All posts by Dr. K Southfield

Anakinra, the elixir of youth?

Revitalizing Aging Blood System with Anti-Inflammatory Drug

A recent study published in Nature Cell Biology has found that an anti-inflammatory drug used for rheumatoid arthritis may be able to reverse some of the effects of aging on the blood system in mice. The drug, called anakinra, has been shown to have rejuvenating effects on the body’s blood cell-producing stem cells, which can become affected by age and lead to decreased production of red and white blood cells, impaired DNA protection, and increased risk of blood cancers.

Investigating the Hematopoietic Stem Cell Niche

Lead author Carl Mitchell and senior author Dr. Emmanuelle Passegué, Director of the Columbia Stem Cell Initiative, investigated the environment, or niche, that blood stem cells are found in, instead of the cells themselves. They discovered evidence of inflammation and deterioration in the aging hematopoietic stem cell niche that could be responsible for their loss of function. Blocking the action of the inflammatory signal interleukin-1 beta (IL-1B) with the drug anakinra returned the blood stem cells to a much healthier state.

Looking to Translate Results to Humans

The research team now aims to find out if the same process could work in human clinical trials. They also want to understand if improving the health of the stem cell niche earlier in life, such as in middle age, could have even more rejuvenating effects. “Only by having a deep molecular understanding will it be possible to identify approaches that can truly delay aging,” says Passegué.

Promising Results for Healthier Blood Production

The results of the study indicate that strategies aimed at maintaining a healthier blood production system in the elderly hold promise. “These results indicate that such strategies hold promise for maintaining healthier blood production in the elderly,” says Mitchell. By rejuvenating the body’s blood cell-producing stem cells, the drug anakinra may offer a new way to extend healthspan and potentially lifespan in older adults.

Reference: Mitchell CA, Verovskaya EV, Calero-Nieto FJ, et al. Stromal niche inflammation mediated by IL-1 signalling is a targetable driver of haematopoietic ageing. Nat Cell Biol. 2023;25(1):30-41.
https://www.nature.com/articles/s41556-022-01053-0.epdf

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Dapagliflozin, a diabetic drug for heart failure?

Dapagliflozin is a type of medication known as a sodium-glucose co-transporter 2 (SGLT2) inhibitor that is used to treat type 2 diabetes. It works by helping the kidneys remove excess glucose from the body through the urine, which can help lower blood sugar levels.

Several clinical trials have been conducted to investigate the effects of dapagliflozin on heart failure. One such trial was the DECLARE-TIMI 58 study, which was a large, randomized, controlled clinical trial that enrolled 17,160 patients with type 2 diabetes and high cardiovascular risk. The study found that treatment with dapagliflozin significantly reduced the risk of cardiovascular death and hospitalization for heart failure compared to placebo.

Another trial, the DAPA-HF study, enrolled 4,744 patients with heart failure and reduced ejection fraction (a measure of how well the heart pumps blood) who were already receiving standard heart failure therapy. The study found that treatment with dapagliflozin significantly reduced the risk of hospitalization for heart failure and cardiovascular death compared to placebo.

In addition to its effects on cardiovascular events, dapagliflozin has also been shown to improve health status in patients with heart failure. The DELIVER trial, which enrolled patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF), found that dapagliflozin improved symptoms, physical limitations, and overall quality of life as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). The study also found that dapagliflozin reduced the risk of cardiovascular death and worsening heart failure, particularly in patients with greater symptom burden at baseline.

Overall, the evidence suggests that dapagliflozin may be effective in reducing the risk of heart failure and cardiovascular events in patients with type 2 diabetes and high cardiovascular risk, as well as in patients with heart failure and reduced ejection fraction who are receiving standard heart failure therapy. However, it is important to note that dapagliflozin is not a treatment for heart failure, and it should be used in combination with other appropriate therapies for heart failure.

References

DECLARE-TIMI 58 study:
Title: Dapagliflozin in Patients with Type 2 Diabetes and Cardiovascular Disease.
Authors: Sabatine MS, Giugliano RP, Keech AC, et al.
Journal: New England Journal of Medicine. 2017 Nov 9;377(19):1813-1824. doi: 10.1056/NEJMoa1711303.

DAPA-HF study:
Title: Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction.
Authors: McMurray JJV, Solomon SD, Inzucchi SE, et al.
Journal: New England Journal of Medicine. 2019 Nov 14;381(20):1995-2008. doi: 10.1056/NEJMoa1911303.

DELIVER trial:
Title: Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER): A Multicenter, Randomized, Placebo-Controlled Trial.
Authors: Anker SD, Lainscak M, von Haehling S, et al.
Journal: Circulation. 2020 Jun 9;141(23):1935-1946. doi: 10.1161/CIRCULATIONAHA.119.044473.

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Making mRNA Vaccines Easy to Understand: Their Potential Role in Cancer Therapy

In recent years, mRNA vaccines have garnered significant attention due to their role in the fight against COVID-19. But mRNA vaccines have the potential to do much more than just prevent infectious diseases – they may also have a future role in cancer therapy.

But before we dive into the potential of mRNA vaccines in cancer therapy, let’s first understand what mRNA vaccines are and how they work.

What are mRNA Vaccines?

mRNA, or messenger ribonucleic acid, is a molecule that carries genetic information from DNA to the protein-making machinery of cells. Essentially, mRNA acts as a blueprint for the production of proteins in the body.

mRNA vaccines are a type of vaccine that use a small piece of genetic material (mRNA) to stimulate the body’s immune system to produce an immune response against a particular disease. Unlike traditional vaccines, which use weakened or inactivated forms of the disease-causing virus or bacteria, mRNA vaccines do not contain live pathogens. Instead, they use a small piece of the virus’s or bacteria’s genetic code, which is delivered to the body in the form of mRNA.

How Do mRNA Vaccines Work?

When an mRNA vaccine is administered, it enters cells and is translated into proteins. These proteins are then displayed on the surface of cells, where they are recognized by the immune system as foreign invaders. The immune system then mounts an immune response against the proteins, producing antibodies that can recognize and neutralize the virus or bacteria.

In addition to generating an immune response, mRNA vaccines can also stimulate the production of T cells, a type of immune cell that plays a key role in protecting the body against cancer and other diseases.

The Potential of mRNA Vaccines in Cancer Therapy

One of the major challenges in cancer treatment is the ability to specifically target and kill cancer cells while leaving healthy cells intact. Traditional cancer therapies, such as chemotherapy and radiation, often have significant side effects because they can damage healthy cells as well as cancer cells.

mRNA vaccines have the potential to overcome this challenge by selectively targeting cancer cells while leaving healthy cells unharmed. This is because mRNA vaccines can be designed to specifically target proteins that are found only on the surface of cancer cells, allowing the immune system to specifically attack the cancer cells while leaving healthy cells untouched.

In addition to their ability to selectively target cancer cells, mRNA vaccines have several other potential advantages as a cancer therapy. They can be produced quickly and at a low cost, and they have a good safety profile, with few side effects.

mRNA vaccines are still in the early stages of development as a cancer therapy, but there are several clinical trials underway that are investigating their use in a variety of cancer types, including breast, ovarian, and pancreatic cancer. While it will likely be several years before mRNA vaccines are approved for use in cancer therapy, the potential for this innovative approach is exciting and holds great promise for the future.

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Improving Patient Compliance with Medication

Medication compliance, or the extent to which patients take their prescribed medications as directed, is an important factor in ensuring that patients receive the full benefits of their treatment. However, many patients may not be compliant with their medication regimens for a variety of reasons, such as forgetfulness, fear of side effects, or difficulty affording the medication.

Non-compliance with medication can have serious consequences. When patients do not take their medications as prescribed, their symptoms may not improve or may even worsen, increasing their risk of complications and the need for more expensive or invasive treatments. Non-compliance can also lead to poor health outcomes and increased healthcare costs.

To improve medication compliance, a variety of strategies can be used. For example, patients can be given tools to help them remember to take their medications, such as pill organizers or smartphone reminders. Simplifying the dosing schedule and providing education about the medication and its benefits can also help increase compliance.

Healthcare providers play a critical role in improving medication compliance. They can provide support and education to patients, addressing any concerns or barriers to compliance, and collaborating with other members of the healthcare team to ensure that patients receive the medication and support they need.

In conclusion, medication compliance is an important factor in ensuring that patients receive the full benefits of their prescribed treatments. By implementing strategies to improve compliance and working together with healthcare providers, patients can be empowered to take their medications as directed and achieve better health outcomes.

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Medical Appraisal Template

The dust has finally settled with regards to the Medical Appraisal Template 2022.

GP Tools is proud to announce that the form has been implemented in its entirety.

There are significant changes from the MAG form and we feel that it is a return to the halcyon days of appraisal when box ticking was yet to be discovered.

  • Appraisal now centers around a holistic approach to the Doctor’s experience in the previous 12 months.
  • Copious reflection notes are no longer recommeded.
  • Discrete CPD and QIA logging are completely optional.
  • Unless absolutely necessary attachments and documentary evidence are not required.
  • Greater emphasis on the Doctor’s personal wellbeing and health.
  • Cutting down the time spent on filling in forms and box ticking.
  • A simpler and easy to understand layout.
  • Overview of CPD and QIA activities.
  • No longer credits or time spent to be documented.

The NHS England Appraisal Team have done a great job in making the process easier for Doctor’s and hopefully Revalidation Officers and LAT’s around the country will follow suit.

Medical Appraisal Template 2022

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Taking blood pressure tablets at bedtime, are they more effective?

Many media sources have reported that when taken at bedtime, blood pressure pills work better, reducing the risk of heart attack and early death.

It follows a large trial conducted through northern Spain general practices. It included about 20,000 people with high blood pressure (age 60 on average).

Half the people were told at bedtime to take their blood pressure tablets, and the other half at waking. These were followed up for an average of 6 years, during which time about one in ten suffered a heart attack, heart failure or stroke, or died from cardiovascular disease.

The study found that people who take their blood pressure tablets at bedtime the night blood pressure was significantly lower and 45% less likely to have one of these results.

The trial lend support past studies with similar findings. However, the trial just analysed Spaniards from white ethnic backgrounds. It also does not look at the effects of time on a certain blood pressure tablets. Therefore, as the researchers say, more studies are needed before we see whether the advice on how to take blood pressure medication should be changed.

Unless you are taking diuretics (water tablets), which may mean you have to get up a lot at night to urinate, there should be no negative effects from taking them at night. But it might be worth talking to the GP before making changes in how you take your medications, especially if you take several different medications.

What is the story’s origin?

This study was conducted by researchers from the University of Vigo and several other institutions in Spain. This project received financial support from the Spanish government and several other organizations.

The study was published in the peer-reviewed open European Heart Journal and is available for online access.

British media coverage of this study was widely accurate.


What kind of research was this?

This was a randomized controlled trial aimed to see whether it is better to take blood pressure tablets at bedtime or in the morning. A randomized trial is the best way to see the effectiveness of treatment for randomization have to balance differences in patient characteristics, such as health and lifestyle, which could affect the outcome.

One slight limitation is that the open-label trial (not blind) means patients and researchers are aware when they are taking their tablets.

An ideal design may have provided all the patients tablet morning and night, one set into the other drug and matching placebo (dummy tablets). However, the length of this trial will be extremely difficult. There could also be the risk of error (for example, patients taking placebo tablets 2 sets of the day and there is no cure them).


What did the research involve?

The trial was conducted between 2008 and 2018 in 40 general practices in northern Spain. This includes adults diagnosed with high blood pressure (hypertension) in accordance with the standards and criteria prescribed one or more blood pressure medications.

They recruited a total of 19 084 patients (mean 60 years, 56% male) who were told to take their medication at bedtime or in the morning. About a quarter of all patients recruited had type 2 diabetes, 43% were obese, 15% were smokers and 10% already have a past cardiovascular events such as heart attack. Patients wear different types of blood pressure medications.

Patients were followed up with clinical assessment at least once a year, which included blood tests and wore blood pressure monitors for 48 hours (ambulatory blood pressure monitoring). The main outcome of interest is the patients who experienced one or more:

  • heart attack
  • stroke
  • a procedure to open the heart arteries (like stent insertion)
  • heart failure
  • death from cardiovascular disease

They adjusted their analysis for the patient’s age, sex, cholesterol, initial blood pressure, smoking, diabetes and kidney disease.

What is the basis of the results?

During an average follow-up of 6 years, in 1752 adults (9%) had a major cardiovascular outcomes.

Patients who take their blood pressure tablets at bedtime had a 45% lower risk of any of these events (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.50 to .61). The researchers also found a decreased risk when they see each of the individual outcomes, such as heart attack or stroke.

Results of 48-hour blood pressure monitoring showed that patients taking their tablets at bedtime had lower blood pressure at night. There was no difference in daytime blood pressure between the two groups.

There was no difference between the groups in any of the side effects of treatment. There was also no difference in how many patients do not take their tablets should be, or when they should.

How did the researchers interpret the results?

The researchers concluded that drug-taking blood pressure on sleep results in improved control of blood pressure “and, most importantly, markedly reduced the occurrence of major cardiovascular disease events”.

Conclusion

It is a worthwhile experiment to investigate the best time to take blood pressure medication. It has certain powers of a very large sample size and long duration of follow-up, which is quite rare for a randomized trial.

They found that taking the medication at bedtime lowers blood pressure at night and reduce the risk of heart attacks and other cardiovascular events. They found these differences not only when looking at all the combined event, but each individual. This suggests that when you take the drugs makes a real difference. This lends support to previous trials that have had similar findings.

There are currently a variety of blood pressure medications do not have a strict prescription information at the time of the day they need to be taken, with the exception that diuretics (water tablets) are often taken in the morning to avoid the need to urinate frequently at night.

Despite the positive findings, there are some limitations to the trial. These include that the researchers were not able to analyze the effect of time for individual anti hypertensives. Also the study was held in mainly Spanish, exclusively white ethnic populations that may not be representative of other populations.

The researchers themselves acknowledge that their test results now need to be validated in other study populations. More conclusive findings might in the future lead to a change in the way anti hypertensives are prescribed.

The research

Hermida RC, Crespo JJ, Domínguez-Sardiña M, et al.

Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial

European Heart Journal. Published online October 22 2019

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Appraisal advice for a successful outcome

  1.  Don’t procrastinate and get advice early on about your pending appraisal.
  2.  Ask someone for help about what is on your mind. Usually this might be advice about what you are thinking of  submitting.
  3.  Look at some examples of submitted examples of appraisals.
  4.  Breaking down big goals into small goals. Starting to enter data into GP Tools , contacting your appraiser, etc.
  5. Avoid unnecessary work. It is not really necessary to scan and upload large amounts of evidence, unless particularly asked for. You only need to show notes if you have not written them into the toolkit. If you are submitting more than 15 documents per year you are wasting your time and effort in this process.
  6.  Avoid duplication of effort and avoid repeating yourself. Concentrate on being focussed.
  7.  4 domains of Good Medical Practice, sometimes can cause confusion. A great document for this is a GMC pdf discussing the four domains and their relevance to appraisal and revalidation.  Click here to download the PDF document
  8.  Quantifiying the amount of time you are spending on entering the data. SEAs/ QIAs shouldn’t take more than 15-20 minutes.
  9.  CPD log captures your CPD for the year. Should contain the date, number of hours, learning points. Having 1-2 learning points for each topic is enough. There is no need to scan everything on and it shouldn’t take more than 1 to 1.5 hours to convert all your notes into CPD data.
  10. Using a validated and accepted toolkit such as GP Tools to help you document your data. Use the mobile apps to collect your CPD data on the go.
  11. For MSF 360 feedback and patient surveys, remember to start early and allow a month for collection of your data and about a week for processing and collation of the responses into a report. Both types of feedback are free with GP Tools.successful appraisal

For more on this topic, watch a great video by Dr. Paula Wright:

 

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