=aBGk6aJM3IU) 

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Transcript

Hello everyone and welcome. My name is Fernando Florido and I am a GP in the United Kingdom.

In today’s episode we are going to look at some of the statements made by NICE in their guideline on CKD and I will try to explain the reasons for these statements. We will look at the aetiology, pharmacology and pathophysiology in the expectation that, if we understand why the recommendations have been made, it will be easier for us to remember them.

Remember that there is also a Youtube version of these episodes so have a look in the description below.

The first thing that I want to say is that in this episode I am not doing a summary of the guideline. For that, please have a look at the corresponding episode on this channel. Instead, we will look at several recommendations made by NICE, which I will review in more details explaining why they may have been made.

I have picked 15 statements, so, let’s get started.

1-NICE says that “reduced muscle mass leads to an overestimation of eGFR and increased muscle mass leads to an underestimation of the eGFR”  

Right, we all see in our patients’ test results that high creatinine levels normally come with low eGFR readings. That is obvious because renal impairment causes creatinine to rise and GFR to decrease. But we must also be aware that we are not talking about real GFR values but about the eGFR, that is the estimated value, which is based on a relatively complex formula that takes into account a number of parameters, including creatinine. The effect of the creatinine in the formula means that the higher the creatinine, the lower the estimated GFR. 

Now, creatinine is a breakdown product of muscle metabolism. Because formation happens almost exclusively in the muscle, creatinine will be higher in, for example, body builders. They, because of the formula would have a lower estimated GFR. On the other hand, a reduction in muscle mass is associated with lower creatinine levels, resulting in a higher estimated GFR. So don’t be fooled by bodybuilders with a borderline low eGFR or by, for example, malnourished elderly patients with a relatively high eGFR, as this may just be the effect of muscle mass on their readings. 

2- NICE also recommends that we should advise patients “not to eat any meat in the 12 hours before having a blood test for eGFRcreatinine”.  

And this is because dietary protein intake can affect creatinine concentrations too. We have just seen that creatinine is a breakdown product of creatine in the muscle. Therefore, ingestion of creatine (either via red meat or supplementation) can increase muscle creatine “pools,” raising the creatinine levels. So, eating less (or no meat) will cause the creatinine to fall and consequently, the eGFR to improve.  This is important because, if we are going to tell a patient that their eGFR is slightly low, we just want to make sure that it is not real and not just that they have binged on red meat for the last few days. 

3- NICE also says that we should “recheck a high ACR between 3 - 70 in a subsequent early morning sample to confirm the result”.

This is because it has been noted in research that the use of early morning urine gives more accurate ACR readings and, additionally, early morning urines allow the exclusion of orthostatic or postural proteinuria. In orthostatic proteinuria significant urinary protein is excreted when standing, but when lying down the urinary protein is completely normal. This usually occurs in young adults, and is a benign condition with no long-term consequences. 

4- NICE also recommends that “after starting or increasing the dose, we will not modify the dose of an ACEI or ARB if either: 

• the eGFR decrease from baseline is less than 25% or 
• the serum creatinine increase from baseline is less than 30%”.  

Right, so let’s remember a little bit of anatomy. The glomerulus receives its blood supply from an afferent arteriole and, unlike most capillary beds, the glomerular capillaries exit into efferent arterioles rather than venules. Let’s also remind ourselves that ACEI prevent the conversion of angiotensin I to angiotensin II, and ARBs block the effect of angiotensin II. This results in relative vasodilation, which preferentially reduces efferent or postglomerular resistance. Consequently, this will lower intraglomerular pressure which will reduce the glomerular filtration rate  or GFR and cause a subsequent rise in creatinine.

An increase in creatinine of up to 30% and a decrease of eGFR of up to 25% are acceptable and. in the absence of renovascular disease, creatinine levels will frequently return to baseline or below if blood pressure is lowered, despite the continued use of an ACEI or ARB.

5- NICE also says that “we will offer antiplatelet therapy only for the secondary prevention of cardiovascular disease, but we need to be aware of the increased risk of bleeding in CKD patients”.   

Why is this? The real cause for the association between CKD and bleeding is not well known but research studies have shown that CKD has been associated with a 1.5-fold increased risk of bleeding. This has been associated with platelet dysfunction and activation of the fibrinolytic system which can lead to a higher risk of bleeding episodes.

However, we also know that the function of the coagulation system in patients with CKD is abnormal because, although some patients are prone to bleeding, other patients may also develop excessive clot formation. Little is known about the reasons why one patient develops bleeding problems, while another tends to head towards excessive clotting.  

So, in summary, for the secondary prevention of CVD, we definitely need to give aspirin, but being aware of the risks.   

6- NICE talks quite a bit about anaemia of CKD and says that “if eGFR is below 30 we will note that anaemia is often caused by CKD”.   

So, let’s have a look at the causes of anaemia of CKD. Anaemia of CKD is generally a normocytic normochromic, hypoproliferative Anaemia. Although the widely accepted aetiology is a decreased renal production of erythropoietin (EPO), the hormone responsible for stimulating red cell production, anaemia of CKD is of multifactorial origin. Other mechanisms include uraemia, folate and vitamin B12 deficiency, iron deficiency, a shortened lifespan of red blood cells and bleeding due to dysfunctional platelets. But we have to emphasise that CKD patients are at significant risk of iron deficiency; therefore, we must always consider iron supplementation as part of their treatment with erythropoietin stimulating agents.

7- NICE says that in CKD patients “treated with iron, ferritin levels should not rise above 800 and that we will review the dose of iron when ferritin reaches 500”.  

So what this means is that we are going to keep giving iron to our patients even when their ferritin is well above the normal range. Why? This is because, in addition to true iron deficiency, CKD patients also have a functional iron deficiency, which is a type of cell iron blockade which results in reduced iron release from body stores which is then unable to meet the requirement for erythropoiesis. By having a higher than normal ferritin level we would expect iron to be released for erythropoiesis more easily. 

8- NICE also states that “we will offer intravenous iron therapy to people on haemodialysis”. 

Why? This is simply because it has been shown that haemodialysis patients also have impaired intestinal iron absorption, which is why intravenous iron is preferred.  

9- The guideline also says that “we will treat clinically relevant hyperparathyroidism to improve the management of the anaemia”.   

Now, this is a little bit more complex. First of all, Anaemia  has been recognized as a possible complication of primary hyperparathyroidism. So, if the hyperparathyroid state can induce Anaemia in patients with normal kidney function, the high PTH levels also found in hyperparathyroidism secondary to CKD will also have an unfavourable effect. 

So, let’s look at the PATHOGENESIS OF RENAL ANAEMIA ASSOCIATED WITH SHPT

Studies have shown that this is mediated via multiple pathways  

1.   Bone marrow fibrosis: a direct effect of the excess secretion of PTH.

2.   Inhibition of EPO synthesis: although the molecular mechanism through which PTH negatively regulates EPO synthesis is mostly unknown.

3.   Inhibition of bone marrow erythroid progenitors: It is suggested that the excessive PTH downregulates the erythropoietin receptors on progenitor cells in the bone marrow. Therefore, physiologic concentrations of EPO can no longer sustain normal red cell counts, so normocytic and normochromic anaemia follows.

4.   A shortened RBC lifespan: because an excessive PTH level increases the osmotic fragility of RBC through enhanced calcium entry into them. 

Moreover, recent clinical studies have shown that the treatment of SHPT either with medication or parathyroidectomy leads to an improvement of the Anaemia, supporting the role of PTH in renal Anaemia. 

10- NICE also indicates that we should “avoid blood transfusions in people in whom kidney transplant is an option”.  

This is because exposure to multiple blood donations may cause alloimmunisation to human leucocyte antigen or HLA class I on white blood cells. HLA antibodies can then react with the transplanted kidney leading to higher rates of acute rejection and poorer long-term graft survival. However, the risk of alloimmunisation has reduced since the introduction of universal leucodepletion of blood components.  

11- The next statement warns us that “the use of ACEIs or ARBs may lead to increase in ESA therapy”.   

Now, why is this? Various mechanisms have been offered to explain this. First, it has been shown that angiotensin II directly increases the proliferation of erythroid progenitor cells in vitro. Therefore, any agent decreasing angiotensin II levels or its effect could potentially have a negative impact on erythropoiesis. Also, ACE inhibitors and ARBs have been found either to increase substances that inhibit erythropoiesis or to reduce others that stimulate it. I will not go into more detail about this because it is quite a complex area.

12- NICE also tells us that “hyperphosphataemia in CKD stage 4 or 5 can be common”  

Now, by way of introduction, we must know that hyperphosphatemia is seen as the "silent killer" because of its dramatic effect on vascular calcifications. Also, hyperphosphatemia explains, at least in part, the onset of the complex mineral and bone disorders associated with CKD, together with hypocalcemia, low vitamin D levels and secondary hyperparathyroidism.  

So, why does this happen? Hyperphosphataemia in CKD tends to occur in the later stages (that is, 4 and 5) because of insufficient excretion of phosphate by the poorly functioning kidneys, leading to an accumulation of phosphate in the body. 

Surprisingly, and not generally adequately considered, the skeleton contributes to the hyperphosphatemia in CKD through the effects of abnormal bone remodelling. This causes excess bone resorption and thereby, they contribute to the hyperphosphatemia by effectively blocking the skeleton from exerting its normal reservoir function of phosphate. 

13- NICE also talks about the effect of CKD “on bone metabolism and osteoporosis”.  

So what is CKD mineral bone disease? It is the disturbed mineral metabolism caused by uraemic toxins or secondary hyperparathyroidism which disturbs bone mineralization and makes it difficult for calcium and phosphate to enter the bones, resulting in increased serum calcium and phosphate.  

The negative balance between bone formation and resorption in CKD results in bone loss and in those cases, bone densitometry will detect osteopenia or osteoporosis. The prevalence of osteoporosis in the population with CKD certainly exceeds the prevalence in the general population.

As we have explained previously, when bone resorption exceeds bone formation, phosphorus and calcium are released and contribute to hyperphosphatemia and hypercalcemia. This is an important stimulus to heterotopic calcifications, especially in the vasculature, which can lead to cardiovascular events and mortality.  

And because of this vascular calcification and osteoporosis are the most common complications related to CKD-MBD.  

And because vitamin D deficiency plays an important role in renal osteodystrophy, vitamin D supplements are important in treating both osteoporosis and vascular calcification at the same time.  

14- Following on this, NICE says that if vitamin D deficiency has been corrected with cholecalciferol or ergocalciferol and symptoms of CKD–mineral and bone disorders persist, “we will offer alfacalcidol or calcitriol to people with a GFR of less than 30 and we will monitor the calcium and phosphate levels”.   

For this we have to understand a bit the vit D metabolism in the human body. The proximal tubular cells in the kidney converts 25 Vit D (that is 25-hydroxy-cholecalciferol, 25-hydroxy-ergocalciferol), into the active form calcitriol also known as 1,25-dihydroxycholecalciferol. Now, as kidney disease worsens, there is a reduction in the renal 1α-hydroxylase activity for converting Vit D into the active form calcitriol. 

Whilst you would think that giving calcitriol straightaway would be the solution, we also know that treatment with vitamin D (that is ergocalciferol or cholecalciferol) has been shown to increase calcitriol levels in both stage 3 and 4 CKD. So this, together with the other benefits of Vit D that we have discussed, is the reason why cholecalciferol and ergocalciferol remain the main therapeutic approach initially.  

However, treatment with ergocalciferol or cholecalciferol has not always lowered PTH levels which can contribute to the persistent CKD mineral and bone disorder symptoms. And this is why therapy with calcitriol or alfacalcidol, which is an analogue of vitamin D, can be used in these cases as second line. 

15-Finally, NICE says that we will need to consider “oral sodium bicarbonate supplementation for if both: 

• the eGFR is less than 30 (GFR category G4 or G5) and 
• a serum bicarbonate concentration of less than 20”.  

Now, why is this? We know that metabolic acidosis has been associated with CKD due to reduced renal acid excretion. Chronic metabolic acidosis is a common complication of CKD and it also appears to contribute to the progression of kidney disease. Existing evidence from clinical trials suggests that alkali therapy, that is treatment with sodium bicarbonate, could slow down the progression of CKD and this is why it is recommended even if the acidosis is not particularly symptomatic.  

We have come to the end of this episode. I hope that you have found it useful. Thank you for listening and good-bye.

My name is Fernando Florido and I am a GP in the United Kingdom. In this video I go through the NICE guidelines “Chronic kidney disease: assessment and management” or NG203, Published on 25 August 2021 

There is a Youtube version of this and other videos that you can access here: 

·      @nicegp : https://www.youtube.com/channel/UClrwFDI15W5uH3uRGuzoovw 

The full NICE guideline on CKD can be found here: 

·      Website: https://www.nice.org.uk/guidance/ng203 or as 

·       PDF: https://www.nice.org.uk/guidance/ng203/resources/chronic-kidney-disease-assessment-and-management-pdf-66143713055173

·      Or download here: https://1drv.ms/b/s!AiVFJ_Uoigq0lgvjCLLzwi5sLeq7?e=JC2Z0g 

The Visual summaries on CKD can be found here:

• Websites:
• Identifying CKD: 

https://www.nice.org.uk/guidance/ng203/resources/visual-summary-identifying-chronic-kidney-disease-in-adults-pdf-9206256493

• Managing proteinuria: 

https://www.nice.org.uk/guidance/ng203/resources/visual-summary-chronic-kidney-disease-g15-a13-managing-proteinuria-pdf-9206256495

• Phosphate binders:

https://www.nice.org.uk/guidance/ng203/resources/visual-summary-chronic-kidney-disease-stages-4-and-5-phosphate-binders-pdf-9206256494

·      Or download here:

o  Identifying CKD: https://1drv.ms/b/s!AiVFJ_Uoigq0lgxMqWAve0P2Uqmw?e=r9Gaj2 

o  Managing proteinuria:

https://1drv.ms/b/s!AiVFJ_Uoigq0lg2n86ZBA-LtN8Sx?e=3iUfe7 

o  Phosphate binders:

https://1drv.ms/b/s!AiVFJ_Uoigq0lg62GGYNQmkebxqF?e=nG7cm6 

CKD tables- 1&2

·      Download: https://1drv.ms/u/s!AiVFJ_Uoigq0lhN1Hnk7TV08C5lC?e=FaLGZo

Abbreviations: ACR, albumin creatinine ratio; CKD, chronic kidney disease; GFR, glomerular filtration rate.

Note: ACR monitoring should be individualised based on a person's individual characteristics, risk of progression and whether a change in ACR is likely to lead to a change in management.

The episodes on the NICE guideline on hypertension are here: 

·      Full guideline: https://youtu.be/dELO3enIhsI

·      Flowchart: https://youtu.be/Ffa6IYrZWeo

·      Shorts: 

o  https://youtu.be/qmLJtwu677I 

o  https://youtu.be/Izo_eSuECEU 

o  https://youtu.be/BnbcUPriJ9g

For guidance on SGLT2 inhibitors for adults with CKD and type 2 diabetes, see chronic kidney disease in NICE's guideline on type 2 diabetes in adults.  

·      Summary of guidance: CKD section of diabetes guideline 1.8.17 

For adults with type 2 diabetes and CKD who are taking an ARB or an ACE inhibitor (titrated to the highest licensed dose that they can tolerate), offer an SGLT2 inhibitor (in addition to the ARB or ACE inhibitor) if:

·      ACR is over 30 mg/mmol and

·      they meet the criteria in the marketing authorisation (including relevant estimated glomerular filtration rate [eGFR] thresholds).

·      Website: Diabetes guideline: 

https://www.nice.org.uk/guidance/ng28/chapter/Recommendations#chronic-kidney-disease 

For guidance on dapagliflozin for adults with CKD, with or without type 2 diabetes, see NICE's technology appraisal guidance on dapagliflozin for treating chronic kidney disease.  

·      Website:

https://www.nice.org.uk/guidance/ta775

·      PDF:

https://www.nice.org.uk/guidance/ta775/resources/dapagliflozin-for-treating-chronic-kidney-disease-pdf-82611498049477

·      Or download here:

https://1drv.ms/b/s!AiVFJ_Uoigq0lg_O0S-awCfFqpI_?e=rrscuF 

For recommendations on hyperkalaemia treatment in adults with categories G3b to G5 chronic kidney disease, see NICE's technology appraisals on sodium zirconium cyclosilicate and patiromer. 

·      Website:

o  Zirconium: https://www.nice.org.uk/guidance/ta599

o  Patiromer: https://www.nice.org.uk/guidance/ta623 

·      PDF:

o  Zirconium:

https://www.nice.org.uk/guidance/ta599/resources/sodium-zirconium-cyclosilicate-for-treating-hyperkalaemia-pdf-82607272135621

o  Patiromer: https://www.nice.org.uk/guidance/ta623/resources/patiromer-for-treating-hyperkalaemia-pdf-82609015577029

·      Or download here:

o  Zirconium:

https://1drv.ms/b/s!AiVFJ_Uoigq0lhLUkpx5T4E0mrE_?e=XcfIQt

o  Patiromer: https://1drv.ms/b/s!AiVFJ_Uoigq0lhARwG8vfMNKvISz?e=VEsKLm 

Follow the recommendations in NICE's guideline on cardiovascular disease: risk assessment and reduction, including lipid modification for the use of statins in adults with CKD.  

·      Website: https://www.nice.org.uk/guidance/cg181

·      PDF:

https://www.nice.org.uk/guidance/cg181/resources/cardiovascular-disease-risk-assessment-and-reduction-including-lipid-modification-pdf-35109807660997 

·      Or download here:

https://1drv.ms/b/s!AiVFJ_Uoigq0lhEqiQX4EhaMN2A3?e=7u5KIK 

Follow the MHRA safety advice on recombinant human erythropoietins:

·      Website:

 https://www.gov.uk/drug-safety-update/recombinant-human-erythropoietins-new-advice-for-prescribing

·      Summary of advice: 

Recombinant human erythropoietins: new advice for prescribing

Over-correction of haemoglobin concentration may increase the risk of death and serious cardiovascular events in patients with chronic kidney disease; it may increase the risk of thrombosis and related complications in patients with cancer.

4-variable Kidney Failure Risk Equation

A person's 5-year risk of needing renal replacement therapy (defined as the need for dialysis or transplant) is estimated, as in Major 2019, as:

In the above, eGFR is reported in ml/min/1.73 m2 and ACR in mg/mmol. Where the term 'male' is used, this should be replaced by a 1 if the person being assessed is male, and a 0 if they are female. This equation and its coefficients are validated in a UK population, and it is important to use this version, and not a version validated in another country.

Hello everyone and welcome to the channel.

Today we are going to look at the NICE guidelines on CKD.

My name is Fernando Florido and I am a GP in the United Kingdom. So, let’s get started.

The first thing that I want to say is that obviously this video is a summary of the guideline. I have removed anything that I thought was common-sense advice (e.g. involve patients in the decision making process, offer information, etc) but on this occasion I have removed all aspects about children and young people with CKD. Although their management is very similar to adults in many ways, most patients with CKD that we will see in general practice will be adults and this is why I have focused on them  

In terms of measuring kidney function, we will look at the eGFR. We need to remember that “e” in eGFR means “estimated” and that eGFRcreatinine may be less reliable in certain situations, for example, acute kidney injury, pregnancy, oedematous states, and has not been well validated in certain ethnic groups, for example, black, and Asian ethnic groups. Also, reduced muscle mass will lead to overestimation and increased muscle mass to underestimation of the GFR and therefore we will need to interpret eGFRcreatinine with caution in extremes of muscle mass, e.g., in bodybuilders, amputation or muscle wasting disorders.

And we shouuldn’t forget to advise patients not to eat any meat in the 12 hours before having a blood test for eGFRcreatinine. This is because meat contains creatinine so when you eat meat the serum creatinine naturally increases. Serum creatinine used in eGFR calculations. And so, eating less (or no meat) will cause the creatinine to fall and consequently, the eGFR to improve. 

The eGFR value is given as a whole number if it is 90 or less, or as 'greater than” 90 

If eGFR is greater than 90, we will use an increase in serum creatinine of more than 20% to infer significant reduction in kidney function. 

We need to interpret eGFR values of 60 or more with caution, as estimates of GFR become less accurate as the true GFR increases. 

And we will also confirm a first ever eGFR result of less than 60 by repeating it within 2 weeks. 

When it comes to proteinuria, we will not use reagent strips to detect it. We will:

·      use urine ACR rather than protein:creatinine ratio (PCR) because of the greater sensitivity for low levels of proteinuria. However, when ACR is 70 mg/mmol or more, PCR can be used as an alternative to ACR. 

• check an ACR between 3 mg/mmol and 70 mg/mmol in a subsequent early morning sample to confirm the result.
• A repeat sample is not needed if the initial ACR is 70 mg/mmol or more. 
• Regard an ACR of 3 mg/mmol or more as clinically important proteinuria. 

And we will routinely measure ACR in:

• diabetes (type 1 or type 2)
• people with an eGFR of less than 60 
• people with an eGFR of 60 or more if there is a strong suspicion of CKD

If unexplained proteinuria is found on a reagent strip, we need to offer testing for CKD using eGFRcreatinine and ACR.  

When it comes to haematuria, we will use reagent strips to test for it and:

• Evaluate further for results of 1+ or higher. 
• Do not use urine microscopy to confirm a positive result because red blood cells may not be seen in microscopy in haemolysed haematuria 

We will regard 2 out of 3 positive reagent strip tests as confirmation of persistent invisible haematuria. Otherwise, it may be transient haematuria

Persistent invisible haematuria, with or without proteinuria, should prompt investigation for urinary tract malignancy in appropriate age groups  

Persistent invisible haematuria in the absence of proteinuria should be followed up annually with repeat testing for haematuria, proteinuria or albuminuria, GFR and blood pressure monitoring as long as the haematuria persists.  

There are certain patients who should be regularly tested for CKD. 

We will monitor GFR at least annually if medicines that can adversely affect kidney function, such as calcineurin inhibitors (for example, ciclosporin or tacrolimus), lithium or non-steroidal anti-inflammatory drugs (long-term chronic use of NSAIDs) are given.  

We will also do eGFRcreatinine and ACR to people with any of the following risk factors:

• diabetes 
• hypertension
• previous episode of acute kidney injury
• cardiovascular disease (ischaemic heart disease, chronic heart failure, peripheral vascular disease, or cerebral vascular disease)
• structural renal tract disease, recurrent renal calculi, or prostatic hypertrophy
• multisystem diseases with potential kidney involvement, for example, systemic lupus erythematosus
• gout
• family history of end-stage renal disease (GFR category G5) or hereditary kidney disease
• incidental detection of haematuria or proteinuria. 

We will also monitor people for the development or progression of CKD for at least 3 years after acute kidney injury (longer for people with acute kidney injury stage 3) even if eGFR has returned to baseline.  

There is a classification of CKD depending on the ACR level (A1, A2 and A3) and the GFR level (G1 to G5).

§ A1: ACR less than 3 mg/mmol

§ A2: ACR 3 to 30 mg/mmol

§ A3: ACR over 30 mg/mmol

§ G1: GFR 90 or over

§ G2: GFR 60 to 89

§ G3a: GFR 45 to 59

§ G3b: GFR 30 to 44

§ G4: GFR 15 to 29

§ G5: GFR under 15  

We need to be aware that:

• increased ACR and decreased GFR is associated with increased risk of adverse outcomes 
• increased ACR and decreased GFR in combination multiply this risk.

The classification table (table 1) with the risk assessment of every category can be found in the video description. 

We will offer a renal ultrasound scan to all adults with CKD who:

• have accelerated progression of CKD (and we will look at the definition of this later)
• have visible or persistent invisible haematuria
• have symptoms of urinary tract obstruction
• have a family history of polycystic kidney disease and are older than 20
• have a GFR of less than 30 (that is GFR category G4 or G5) 
• are considered by a nephrologist to need a renal biopsy. 
•  

When it comes to the frequency of monitoring, we will bear in mind that CKD is not progressive in many people. 

There is also a table (table 2) to guide the minimum frequency of eGFRcreatinine monitoring depending of the CKD classification- you can see this table in the video description too. 

Generally, it would be:

1.    once a year for G1, G2 and G3a if the ACR is less than 30

2.    twice a year for G3a A3 (that is ACR more than 30) and also G3b and G4 if the ACR is less than 30

3.    three times a year for G4A3 (that is ACR more than 30)

4.    four times a year or more for G5 

Monitoring should be tailored according to:

• the underlying cause
• the rate of decline in eGFR or increase in ACR
• other risk factors, including heart failure, diabetes and hypertension
• changes to their treatment (such as renin–angiotensin–aldosterone system [RAAS] antagonists, NSAIDs and diuretics)
• intercurrent illness (for example acute kidney injury)

We will define accelerated progression of CKD as:

• a sustained decrease in GFR of 25% or more and a change in GFR category within 12 months or
• a sustained decrease in GFR of 15 per year. 
• These people are at high risk of progression to end stage renal disease 

If we are worried and we want to identify the rate of progression of CKD:

• We will obtain a minimum of 3 GFRs over no fewer than 90 days.
• If we see a low GFR for the first time, we will repeat the GFR within 2 weeks to exclude acute deterioration e.g. acute kidney injury or secondary to starting renin–angiotensin system antagonist therapy.  

Risk factors for CKD progression are:

• cardiovascular disease 
• proteinuria
• previous episode of acute kidney injury
• hypertension 
• diabetes 
• smoking
• African, African-Caribbean or Asian family origin
• chronic use of NSAIDs 
• untreated urinary outflow tract obstruction. 

When it comes to patient education, we will encourage exercise, a healthy weight and stop smoking. We will also offer dietary advice about potassium, phosphate, calorie, and salt intake appropriate to the severity of CKD. But we will not offer low-protein diets.  

There is a 4-variable Kidney Failure Risk Equation that can be used to give information about the 5-year risk of needing. Those who are interested in it can find more details in the video description.

We will refer for specialist assessment if they have:

• a 5-year risk of needing renal replacement therapy of greater than 5%
• an ACR of 70 mg/mmol or more, unless known to be caused by diabetes and already appropriately treated 
• an ACR of more than 30 mg/mmol (ACR category A3), together with haematuria
• accelerated progression of CKD , i.e., a sustained decrease in eGFR of 25% or more and a change in eGFR category within 12 months or a sustained decrease in eGFR of 15 ml/min/1.73 m2 or more per year
• poorly controlled hypertension despite 4 antihypertensive medicines
• known or suspected rare or genetic causes of CKD
• suspected renal artery stenosis. 

We will refer people with CKD and renal outflow obstruction to urological services 

When it comes to blood pressure control in adults with CKD and an ACR under 70, we will aim for a clinic BP below 140/90 mmHg 

However, in CKD and an ACR of 70 or more, aim for a clinic BP below 130/80. 

In order to treat hypertension, if the ACR is 30 or less (that is ACR categories A1 and A2), we will simply follow the NICE guideline on hypertension. And you can check out the corresponding episode on this channel. 

But for people with CKD who have hypertension and an ACR over 30 (that is an ACR category A3), we will definitely offer an ARB or an ACE inhibitor and we will titrate it to the highest licensed dose that the person can tolerate. If they also have diabetes, we will also give an ARB or ACEI if the ACR is 3 mg/mmol or more.  

SGLT2 inhibitors have been proven to help CKD in both people with and without diabetes. The guidance on their use is outside the scope of this guideline but I will put links to the guidance in the video description. 

Going back to the renin–angiotensin system antagonists, that is, ARBs and ACEIs, we will not offer a combination of both these agents. 

We will measure potassium and eGFR before starting an ARB or ACEI and between 1 and 2 weeks after starting treatment and after each dose increase. More frequent monitoring of serum potassium may be needed if medicines known to promote hyperkalaemia are prescribed alongside them 

We will not routinely offer an ARB or ACEI if their pre-treatment potassium is greater than 5.0 mmol/litre. In these cases, we will: 

• assess for and treat any other factors that promote hyperkalaemia and
• recheck serum potassium concentration.  

We will stop ARBs and ACEIs if the potassium level increases to 6.0 mmol/litre or more and other medicines known to promote hyperkalaemia have been discontinued.  

There is a separate guidance on hyperkalaemia treatment- see link in the video description. 

Because their mode of action, ARBs and ACEIs can reduce the GFR and increase the creatinine levels. However, after starting or increasing the dose of an ACEI or ARB, we will not modify the dose if either:

• the GFR decrease from pretreatment baseline is less than 25% or
• the serum creatinine increase from baseline is less than 30%. 
• In that case, we will repeat the test in 1 to 2 weeks and we will not change anything if the decrease in eGFR remains less than 25% or the increase in serum creatinine remains less than 30%. 

If the eGFR decrease is 25% or more, or the increase in creatinine is 30% or more:

• We will investigate other causes of a deterioration in kidney function, such as volume depletion or concurrent medication (for example, NSAIDs) 
• And if no other cause for the deterioration is found, we will stop the ARB or ACEI or reduce the dose to a previously tolerated lower dose, and add an alternative antihypertensive medication if needed. 

The advice on statins inn CKD is covered in a different NICE guideline. I will put it link to it in the video description.

We will offer antiplatelet medicines only for the secondary prevention of cardiovascular disease, but we need to be aware of the increased risk of bleeding. 

When it comes to anaemia, we will consider investigating and managing anaemia in CKD if:

• their Hb level falls to 110 g/litre or less or
• they develop symptoms attributable to anaemia (such as tiredness, shortness of breath, lethargy and palpitations). 

And in people with anaemia:

• If eGFR is above 60, investigate other causes as unlikely to be CKD.
• If eGFR is between 30 and 60 ml/min/1.73 m2:
• investigate other causes of anaemia, but
• use clinical judgement to decide how extensive this investigation should be, because the anaemia may be caused by CKD.
• If eGFR is below 30 ml/min/1.73 m2, think about other causes of anaemia but we will note that anaemia is often caused by CKD in these circumstances. 

We will need to determine the iron status in these cases and we will test for iron deficiency every 3 months, or every 1 to 3 months if haemodialysis. And to diagnose iron deficiency, we will:

• Use the percentage of hypochromic red blood cells (% HRC; more than 6%).
• If this is not possible, we will use the reticulocyte Hb content (CHr; less than 29 pg).
• And if these tests are not available or the person has thalassaemia or thalassaemia trait, we will use a combination of transferrin saturation (less than 20%) and serum ferritin measurement (less than 100 micrograms/litre). However, we will not routinely use transferrin saturation or serum ferritin measurement alone to assess iron deficiency status in people with anaemia of CKD. 

Equally we will not routinely measure erythropoietin levels for the diagnosis or management of anaemia of CKD. 

 In order to manage anaemia, there is separate guidance and I will put the link to it in the video description. But the management of anaemia in CKD is based on iron therapy, ESAs (erythropoietic stimulating agents) and blood transfusions.

 We will not start ESA therapy without managing possible iron deficiency. 

 In people treated with iron, serum ferritin levels should not rise above 800 micrograms/litre. In order to prevent this, we will review the dose of iron when serum ferritin levels reach 500 micrograms/litre. 

 We will not prescribe androgens, supplements of vitamin C, folic acid or carnitine as adjuvants specifically for the treatment of anaemia of CKD. But we will treat clinically relevant hyperparathyroidism to improve the management of the anaemia. 

 We will avoid blood transfusions in people in whom kidney transplant is an option. This is because exposure to multiple blood donations may cause alloimmunisation to human leucocyte antigen or HLA class I antigens on white blood cells. HLA antibodies can react with the transplanted kidney leading to higher rates of acute rejection and poorer long-term graft survival. However, the risk of alloimmunisation has reduced since the introduction of universal leucodepletion of blood components.

The dose and frequency of ESA should be:

• determined by the duration of action and route of administration of the ESA 
• adjusted to keep the rate of Hb increase between 10 -20 g/litre/ month. 

And we will not routinely correct Hb to normal levels with ESAs in people with anaemia of CKD.

• We will typically maintain the aspirational Hb range between 100 and 120 g/litre. 
• To keep the Hb level within the aspirational range, we will not wait until Hb levels are outside the aspirational range before adjusting treatment (for example, we will take action when Hb levels are within 5 g/litre of the range's limits, that is 105 and 115 g/litre).

There is MHRA advice on the prescribing of ESAs. I will put in the video description the link to these details. In particular, we will follow their advice to avoid Hb levels above 120 g/litre because of the increased risk of death and serious adverse cardiovascular events in people with CKD. We will use the lowest dose of ESA to provide adequate control of the anaemia symptoms and we will consider accepting Hb levels below the aspirational range if:

• high doses of ESAs are needed to achieve the aspirational range or
• the aspirational range is not achieved despite escalating ESA doses.

The use of ACEIs or ARBs is not precluded, but if they are used, we need to be aware that an increase in ESA therapy may be needed. 

 We will offer iron to people with anaemia of CKD who are receiving ESAs to achieve:

• percentage of hypochromic red blood cells less than 6% (unless ferritin is greater than 800 micrograms/litre)
• reticulocyte Hb count or equivalent tests above 29 pg (unless serum ferritin is greater than 800 micrograms/litre).
• If these tests are not available or the person has thalassaemia or thalassaemia trait, iron therapy should maintain transferrin saturation greater than 20% and serum ferritin level greater than 100 micrograms/litre (unless serum ferritin is greater than 800 micrograms/litre).

Most adults will need 500 to 1,000 mg of iron (equivalent doses for children) in a single or divided dose depending on the preparation. Intravenous iron should be administered in a setting with facilities for resuscitation.

• For people who are not having haemodialysis, we will consider a trial of oral iron before offering intravenous iron therapy. If they are intolerant of oral iron or target Hb levels are not reached within 3 months, we will offer intravenous iron therapy. 
• For people who are having haemodialysis, we will offer intravenous iron therapy. We will offer oral iron therapy to people who are having haemodialysis only if:
• intravenous iron therapy is contraindicated or
• the person chooses not to have intravenous iron therapy 

We will also offer intravenous iron therapy to adults with anaemia of CKD who are iron deficient and who are receiving ESA therapy. In these cases we will only offer oral iron if:

• intravenous iron therapy is contraindicated or
• the person chooses not to have intravenous iron therapy. 

When offering intravenous iron therapy to people not having haemodialysis, consider high‑dose low‑frequency intravenous iron as the treatment of choice.

High-dose and low-frequency iron is a maximum of 2 infusions, with a minimum of 500 mg of iron in each infusion for adults. Low dose and high frequency is more than 2 infusions with 100 mg to 200 mg of iron in each infusion for adults.

We will not check iron levels earlier than 1 week after intravenous iron and we will carry out routine ferritin every 1 to 3 months to prevent iron overload

 In anaemia of CKD, we will monitor Hb:

• every 2 to 4 weeks in the induction phase of ESA therapy
• every 1 to 3 months in the maintenance phase of ESA therapy
• more frequently after an ESA dose adjustment

After other causes of anaemia have been excluded, we will regard anaemia of CKD as resistant to ESAs when:

• an aspirational Hb range is not achieved despite high doses of ESAs or 
• there is a continued need for the administration of high doses of ESAs to maintain the aspirational Hb range. 

In people with CKD, pure red cell aplasia (PRCA) is indicated by a low reticulocyte count, together with anaemia and the presence of neutralising antibodies. In addition, aluminium toxicity should be considered as a potential cause of ESA resistance after other causes have been excluded. 

 If aluminium toxicity is suspected in a person with anaemia of CKD having haemodialysis, we will need to test for desferrioxamine and review the management

 We will consider specialist referral for people with ESA‑induced pure red cell aplasia or PRCA. 

 We will take into account symptoms, quality of life, underlying conditions and the chance of a future successful kidney transplant, in addition to Hb levels, when thinking about the need for red cell transfusion. 

Hyperphosphataemia in people with CKD stage 4 or 5 can be common and when it comes to managing hyperphosphataemia, a specialist renal dietitian should be involved. 

 And before starting phosphate binders we will optimise:

• diet
• dialysis, for people who are having this. 

 We will first offer adults with CKD stage 4 or 5 and hyperphosphataemia calcium acetate to control serum phosphate levels.

We will then offer sevelamer carbonate if calcium acetate is not indicated (for example, because of hypercalcaemia or low serum parathyroid hormone levels) or not tolerated.

 If calcium acetate and sevelamer carbonate cannot be used, we will consider:

• sucroferric oxyhydroxide, for adults on dialysis if a calcium-based phosphate binder is not needed or
• calcium carbonate, if a calcium-based phosphate binder is needed.

We will only consider lanthanum carbonate if other phosphate binders cannot be used.

If patients remain hyperphosphataemic after taking the maximum dose of a calcium-based phosphate binder:

• we will check that they are taking it as prescribed
• we will consider combining a calcium-based phosphate binder with a non-calcium-based phosphate binder, titrating the dosage to achieve the best possible control of serum phosphate while keeping serum calcium levels below the upper normal limit. 

At every routine clinical review, we will assess the person's phosphate, taking into account:

• diet
• whether they are taking the phosphate binders as prescribed
• other relevant factors, such as vitamin D levels, serum parathyroid hormone levels, alkaline phosphatase, serum calcium, medications that might affect serum phosphate, or dialysis.

There are other complications in CKD such as the effect on bone metabolism and osteoporosis.

 We will not routinely measure calcium, phosphate, parathyroid hormone and vitamin D levels in adults with a GFR of 30 ml/min/1.73 m2 or more (GFR category G1, G2 or G3). But we will measure serum calcium, phosphate and parathyroid hormone concentrations in adults with a GFR of less than 30 ml/min/1.73 m2 (GFR category G4 or G5).

 We will offer bisphosphonates if indicated for the prevention and treatment of osteoporosis in adults with a GFR of 30 ml/min/1.73 m2 or more (GFR category G1, G2 or G3). 

 We will not routinely offer vitamin D supplementation to manage or prevent CKD–mineral and bone disorders but we will offer colecalciferol or ergocalciferol to treat proven vitamin D deficiency. 

 If vitamin D deficiency has been corrected and symptoms of CKD–mineral and bone disorders persist, we will offer alfacalcidol or calcitriol to people with a GFR of less than 30 ml/min/1.73 m2 (GFR category G4 or G5) and we will monitor the calcium and phosphate levels. 

 Finally, we will consider oral sodium bicarbonate supplementation for if both:

• the GFR is less than 30 ml/min/1.73 m2 (GFR category G4 or G5) and
• a serum bicarbonate concentration of less than 20 mmol/litre. 

We have come to the end of this video. I hope that you have found it useful and, if so, please hit the like and subscribe buttons. Thank you for watching and good-bye

My name is Fernando Florido and I am a GP in the United Kingdom. In this episode I go through the NICE guidelines “Chronic heart failure in adults: diagnosis and management” or NG106, Published on 12 September 2018 

There is a YouTube version of this and other episodes that you can access here: 

·      https://www.youtube.com/@nicegp 

The NICE guideline on chronic heart failure can be found here:  

·      Website: https://www.nice.org.uk/guidance/ng106/chapter/Recommendations or as PDF: https://www.nice.org.uk/guidance/ng106/resources/chronic-heart-failure-in-adults-diagnosis-and-management-pdf-66141541311685

·      Or download here: https://1drv.ms/b/s!AiVFJ_Uoigq0lgl6iwROprZsSZ2u?e=G7Lte2 

The NICE recommendations on dapaglifozin and empaglifozin in HF can be found:

·      On website here:

o  Dapaglifozin in HF: https://www.nice.org.uk/guidance/ta679 or https://www.nice.org.uk/guidance/ta679/resources/dapagliflozin-for-treating-chronic-heart-failure-with-reduced-ejection-fraction-pdf-82609327985605

o  Empaglifozin in HF: https://www.nice.org.uk/guidance/ta773 or https://www.nice.org.uk/guidance/ta773/resources/empagliflozin-for-treating-chronic-heart-failure-with-reduced-ejection-fraction-pdf-82611494690245 

·      Or downloaded here:

o  Dapaglifozin: https://1drv.ms/b/s!AiVFJ_Uoigq0lgfx8IoyYutMx9rh?e=1Fc3uc

o  Empaglifozin: https://1drv.ms/b/s!AiVFJ_Uoigq0lggUBPl4p_XX1XzF?e=aMVtBp 

The Visual summaries on diagnosis and management of heart failure can be found here:

• Website:

1-Diagnosis: https://www.nice.org.uk/guidance/ng106/resources/chronic-heart-failure-diagnosis-visual-summary-pdf-6663137726

2-Management:  https://www.nice.org.uk/guidance/ng106/resources/chronic-heart-failure-management-visual-summary-pdf-6663137725

·      Or download here:  

1-Diagnosis: https://1drv.ms/b/s!AiVFJ_Uoigq0lgW9dPRAHiaT3Ueg?e=hfuU3x

2-Management:

https://1drv.ms/b/s!AiVFJ_Uoigq0lgZLGWycIkNN-Mcu?e=bTlnAN

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Transcript

Hello everyone and welcome.

Today we are going to look at the NICE guidelines on Chronic heart failure.

My name is Fernando Florido and I am a GP in the United Kingdom. Remember that there is also a YouTube version of these episodes so have a look in the podcast description. Let’s jump straight into it.

The first recommendation given by NICE is probably something that is often neglected. And this is to write a care plan for every patient with HF. This care plan must include:

·      diagnosis and cause

·      medication and monitoring

·      functional abilities and any social circumstances

·      details of clinical management including

• symptoms to look out for in case of deterioration

o  how to access the specialist team

o  contact details for a named healthcare coordinator or alternative specialist care providers, for urgent care or review.

When it comes to making the Diagnosis we will base it initially on the history, and clinical examination.

Some of the typical symptoms of HF may include:

·      Shortness of breath on exertion or when lying down

·      Fatigue and weakness

·      Bilateral leg, ankle or foot swelling

·      Rapid or irregular pulse

·      Reduced ability to exercise

·      Persistent cough or wheezing

·      Abdominal swelling and

·      Very rapid weight gain from fluid retention

Examples of examination findings in

left-sided heart failure include cool clammy skin, cyanosis, a laterally displaced point of maximum impulse consistent with an enlarged ventricle and on auscultation we can find lung crackles and a gallop rhythm. Signs in right sided heart failure include an elevated JVP, ankle of leg edema, ascites, hepatomegaly, a parasternal heave and hepatojugular reflux. Signs of both left and right sided heart failure can be present.

In order to confirm the diagnosis

We will measure the N-terminal pro-B-type natriuretic peptide (NT‑proBNP), which I will refer to now as simply BNP. 

And we will refer for a transthoracic echocardiography:

·      within 2 weeks if the NT-proBNP level is above 2,000 ng/litre (236 pmol / litre) and the urgency is because very high NT-PproNP levels carry a poor prognosis or refer

·      within 6 weeks if the NT-proBNP level is between 400 and 2,000 ng/litre (47 to 236 pmol/litre)

·      a NT-PROBNP level of less than 400 ng/litre (47 pmol/litre) in an untreated person makes a diagnosis of heart failure less likely. In these cases, we will look for alternative causes. 

But remember:

·      the NT-PROBNP level does not differentiate between heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. 

·      The NT-PROBNP level can be reduced by obesity, African or African–Caribbean family background, or treatment with HF drugs such as diuretics, ACE inhibitors, ARBs, beta‑blockers, or mineralocorticoid receptor antagonists (MRAs)

·      The NT-PROBNP level can be increased due to causes other than heart failure (for example, age over 70 years, left ventricular hypertrophy, ischaemia, tachycardia, right ventricular overload, hypoxaemia [including PE and COPD], eGFR less than 60, sepsis, diabetes, or liver cirrhosis). 

The purpose of transthoracic echocardiography is to exclude valve disease, assess the systolic and diastolic ventricular function, and detect intracardiac shunts. Heart failure caused by valve disease will need specialist referral. 

We will arrange alternative imaging (for example, radionuclide angiography, cardiac MRI or transoesophageal echocardiography) if the transthoracic echocardiography gives a poor image. 

We will also arrange other tests including:

·      ECG

·      chest X-ray

·      blood tests including full blood count, renal, liver and thyroid function as well as a lipid profile and HbA1c

·      urinalysis

·      peak flow or spirometry. 

In order to give the necessary information to the patient, NICE recommends an extended first consultation, followed by a second consultation 2 weeks later.

When it comes to treatment, there are specific recommendations for HFrEF but first we will look at the advice for all types of heart failure

Firstly, we will give Diuretics for the relief of congestive symptoms and fluid retention and titrate them up and down according to need. In particular, in heart failure with preserved ejection fraction we will normally give no more than a low to medium dose of loop diuretics (for example, less than 80 mg furosemide per day) and refer if this is not enouogh. 

By the way, I just wish to clarify that heart failure with preserved ejection fraction is usually associated with impaired left ventricular relaxation, rather than left ventricular contraction, and is characterised by normal left ventricular ejection fraction with evidence of diastolic dysfunction.

Amiodarone initiation will be by a specialist and we will review the need to continue at every 6‑monthly clinical review. Amiodarone monitoring must include 6 monthly liver and thyroid function tests. 

In sinus rhythm, anticoagulation should be considered for those with a history of thromboembolism, left ventricular aneurysm or intracardiac thrombus. 

We will now focus on the treatment of heart failure with reduced ejection fraction. By the way, I just want to clarify that Heart failure with reduced ejection fraction is when the ejection fraction is below 40%.

By way of introduction, we will say that some SGLT2 inhibotors such as dapaglifozin and empaglifozin have been shown to help in HFrEF even in the non-diabetic population. The guidance on their use in HF is covered outside this guideline, but in summary, NICE says that both Dapagliflozin and empaglifozin are recommended as an option for treating symptomatic chronic heart failure with reduced ejection fraction in adults, only if it is used as an add- on to optimised standard care with ACE inhibitors or ARBs, and beta blockers, mineralocorticoid receptor antagonists (MRAs) or sacubitril valsartan. I will put the link to the full SGLT2 guidance in the video description.

See NICE's technology appraisal guidance on dapagliflozin and empagliflozin for treating chronic heart failure with reduced ejection fraction

In terms of Calcium-channel blockers, we will avoid verapamil, diltiazem and short-acting dihydropyridine agents (like standard release nifedipine) in heart failure with reduced ejection fraction. 

The First-line treatment in heart failure with reduced ejection fraction is as follows:

1.     An ACE inhibitor and a beta‑blocker licensed for heart failure. The beta-blockers licensed in the UK for the treatment of heart failure are bisoprolol, carvedilol, and nebivolol. And we will use our clinical judgement when deciding which drug to start first. But we will not give an ACE inhibitor if there is haemodynamically significant valve disease until the valve disease has been assessed by a specialist.

a.     We will give an ARB licensed for heart failure if there are side effects with ACE inhibitors. ARB licensed for heart failure in the UK are Candesartan, losartan, and valsartan.

b.     If neither ACE inhibitors nor ARBs are tolerated, we will seek specialist advice, in order to consider hydralazine in combination with nitrate. 

c.      We will not withhold beta-blockers only because of age or the presence of peripheral vascular disease, erectile dysfunction, diabetes, interstitial pulmonary disease or chronic obstructive pulmonary disease.

d.     And, if stable, we will switch people already taking a beta-blocker for a comorbidity (for example, angina or hypertension), to a beta-blocker licensed for heart failure. That is again bisoprolol, carvedilol, and nebivolol in the UK.

2.     If there are persistent symptoms, we will then give an mineralocorticoid receptor antagonists (MRA), such as spironolactone or eplerenone, in addition to an ACE inhibitor (or ARB) and beta-blocker. 

Now, for all these drugs, that is ACEI, ARB, betablocker and MRA:

We will start at a low dose and titrate upwards at short intervals (for example, every 2 weeks) until the target or maximum tolerated dose is reached. 

We will measure BP and renal function, including sodium and potassium levels, before and 1 to 2 weeks after starting the drug, and after each dose increment. We will also assess heart rate if giving betablockers.

Once the target or maximum tolerated dose is reached, we will monitor treatment monthly for 3 months and then at least every 6 months, and at any time the person becomes acutely unwell. 

NICE recommends that the following drugs should be initiated by a Specialist

·      Ivabradine

·      Sacubitril valsartan

·      Hydralazine in combination with nitrate

·      Digoxin

Ivabradine is recommended if:

·      NYHA class II to IV stable chronic heart failure with systolic dysfunction and

·      sinus rhythm with a heart rate of 75 beats per minute (bpm) or more and

·      in combination with standard therapy including beta-blocker therapy, ACE inhibitors and aldosterone antagonists, or when beta‑blocker therapy is contraindicated or not tolerated and

·      with a left ventricular ejection fraction of 35% or less. 

Sacubitril valsartan is recommended if:

·      NYHA class II to IV symptoms and

·      with a left ventricular ejection fraction of 35% or less and

·      already taking a stable dose of ACE inhibitors or ARBs. 

By the way, if you want to learn a bit more about Sacubitril valsartan, stick around until the end, when I will give you a bit more information about it.

Hydralazine in combination with nitrate, is recommended especially if:

·      the person is of African or Caribbean family origin and

·      has moderate to severe heart failure NYHA class III/IV with reduced ejection fraction. 

Digoxin is recommended for worsening or severe symptoms despite first-line treatment. Routine monitoring of serum digoxin concentrations is not recommended. A digoxin concentration measured within 8 to 12 hours of the last dose may be useful to confirm a clinical impression of toxicity or non‑adherence. 

There are special considerations when treating heart failure with reduced ejection fraction in people with chronic kidney disease or CKD

If the eGFR is between 30 and 45 we will offer the same treatment but using lower doses and/or slower titration of ACEI, ARBs, MRAs and digoxin. 

If the eGFR is below 30 we will involve the renal team. 

And we will monitor closely the medication of CKD patients because of the increased risk of hyperkalaemia. 

Other general recommendations in terms of management are:

1.     an annual flu vaccination and a once only pneumococcal vaccination

2.     Contraception and pregnancy for women of childbearing potential

3.     Give appropriate advice on Smoking and alcohol

4.     Air travel will be possible for most, depending on their clinical condition. 

5.     In terms of driving, there may be restrictions for Large Goods and Passenger Carrying Vehicles and, in the UK, we will check the DVLA website for regular updates. 

6.     We will not routinely restrict sodium or fluid consumption. Instead, we will ask about salt and fluid consumption and:

o  advise fluid restriction if there is dilutional hyponatraemia

o  advise reducing intake if there are high levels of salt and/or fluid consumption. 

o  We will however advise to avoid salt substitutes that contain potassium. 

In terms of further monitoring for all types of heart failure

Apart from what has already been discussed, we will carry out full clinical assessment at every review.

If a person is taking digoxin or an MRA we will monitor potassium levels closely. 

And we will consider monitoring NT-PROBNP levels only if:

·      under 75

·      there is heart failure with reduced ejection fraction and

·      the eGFR is above 60 . 

In terms of Interventional procedures

1.     Coronary revascularisation should not be routinely offered but

2.     Cardiac transplantation, Implantable cardioverter defibrillators and cardiac resynchronisation therapy can be offered to the right patients.

Cardiac rehabilitation should normally be offered unless the HF is unstable.

And finally, in Palliative care

We will not offer long-term home oxygen therapy, although it may still be offered for comorbidities, such as for some people with COPD.

Now, this is the end of the actual NICE guideline on chronic heart failure. But if you are interested in learning how Sacubitril/valsartan works, here is some background information.

The first thing to understand is that the pathophysiology of heart failure involves an abnormal activation of the renin-angiotensin-aldosterone system (RAAS). This leads to vasoconstriction, hypertension, increased aldosterone levels, increased sympathetic tone, and eventually, cardiac remodelling, all of which worsen the disease over time. ACEIs or ARBs play a major role in reducing HF morbidity and mortality by blocking this abnormal activation

At the same time that the renin-angiotensin-aldosterone system is activated, the natriuretic peptide system is also activated, hence the elevated BNP and NT-pro BNP seen in heart failure. This compensatory mechanism leads to vasodilation, natriuresis, and diuresis. As a result, the natriuretic peptide system decreases blood pressure, lowers the sympathetic tone, and reduces aldosterone levels. The natriuretic peptide system functions antagonistically to the renin-angiotensin-aldosterone system and has favourable impact on heart failure. Natriuretic peptides are broken down by an enzyme called neprilysin.

Sacubitril/valsartan is a combination product. Sacubitril is a pro-drug that, upon activation, acts as a neprilysin inhibitor. So it works by blocking the action of neprilysin, thus preventing the breakdown of natriuretic peptides, which leads to a prolonged duration of the favourable effects of these peptides.

However, because neprilysin also breaks down angiotensin II, inhibiting neprilysin will accumulate angiotensin II. For this reason, a neprilysin inhibitor cannot be used alone; it must always be combined with an ARB to block the effect of the excess angiotensin II. This is why Valsartan is used.

Another important substance broken down by neprilysin is bradykinin; neprilysin inhibition will also cause a build-up of bradykinin. Therefore, sacubitril cannot be used with an ACEI due to an increased risk of angioedema if both these drugs are combines or given in a short timeframe. And this is why when switching between ACEI and sacubitril/valsartan, the patient must undergo a 36-hour washout period to lower the risk of angioedema.

We have come to the end of this video. I hope that you have found it useful and, if so, please hit the like and subscribe buttons. Thank you for watching and good-bye

My name is Fernando Florido and I am a GP in the United Kingdom. In this podcast I I give my summary of the online course by the EASD learning website “Cardiovascular health and diabetes”.

This podcast will be saved on a website.

There is also a YouTube video on this subject and other NICE guidance. You can access the channel here:

https://www.youtube.com/channel/UClrwFDI15W5uH3uRGuzoovw 

The online course can be found on the EASD learning website:

https://easd-elearning.org/courses/cardiovascular-health-and-diabetes/

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Transcript

Hello everyone and welcome to the channel. My name is Fernando Florido and I am a GP in the United Kingdom. Today we are going to talk about the link between cardiovascular health and diabetes. The information that I am going to give is based on an online course that is available on the EASD learning website. I highly recommend it and I will put the link to access this course in the episode description. It has seven modules and it is likely to take you between 5 and 7 hours to complete it, depending on how quickly you can process the information. Today’s episode is a summary of the course, which I hope that you will find useful.

 As ever, remember that there is a YouTube version of this episode and the link to the YouTube channel is also in the episode description.

People with type 2 diabetes have twice as many coronary heart disease and strokes as those without it. At first glance, you could think it was too much, but in reality, this is a significant improvement. Previous data indicated that the risk of cardiovascular disease increased by around four to six times. Thus, doubling the risk indicates a significant improvement. Blood pressure control and strict cholesterol treatment are now standard management. And as a result, there are far fewer atherosclerotic events that affect persons with type 2 diabetes. However, as a result, heart failure is now becoming more common.

According to research, people with type 1 diabetes have steadily experienced a decline in CVD, CV mortality, and CV hospitalisation. However, there is still a significant gap between those who have type 1 diabetes and those who do not.

The same research, however, revealed that those with type 2 diabetes had experienced a far bigger improvement, resulting in, at worst, a doubling of the risk of cardiovascular disease (CVD), hospitalisation for CVD, and cardiovascular mortality. And once more, this has been associated with intensive blood pressure and cholesterol management; perhaps this is something that might be applied to patients with type 1 diabetes, where the focus is still often on glycaemia-related issues.

According to other studies, people with type 2 diabetes have an increased chance of developing heart failure. This increased risk is most noticeable in the middle-aged group, perhaps those up to the age of 55, and it appears to be less of an issue as people get older. Therefore, heart failure is now one of the most significant CVD symptoms in persons with type 2 diabetes.

Atherosclerotic disease, coronary heart disease, or strokes are still the earliest signs of vascular illness in the non-diabetic population. However, peripheral vascular disease or heart failure are the most typical early presentations of vascular disease in persons with type 2 diabetes.

Heart failure in diabetics is caused by a number of different ways. First, excess atherosclerotic disease. Also, the heart's ability to operate can then be impacted by hypertension itself. Additionally, a lot of our patients are now recovering from myocardial infarctions, and as time passes, the ventricle develops scarring that exacerbates heart failure. Furthermore, apart from atherosclerosis and hypertension, there is a heart condition known as "diabetic cardiomyopathy" that damages the myocardium. The ventricle becomes extremely stiff due to a combination of metabolic and pathological causes, making it difficult for the ventricle to relax and fill. And finally, diabetic autonomic neuropathy also plays a role in the development of heart disease in patients with diabetes.

Variations in glycaemic control and chronic hyperglycaemia are recognised epidemiologically as risk factors for cardiovascular disease in people with diabetes.

There are now numerous things we can do for our patients with diabetes to lower cardiovascular risk, just as there are numerous risk factors for heart disease in those with diabetes. One factor we take into account is lifestyle, but studies have shown that this is a pretty unsatisfactory intervention when we focus on heart disease, frequently failing to show any benefit on lowering cardiovascular disease rates. However, we continue to believe that lifestyle intervention is crucial for some people.

After bariatric surgery, cardiovascular morbidity and death have been demonstrated to decrease in people with type 2 diabetes.

Controlling glycaemia, blood pressure, and cholesterol are crucial for patients with diabetes.

Numerous trials have examined glycaemic control in persons with type 1 and type 2 diabetes. The effects of intensive glycaemic control on microvascular and macrovascular complications were investigated in these trials.

In the DCCT study which looked at type 1 diabetes patients, strict glycaemic management resulted in a highly significant decrease in retinopathy and nephropathy. Although the initial decline in cardiovascular events was modest, subsequent studies revealed that, up to 30 years after the initial intense management, the persons who received intensive management saw a decline in cardiovascular disease, as well as total mortality. As a result, a relatively short time of intense control has long-lasting repercussions on the cardiovascular system. This phenomenon is known as the "legacy effect" or "metabolic memory."

The UKPDS trial showed that strict glycaemic control in the first 10 years from diagnosis resulted in significant decreases in retinopathy, nephropathy, and neuropathy in individuals with newly diagnosed type 2 diabetes. There was, however, a rise in serious hypoglycaemia as well. Following UKPDS for a further 10 years, that is, for a total of 20 years of follow-up, there was a highly significant reduction in myocardial infarctions and mortality even if the initial reduction in myocardial infarction was not statistically significant. Again, the initial 10-year period of strict management following diagnosis has been shown to have long-lasting effects in lowering cardiovascular disease.

In contrast, other studies that examined the intensive management of glycaemia in individuals with type 2 diabetes who had this condition for a while revealed either no benefit in terms of cardiovascular disease or an increase in mortality in the intensive treatment group as a result of individuals receiving large amounts of insulin, massive weight gain, and very frequent hypoglycaemia.

A meta-analysis of all type 2 diabetes research findings revealed a decline in coronary heart disease but no impact on overall mortality. In light of this, we can say that glycaemic control does not have a very potent effect when compared, for instance, to blood pressure or cholesterol.

In conclusion, it is best if rigorous glycaemic intervention occurs as soon as possible following diagnosis if we are to receive cardiovascular benefits from it. And once someone has had diabetes for ten years or longer, it is doubtful that treating their glycemia will result in any significant cardiovascular benefits. At least this is supported by the evidence from older anti-diabetic medications. Research results may vary with newer medications because more advanced diabetic treatments now show improved cardiovascular risk in addition to lowering blood pressure and producing weight loss.

We will now look at individual treatments and their effect on cardiovascular disease.

The data for metformin comes from the UKPDS, where a very small subset experienced further benefits in terms of lower rates of myocardial infarction, cardiovascular disease, and overall mortality.

Secondary outcome data for pioglitazone showed significant decreases in cardiovascular death, myocardial infarction, and stroke. However, there were also adverse effects such weight gain, fluid retention, and a rise in fractures. As a result, pioglitazone is not that frequently used.

DPP4Inhibitors have been the subject of numerous studies. Major adverse cardiovascular events, or MACE, which were the focus of all these investigations, were unaffected. These medications have a modest glycaemic impact and are not extremely powerful. Therefore, it is not that surprising that MACE have not been affected.

A surprise side effect of saxagliptin and a subgroup of individuals using alogliptin was a large rise in heart failure hospitalizations. In conclusion, we can state that DPP-4 inhibitors do not affect MACE and that some of them have increased hospitalisation for heart failure, even if this has not always been confirmed in the other trials.

SGLT-2 inhibitors have been investigated in numerous cardiovascular outcome trials.

Empagliflozin, canagliflozin, and dapagliflozin have all demonstrated a highly significant decrease in heart failure hospitalisation and a significant decrease in severe adverse cardiovascular events (MACE).

A meta-analysis of SGLT2 inhibitor studies was able to show that the SGLT-2 inhibitors significantly decreased subsequent MACE events for patients with atherosclerotic disease. A very substantial decrease in heart failure hospitalisation followed for patients with heart failure or had a high cardiovascular risk.

Although it has been noted that SGLT-2 inhibitors have a fairly early onset of benefit, the mechanism of benefit is yet unknown.

A number of cardiovascular outcome trials using GLP 1 agonists have demonstrated significant decreases in major adverse cardiovascular events, cardiovascular mortality, and overall mortality. However, there was no impact on heart failure hospitalisation.

 The GLP-1 receptor agonists' mechanism of action is equally unknown. However, it has been noted that the improvement appears to be gradual rather than abrupt, as was the case with SGLT-2 inhibitors. And it has been widely assumed that the advantages relate to a slowing down of atherosclerosis progression. Theoretically, combining SGLT-2 inhibitors with GLP-1 receptor agonists may result in additional cardiovascular benefits and this is also a new area of research.

 Several recommendations and consensus statements have recently taken into account the findings of the cardiovascular outcome trials using SGLT-2 inhibitors and GLP-1 receptor agonists. The joint ADA/EASD consensus statement is a good illustration of this. It advises that, after metformin, you thoroughly assess the patient's cardiovascular status and that, if the patient has heart failure, you should consider SGLT-2 inhibitors as the next therapy. Consider using either SGLT-2 inhibitors or a GLP-1 receptor agonist if the patient has atherosclerotic disease or is at high risk of it.

One of the most researched strategies to try and lower cardiovascular risk in patients with diabetes is lipid lowering, notably using statins. We can now confirm, thanks to a meta-analysis, that coronary disease, stroke, and coronary revascularization can all be reduced by up to 25% for every 1 mmol decrease in LDL cholesterol. The meta-analysis included participants with existing cardiovascular disease (or "secondary prevention") as well as those without known cardiovascular disease (or "primary prevention"). And both groups experienced a similar reduction of about 25%.

A second meta-analysis revealed that those with diabetes who took high-dose statins benefited even more.

Renal outcomes were the subject of a third meta-analysis. It was confirmed in this meta-analysis that patients with diabetes and chronic kidney disease, or CKD, also benefited from decreases in atherosclerotic events. Therefore, it appears that statins are a treatment that can lower cardiovascular events in diabetes at all stages, including CKD as well as primary and secondary prevention.

Other methods of lowering cholesterol have been less promising.

Only minimal improvements for patients with diabetes were seen in trials with ezetemibe and fibrates.

Trials using PCSK9-inhibitors, a different innovative family of lipid-lowering medications, have been more encouraging, showing a significant decrease in adverse cardiovascular events.

All of the individuals who participated in these lipid-lowering investigations were older than 40. Therefore, the data suggests that statins are beneficial for diabetic patients over the age of 40, regardless of the baseline risk. Therefore, recommendations state that, in diabetes, statins should be started as soon as you reach the age of 40, regardless of your baseline risk or cholesterol level. The extent to which this benefit is reduced for those who are younger remains unknown, and different guidelines take different approaches to this. In general, the guidelines try to identify younger subjects who have other cardiovascular risk markers, such as microalbuminuria, or perhaps other microvascular complications, such as retinopathy. According to some recommendations, statins should be started in the younger age group for those who have these comorbidities.

Patients with diabetes have been included in many blood pressure-lowering trials over the years because high pressure is a clear risk factor for the development of cardiovascular disease. The advantages of decreasing blood pressure in persons with diabetes have been highlighted by combining all of these research studies into one very thorough meta-analysis.

Lowering of blood pressure led to a decrease in total mortality, cardiovascular disease, coronary heart disease, and strokes. Lowering blood pressure also slowed the onset of heart failure. The meta-analysis also took a look at microvascular events and found that reducing blood pressure has definite advantages in the development of renal failure, retinopathy, and albuminuria. Therefore, there is no question that decreasing blood pressure is advantageous in diabetes in both large and small vessel disease.

Other meta-analyses have demonstrated that lowering blood pressure is more important than the antihypertensive medication used. Since ACE inhibitors and angiotensin receptor blockers appear to have a minor advantage over other blood pressure-lowering medications, most guidelines recommend using them as a first line of treatment in diabetes.

Although studies in the non-diabetic population have recommended lower BP targets, such as a systolic BP of 120 mmHg, different guidelines now come out with somewhat different targets due to a variation in the outcomes of the diabetic and non-diabetic research. The majority of guidelines advise starting blood pressure medication for those with diabetes if their readings are over 140/90, but after that, the objectives can range from 140/80 to 130/80 mmHg, with the lower target being set for those with higher cardiovascular risk.

Aspirin medication has been the subject of many meta-analyses looking at primary prevention in diabetes. There hasn't been any evidence of a clear benefit, and risks have been identified, including a rise in gastrointestinal bleeding and the risk of developing haemorrhagic stroke.

Again, trials and their subgroups have been interpreted slightly differently. And some guidelines now advise against using aspirin for primary prevention in anyone who has diabetes. However, other guidelines would suggest trying to identify group of subjects at a greater risk, maybe due to comorbidities like CKD, and use aspirin in those people. However, it should be highlighted that in those people, the risk of bleeding also tends to be higher.

Research studies on multiple risk factor interventions have also been conducted, examining the combined effects of lipid-lowering therapy, blood pressure-lowering therapy, and better glycaemic management.

Unsurprisingly, after four years of intervention, there was a 50% reduction in the risk for diabetic nephropathy, retinopathy, and neuropathy development. After eight years, there was a 50% relative risk decrease for coronary bypass procedures, myocardial infarction, strokes, amputations, and CVD death.

After a 13-year follow-up, there was a 50% relative risk decrease in the rate of mortality. And finally, a 21-year follow-up revealed that this early, multiple risk factor intervention in our patients increased their life expectancy by over eight years. As a result, we can conclude that using all of these treatments together has an even bigger impact.

The fact that all SGLT2 inhibitors regularly reduced the number of heart failure hospitalizations led researchers to wonder if they would also be able to treat heart failure in persons without diabetes. As a result, more studies investigating SGLT2 inhibitors in heart failure populations without diabetes were carried out.

The outcomes are remarkably reliable. There were significant decreases in total mortality as well as a decline in cardiovascular death and heart failure hospitalizations. So, it was shown that, whether you had diabetes or not, the benefit was proportionately the same.

Dapagliflozin currently has a licence in Europe for the treatment of heart failure in both diabetic and non-diabetic patients. As a result, we'll start to notice regular use of these medications in non-diabetic patients.

It's critical that the patient's primary care physician is aware of the rationale behind prescribing the SGLT2 inhibitor, including whether it is given for diabetes control, for the improvement of heart failure prognosis or, of course, the third indication, which is now giving it to patients with chronic kidney disease (CKD) to enhance their renal prognosis.

If we're going to begin treating people with heart failure with dapagliflozin, or any other SGLT2 inhibitor, it's crucial that we first fully characterise the patient. We must determine whether a patient has diabetes or not and, if so, what medications are being used to manage it. If a patient has low HbA1c levels, taking, for example, a sulphonylurea or insulin, and is then given an SGLT-2 inhibitor for heart failure prognosis, there is a risk that this will result in hypoglycaemia. In these patients, it would be necessary to lower the insulin dosage or perhaps even discontinue some forms of treatment. On the other end of the spectrum, introducing an SGLT-2 inhibitor to a patient with a very high HbA1c without lowering the HbA1c first, would potentially increase the risk of ketoacidosis. Therefore, communication between cardiologists and diabetologists will be crucial in this regard.

We have come to the end of this episode. I hope that you have enjoyed it and found it useful and I hope that you will join me in the next one. Thank you for listening and goodbye.

THIS GUIDELINE IS NOW OBSOLETE. PLEASE CHECK THE UPDATED 2024 ASTHMA GUIDELINE AVAILABLE ON THIS CHANNEL. YOU CAN FIND IT IN THE VIDEO DESCRIPTION, BY CLICKING THE LINK IN THE TOP-RIGHT CORNER OF THIS VIDEO, OR ON THE END SCREEN.

The asthma playlist including the 2024 asthma guideline can be found here:

https://youtube.com/playlist?list=PLkDRVxR2chuhrU7IiPYiFYj7Wu_h3PURb&si=DmdpArNj9anQa5qx

My name is Fernando Florido and I am a GP in the United Kingdom. With today’s episode I continue with the series on asthma, focusing on the NICE guidelines on the diagnosis and management asthma. Firstly, I am going to go through the diagnosis flow charts and I am going to do them over 3 different episodes. In today's episode, the third one, I consider the diagnostic tests for adults. In the first one I go through the initial clinical assessment for all patients and in the second one I go through the objective tests for children and young people. There will be other videos on the pharmacological treatment of asthma so make sure you subscribe and stay tuned.

There is YouTube version of the podcast and other guidance that you can access here: 

·      https://www.youtube.com/channel/UClrwFDI15W5uH3uRGuzoovw

The full NICE guideline on asthma can be found here:

·      Website:

https://www.nice.org.uk/guidance/ng80

·      Or download here:

https://1drv.ms/b/s!AiVFJ_Uoigq0lgCTpT8m-jvCCavu?e=z1Vs5z

The diagnostic flow chart “initial assessment” (Episode 1) can be

·      Viewed on website: https://www.nice.org.uk/guidance/ng80/resources/algorithm-a-initial-clinical-assessment-for-adults-young-people-and-children-with-suspected-asthma-pdf-4656176749

·      Or, if outside the UK, downloaded here:

o  Image: https://1drv.ms/u/s!AiVFJ_Uoigq0lXZgO7_Zad1zMIfX?e=cmzv91

o  PDF: https://1drv.ms/b/s!AiVFJ_Uoigq0lXWWt7TqIN0Cye1M?e=kL0i0p

The diagnostic flow chart “children and young people” (Episode 2) can be

·      Viewed on website: https://www.nice.org.uk/guidance/ng80/resources/algorithm-b-objective-tests-for-asthma-in-children-and-young-people-aged-5-to-16-pdf-4656176750

·      Or, if outside the UK, downloaded here:

o  Image: https://1drv.ms/u/s!AiVFJ_Uoigq0lXTL5o5XU2aOfChx?e=6qJk1M

o  PDF: 

https://1drv.ms/b/s!AiVFJ_Uoigq0lXlBBD1Wq7lak-mg?e=iLpgAX

The diagnostic flow chart “adults” (Episode 3) can be

·      Viewed on website: https://www.nice.org.uk/guidance/ng80/resources/algorithm-c-objective-tests-for-asthma-in-adults-aged-17-and-over-pdf-4656176751

·      Or, if outside the UK, downloaded here:

o  Image: https://1drv.ms/u/s!AiVFJ_Uoigq0lXgUR4QxwwxNNynL?e=OrBRwi

o  PDF: 

https://1drv.ms/b/s!AiVFJ_Uoigq0lXcaf4BUKI2k3TsR?e=tCn86P

Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release]

Music provided by Audio Library Plus

Watch: https://youtu.be/aBGk6aJM3IU

Free Download / Stream: https://alplus.io/halfway-through