An unusual case of a Long Covid patient’s legs turning blue after 10 minutes of standing highlights the need for greater awareness of this symptom among people with the condition, according to new research published in theLancet.
The paper, authored by Dr Manoj Sivan at the University of Leeds, focuses on the case of one 33-year man who developed with acrocyanosis – venous pooling of blood in the legs.
A minute after standing, the patient’s legs began to redden and became increasingly blue over time, with veins becoming more prominent. After 10 minutes the colour was much more pronounced, with the patient describing a heavy, itchy sensation in his legs. His original colour returned two minutes after he returned to a non-standing position.
The patient said he had started to experience the discolouration since his COVID-19 infection. He was diagnosed with postural orthostatic tachycardia syndrome (POTS), a condition that causes an abnormal increase in heart rate on standing.
Dr Sivan, Associate Clinical Professor and Honorary Consultant in Rehabilitation Medicine in the University of Leeds’ School of Medicine, said: “This was a striking case of acrocyanosis in a patient who had not experienced it before his COVID-19 infection.
“Patients experiencing this may not be aware that it can be a symptom of Long Covid and dysautonomia and may feel concerned about what they are seeing. Similarly, clinicians may not be aware of the link between acrocyanosis and Long Covid.
“We need to ensure that there is more awareness of dysautonomia in Long Covid so that clinicians have the tools they need to manage patients appropriately.”
Long Covid affects multiple systems in the body and has an array of symptoms, affecting patients’ ability to perform daily activities. The condition also affects the autonomic nervous system, which is responsible for regulating blood pressure and heart rate.
Acrocyanosis has previously been observed in children with dysfunction of the autonomic nervous system (dysautonomia), a common symptom of post-viral syndromes.
Previous research by Dr Sivan’s team has shown that both dysautonomia and POTS frequently develop in people with Long Covid.
Dysautonomia is also seen in a number of other long-term conditions such as Fibromyalgia and Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome or ME.
Dr Sivan said: “We need more awareness about dysautonomia in long term conditions; more effective assessment and management approaches, and further research into the syndrome. This will enable both patients and clinicians to better manage these conditions.”
The research is the latest work by the team in the field of autonomic medicine. Other developments include a home test for people with symptoms of autonomic dysfunction in conditions such as long COVID, chronic fatigue syndrome, fibromyalgia, and diabetes 1 and 2, where people experience dizziness or blackouts.
Recreational drug use may be a factor in a significant proportion of admissions to cardiac intensive care, with various substances detected in 1 in 10 such patients, suggest the findings of a multicentre French study published online in the journal Heart.
Drug use was also associated with significantly poorer outcomes, with users nearly 9 times as likely to die or require emergency intervention as other heart patients while in hospital, and 12 times as likely to do so if they used more than one drug.
Recreational drug use is a known risk factor for cardiovascular incidents, such as a heart attack or abnormal heart rhythm (atrial fibrillation), explain the researchers. An estimated 275 million people around the globe indulged in this activity in 2022, a 22% increase on the figure for 2010, they add.
But it’s not clear how common recreational drug use is among patients admitted to hospital with heart problems, or to what extent this affects the likely course of their condition.
To try and find out, the researchers analysed the urine samples of all patients admitted to cardiac intensive care in 39 French hospitals during one fortnight in April 2021, with a view to detecting recreational drug use.
During this period, 1904 patients were admitted, 1499 of whom provided a urine sample – average age 63, 70% male. Of these, 161 (11%) tested positive for various recreational drugs, but only just over half (57%) of whom admitted to using.
Prevalence was even higher among the under-40s, 1 in 3 (33%) of whom tested positive for recreational drugs.
The most frequently detected substance was cannabis (9%), followed by opioids (2%), cocaine (just under 2%), amphetamines (nearly 1%), and MDMA or ecstasy (just over 0.5%).
Compared with other non-using heart patients, users were more likely to die or to require emergency intervention for events such as cardiac arrest or acute circulatory failure (haemodynamic shock) while in hospital: 3% vs 13% – especially if they had been admitted for heart failure or a particular type of heart attack (STEMI).
After adjusting for other underlying conditions, such as HIV, diabetes, and high blood pressure, users were nearly 9 times as likely to die or require emergency treatment.
While cannabis, cocaine, and ecstasy were each independently associated with these incidents, and single drug use was detected in nearly 3 out of 4 patients (72%), several drugs were detected in more than 1 in 4 (28%) users: these patients were at even greater risk, being 12 times as likely to die or require emergency treatment.
This is an observational study, so can’t establish that recreational drug use resulted in admission to cardiac intensive care. The researchers also acknowledge that the study was only conducted over 1 fortnight in April, so the findings might not be applicable to other months of the year or the longer term.
And they caution: “Although the strong association between the use of recreational drugs and the occurrence of [major adverse events] suggests an important prognostic role, the limited number of events requires caution in the clinical interpretation of these findings.”
But recreational drugs can increase blood pressure, heart rate, temperature, and consequently the heart’s need for oxygen, they explain.
And they conclude: “While the current guidelines recommend only a declarative survey to investigate recreational drug use, these findings suggest the potential value of urine screening in selected patients with acute cardiovascular events to improve risk stratification in [cardiac intensive care].”
In a linked editorial, doctors from London’s St Bartholomew’s Hospital and Queen Mary’s University of London reiterate that the study wasn’t designed to uncover a causal relationship. Larger studies would be needed to try and establish that.
But the study findings prompt two obvious questions, they suggest: “(1) Should patients admitted to intensive cardiac care units be screened for recreational drug use: and (2) What, if any, interventions might be implemented following a positive patient test result?”
Knowing that a patient had used recreational drugs might shed light on the cause of their condition and inform how it’s managed, they suggest. It might have other benefits too.
“A positive test result would provide an opportunity for counselling about the adverse medical, psychological, and social effects of drugs, and for the implementation of interventions aimed at the cessation of drug use,” they write.
But quite apart from the cost, screening raises issues of patient confidentiality and the potential for discrimination in how targeted screening might be applied, they say.
And they conclude: “There is a considerable way to go, however, before screening for recreational drug use can be recommended.”
In countries which allow the practice, assisted suicide would seem to be an alternative to conventional suicide – but new research shows that this is not a simple relationship. An analysis published in Cancer Medicine reveals the trends of self-initiated deaths – including assisted suicide (AS) and conventional suicide (CS) – in Switzerland over a 20-year period, focusing on people who suffered from cancer. While cancer-related AS rose, CS fell but then stabilised – suggesting that cancer-related CS has more complex reasons behind it.
Although supporters of assisted dying state that access to AS should lead to a reduction in violent CS, the study’s findings do not confirm this assumption. The situations and motivations for cancer-associated CS seem to be clearly different from those for cancer-related AS.
In Switzerland, assisting in a suicide is not punishable as long as it does not serve selfish motives. In this analysis of data from 1999–2018, investigators found that cancer was the most often listed principal disease for AS: 3580 people with cancer died by AS, representing 41.0% of AS cases. Cancer was listed in only a small minority of CS cases (832 people, representing 3.8% of CS cases).
There was approximately a doubling of AS cases among patients with cancer every 5 years. Also, the percentage of cancer-associated AS in relationship with all cancer-associated deaths increased over time to 2.3% in 2014–2018. The numbers of cancer-associated CS showed a downward trend in 1999–2003 and were stable through 2009–2018.
“Obviously, the situations and motivations for cancer-associated CS seem to be clearly different from those for cancer-related AS,” said corresponding author Uwe Güth, MD, of the University of Basel.
People often say whether they feel like their immune system is ‘down’ – but could there be some truth to this? A recent study showed that when freshly vaccinated people self-assessed the strength of their immune response, their estimates correlated well to their measured antibody levels. They were even more accurate when their immune response was weak. The results were published in the journal Biological Psychology.
At the University of Konstanz, Stephanie psychologist Dimitroff researches the connection between our brain and our immune system. “Listen to your body,” she concludes from her study. “The field of medicine is moving towards greater patient orientation. Our findings support the idea that patients’ self-perceptions provide valuable clues about their state of health. Physicians should listen to them more.”
Communication between the immune and nervous systems
One part of our brain, the insula, receives information from the body and gives us a basic impression of its condition, which until now was assumed to be quite general in nature. Stephanie Dimitroff’s study now suggests that our brain can perceive the body’s condition more specifically than previously thought. Is it possible that our brain can assess the state of our immune system?
“Of course, our brain does not count antibodies. But our immune system is intrinsically connected to the central nervous system,” Dimitroff explains. “The immune system is regulated via this connection. And our brain also receives information from the immune system.”
This communication between the immune system and the central nervous system is key for our sense of well-being or illness. “It is important to know here: When we feel ill, for example, we have a cold, this feeling is caused quite significantly by the immune system’s communication with the central nervous system,” says Dimitroff. “The brain receives signals that something is wrong with the body and causes the feeling of illness as a result.”
The same flow of information between the immune and nervous systems can generally also take place when the body is not ill. This means it could be possible that this communication process gives us an impression of our immune system even when we are healthy. Stephanie Dimitroff’s study investigates whether this is actually the case.
Results of the study
The study looked at people who had received the COVID-19 vaccine. This group of participants was chosen because a particularly large number of people received the vaccine in the summer of 2021, when the study was conducted. 166 people between the ages of 18 and 59 participated in the study.
After vaccination, the participants in the study were able to assess surprisingly well how strongly their immune system was positioned to fight the respective illness. This was especially true for people who had developed only a few antibodies. In fact, 71% of participants who did not feel well protected after vaccination also had a below-average immune response. “Our most notable finding is that those who felt they had not produced high levels of antibodies after vaccination were often correct in their assessment.”
By contrast, participants who assessed their immune response as good were not always right. However, all of those who had a particularly strong immune response also reported feeling well protected.
Alternative interpretations
For Stephanie Dimitroff, however, it is still too early to draw any final conclusions. The psychologist is considering other possible causes, including the placebo effect. This is because communication between the brain and the immune system runs in both directions. The signals from our brain can therefore also influence our immune system. People who firmly believe in vaccination or are basically optimistic could thus actually develop a better immune defence (placebo effect) and also feel better protected. It is therefore possible that belief in the effectiveness of a vaccine is what improves its efficacy, and this could also explain the high accuracy of the self-assessments.
“Our results suggest that it is quite likely that people have a real ability to assess their own health. However, I cannot rule out that there is a combination of effects at play, including the placebo effect and/or feelings of optimism,” Dimitroff says. In her view, it would make sense to repeat the study in order to confirm the results and rule out alternative causes.
Cancer researchers have shown that immunotherapy after stem cell transplantation effectively combats neuroblastomas in children. Crucially, stem cells from a parent provide children with a new immune system that responds much better to immunotherapies. These results of an early clinical trial were published in the Journal of Clinical Oncology.
Tumours of the nervous system, neuroblastomas are associated with an unfavourable prognosis if the tumour is classified as a high-risk type. and particularly poor for patients in the relapsed stage. In this study by scientists at St. Anna Children’s Cancer Research Institute and the Eberhard Karls University of Tübingen, immunotherapy following stem cell transplantation is now associated with long-term survival in a substantial proportion of the patients. Compared to an earlier study the survival rate was increased.
“After the transplantation of stem cells from a parent, the patients are equipped with a new immune system. This enables a better immune response to the subsequent immunotherapy and clearly improves the outcome,” explains Prof Ruth Ladenstein, MD, co-first author.
Five-year survival exceeds 50%
“After a median follow-up of about eight years, we see that more than half of the study patients live five years or longer with their disease,” Prof Ladenstein reports (5-year overall survival: 53%). In comparison, the 5-year overall survival in an earlier study, in which stem cell transplantation was not followed by immunotherapy, was only 23%. Those patients who showed a complete or partial response to prior treatment had significantly better survival.
“In summary, immunotherapy with dinutuximab beta following transplantation of stem cells from matched family donors resulted in remarkable outcomes when patients had at least a partial response to prior treatment,” says Prof Ladenstein. “In our study, there were no unexpected side effects and the frequency of graft-versus-host-disease was low.”
Restoring natural killer cell potency
Dinutuximab beta is a monoclonal antibody that binds to a molecule, GD2, on the surface of tumour cells, marking them for destruction by natural killer cells. But prior chemotherapies may impair natural killer cells. “Therefore, a transplantation of intact natural killer cells from matched family donors seems reasonable before immunotherapy is administered. The transplanted, new natural killer cells are now able to target the tumour cells more efficiently – by means of an antibody-dependent reaction,” explains Prof Ladenstein.
According to the authors, further studies are needed to determine the individual components of the therapeutic approaches. Recently, conventional chemotherapy has also been combined with immunotherapy early in the treatment strategy, resulting in similarly improved response rates. The hope is that a renewed immune system through a healthy parent in combination with the described transplantation procedure could further increase survival rates: “Our approach could thus result in stronger and longer lasting tumour control. A randomised study would be necessary to scientifically substantiate the additional potential benefit of a new immune system in the context of relapse therapy,” Prof Ladenstein adds.
Specially trained and accredited pharmacists in South Africa will now be allowed to provide people with medicines to prevent HIV and tuberculosis (TB) and to treat uncomplicated HIV without a doctor’s script. This is because the North Gauteng High Court this week ruled against an application by the IPA Foundation (an association of private doctors) attempting to block the implementation of Pharmacist-Initiated Management of Antiretroviral Therapy (PIMART).
PIMART involves the introduction of a legislative framework, a specialised training course, and an accreditation process to allow pharmacists to supply HIV and TB medicines to people visiting pharmacies, under certain conditions, without a doctor’s script.
While PIMART has been delayed for two years by the IPA Foundation’s legal challenge, Judge van der Schyff’s ruling now clears the way for the SAPC to proceed with its implementation.
Steve Letsike, Chair of the SAPC’s Health Committee and PIMART Task Team, said in a media conference on Thursday that the IPA Foundation has until 8 September to appeal the High Court’s decision. Speaking at the same media conference, Mogologolo Phasha, President of the SAPC, indicated that if the IPA Foundation appeals the ruling, the SAPC will continue to fight to preserve the initiative in higher courts.
Spotlight asked the IPA Foundation whether they plan to appeal the decision, but no response was received by time of publication.
The background
The introduction of PIMART was proposed by the SAPC in 2018 in response to a request from the National Department of Health for the SAPC to develop an intervention to enable pharmacists to help get HIV prevention treatment to more people quicker.
Pharmacists trained and accredited under the PIMART initiative will be able to provide preventative therapy for HIV (both post-exposure and pre-exposure prophylaxis – PEP and PrEP), TB preventive therapy, and first-line antiretroviral treatment for uncomplicated HIV.
According to Phasha, around 900 pharmacists, or 5% of pharmacists on the register have already undertaken specialised, supplementary training to enable them to provide PIMART services. He noted, however, that before trained pharmacists would be able to start providing PIMART services they would need to receive accreditation in the form of a permit granted by the National Department of Health under Section 22(A)15 of the Medicines and Related Substances Act.
The court’s response to the IPA Foundation’s arguments
In February 2022, the IPA Foundation filed an affidavit with the North Gauteng High Court seeking review and dismissal of the SAPC’s decision to implement PIMART and related legislation.
In its affidavit, the IPA Foundation argued that the provision of PIMART services falls within the domain of medical doctors and that pharmacists do not have the required training and competencies to provide these services. The IPA Foundation further argued that the SAPC does not have the legislative mandate to introduce PIMART, that the SAPC’s reasons for implementing PIMART were not adequately explained, and that the SAPC’s procedures for implementing PIMART were not procedurally fair and did not provide adequate opportunity for interested parties to comment.
The IPA Foundation warned of a “slippery slope” resulting from PIMART’s introduction, adding “this objection essentially warns of the opening of the floodgates or perhaps an anticipated negative precedent setting occurrence relevant to the provision of medication… without prescription”.
In her ruling, Judge van der Schyff noted that while tension between healthcare cadres regarding their scopes of practice is common, the World Health Organization calls for “a collaborative approach to primary healthcare issues and the embracing of task-shifting”.
She added that “competition, per se, does not limit or curtail the rights of medical practitioners to continue providing the services that they currently provide,” further stating that “even if the assumed competition is regarded to affect family practitioner’s rights adversely, the alleged adverse effect it holds for medical practitioners has to be considered against the need to expand primary healthcare services aimed at preventing and treating HIV”.
Judge van der Schyff dismissed the IPA Foundation’s argument that the SAPC is not mandated to introduce PIMART, stating that “the SAPC is empowered to prescribe the scope of practice of the various categories of persons registered in terms of the Pharmacy Act”. She added, “The development and implementation of PIMART, does not expand the existing scope of practice of pharmacists that generically provides for PIT [pharmacist-initiated therapy] and PCDT [primary care drug therapy]. It introduced a specialised category of PIT and PCDT focused on preventing and treating HIV.”
Judge van der Schyff also rejected the IPA Foundation’s arguments that PIMART’s introduction was procedurally unfair and the decision for its implementation was not properly explained, arbitrary, or capricious. She says that “through its collaboration with the Southern African HIV Clinicians Society, whose members include numerous medical doctors, the development of PIMART was given great exposure”.
“The need to widen access to first-line ART [antiretroviral therapy] and TPT [TB preventative therapy] on a community level is not a figment of SAPC’s imagination, but a dire need that is also evinced in other countries,” held van der Schyff.
Finally, Judge van der Schyff rejected the argument that pharmacists are not adequately trained to provide PIMART services, stating, “The PIMART training course was developed to ensure that pharmacists who successfully completed the training would be ‘suitably qualified to safely and effectively assist in providing ART’.” She adds that the PIMART training course was “developed by suitably qualified experts in the field, which experts include medical practitioners”.
The ruling was welcomed by the SAPC and several HIV groups.
“The superior court yesterday (Wednesday) confirmed what has been our long-held view that PIMART is a necessary and competently designed intervention programme to support South Africa’s efforts in providing access to patients diagnosed with HIV and AIDS,” said Phasha. “The programme may also arrest and lower the ballooning HIV budget, which is nearly half the national health budget, by reducing the rate of new infections.”
Nelson Dlamini, Head of Communications at the South African National AIDS Council (SANAC), told Spotlight that SANAC welcomes the court ruling.
“The magnitude of South Africa’s HIV burden requires innovative ways of accessing HIV treatment, care, and support. PIMART is one such approach that will improve access to antiretroviral therapy for people living with HIV and those requiring PEP & PrEP,” said Dlamini.
Sibongile Tshabalala, Chairperson of the Treatment Action Campaign (TAC), said the organisation also welcomes the ruling. “The challenges that we are facing in the country include one of people queuing for a long time in facilities… and also the attitude of nurses in facilities which chases away so many people from facilities. We also have the issue of key populations that are not comfortable to go in public health facilities to access medication… so if a pharmacist is able to issue and prescribe ARVs and TB medication it will mean that we will be able to cover a lot of people.”
*NOTE:A representative of the TAC is quoted in this article. Spotlight is published by SECTION27 and the TAC, but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.
