A review published in Developmental Medicine & Child Neurology investigates the knowledge base of cannabis-based medicinal products in paediatric epilepsies, highlighting areas in need of additional research.
Following reports in the media of children with epilepsies apparently deriving benefits from medical marijuana (or cannabis-based medicinal products) accessed abroad, the UK government allowed clinicians to prescribe these products. A previous review found that there was some benefit in certain drug-resistant epilepsies in children.
In the review, the authors also looked at the prescribing environment surrounding these products. They found that the major obstacle to prescribing is a lack of quality evidence for efficacy and safety. The authors stress that unlicensed cannabis-based medicinal products should not circumvent the usual regulatory requirements before being prescribed. They are also concerned that children with epilepsy are at risk of being exploited as a “Trojan horse” for the cannabis industry, with widespread acceptance of medicinal cannabis accelerating the wider legalisation of marijuana and opening up a highly lucrative commercial market.
Impel NeuroPharma announced that the US Food and Drug Administration (FDA) approved TRUDHESA™ (dihydroergotamine mesylate) nasal spray (0.725 mg per spray) for the acute treatment of migraine with or without aura in adults.
The innovative system delivers dihydroergotamine mesylate (DHE) through the vascular-rich upper nasal space, bypasses the gut and potential absorption issues, offering rapid, sustained, and consistent symptom relief without injection or infusion, even when administered hours after a migraine attack starts.
During the Phase 3, open-label, pivotal safety study, STOP 301, more than 5,650 migraine attacks were treated over 24 or 52 weeks during the study. The primary objective of the study was to assess the safety and tolerability of TRUDHESA. TRUDHESA was generally well tolerated and exploratory efficacy findings showed it provided rapid, sustained, and consistent symptom relief. STOP 301 reported TRUDHESA offered consistent efficacy even when taken late into a migraine attack.
“Many of my patients need more from their migraine treatment, and TRUDHESA offers a non-oral, fast-acting, reliable option that overcomes many current medication challenges,” said Stephanie J. Nahas-Geiger, MD, MSEd, Associate Professor in the Department of Neurology, and Program Director of the Headache Medicine Fellowship Program, Thomas Jefferson University. “Its upper nasal delivery circumvents the GI tract and common phenomena associated with migraine, such as nausea and gastroparesis, that can impact the effectiveness of oral treatments. And, importantly, it is a self-administered, single dose that can be taken anytime during a migraine attack, so patients don’t need to worry about missing the opportunity to benefit from using TRUDHESA within a certain timeframe. I think patients will be very receptive to this treatment, because it pairs the long-proven benefits of DHE with a patient-friendly delivery system.”
There were no serious adverse events were observed in the study, and most adverse events were mild and transient in nature.
In the STOP 301 study, patient-reported efficacy showed that 38% of patients had pain freedom, 66% had pain relief, and 52% had freedom from their most bothersome migraine symptom at two hours after their first dose of TRUDHESA. In 16% of patients, pain relief started as early as 15 minutes. Of patients who were pain free at two hours, 93 percent were still pain free at 24 hours, and 86 percent were still pain free through two days. The great majority of patients (84%) reported that TRUDHESA was easy to use10 and preferred it over their current therapy.
Medical students who experienced mistreatment during medical school were more likely to become exhausted or disengaged, have less empathy, and have career regret, a new study has revealed.
Among a large national sample of trainees, the 22.9% of respondents who reported mistreatment on the Association of American Medical Colleges’ Medical School Year 2 Questionnaire (Y2Q) had higher exhaustion and disengagement scores on the Graduation Questionnaire (GQ) 2 years later, reported Liselotte Dyrbye, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues writing in JAMA Network Open.
Furthermore, of those who had experienced mistreatment, 18.8% reported career regret on the GQ.
Conversely, medical students who experienced a better environment more likely to:
Have lower exhaustion scores: for each 1-point increase on the Y2Q, there was a 0.05 reduction in exhaustion score Report lower disengagement scores on the GQ: for each 1-point increase on the Y2Q, there was a 0.04 reduction in disengagement score Further, reports of having positive interactions with faculty on the Y2Q were associated with higher empathy scores on the GQ. For each 1-point increase, there was a rise of 0.02 in empathy score. Positive student-to-student interactions were linked to having lower odds of career regret during the last year of medical school.
“The potential protective effect of positive experiences within the learning environment may provide insight into strengths that organizations can amplify to mitigate burnout, decline in empathy, and career choice regret among their students,” wrote Dyrbye and colleagues.
The team noted the opportunity for potential interventions. “Although the most effective approaches to addressing mistreatment of learners remain elusive, the frequency of mistreatment varies between educational programs, suggesting there are likely to be levers within the control of the organisation that adequate commitment, leadership, infrastructure, resources, and accountability can lead to a meaningful reduction in mistreatment.”
Average age of the respondents was 28 years, 52% were women, 72.8% were single, and 91% reported having no dependents. The study also found that older medical students reported higher disengagement scores, and that women reported lower exhaustion (by 0.27 points) and disengagement (by 0.47 points) scores on the GQ.
However, women and older medical students had higher empathy scores compared with their male peers (0.74 points and 0.05 points, respectively).
The researchers observed that conflicting findings on burnout among women in medicine have been reported. For example, a longitudinal cohort study of resident physicians across specialties in the US found that female residents were “more likely to develop burnout and have worsening in the severity of their emotional exhaustion between the second and third year of training compared with male residents, even after controlling for various forms of mistreatment.”
Limitations of their own study, the researchers noted, included unestablished differences between the exhaustion, disengagement, and empathy scale measures that were used in the questionnaires; and the varying response rates between questionnaires: 55.5% for the Y2Q and 81.5% for the GQ.
In a circular sent to medical insurance schemes this week, the Council for Medical Schemes (CMS) has recommended that contribution increases be limited to 4.2% in 2022.
“In instances where it is economically feasible to implement a lower contribution increase than the CMS recommended CPI-linked rate, Trustees are encouraged to adopt innovative pricing models, subject to an independent actuarial evaluation,” it said.
“The CMS is also cognizant of the heightened uncertainty regarding the impact of the pandemic on healthcare claims costs, as well as how quickly member’s health-seeking behaviour will normalise.
“As such, pricing decisions for the 2022 benefit year should be largely data-dependent and sensitive to the demographic risk profile and financial position of each scheme.”
There are roughly 4 million medical scheme members, with almost 9 million beneficiaries. This represents a little more than one in seven of South Africa’s population of nearly 60 million.
Claims may spike
Some medical schemes may experience sudden spikes in high-cost claims as the pandemic progresses over coming months – though the final economic impact of the pandemic remains uncertain, the CMS said. The schemes’ demographic risk profiles, the size of the population covered, and the extent of existing cross-subsidies within benefit options or schemes will affect the impact.
Additionally, the financial position of each medical scheme prior to the pandemic will dictate how it is able to absorb high-cost claims from the pandemic, it said.
Pent-up demand
The CMS said schemes should also be cautious of pent-up demand as South Africans aim to make use of their medical aids as concerns around COVID decrease. As treatments for some minor medical conditions were postponed, with increasing vaccination rates, many of these conditions would now require more complex and expensive treatment. The CMS also noted that some healthcare services will be completely forgone, resulting in lower than projected claims costs.
“Studies also indicate that as countries move out of different Covid-19 waves, hospital visit volumes slowly recover, although the utilisation rates of different services remain well below pre-pandemic levels.”
Of 253 drugs approved via the FDA’s accelerated approval pathway, clinical effectiveness has been confirmed in 112, according to a new investigation by The BMJ.
Clinical reporter Elisabeth Mahase found that, as of the end of last year, 24 of those 112 drugs have been on the market for more than 5 years, and some have been on the market for more than 2 decades — often with a high price tag, according to.
Though the accelerated approval pathway allows drugs onto the market before efficacy has been established, the manufacturer has to perform confirmatory trials or else the approval will be rescinded.
However, Mahase noted that only 16 drugs authorised through the accelerated approval pathway have been withdrawn since its creation in 1992 . Most of those were shown to lack efficacy, but in some cases, confirmatory trials were simply never done. Celecoxib (Celebrex), for example, was given accelerated approval in 1999 for the treatment of familial adenomatous polyposis, a genetic disorder that carries a high risk of bowel cancer if untreated, remained on the market for about 12 years before the FDA asked Pfizer to voluntarily withdraw it for this specific indication because efficacy trials were never completed.
The BMJ asked the manufacturers of 24 drugs that have been on the market for more than 5 years if they had conducted phase IV trials. Six drugs had been withdrawn, approved, or postponed. Of the remaining 18 drugs, relevant trial information was provided for a third. Four manufacturers of those six drugs were recruiting participants, and two reported talking to the FDA about final trial design. Eleven companies representing 12 drugs did not respond.
FDA response
“We are committed to ensuring the integrity of the accelerated approval program, which is designed to bring safe and effective drugs to patients with unmet medical needs as quickly as possible,” an FDA spokesperson said in a statement provided to MedPage Today. “The program allows the FDA to approve a drug or biologic product intended to treat a serious or life-threatening condition based on an outcome that can be measured earlier than survival that demonstrates a meaningful advantage over available therapies.”
The FDA could choose to initiate proceedings to withdraw a drug’s approval should post-marketing trials show no benefit or not be performed in time, added the spokesperson.
“Because the FDA continues to use this pathway to accelerate access to drugs for serious and life-threatening diseases for which there is an unmet medical need, at any point in time there will be drugs that are not converted because the confirmatory trials are ongoing,” the spokesperson said.
“Despite the pathway’s good intentions to accelerate ‘the availability of drugs that treat serious diseases,’ experts are concerned that it is now being exploited, to the detriment of patients — who may be given a drug that offers little benefit and possible harm — and of taxpayers,” she continued.
Fixing the accelerated approval pathway
Concerns about the accelerated approval pathway include a lack of threats from the FDA to withdraw a drug should confirmatory trials not be done, the agency’s use of indirect (or surrogate) measures of clinical benefit in some cases, and the potential for drug manufacturers to take advantage of the pathway when it comes to actual measures of safety and effectiveness, Mahase wrote.
Nevertheless, experts still agree that the accelerated approval pathway is of benefit, she noted. Suggested changes to the pathway include planning or starting confirmatory trials as part of the approval as well as closer examination of surrogate measures.
A recent example is Biogen’s controversial Alzheimer’s disease treatment aducanumab (Aduhelm) received FDA approval via the process last month, which was based on the surrogate endpoint of reduction of amyloid-beta plaque in the brain.
The drug has attracted criticism since its recent fast-track approval, with critics pointing out that the drug has not been proven effective and its $56 000 annual price is unreasonable.
Journal information: Mahase E “FDA allows drugs without proven clinical benefit to languish for years on accelerated pathway” BMJ 2021; DOI: 10.1136/bmj.n1898.
Pharmacy and health and beauty retail group Clicks has reported estimated losses of R5 billion resulting from damage to and looting of stores at shopping malls and distribution centres across South Africa, according to BusinessTech.
Clocks said that it has been forced to close all of its 110 stores in KwaZulu-Natal and 130 of its stores in Gauteng, with long lines reported at those stores that have remained open in the province. Nationwide, 279 stores have been closed and 52 have been damaged. Guidance for those needing medication is available on its website, and online deliveries have been affected as its warehouse is in Johannesburg.
106 vaccination sites have been closed across the country, the group said in a statement, as looting and vandalism continued into Wednesday, predominantly in KwaZulu-Natal and Gauteng. They advise that all vaccination sites are now accepting walk-in appointments. Dis-Chem has advised that its vaccination sites in KwaZulu-Natal are closed, as well as three of its seven sites in Gauteng.
The group had previously been forced to close its stores in September 2020 due to threats from the EFF over allegations of racism in its advertising.
Clicks has 760 stores and over 600 in-store pharmacies around country.
“The disruption of services means affected Clicks stores will be temporarily unable to administer vaccinations and provide medication to customers, along with public sector medicine pick-up points being temporarily unavailable.
“Contingency plans are being put in place to provide alternative arrangements for delivery of chronic medication and rescheduling of vaccinations, where possible,” the group said.
The unrest began with protests against the arrest and incarceration of former president Jacob Zuma, but has since degenerated into looting and destruction.
Clicks said that the full cost of the looting and damages to stores is still to be determined given the ongoing unrest.
Health groups are seeking detailed information on the workings of South Africa’s new National Health Insurance (NHI) scheme, particularly on its financial feasibility.
The Khayelitsha and Klipfonetin health forums said in a presentation to parliament that a proper analysis is necessary to see if South Africa can even afford to fund the NHI. This is a concern that has been echoed by experts. The analysis should also find out if the public trusts the government to be able to deliver an NHI that is fully inclusive of community participation, the forums said.
“There is a view that perhaps we need to be building our public healthcare system as a priority to ensure a successful transition to an NHI Fund,” it said.
The forums also raised concerns around what the NHI will mean for existing healthcare systems – including the future of the country’s medical aids.
“Clarity is needed with respect to how the NHI Bill will address the transition between private medical aids and a universal healthcare system for all.
“The gap between private and public healthcare needs to be bridged and how this is done is important.”
Other critics have also pointed out that the scheme does nothing to address the serious gaps and flaws in South Africa’s healthcare system.
The fate of medical aids
The NHI Bill currently states that when the system is “fully implemented”, services that are paid for by the NHI will not be covered by medical aids.
Discovery Health has said that while it is in general supportive of the structural changes being introduced through the NHI, medical aids should not be limited.
“Our strong view is that limiting the role of medical schemes would be counterproductive to the NHI because there are simply insufficient resources to meet the needs of all South Africans.
“Limiting people from purchasing the medical scheme coverage they seek will seriously curtail the healthcare they expect and demand. It poses the risks of eroding sentiment, and of denuding the country of critically needed skills, and is impacting negatively on local and international investor sentiment and business confidence.”
Crucially, by preventing those who can afford it from using their medical scheme cover, and forcing them into the NHI system, this approach will also have the effect of increasing the burden on the NHI and will drain the very resources that must be used for people in most need, the scheme said. Significantly, there is no indication by government as to how the NHI will be paid for, or whether it can even be afforded, with only mention made to payroll taxes and other revenue streams being tapped.
Medical aid scheme executives have pointed out that the latest budget means that medical aid schemes may no longer need to contribute for the vaccination of the South African population without medical insurance.
South Africa’s medical insurance schemes had been in discussions on funding at least part of the government’s vaccine rollout for uninsured members of the public.
The R9 billion allocated in the budget may be enough to cover the vaccine costs of the entire country, said executives from the two leading medical aid schemes.
About 7 million people are covered by medical aid schemes, about a quarter of the country’s population. Discovery Health, Medscheme and Momentum together administer some 80% of private sector medical aid plans.
“I think the government is looking at this and saying this is our role,” said Damian McHugh, executive head of sales and marketing at Momentum Health Solutions. He agreed with the idea that the budget figure implied that schemes may not have to help cover vaccinations for non-members, although it did not remove the discussion of subsidies.
McHugh went on to explain that the costs would depend on which vaccines were procured, and schemes would still have to contribute in case booster shots or new vaccination rounds became necessary.
However, given record additions to their reserves last year due to medical services not being taken or postponed, along with not having to contribute to the vaccination of non-members, medical aid schemes stand to reap even greater benefits.
At the virtual launch of Global Citizen’s Recover Better Together Campaign, access to vaccines and medical resources was highlighted as a key area to address.
“Covid-19 has threatened the lives and livelihoods of everyone on the planet. To respond, we must take several urgent actions. The only way that we will be able to recover better, together is by defeating the virus everywhere through universal access of vaccines, diagnostics, and therapeutics,” said World Health Organization Director-General Dr Tedros Adhanom Ghebreyesus.
To this end, the Recover Better Together Campaign, an initiative organised by the Global Citizen, the European Commission and the WHO, aims to create momentum for global COVID pandemic recovery, with a return to the implementation of global goals.
“To fight the pandemic, we need to pool resources, capabilities, knowledge and intellectual property. That is why we continue to call on world leaders to support the COVAX facility to ensure rapid and equitable access to Covid-19 vaccines for all countries. Another important step is to enable the transfer of medical technology for the duration of the pandemic,” said President Cyril Ramaphosa.
One of key medical resource is oxygen, which is in short supply in many low- and middle-income countries, which have to provide enough for up to half a million COVID patients. WHO data shows that 1.1 million cylinders are needed daily in developing countries, with Africa seeing the biggest surge in demand. Hospitals in Nigeria have reported running out of oxygen, leading to preventable deaths.
According to the WHO, public hospitals across 41 African countries have fewer than 2000 working ventilators. In comparison, the United States has more than 170 000 ventilators. The South African private sector has about 4000 ventilators, and around 2000 in the public sector. The WHO said the launch of the Covid Tools Accelerator Therapeutics pillar, co-led by Unitaid and Wellcome, has improved access to oxygen. On 25 February the Covid-19 Oxygen Emergency Taskforce was also launched by the WHO.
Unitaid Executive Director Dr Philippe Duneton said the Taskforce now needs an additional $90 million US for delivery of oxygen in up to 20 countries including Malawi, Nigeria and Afghanistan.
“This is a global emergency that needs a truly global response, both from international organisations and donors. Many of the countries seeing this demand struggled before the pandemic to meet their daily oxygen needs,” said Duneton. “Now it’s more vital than ever that we come together to build on the work that has already been done, with a firm commitment to helping the worst-affected countries as quickly as possible.”
The failure of a joint corporate medical insurance venture to cover the employees of three corporate giants nevertheless holds lessons for the future, its former CEO revealed.
Headed by author, innovator, and surgeon Atul Gawande, MD, Haven was created by Berkshire Hathaway, Amazon, and JP Morgan Chase to provide revolutionary healthcare insurance for their 150 000 employees, delivering high quality at an affordable price. More than just a healthcare system, it was aimed to provide an example for the rest of the United States to follow. Its team of experts created a system of coverage with no co-insurance, no deductibles, 60 critical drugs at no cost, and low-cost mental health services and primary care.
Yet, less than three years after its inception, it is soon to shut down. Dr Gawande had already stepped down as chairman in May 2020, and in a ‘grand rounds’ discussion with Robert Wachter, MD, chair of the University of California San Francisco’s department of medicine he explained the problems behind it. He said that, simply put, the system is fatally flawed — a weakness that was laid bare by the enormous job losses of the COVID pandemic.
“We have an employer-based system. A job-based system is a broken system in a world where people are moving every couple of years to different roles and many, many, kinds of jobs,” Dr Gawande said.
“The pandemic has really brought this out in spades,” he said. The lockdowns cost many workers their jobs and the benefits that came with them. At the end of 2020, there were 9.4 million fewer jobs in the US.
“The vulnerability we have of tying your healthcare to your job, that remains still a big hill to climb, and the government has to solve it. That is a public core issue that we still have not faced up to,” Dr Gawande said.
He explained that a job-based healthcare system cares only about costs this year, not over the worker’s lifetime. “That’s why we have fights over whether we’ll pay for a hepatitis C treatment that costs $50 000 and up but avert $1 million in costs over the course of a life. We need that life-course commitment and view, and we have not aligned around that,” he said.
But that wasn’t the only reason behind Haven’s dissolution; it proved extremely difficult to make an insurance plan that worked across three different companies with different organisational cultures and employees in different cities, with different populations.
“Once that became clear, then Haven threatens to become a very expensive think tank,” Dr Gawande said. Originally, Haven was supposed to assume benefits management responsibility at the three companies, he explained. But it eventually became clear that “didn’t have the potential to say we’ll take over all of the benefits and running of the insurance for all you three organisations and then add more and more and more and more.”
However, Dr Gawande doesn’t think Haven was a failure. “It definitely did not become what we thought it would be,” he confessed. But the experience enabled him to start called CIC Health, a new venture which launched COVID testing efforts in the Boston area last fall and now has major COVID vaccination efforts underway with more coming.
