GP Tools Blog

A substantial cohort study suggests that for adults who cannot or do not prefer regular exercise, engaging in short bursts of vigorous activity, as simple as climbing a flight of stairs, may still significantly reduce their risk of cancer. The study, led by Dr. Emmanuel Stamatakis and his team from the University of Sydney in Australia, found that even as little as 1 minute of vigorous intermittent lifestyle physical activity (VILPA) per day, totaling 4.5 minutes weekly, was associated with a 20% decrease in the overall risk of cancer.

The researchers also observed a 31% reduction in the risk of physical activity-related cancer, which includes cancer types known to be possibly linked to low levels of physical activity. These findings were published in JAMA Oncology.

The potential impact of VILPA on cancer prevention is promising, particularly for individuals who cannot or lack motivation to exercise during leisure time. The study’s authors advocate for further exploration through long-term trials with cancer-related biomarkers and well-designed cohort studies using wearable devices to better understand VILPA’s potential as a cancer prevention intervention for non-exercisers and those who find traditional exercise unappealing.

Interestingly, the researchers found that even a “minimal dose” of VILPA, equivalent to 3.4 minutes of vigorous activity per day, was associated with a 17% reduced risk of total cancer incidence. Likewise, 3.7 minutes of daily vigorous activity was linked to a 28% decreased risk of physical activity-related cancer incidence.

An editorial accompanying the study emphasizes that physical activity can have additional benefits, such as improving physical fitness, muscle strength, fatigue related to cancer, and overall quality of life for cancer survivors. However, more research is needed to determine if the results can be applied to cancer patients specifically.

The study involved 22,398 adults from the U.K. Biobank accelerometry subsample, with participants who reported no leisure time exercise and engaged in one or fewer recreational walks per week. Vigorous intermittent lifestyle physical activity was defined as short bursts of intense physical activity, like fast walking or stair climbing, and was measured using wearable trackers, such as wrist-worn accelerometers.

The participants were followed for an average of 6.7 years, during which 2,356 new cancer events were reported, including 1,084 cases related to physical activity. The analyses were adjusted for various factors such as age, sex, body mass index, education level, smoking status, alcohol consumption, sleep duration, fruit and vegetable consumption, medications, parental cancer history, cardiovascular disease, daily durations of light- and moderate-intensity physical activity, and daily duration of longer vigorous exercise bouts.

The study highlights the importance of incorporating even sporadic episodes of brief, vigorous physical activity into daily life as it positively impacts health and helps reduce the risk of disease. Ultimately, any form of physical activity is beneficial, and the key is to establish exercise as a regular habit for overall well-being.

The Competition and Markets Authority (CMA) has called for an indepth inquiry into the EMIS Health PLC acquistion by United Health Group (UNH) Inc.

The reasons cited are:

• The combined market share of UNH and EMIS in the supply of healthcare IT systems to GPs in the UK.
• The potential for the merger to lead to higher prices or reduced innovation in the market.
• The potential for the merger to make it more difficult for new entrants to compete in the market.

These are valid concerns and we agree with them.

However, there is an unmitigated disaster looming on the horizon if the acquisition goes ahead for all individuals who have their data stored with EMIS health.

To say it in simple terms it is that the largest health insurance provider on the planet will have potential access to all EMIS patient data.

What can they do with that data, and why does it matter? Currently, for the most part the NHS is the provider for health services in the UK, in the future this might change-, with the government and bureaucracy intending to follow the Australian mode of health insurance.

This is then where things become ugly, and several conflicts of interest arise: (UNH means UnitedHealth Group or its subsidiaries)

1. Access to Sensitive Information: UNH may have access to detailed medical records of patients, which could potentially influence their decisions regarding coverage, claims, or treatment options. This raises concerns about the privacy and security of patients’ personal health information.
2. Denial of Claims: UNH may have a financial incentive to deny or restrict coverage based on the information obtained from EMIS. They could use this information to argue that certain medical conditions were pre-existing or that specific treatments are not medically necessary.
3. Premium Setting: The ownership of EMIS could provide UNH with insights into patients’ health profiles. This information could potentially be used to set premiums or adjust coverage options based on individuals’ health risks, which may not align with fair and equitable pricing practices.
4. Provider Selection Bias: UNH might be inclined to steer patients toward healthcare providers or facilities associated with EMIS or UNH, even if there are better options available elsewhere. This could limit patients’ choices and potentially compromise the quality of care.
5. Data Monopolization: If UNH has exclusive ownership or control over EMIS, it could create a monopoly or dominant position in the market. This can hinder competition and limit patients’ access to alternative healthcare data management services.
6. Ethical Dilemmas: UNH might face ethical challenges when it comes to managing and safeguarding patients’ data. Conflicting interests could arise between prioritizing profit margins and ensuring the privacy, security, and appropriate use of medical records.
7. Patient Consent and Control: Patients may have concerns about who has access to their medical records, how the data is used, and whether they have given informed consent for their records to be shared between UNH and EMIS. Lack of transparency or control over their own data can erode patient trust.

It is important that the inquiry is widened to incorporate these concerns and in our opinion the acquisition should be blocked.

The CMA has proven that it is an independent body relying on evidence and working for the public good cf. Activision and Microsoft merger was blocked.

References:

1. UnitedHealth Group / EMIS merger inquiry – GOV.UK: https://www.gov.uk/cma-cases/unitedhealth-group-slash-emis-merger-inquiry
2. CMA provisionally finds UnitedHealth Emis tie-up could reduce competition – Digital Health: https://www.digitalhealth.net/2023/03/cma-provisionally-finds-unitedhealth-emis-tie-up-could-reduce-competition/
3. UnitedHealth Deal Questioned by DOJ on Risk of Data Misuse: https://www.bloomberg.com/news/articles/2022-08-10/unitedhealth-internal-audit-shows-data-misuse-risks-doj-says

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.”

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

References:

1. Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews. BMJ 2023; 380 doi: https://doi.org/10.1136/bmj-2022-072415 (Published 01 February 2023).  https://www.bmj.com/content/380/bmj-2022-072415
2. Chronic pain (primary and secondary) in over 16s: assessment of all chronic pain and management of chronic primary pain .NICE guideline [NG193]. https://www.nice.org.uk/guidance/NG193

Introduction

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.

Background

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.

Methods

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.

Results

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

References

https://www.nejm.org/doi/full/10.1056/NEJMoa2117175

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.

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.

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.