A survey conducted in the UK found that people with severe to profound hearing loss who were eligible for cochlear implants were less likely to be referred if they lived in deprived areas and were male.
The study, published in PLOS Medicine, was carried out to determine the rates at which people in the UK with hearing loss were getting correctly referred for implants under the NHS, and where disparities might exist. Referrals were to be made on the basis of meeting pure tone audiometric threshold criteria.
Of 6171 participants in the survey who underwent the pure tone test and already did not have a cochlear implant, only 38% were informed of their eligibility and a mere 9% were actually referred for assessment.
Participants were less likely to be referred if they lived in more economically deprived areas and also within London, were male or were older. In addition to these factors, living in more remote areas, and being Black or Asian also reduced the likelihood of being informed of eligibility.
Lower odds of referrals in economically deprived areas is in line with data from both public and private healthcare sectors in Australia and the U.S.
The researchers also found that the presence of a “cochlear implant champion” increased the likelihood of discussions around cochlear implants but not referrals. That males were less likely to be referred or informed to were interpreted as stemming from men’s differences in health-seeking behaviour compared to women.
Limitations included the observational nature of the study, reliance on accurate documentation of the referring service, and potential underrepresentation of certain demographic groups.
A neurosurgeon alleged during his employment tribunal that a “gang culture” exists within the neurosurgery department of an NHS hospital already beset by claims of a toxic culture and investigations into negligence.
As reported by the BBC, Dr Mansoor Foroughi was dismissed from University Hospitals Sussex in 2022 for misconduct. At a separate employment tribunal, Krish Singh, the former clinical director for general surgery, claimed that rota changes reduced the number of “safe” consultants, putting patients at risk.
Four whistleblowers had also told the BBC of a “Mafia-like” culture, where patients had died unnecessarily and others “maimed”. These new allegations came to light as the BBC and The Times fought a nine-month court battle to have the employment tribunal documents unsealed.
Dr Foroughi alleges that one colleague was signed off to do complex spinal procedures despite lacking training, another performed procedures with a “disproportionate” mortality rate, and yet another took on private work while on call to the NHS – a serious breach of conduct.
University Hospital Sussex encompasses several hospitals, which includes Royal Sussex Country Hospital, which has been the source of many complaints, and a history of poor service delivery, which was put into special measures between 2016 and 2019.
At least 105 cases of alleged medical negligence from failings at the hospital’s neurosurgery and general surgery departments are being investigated by police. According to court documents, there was “serious dysfunctionality in the neurosurgery department” with “stark divisions between colleagues”.
An investigation by the Royal College of Surgeons found that “a culture of fear” existed in the hospital’s surgery department, and that senior staff were “dismissive and disrespectful”. Two staff were allegedly assaulted.
In a statement, the trust said: “The trust will vigorously contest these claims at the Employment Tribunals, which we are keen take place at the earliest opportunity so they can be examined properly and fairly.
“Dismissing anyone, or removing someone from a leadership role, is an absolute last resort and we would always seek to avoid this outcome if possible.
“In both of these cases, due process was followed, and we are confident we did the right things, in the right way, for the benefit of our patients, their care and safety.”
A Swedish study of more than 140 000 individuals with attention-deficit/hyperactivity disorder (ADHD) found that initiation of ADHD medication was significantly associated with a 21% lower mortality two years after diagnosis, according to results published in JAMA. This reduction was especially pronounced for unnatural-cause mortality. Females and males also saw different reductions in types of mortality.
ADHD is the most prevalent neurodevelopmental condition, affecting 5.9% of youths and 2.5% of adults worldwide, according to the 2021 World Federation of ADHD International Consensus Statement. The disorder is associated with a broad range of psychiatric and physical comorbidities, as well as adverse functional outcomes. Furthermore, individuals with ADHD are at twice the risk of premature death, mainly due to unnatural causes.
Randomised controlled trials have demonstrated that ADHD medications, including stimulant and nonstimulant medications, are effective in reducing core ADHD symptoms for children and adults with ADHS. Pharmacoepidemiological studies have also shown reduced risks of negative outcomes, including injuries, traffic collisions, and criminality, which would be expected to decrease the mortality rate. However, there are concerns regarding the cardiovascular safety of ADHD medications, especially following long-term use, which could increase the mortality rate.
To date, three studies have examined the association between ADHD medication and mortality with mixed results. These studies had significant limitations, such as the absence of a control group. To date, there has been no study on the association in adults with ADHD. There are increasing diagnoses of ADHD among adults, who have a higher prevalence of somatic comorbidities, including cardiovascular diseases and other conditions, compared with children and adolescents.
Using the Swedish national registers, the researchers investigated whether initiation of ADHD medication was associated with mortality, using the target trial emulation approach to avoid key biases in pharmacoepidemiological studies.
They assessed for all 6 medications licensed for ADHD treatment in Sweden (methylphenidate, amphetamine, dexamphetamine, lisdexamfetamine, atomoxetine, and guanfacine) during the 2007-2020 period. Analysis of the data showed that, for a two-year follow-up, lower all-cause (hazard ratio [HR], 0.79) and unnatural-cause (HR, 0.75) mortality for the ADHD medication group, but there was no significant association with natural-cause mortality (HR, 0.86). Under unnatural causes, accidental poisoning mortality was halved (HR, 0.47).
Subgroup analysis revealed that for females, the only significant reduction in mortality was for natural causes. The authors noted that this may be due to higher rates of comorbid depression, sleep disorder, atrial fibrillation, and asthma.
When follow-up was extended to five years, associations attenuated save for unnatural-cause mortality (HR, 0.89).
The authors concluded, “ADHD medication may reduce the risk of unnatural-cause mortality by alleviating the core symptoms of ADHD and its psychiatric comorbidities, leading to improved impulse control and decision-making, ultimately reducing the occurrence of fatal events, in particular among those due to accidental poisoning.”
For limitations, the observational nature of the study cannot establish causation, and the authors noted confounding effects such as nonpharmaceutical treatment of ADHD. Potential type I error resulting from multiple comparisons regarding cause-specific mortality and subgroup analyses meant the results are only exploratory. Two more limitations were uncertain adherence to medication and potential misclassification of deaths such as potential cases of suicide being marked as accidental poisoning.
Ischaemic and haemorrhagic stroke. Credit: Scientific Animations CC4.0
Early neurological deterioration (END) within the first 48 hours after acute ischaemic stroke (AIS) onset is relatively common, and is a predictor of poor outcomes. Treatment options are limited and unproven, but but a clinical trial has shown that the anticoagulant argatroban was safe and effective in improving outcomes. The results were published in JAMA Neurology.
Apart from straightforward causes, such as intracerebral haemorrhage and malignant oedema, the mechanism of END remains mostly unclear. Interventions for unexplained END can include plasma volume expansion, induced hypertension, and intensified antithrombotic therapy, but none has been formally proved so far.
The direct thrombin inhibitor argatroban is rapid acting, short acting, and has low bleeding rates, which could help prevent thrombus propagation and provide additional benefit after stroke/TIA. Argatroban has been associated with a reduction in ischaemic stroke damage but the safety and efficacy of argatroban is not well established for AIS treatment, and evidence is lacking for the effect of argatroban in patients with AIS and END.
Researchers conducted a randomised clinical trial that initially included 628 patients, average age 65 and 400 (63.7%) male. Eligible patients were adults with AIS who experienced END, which was defined as an increase of 2 or more points on the National Institutes of Health Stroke Scale within 48 hours from symptom onset.
Patients were randomly assigned to the argatroban group and control group within 48 hours of symptom onset. Both groups received standard therapy based on guidelines, including oral mono or dual antiplatelet therapy. The argatroban group received intravenous argatroban for 7 days (continuous infusion at a dose of 60mg per day for 2 days, followed by 20mg per day for 5 days) in addition to standard therapy.
The results showed that good neurological function at 90 days in those randomised to receive argatroban plus antiplatelet compared with antiplatelet alone was observed in 80.5% vs 73.7%)of participants, a statistically significant difference.
The authors concluded that the trial “shows that the combination of argatroban and antiplatelet therapy resulted in a significantly greater likelihood of good functional outcome at 90 days in patients with END after AIS, with no additional risk of major intracranial or extracranial haemorrhage.”
Mediaeval tyrant and inspiration for vampires, protein analysis reveals health secrets about Vlad the Impaler
New research analysing ancient protein residues left in letters written by the sadistic 15th century tyrant – and vampire inspiration – Vlad Dracula the Impaler suggests that he suffered from a number of health conditions. One of these conditions seemingly confirms one of the more outlandish tales about him – that he cried tears of blood.
Vlad the Impaler got his nickname because he impaled thousands of people on stakes: enemies (mainly the Ottoman Empire), criminals and anyone suspected of conspiring against his rule. He was eventually defeated in 1460, but the newly invented printing press spread the tale of his gruesome deeds all over Europe. Tales surrounding him may have inspired the iconic character of Bram Stoker’s Count Dracula in 1897. Nevertheless, more modern vampire stories such as Netflix’s ‘Castlevania’ make use of Vlad as inspiration.
This terrifying reputation made him an interesting topic for a bit of genetic archaeology in a paper published in Analytical Chemistry. Using sophisticated proteomic techniques, scientists analysed three letters written in 1457 and 1475 by the voivode of Wallachia, Vlad III, also known as Vlad the Impaler, or Vlad Dracula. This allowed them to tease out information about the man who wrote the letters as well as general information about the environmental conditions of 15th century Wallachia, a place of regional trade and conflict as well as disease transmission.
While centuries-old paper is unlikely to hold entire DNA strands, scientists were still able to piece together genetic information about the writer. The technique depends on the notion that a person’s writing hand will tend to rest on the paper being written upon, rubbing off a surprising amount of organic molecules in the process. They applied ethylene vinyl acetate to the papers, and with mass spectrometry, they discovered over 500 peptides – short chains of amino acids – with about 100 being of human origin, which they looked up in database searches.
Figure 1. (a) First letter (archive catalog number is II 365), dated August 4, 1475, here investigated, also showing the positions of the EVA strips (brownish rectangles) applied to its surface for capturing biological material; (b) mapping of the fluorescence of phenylalanine, tyrosine, and tryptophan under flash UV illumination (see the original article). Anal. Chem. 2023, 95, 34, 12732-12744
The researchers noted that while many mediaeval people may have handled these papers, it is also presumable that the most prominent ancient proteins can be attributed to the one who wrote and signed them – Prince Vlad the Impaler.
First, they discovered proteins pointing to ciliopathy, which affects the cellular cilia or the cilia anchoring structures, the basal bodies or ciliary function. This can manifest in a wide range of disorders, ranging from cerebral malformation to liver disease and intellectual disability.
They also uncovered signs of an undetermined inflammatory disease which likely involved his skin and respiratory tract.
Proteomics data also suggests that, according to some stories, he might also have suffered from a pathological condition called haemolacria – he could shed tears admixed with blood. This appears to confirm what some stories said about Vlad – that he sometimes cried tears of blood. While it is a known medical condition, it would have no doubt been terrifying for superstitious mediaeval people to behold when seen in someone with a reputation like Vlad the Impaler’s.
Non-human peptides also proved to be a window into the conditions of the time, hinting at common foods, pests and diseases. Database searches of the identified, as potential endogenous original components, 3 proteins from bacteria, 24 from viruses, 4 from fungi, 17 from insects (suggesting fruit flies), and 5 from plants (including rice, wheat and thale cress). Of the bacteria, they noted that some peptides related to Enterobacterales are specific to Yersinia pestis, the pathogenic bacterium causing plague, whereas another group is specific to E. coli.
The furore over claims of fraudulent account manipulation happening at Mediclinic hospitals continues to grow, as the initial whistleblower responded to a challenge for more information by providing a detailed list of of starting points for investigators, according to Daily Maverick.
Widely reported in media outlets such as News24, Radio 702, and eNCA, the initial email alleged that hospital codes were being altered to ones which drew higher remunerations from medical aid schemes and therefore which financially benefitted the hospitals. They further claimed that no action was being taken against employees who were engaging in this practice, which was supposedly happening at six hospitals.
The Council for Medical Schemes noted that hospital charges to beneficiaries had increased by nearly 19% from R7039.74 in 2020 to R8346.40. Just over 92% of the total hospital expenditure was paid to private hospitals.
Greg van Wyk, CEO of Mediclinic Southern Africa, was also emailed among the initial recipients. He responded swiftly, writing in a reply to all the cc’d recipients last week that Mediclinic had appointed Steven Powell, head of law firm ENSafrica’s forensics practice, to head its independent audit.
The Mediclinic CEO also challenged the anonymous whistleblower to come forward and reveal themselves, the whistle-blower then responded with an email cc’d to medical schemes and the media. The email contained extensive of details of the alleged fraud – plenty of information for investigators to get started with.
The whistle-blower told News24 that, for example, “When a patient died in a hospital emergency room, sometimes Mediclinic case managers were expected to change their accounts to reflect an ICU death instead. This is because of the fixed fees associated with emergency room deaths, which are lower than ICU-related fees.”
By HualinXMN – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=133759262
According to results from the SELECT trial run by Novo Nordisk, semaglutide dramatically reduces the risk of major adverse cardiovascular events (MACEs) in addition to its obesity benefits. This is bolstered by the results of another trial, STEP-1, which also suggested significant reduction in future cardiovascular events. These results have captured the attention of researchers, who commented in Nature that they could change the practice of cardiology.
Semaglutide, sold in the US for the treatment of both obesity (Wegovy) and diabetes (Ozempic), is an agonist for glucagon-like peptide 1 (GLP-1), a hormone associated with appetite.
”It’s hard to think of other [drugs], apart from statins, that have shown such a profound effect,” says Martha Gulati, director of preventive cardiology at Cedars-Sinai Medical Center in Los Angeles, USA.
It was expected that semaglutide would have cardiovascular benefits through promoting weight loss, but evidence shows that drugs mimicking GLP-1 can improve fatty-acid metabolism and reduce inflammation, for example, says Gulati. “This is what’s so fascinating about these drugs. They work on the brain, the pancreas, the cardiovascular system, the gastrointestinal tract … There’s more to them than simply weight loss.”
Recent studies have been encouraging in terms of semaglutide’s benefits for reducing cardiovascular disease risk. Earlier this month, Novo Nordisk announced the headline results from the SELECT cardiovascular outcomes trial. The double-blinded trial compared subcutaneous once-weekly semaglutide 2.4mg with placebo as an adjunct to standard of care for prevention of MACEs over a period of up to five years. The trial enrolled 17 604 adults aged 45 years or older with overweight or obesity and established cardiovascular disease (CVD) with no prior history of diabetes.
The trial showed 20% reduction in MACEs for people treated with semaglutide 2.4mg compared to placebo. The primary endpoint was a composite outcome of the first occurrence of MACE cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. All three of these components contributed to the MACE reduction. 1270 first MACEs were accrued.
Expanding GLP-1 analogues to cardiovascular disease prevention may not be without challenges, as the European Medicines Agency opened investigations into semaglutide and liraglutide over reports of suicidal thoughts and self-harm.
A separate study based on the STEP 1 trial data found that 93 million adults in the US could benefit from semaglutide, from a combination of weight loss and reduced cardiovascular benefits. They estimate a reduction in relative risk of 18% with the drug.
A study of healthcare workers (HCW) found that those who picked their nose were more likely to get COVID than the people who refrained from such explorations. The Dutch researchers published their probing results in the journal PLOS One.
In the early stages of the COVID pandemic, researchers noted a wide range of efforts to prevent the spread of SARS-CoV-2, such as the wearing of personal protective equipment and maintaining social distancing, especially in the hospital setting. Much research went into the impacts of, eg, wearing glasses on the effectiveness of masking, but little if any attention was paid to a widespread but secretive habit.
Sikkens and colleagues retrospectively surveyed healthcare workers at Amsterdam University Medical Centers were in December 2021 about their behaviours during the first and second waves of the pandemic. They matched these responses were matched against prospectively collected COVID test results at the hospitals from March to October 2020. The nose pickers were nearly three times more likely to catch COVID (17.3% vs 5.9%) than those who refrained at all costs. Surprising results were found for those HCWs who owned up to the habit.
Secret nose pickers can take some comfort in that 85% of the cohort admitted that they picked their nose either daily, weekly, or monthly, and nose pickers tended to be younger. More men picked their nose (90%) than women (83%), and doctors were the most likely to be among the nose-picking offenders: 100% of residents admitted to it, along with 91% of specialists.
Sikkens et al. noted that one limitation of the study was that nose pickers were not asked about “the depth of penetration and eating of boogers”.
Other behaviours such nail biting, having a beard were not associated with COVID infection, nor was wearing glasses, though it showed a relevant trend. Interestingly, nose picking frequency was not linked to difference in COVID infection risk; 27% of those who reported monthly picking, 35% among weekly pickers, and 32% of daily pickers.
Frequency of nose picking did not appear to be linked with any difference in COVID infection risk, with positive cases in 27% of those who reported monthly picking, 35% among weekly pickers, and 32% of daily pickers. No participants reported picking their nose every hour, thankfully.
One-third of the cohort reported nail biting, two-thirds wore glasses, and 31% of the men had beards.
A study strength was that SARS-CoV-2 positivity was determined by prospective longitudinal serological sampling, though this may not be generalisable to the current era of vaccines and circulating Omicron variants. The retrospective nature of the survey may have introduced recall bias.
Sikken et al. noted that it is surprising that SARS-CoV-2 transmission routes had been so thoroughly researched, yet simple behaviours had been overlooked. “Possibly this sensitive subject is still taboo in the health care profession. It is commendable we assume HCWs to not portray bad habits, yet we too are only human after all, as illustrated by the pivotal proportion of nose pickers in our cohort (84.5%).”
In a media briefing on Tuesday, 8th August, the Council for Medical Schemes (CMS) sought to clarify its process and recommendations over the approved 5% increase to medical aid scheme contributions, levels above which the medical schemes must motivate for. As for low-cost benefit options (LCBO), the CMS indicated that they would only provide a report to the Health Minister by the end of the month. This could prevent medical schemes from applying for new LCBOs in 2023.
Mr Mondi Govuzela, Senior Manager of Benefits Management, explained that the 5% approved increase is based on the Consumer Price Index (CPI) for 2022, which indicated a 4.9% increase. Schemes therefore may raise contributions by 5%, in line with the Reserve Bank’s inflation prediction for 2024. A prudent percentage markup should be incorporated to take into account cost increases and demographic changes, he advised. Before COVID, contribution increases have typically been 2.4–5% above CPI. The years 2020 to 2022 saw contribution increases dip below CPI.
One of the cost drivers that Mr Govuzela noted in the media briefing was supplier pressure stemming from fewer doctors and specialists, who were pushing for higher remunerations. Increased costs elsewhere in the healthcare industry. On the member side, growing rates of chronic diseases, membership ageing and coverage for medical services also added pressure.
LCBO would appear to be a solution for many individuals to access private healthcare for at least some urgent conditions, but the CMS has yet to comply with a Pretoria High Court ruling ordering that they provide a report on their moratorium on granting exemptions to medical schemes to provide LCBO benefits. The case was brought by the Board of Health Funders (BHF).
As to what the CMS’s response to the LCBO ruling was, CMS Registrar Dr Sipho Kabane said that the CMS was preparing a report that would be delivered to the Health Minister “by the end of the month”, but would not be drawn on what it might say. The deadline for registering new benefit options is September 1.
In their circular explaining the decision increase, the CMS acknowledged the persistent macroeconomic headwinds facing medical schemes and their members, with a meagre 1% increase predicted for SA’s GDP next year. “Against the backdrop of the current adverse macroeconomic conditions characterised by multi-year higher interest rates due to stubbornly higher inflation rate, volatile domestic currency and surging energy prices and overall lacklustre economic growth, it is evident that most household budgets will remain constrained for a foreseeable future, leaving most consumers under a precarious financial position. To cushion members of medical schemes against further financial distress and the probable risk of losing their health insurance cover due to affordability constraints, medical schemes are advised to limit their cost increase assumptions for contribution increases for the 2024 benefit year to 5.0%, in line with CPI.”
Assembled human PCNA (PDB ID 1AXC), a sliding DNA clamp protein that is part of the DNA replication complex and serves as a processivity factor for DNA polymerase. The three individual polypeptide chains that make up the trimer are shown. Source: Wikimedia CC0
A ‘cure for cancer’ has long been something of a holy grail for medical research – but experience has shown that cancers are highly individualised and respond differently to therapy, adapting to resist them. Now, in an early study, researchers have tested a cancer drug that kills all solid cancer tumours while leaving other cells unharmed and resulting in no toxicity. The new molecule targets a common key cancer cell protein, the proliferating cell nuclear antigen (PCNA), that is key to helping them grow and metastasise – a target previously believed to be ‘undruggable’.
The new drug, AOH1996, was tested in vitro against 70 different cancer cell lines, including breast, prostate, brain, ovarian, cervical, skin, and lung cancer. It proved effective against all of them, as well as sparing healthy cells. What’s more, developing resistance against the drug is unlikely due to the nature of PCNA as a mistranslation rather than a mutation. The results were published in Cell Chemical Biology. Instructions for synthesis were included in supplementary material.
The research was led by Dr Linda Malkas, a professor at City of Hope Hospital, who said that the molecule selectively disrupts DNA replication and repair in cancer cells, leaving healthy cells unaffected. Animal models also showed a reduction of tumour burden with no apparent adverse effects, with the no observed adverse effect level (NOAEL) calculated being six times higher than the administered dose.
She explained the drug in simple terms to the Daily Mail: “Most targeted therapies focus on a single pathway, which enables wily cancer to mutate and eventually become resistant,” she said. “PCNA is like a major airline terminal hub containing multiple plane gates.
“Data suggests PCNA is uniquely altered in cancer cells, and this fact allowed us to design a drug that targeted only the form of PCNA in cancer cells. Our cancer-killing pill is like a snowstorm that closes a key airline hub, shutting down all flights in and out only in planes carrying cancer cells.”
Dr Malkas said results so far have been ‘promising’ as the molecule can suppress tumour growth on its own or in combination with other cancer treatments without resulting in toxicity.
The development of AOH1996 is the culmination of nearly two decades of work by City of Hope Hospital in Lose Angles.
Decades in the making
PCNA in breast cancer was identified as a potential target in 2006 since it is an isomer, allowing antibodies to target it. The researchers’ first attempts with antibodies to target PCNA were unsuccessful as these were too big to penetrate into solid tumours. Next, they tried a small molecule, which appeared to work in vitro but in vivo proved to have a half-life of only 30 minutes. But they were able to tweak that molecule and arrive at the current drug, AOH1996. It was named after Anna Olivia Healy who died in 2005 from neuroblastoma, and she became the inspiration for the research.
“She died when she was only 9 years old from neuroblastoma, a children’s cancer that affects only 600 kids in America each year,” Malkas said. “I met Anna’s father when she was at her end stages. I sat him down for two hours in my office and showed him all of my data on this protein I had been studying in cancer cells.”
At the time, Dr Malkas was researching breast cancer, studying a protein found in cancer cells but not normal cells. Dr Malkas eventually took Anna’s father, Steve, and his wife, Barbara, to see her lab.
“[Steve] asked if I could do something about neuroblastoma and he wrote my lab a cheque for $25 000,” Dr Malkas said. “That was the moment that changed my life – my fork in the road. I knew I wanted to do something special for that little girl.”
