New meta-analysis included 15 randomised controlled trials involving 598 patients with Alzheimer’s disease and found improvements in sleep and psycho-behavioural symptoms.
Photo by Matteo Vistocco on Unsplash
Light therapy leads to significant improvements in sleep and psycho-behavioural symptoms for patients with Alzheimer’s disease, according to a new study published this week in the open-access journal PLOS ONE by Qinghui Meng of Weifang Medical University, China, and colleagues.
The cognitive decline associated with Alzheimer’s disease is often accompanied by sleep disturbances and psycho-behavioural symptoms including apathetic and depressive behaviour, agitation and aggression. Photobiomodulation is a non-pharmacological therapy that uses light energy to stimulate the suprachiasmic nucleus (SCN), a sleep modulator in the brain. Despite light therapy receiving increased attention as a potential intervention for Alzheimer’s, a systematic evaluation of its efficacy and safety has been unavailable.
In the new study, researchers searched multiple research databases to identify all randomised controlled trials related to light therapy intervention for Alzheimer’s disease or dementia. Fifteen high-quality trials with available methods and relevant outcomes were selected for further analysis. The included trials were written in English, published between 2005 and 2022, and performed in seven countries. They included a combined 598 patients.
The meta-analysis of all fifteen trials found that light therapy significantly improved sleep efficiency, increased interdaily stability (a measure of the strength of circadian rhythms), and reduced intradaily variability (a measure of how frequently someone transitions between rest and activity during the day). In patients with Alzheimer’s disease, light therapy also alleviated depression and reduced patient agitation and caregiver burden.
Given the limited sample sizes in studies included in this meta-analysis, the authors advocate for larger future studies, which could also explore if bright light exposure could cause any adverse behaviour in patients. They conclude that light therapy is a promising treatment option for some symptoms of Alzheimer’s disease.
The authors add: “Light therapy improves sleep and psycho-behavioral symptoms in patients with Alzheimer’s disease and has relatively few side effects, suggesting that it may be a promising treatment option for patients with Alzheimer’s disease.”
The BASHIR™ Endovascular Catheter (THROMBOLEX, Inc.), recently approved by the US Food and Drug Administration (FDA), is paving the way to more effective and safe treatment for acute pulmonary embolism. Already demonstrated to be effective for reducing blockages in lung arteries, a new study in JACC: Advances shows that the BASHIR™ catheter also reduces blockages in the smaller segmental pulmonary artery branches. These branches are ultimately responsible for oxygenating the blood in the lungs.
The new study from Temple University which was part of the National Institutes of Health-sponsored multicentre RESCUE clinical trial, further showed a correlation between decreased numbers of blockages in the small lung arteries and functional recovery of the right ventricle of the heart, which pumps blood into the main pulmonary artery of the lungs.
Compared to other devices, the BASHIR™ catheter also had significantly lower bleeding rates, a key advance in acute pulmonary embolism treatment.
“Blockages in these smaller, distal pulmonary arteries have never previously been explored in patients treated for acute pulmonary embolism,” explained Riyaz Bashir, MD, FACC, Professor of Medicine, Director of Vascular and Endovascular Medicine in the Section of Cardiology, Department of Medicine at the Lewis Katz School of Medicine and Temple University Hospital, co-inventor of the BASHIR™ Endovascular Catheter, and first author on the new report.
The BASHIR™ catheter is a small tube-like device that consists of a helical basket with six mini-infusion catheters at its farthest end.
When the infusion basket is expanded within a clot in a large blood vessel, new channels open, enabling blood to flow through the clot. The blood carries the body’s clot-dissolving chemicals into the channels, accelerating clot breakdown.
Researchers at THROMBOLEX™ Inc. were involved in developing and commercialising this platform technology.
The occlusion of small lung arteries is the major reason for the reduction in blood flow in patients with acute pulmonary embolism.
“The more occlusions a patient has, the lower their survival,” Dr Bashir said.
“Among the treatment goals is relieving obstructions in both large and small arteries.”
Patients who survive may, over more extended periods, be at high risk of developing chronic thromboembolic pulmonary hypertension (CTEPH), which is a life-threatening condition caused by increased blood pressure in the lungs.
In the new study, Dr Bashir and colleagues observed reductions in occlusions in segmental and proximal branches of the pulmonary artery 48 hours following treatment with the BASHIR™ catheter.
The blockages decreased even in those arteries that were distant from where the infusion basket was located, enabling improved blood flow and healing of the right ventricle.
“We suspect that the improvements in blood flow are due to both the expansion of the basket and the flow of the body’s clot dissolving molecules into the clot, which cause the blockage to shrink,” Dr. Bashir said.
“As the volume of blood flow improved, right ventricular function also improved, which could translate to better survival.”
In future work, Dr Bashir and colleagues plan to investigate mechanisms behind the observed reductions in arterial blockage.
Further trials are also needed to understand better the impact of treatment with the BASHIR™ catheter on patient survival and incidence of CTEPH.
On 29 October, during its annual scientific meeting at the Sandton Convention Centre in Johannesburg, the South African Heart Association (SA Heart®) met with members of the National Department of Health (NDoH), Council for Medical Schemes (CMS), South African Medical Association, medical aid industry, pharmaceutical and medical device industry, as well as the Global Heart Hub – which supports patient advocacy for cardiovascular disease – with the intention to develop an advocacy forum to create a more empowered and engaged community of patients living with cardiovascular disease.
During the symposium, SA Heart® emphasised the cardiac profession’s difficulty in obtaining approval and full reimbursement for the evidence-based treatments, shown to improve patient outcomes. The rules and regulations surrounding the availability of treatments, variously determined by the NDoH, the CMS and funders, currently inhibit access to effective cardiovascular disease management. SA Heart®, an affiliate member of the European Society of Cardiology (ESC), adopts the ESC’s guidelines as its own, supplemented by consensus statements that take prevailing local circumstances into account. Instead of following the up-to-date recommendations of the ESC, both the NDoH and various private sector funders rather give preference to the CMS algorithms that are years out of date. These anachronisms determine standards of care, despite ongoing advances in evidence-based medicine.
Prescribed Minimum Benefits (PMB’s) are a set of defined benefits to ensure that all medical scheme members have continuous access to defined minimum health services, regardless of the benefit option they select. PMB’s are limited in their reach. Private sector funders often retreat behind rules and regulations within the state sector, as to the type and level of treatment that they approve. Each funder independently determines what will be funded and at what level. Based upon their unique Health Technology Assessments, each funder then decides what treatment is approved or declined. It is unfair to restrict treatment to what is available only in the state sector. Novel therapies could be more widely available if there were more constructive agreements between state and industry. The CMS is currently reviewing the PMB package and defining patient entitlement.
SA Heart® pointed out that physicians are at the interface between the patient and the funder. Frequently, the patient misunderstands their own relationship with their medical aid and may deem the practitioner responsible for limitations imposed on his/her treatment. The administrative burden on clinicians is often intolerable, requiring repeat motivations, chronic medication forms, PMB applications and telephone calls to funders.
During the symposium pertinent questions were raised around funder and regulator reimbursement decisions, as well as the obscure mechanisms governing the pricing of medicines and devices. SA Heart® also raised concerns about the future of both the public and private healthcare system. A balance between the two sectors is a delicate one, requiring careful policy decisions to ensure that both systems will contribute effectively to the overall health of our country. Debates often focus around issues of equity and quality of service. The idea of centralizing decisions and distribution in the pharmaceutical and medical device sectors can be seen as an effort to ensure equitable access to essential medicines and equipment. However, this approach could negatively impact the ability to cater for South Africa’s diverse and specific needs – with more bureaucracy and inefficiency.
The meeting was called to determine interest amongst the various parties in establishing a forum to find solutions to these problems, and to harmonise the regulations around access to both medications and devices. The panellists were unanimous in their agreement that the current rules, regulations and disparities between the public and private sectors need to be reworked and there was consensus that a forum should be created to continue these discussions and arrive at effective, durable solutions. SA Heart® committed to driving this process, and will regularly engage all stakeholders in future meetings, with the ultimate goal of improving patient access to innovative cardiovascular treatments.
After the stupendous effort for COVID vaccines and treatments, it may seem like other diseases were being neglected. Nevertheless, the US Food and Drug Administration suddenly had a fire lit underneath it, and got cracking with accelerated drug approvals. Now, 2023 seems to have brought plenty of new drugs to bolster the physician’s armamentarium – some are the first-ever treatment for their indications. Hopefully, with FDA and European Medicines Agency (EMA) approvals, South African approvals should not be too far behind.
Since the pandemic, hotly anticipated drugs have made a big splash or sunk without a trace. In 2021, semaglutide was approved for weight management, unleashing a wave of people using (and some abusing) the GLP-1 agonist for weight loss. Adagrasib, which targets KRAS, previously thought undruggable, was a major advance for the treatment of non-small-cell lung cancer and was one of a few notable new non-COVID pharmaceuticals.
Aducanumab/Aduhelm was the top tip for new drugs in 2021, but turned out to be an absolute debacle: it wound up being an astronomically expensive, mostly ineffective drug with significant side effects. There were even questions raised over how it got approved in the first place.
Alzheimer’s disease
Last year, Aduhelm seemed like yet another false start in the long battle against Alzheimer’s disease. This year though, it looks like help finally arrived for fight against the dreaded neurodegenerative disease with not one but two breakthrough drugs, both antiamyloid antibodies.
Up first is lecanemab/Leqembi from Eisai/Biogen. It targets the buildup of amyloid proteins in the brain, which otherwise lead to the formation of amyloid plaques and neurofibrillary tangles of tau protein, the hallmarks of the disease.
The other candidate is donanemab, which did not secure FDA approval last year, after pharma company Eli Lilly witnessed the disaster that was Aduhelm. It did show a reduction in decline in one measure of Alzheimer’s disease but not another, so its effects are a mixed bag.
Like Aduhelm, donanemab and lecanemab both have a serious downside: brain swelling, which claimed the lives of at three donanemab trial participants.
RSV
Previously minimised by the pandemic’s social distancing and routine masking, respiratory syncytial virus (RSV) experienced a resurgence in the wake of lifting these restrictions. RSV afflicts primarily those over 60 and young children. Among those 65 and older with RSV in the US, the Centers for Disease Control estimated 120 000 annual hospitalisations, with up to 10 000 of whom dying. Among children under 5, the figures are 58 000 annual hospitalisations and 100 to 300 deaths. Historically, RSV vaccine developments wound up being ineffective. Fortunately, this year saw the first approval for an RSV vaccine. A 120µg dose of their Arexvy vaccine produced statistically significant and clinically meaningful reductions in cases of lower respiratory tract disease caused by RSV in adults aged 60 years and older. Pfizer and Moderna are hot on HSK’s heels with their own vaccine applications.
Age-related macular degeneration
Apellis got an approval for pegcetacoplan this year, for geographic atrophy (GA) secondary to age-related macular degeneration, in its intravitreal injection. This is the first and so far only treatment for this indication. “The approval of SYFOVRE is the most important event in retinal ophthalmology in more than a decade,” said Eleonora Lad, MD, PhD, lead investigator for the phase 3 study. “Until now, there have been no approved therapies to offer people living with GA as their vision relentlessly declined. With SYFOVRE, we finally have a safe and effective GA treatment for this devastating disease, with increasing effects over time.”
Interestingly, Apellis also got an approval for paroxysmal nocturnal haemoglobinuria (PNH) with a patient-injectable version of pegcetacoplan. The disease results from the destruction of red blood cells by the immune system.
Lymphoma
Abbvie and Genmab’s epcoritamab, for certain cases of large B-cell lymphoma (LBCL), got accelerated FDA and EMA approval earlier this year. The FDA has also granted accelerated approval to Roche’s glofitamab. The drugs bind to binding to CD20 on malignant B cells and CD3 on T cells to kill cancer cells, creating an effect like CAR-T cell therapy but without the complexity (and presumably, cheaper too).
Major depressive disorder, postpartum depression
Mental health is full of gaps needing to be filled by effective treatments. Not much has made been added for depression since selective serotonin reuptake inhibitors (SSRIs) came onto the market in the 1990s. Zuranolone, from Biogen and Sage Therapeutics, is the first oral treatment for postpartum depression, which previously was treated only by IV injection in a healthcare facility. Unlike slow-acting SSRIs, this treatment, which targets the GABA-A receptor, is a short course.
Inflammatory bowel disease
There has been a steady drip of new biologic drugs for inflammatory diseases, such as bimekizumab (psoriasis and deucravacitinib which recently received FDA approval. Eli Lilly entered this crowded marketplace with ixekizumab. Now, after trouncing Novartis’ Cosentyx for psoriasis with its own mirikizumab, it pulled its application for that indication and switched it to ulcerative colitis – beating about a dozen competitors to be the first IL-23 inhibitor. It aims to get an approval for Crohn’s disease in 2025. Pfizer’s etrasimod for ulcerative colitis got approval in October 2023, and should receive EMA approval in 2024. Its phase 3 trial achieved 27% remission versus 7.4% for placebo.
Pulmonary arterial hypertension
Last is sotatercept, a new drug for pulmonary arterial hypertension (PAH), which previously had no real treatment. Unlike the current therapy aimed at simply dilating blood vessels, sotaracept targets BMPR-II signalling, addressing the cause of PAH. It earned a priority preview by the FDA based on its phase 3 trial data, with possible approval by March 2024.
