All posts by James Hunt

Can a HIV drug help prevent dementia?

cleansing mechanism of the nuerons and HIV drug work to help prevent dementia
A common characteristic of neurodegenerative diseases such as Huntington’s disease and various forms of dementia is the build-up in the brain of clusters—known as aggregates—of misfolded proteins, such as huntingtin and tau. These aggregates lead to the degradation and eventual death of brain cells and the onset of symptoms.

One method that our bodies use to rid themselves of toxic materials is autophagy, or ‘self-eating,” a process whereby cells ‘eat’ the unwanted material, break it down and discard it. But this mechanism does not work properly in neurodegenerative diseases, meaning that the body is no longer able to get rid of the misfolded proteins.

In a study published today in Neuron, a team from the Cambridge Institute for Medical Research and the UK Dementia Research Institute at the University of Cambridge has identified a process that causes autophagy not to work properly in the brains of mouse models of Huntington’s disease and a form of dementia—and importantly, has identified a drug that helps restore this vital function.

The team carried out their research using mice that had been genetically-altered to develop forms of Huntington’s disease or a type of dementia characterized by the build-up of the tau protein.

Using mice, the team showed that in neurodegenerative diseases, microglia release a suite of molecules which in turn activate a switch on the surface of cells. When activated, this switch—called CCR5—impairs autophagy, and hence the ability of the brain to rid itself of the toxic proteins. These proteins then aggregate and begin to cause irreversible damage to the brain—and in fact, the toxic proteins also create a feedback loop, leading to increased activity of CCR5, enabling even faster build-up of the aggregates.

When the researchers used mice bred to ‘knock out’ the action of CCR5, they found that these mice were protected against the build-up of misfolded huntingtin and tau, leading to fewer of the toxic aggregates in the brain when compared to control mice.

This discovery has led to clues to how this build-up could in future be slowed or prevented in humans. The CCR5 switch is not just exploited by neurodegenerative diseases—it is also used by HIV as a ‘doorway’ into our cells.

The team used maraviroc to treat the Huntington’s disease mice, administering the drug for four weeks when the mice were two months old. When the researchers looked at the mice’s brains, they found a significant reduction in the number of huntingtin aggregates when compared to untreated mice.

The same effect was observed in the dementia mice. In these mice, not only did the drug reduce the amount of tau aggregates compared to untreated mice, but it also slowed down the loss of brain cells. The treated mice performed better than untreated mice at an object recognition test, suggesting that the drug slowed down memory loss.

Professor Rubinsztein added: “We’re very excited about these findings because we’ve not just found a new mechanism of how our microglia hasten neurodegeneration, we’ve also shown this can be interrupted, potentially even with an existing, safe treatment.”

“Maraviroc may not itself turn out to be the magic bullet, but it shows a possible way forward. During the development of this drug as a HIV treatment, there were a number of other candidates that failed along the way because they were not effective against HIV. We may find that one of these works effectively in humans to prevent neurodegenerative diseases.”

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Challenges of Treating Chronic Pain

Challenges of Treating Chronic Pain

Chronic pain is a complex and difficult condition to treat despite the progress in neuroscience research over the last two decades. A recent overview by Ferreira and colleagues has added to the growing body of evidence on the use of medicines for pain, highlighting the limitations of current medical treatments.

Assessment of Antidepressants for Chronic Pain

In recent guidance from the UK National Institute for Health and Care Excellence, only antidepressants were found to have a favorable balance of benefits and harms for chronic primary pain. However, Ferreira and colleagues found that the evidence for their effectiveness in a wider range of chronic pain conditions was limited, with only 11 of 42 comparisons showing some level of effectiveness, none of which was of high quality. This suggests that most people living with chronic pain are unlikely to experience significant relief from antidepressant treatment.

Alternative Options for Pain Management

Group exercise, led by qualified instructors, has been shown to be effective in managing pain symptoms and has many other health and well-being benefits. In addition, non-medical services such as mobility support, debt management, and social connection can be helpful for people living with pain. Social prescribing, which refers to linking people with appropriate local support, is a promising approach, but its effectiveness is still evolving.

The Importance of Personalized Care

A strong, empathetic relationship with a care provider is crucial for successful pain management. People living with pain value time to discuss their concerns and easy access to support, and personalizing care is crucial for successful pain management. Research has traditionally focused on measures like pain scales and physical function tests, but new research should aim to understand the broader experience of living with pain.

Public Involvement in Pain Research

Public involvement in health research is crucial to ensure that pain research is meaningful and relevant to those living with pain and their clinicians. Researchers must involve people living with pain in their studies and overcome the barriers to public involvement in health research. Building new partnerships between clinicians, people living with pain, and researchers is crucial to improve care and research for chronic pain.


Chronic pain is more than just a medical condition and the limitations of current medical treatments present an opportunity to change the way we think about pain and focus on the individual experience of living with it. All stakeholders must share the responsibility of building these new partnerships to improve care and research for chronic pain.



  1. Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews. BMJ 2023; 380 doi: (Published 01 February 2023).
  2. Chronic pain (primary and secondary) in over 16s: assessment of all chronic pain and management of chronic primary pain .NICE guideline [NG193].
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Sickle cell cure with LentiGlobin


Sickle cell disease is a genetic disorder that affects the hemoglobin in red blood cells. It is caused by a single point mutation in the gene encoding β-globin (HBB), leading to the production of sickle hemoglobin and impaired red-cell function. Patients with sickle cell disease often have vaso-occlusive events, progressive vasculopathy, and chronic hemolytic anemia. These are associated with complications and an increased risk of early death. Current supportive treatment options can only manage the disease without halting its progression.


Sickle cell disease is a debilitating condition that affects millions of people worldwide. Current supportive treatment options can only manage the disease without halting its progression. HLA-matched sibling allogeneic hematopoietic stem-cell transplantation is a potentially curative treatment option, but it is limited by the fact that only a small percentage of patients have HLA-matched donors, and there is a risk of graft-versus-host disease and graft rejection, as well as the risk of transplantation-related death. Gene therapies that use autologous stem cells may overcome these hurdles and are advancing into clinical trials.


LentiGlobin for sickle cell disease (bb1111; lovotibeglogene autotemcel, Bluebird Bio) consists of the autologous transplantation of hematopoietic stem and progenitor cells (HSPCs) transduced with the BB305 lentiviral vector encoding a modified β-globin gene. This results in the production of an antisickling hemoglobin, HbAT87Q. HbAT87Q is a modified adult hemoglobin with an amino acid substitution (threonine to glutamine at position 87) designed to sterically inhibit polymerization of sickle hemoglobin. In this ongoing phase 1-2 study, the researchers optimized the treatment process in the initial 7 patients in Group A and 2 patients in Group B with sickle cell disease. Group C was established for the pivotal evaluation of LentiGlobin for sickle cell disease, and a more stringent inclusion criterion was adopted that required a minimum of four severe vaso-occlusive events in the 24 months before enrollment.


In this unprespecified interim analysis, the researchers evaluated the safety and efficacy of LentiGlobin in 35 patients enrolled in Group C. Included in this analysis was the number of severe vaso-occlusive events after LentiGlobin infusion among patients with at least four vaso-occlusive events in the 24 months before enrollment and with at least 6 months of follow-up. As of February 2021, cell collection had been initiated in 43 patients in Group C; 35 received a LentiGlobin infusion, with a median follow-up of 17.3 months (range, 3.7 to 37.6). Engraftment occurred in all 35 patients. The median total hemoglobin level increased from 8.5 g per deciliter at baseline to 11 g or more per deciliter from 6 months through 36 months after infusion. HbAT87Q contributed at least 40% of total hemoglobin and was distributed across a mean (±SD) of 85±8% of red cells. Hemolysis markers were reduced. Among the 25 patients who could be evaluated, all had resolution of severe vaso-occlusive events, as compared with a median of 3.5 events per year (range, 2.0 to 13.5) in the 24 months before enrollment. Three patients had a nonserious adverse event related or possibly related to LentiGlobin that resolved within 1 week after onset. No cases of hematologic cancer were observed



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Exploring the Dangers and Promise of TikTok’s Viral #MentalHealth Videos on ADHD

The social media platform TikTok has seen a surge in the popularity of videos related to attention deficit hyperactivity disorder (ADHD) during the COVID-19 pandemic. The #ADHD channel on the platform now has 2.4 billion views and content related to the mental disorder has been shared by both individuals with no medical credentials and licensed psychiatrists and therapists. While some argue that TikTok can destigmatize mental disorders, foster community, and make research accessible to a wider audience, others caution that it can lead to self-diagnosis, overwhelm unqualified content creators with requests for help, and perpetuate misinformation about ADHD.

One of the benefits of ADHD content on TikTok is that it makes strategies for managing the disorder more accessible to those who may not have access to traditional mental health resources. Many creators on the platform share their personal experiences and research on ADHD, often without seeking financial compensation. Some licensed professionals, such as Dr. Edward Hallowell, a renowned ADHD psychiatrist, have also used the platform to provide advice and education on the disorder.

However, there are also risks associated with the proliferation of ADHD content on TikTok. Some content creators, who may have no formal training or qualifications in mental health, are being treated as experts on the disorder. This can lead to confusion and misunderstandings about ADHD, and may discourage individuals from seeking professional help. In addition, the platform’s algorithm can surface misleading or false information about ADHD, further perpetuating stigma and misinformation about the disorder.

Overall, it is important for individuals seeking information about ADHD to be cautious about the sources they rely on and to seek out qualified professionals for accurate information and support. While TikTok can be a useful resource for learning about ADHD and connecting with others who have the disorder, it should not be the sole source of information or treatment.

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Blood pressure variability: a new and unique risk factor

Blood pressure variability is a new and unique factor that is gaining more and more attention in the medical community. It refers to the fluctuation of blood pressure over time, and it can be caused by a variety of factors including stress, exercise, and even the time of day.

One important aspect of blood pressure variability is that it can be measured and tracked. This can be done through the use of a blood pressure monitor, which can be worn on the wrist or upper arm and measures blood pressure at regular intervals throughout the day. By tracking blood pressure variability, individuals and their healthcare providers can get a better understanding of their overall cardiovascular health and identify potential risk factors for conditions such as hypertension and heart disease.

Research has shown that blood pressure variability is a strong predictor of future cardiovascular events, such as heart attack and stroke. In fact, studies have shown that individuals with higher levels of blood pressure variability are at an increased risk for these types of events. For example, one study found that individuals with high blood pressure variability were 63% more likely to experience a stroke compared to those with low blood pressure variability (reference: “Blood Pressure Variability and Risk of Stroke: A Meta-Analysis”, Zhang et al., Stroke, 2012). Another study found that blood pressure variability was associated with a 2.5-fold increased risk of heart attack (reference: “Blood Pressure Variability and Risk of Myocardial Infarction: A Meta-Analysis”, Song et al., American Journal of Hypertension, 2014).

So what can be done to reduce blood pressure variability and the associated risks? One effective way is through lifestyle changes, such as eating a healthy diet, exercising regularly, and reducing stress. These changes can help to lower blood pressure and reduce fluctuations over time. In some cases, medication may also be necessary to manage blood pressure and reduce variability.

It is important to note that blood pressure variability is a complex and multifaceted issue, and further research is needed to fully understand its impacts on cardiovascular health. However, what is clear is that blood pressure variability is a unique and important factor that should be taken into consideration when evaluating an individual’s overall cardiovascular health. By tracking and managing blood pressure variability, individuals can take steps to improve their heart health and reduce their risk of future cardiovascular events.

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QRISK 3 – what’s new? a deeper look inside.

Qrisk logo

QRISK has been used in the general practice setting since 2007. It has been upgraded to QRISK 2. It is a 10 year cardiovascular risk tool. There is a proposal to upgrade to a newer version of the algorithm called QRISK 3. This has been outlined in a recent paper published by Julia Hippisley-Cox, professor of clinical epidemiology and general practice1,Carol Coupland, professor of medical statistics in primary care and Peter Brindle, evaluation and implementation theme lead, NIHR CLAHRC West. The paper was published in the 23rd May 2017 issue of the BMJ. BMJ 2017; 357 doi:

Currently QRISK 2 includes the ages of 25 to 84 and includes

  • Ethnicity
  • Deprivation (the Townsend score)
  • Systolic blood pressure
  • BMI
  • Total cholesterol/HDL ratio
  • Smoking
  • Family history of coronary artery disease in a first-degree relative aged less than 60
  • Type I diabetes
  • Type II diabetes
  • Treated hypertension
  • Rheumatoid arthritis
  • Atrial fibrillation
  • Chronic kidney disease (stage 4 or 5)

QRISK 3 will include the following additional factors:

  • Chronic kidney disease (stage 3, 4, or 5)
  • Systolic blood pressure variabilit
  • Migraine
  • Corticosteroid use
  • Systemic lupus erythematosus
  • Atypical psychotics
  • Severe mental illness,
  • Erectile dysfunction in men

Overall the calculator performed as the previous version. The new added risk factors were found to increase risk by about 10%, the only exception being HIV/AIDS.

You can use the new risk calculator here:


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2017/18 QOF update – Moderate to Severe Frailty

Electronic frailty index

The new 2017/18 Qof with the frailty index does away with the bureaucratic unplanned admissions direct enhanced service and replaces it with indentifying and managing the over 65s with moderate to severe frailty.

What is the electronic frailty index (eFI)?

The electronic Frailty Index (eFI), which has been developed by the  University of Leeds, TPP (System One), Bradford Teaching Hospitals NHS Foundation Trust, Bradford University and Birmingham University, is an evidence based criteria for identifying frail patients.

It is based upon 36 deficits comprising 2000 Read codes . The score is strongly predictive of adverse outcomes and has been validated in large international studies.

The eFI score is out of 36. For example if 9 deficits are present then the socre will be (9/36) or 0.25. In this way the following frailty categories can be defined:

eFI Score Category
0 – 0.12 Fit
0.13 – 0.24 Mild Frailty
0.25 – 0.36 Moderate Frailty
> 0.36 Severe Frailty
1. Fit (eFI score 0-0.12)– People who have no or few long-term conditions that are usually well controlled. This group would mainly be independent in day to day living activities.
2. Mild frailty (eFI score 0.13 –0.24) – People who are slowing up in older age and may need help with personal activities of daily living such as finances,shopping, transportation.
3. Moderate Frailty (eFI score 0.25 –0.36)–People who have difficulties with outdoor activities and may have mobility problems or require help withactivites such as washing and dressing.
4. Severe Frailty (eFI score > 0.36) – People who are often dependent for personal cares and have a range of long – term conditions/multimorbidity. Some of this group may be medically stable but others can be unstable and at risk of dying within 6 – 12 months.
How to get the eFI score and the list of moderately and severely frail patients?
This should be built in to your electronic care record system already (EMIS and System One). Running the search will produce a list of your moderately and severely frail patients.
What your practice needs to do:

For those patients identified as living with severe frailty, practices should provide a clinical review, which should include an annual medication review and, where appropriate, discuss whether the patient has fallen in the last 12 months. Any other clinically-relevant intervention should also be provided. In addition, where a patient does not already have an enriched Summary Care Record (SCR) the practice will promote this seeking informed patient consent to activate the enriched SCR.

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Why GP Tools will never upsell.

Wikipedia defines Upselling as a sales technique whereby a seller induces the customer to purchase more expensive items, upgrades or other add-ons in an attempt to make a more profitable sale.

We believe that the whole revalidation industry that has sprouted out of nowhere is at its core built on upselling. If it were up us at GP Tools, we would provide this toolkit completely free to our users. Unfortunately, in the post-truth world that we live in, offering something for free implies a catch somewhere down the road or some other negative connotation.

Which is why we are not surprised when we receive emails from Doctors’ who have been somehow manaevred into buying unnecessary add-ons from other toolkit providers.

Our company ethos at it’s most basic level prevents us from engaging in predatory business practices such as upselling. Nowhere on the site will you ever be bombarded with messages forcing you to take out a learning module subscription, nor will we ever email you anything similar.

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Revalidation update – requirements relaxed

Due to guidance from the GMC and the revalidation survey carried out this year which is finally coming to a conclusion, the vast majority of Royal College’s have updated the requirements for revalidation. Because of the underlying tone of revalidation being seen as an onerous activity detracting from patient care, the criteria have been relaxed. It seems that most UK doctors are unaware of these updated points and in fact talking to appraiser’s regularly it seems that they are as well.

For GPs, the RCGP has published a very useful document called RCGP Revalidation Mythbusters , in which the following key changes are worth mentioning. It should be pointed out that the revalidation requirements have been considerably downgraded after feedback from the GMC and RCGP revalidation survey.

Current revalidation myths, in order of importance (these are all FALSE).

  • I have to use a portfolio defined by my responsible officer to revalidate.

The RO has no mandate to force upon doctors any particular toolkit. If your RO or local appraisal team is bullying or coercing you into using a particular legacy commercial toolkit then you are within your rights to make a formal complaint about the RO to the national revalidaiton support team at:

[email protected]

  • I can’t claim credits for impact now.

You can now claim as many credits for subsequent hours of work that you think have made an impact. e.g. if doing a search and implementing protocols took you 3 hours then 3 credits can be claimed regardless of how much time the initial learning activity took.

  • I have to include two significant events every year.

No longer a requirement. Events that caused no harm to patients should be documented under an alternatvie category.

  • I have to do at least one clinical audit in the five year cycle.

Transformed into QIAs, case reviews, patient journeys, reflection on how to improve patient care, and how you are providing patient care.

  • My appraisal portfolio is entirely confidential.

Unfortunately this is not the case, and a recent court case demonstrated that your appraisal reflections can be used against you if a complaint has been taken to court.  Trainee’s portfolio ‘used as evidence against them’ in legal case.

  • I need to scan certificates to provide supporting information about my CPD. This is not a GMC requirement, but you know how GP Tools makes it easy for you if you want to.
  • I have to write a separate reflective note for every hour of CPD I do.  One reflective note for each activity even if it lasts all day.
  • I can choose my designated body / where to have my appraisal.
  • Appraisal is the main way to identify concerns about doctors.
  • Appraisal is a pass/fail event.
  • My appraiser will decide about my revalidation recommendation.
  • I need to undertake a minimum number of GP sessions to revalidate as a GP
  • I have to document all my learning activities. Put down the highest quality one’s to get to 50 hrs of learning.
  • It is reasonable to spend a long time getting the supporting information together for my appraisal. You should not spend more than 3.5 to 4 hours gathering this information. In fairness, this should not take any time if you have been using GP Tools regularly.
  • I only need to provide all six types of GMC supporting information about my clinical role.
  • All my supporting information has to apply to work in the NHS.
  • Supporting information from work overseas cannot be included in my appraisal portfolio.
  • Documented reflection has to be longwinded. It should be brief and to the point.
  • Reflection is difficult. How they describe reflection now as thinking critically about what we do does make it seem easier.
  • Only courses and conferences count as CPD. GP Tools has made it clear that this is not the case.
  • I have to do an equal amount of CPD every year despite different circumstances.
  • As a part-time GP, I only need to do part-time CPD.
  • My CPD for each part of my scope of work has to be different.
  • My supporting information from part of my scope of work already discussed elsewhere has to be presented again at my medical appraisal for revalidation.
  • The GMC requires GPs to complete Basic Life Support and Safeguarding Level 3 training annually in order to revalidate successfully.
  • I cannot claim any credits for a learning activity if I do not learn anything new.
  • My appraiser will be impressed by my hundreds of credit. Some of them are born not be impressed!
  • I have to do 50 credits of CPD every year. Well, to keep the RO of your back, probably best to comply with this on an average of 50/year.
  • I need 50 credits of clinical CPD every year. Across your whole scope of work.
  • I have to demonstrate 50 credits each year even if I have not been able to practise for much of the time. Exceptional circumstatnces may be invoked.
  • I can stop learning and reflecting once I have reached 50 credits of CPD.
  • Time spent on Quality Improvement Activities (QIA) is not CPD. Again,  GP Tools has always made it clear that this is not the case.
  • I have to do all of my Quality Improvement Activity (QIA) myself.
  • There are specific types of Quality Improvement Activities (QIA) that I must include. You do not have to include any specific type of quality improvement activity but you must reflect on the quality of your practice and how you meet the requirements of Good Medical Practice (GMP).
  • GMC Significant Events are the same as GP significant events. Events that do not cause harm to the patient are not the same as GMC SEAs.
  • I have to use the GMC questionnaire for my patient and colleague feedback.  The main patient survey from your clinical work and the main colleague survey from your  clinical work, normally undertaken once every five years,  should be fully GMC compliant, but other feedback need not be.
  • All my patient and colleague feedback has to meet the GMC requirements.
  • I have to do a patient survey every year.
  • I have to find other ways to get feedback from patients every year.
  • My Personal Development Plan (PDP) must include…
  • My Personal Development Plan (PDP) cannot include…
  • I have to have 3/4/5 Personal Development Plan (PDP) goals (or I have to have 3/4/5 clinical PDP goals).


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