One of the diabetic screening programmes within an emergency department lets the patient identify undiagnosed disease as well as prediabetes.

A Chicago hospital emergency department’s pilot study can very well pave the way for the overall development of diabetic screening programs. It is estimated that worldwide, around 415 million people are suffering from diabetes, and the startling part is that a whopping 46% of those with this condition aren’t even aware of it.

Although there is an emergency department that is created in order to give critical access to healthcare, it is also an opportunity to pinpoint and thereafter link patients to other services as well. For instance, the screening services that exist within the emergency department have been created for HIV as well as for disorders related to substance use. Moreover, one Australian study from 2016 that involved regular ED HbA1c testing in a location that had a high penetration of diabetes put out the fact that an initiative such as this was indeed a feasible way to pick out those with the undiagnosed disease and also provided an opportunity to enhance patient care. The notion has been recognised, especially in the US, that ethnic minorities as well as low-income adults have been inadvertently affected by diabetes, leading to increased diabetic complications and mortality risk.

Because of this, in the present study, scientists examined if the pilot programme concerning diabetes screening performed within an emergency department would enable the condition’s identification, especially in those from ethnic minorities.

The researchers have come up with a best practice alert that is built into an electronic medical record that flagged patients from ED who had the risk of diabetes i.e. patients aged 45 years or more or even those falling under the 18-44 year old bracket having a BMI of 25 or higher with no history of diabetes or HbA1c analysis in the last three years. Thereafter, the team looked to get in touch with all potentially eligible individuals.

Detection of diabetes and the diabetic screening programme

Overall, 352 apt candidates with a mean age of 52.2 years, of whom 54.5% were female, were identified. Of the group, 264 were detected as having prediabetes, i.e., a HbA1c level of up to 6.4%, and 88 had a HbA1c of more than 6.5%. 62 had severe diabetes with an HbA1c level of more than 10%. Interestingly, within the group, almost 75% had no prior diagnosis of prediabetes or diabetes. Although the scientists were able to successfully pinpoint patients with undiagnosed diabetes, especially among the ethnic minorities, there were still questions that loomed around the value of taking up diabetic screening in EDs in other areas and whether such a step would prove to be cost-effective or not.

Representatives from the US FDA Center for Biologics Evaluation and Research Office of Tissues and Advanced Therapies have said that the gene therapy clinical trials depend on the nature of the disease being treated and that the diseases that happen to be more progressive or that have a rapid onset may have shorter trials.

This was one of the many learnings which was imparted by the officials during the virtual town hall meeting on February 7 so as to answer the questions from the stakeholders on the clinical development of gene therapy for rare diseases that were outside the scope of oncology and hematology. The town hall happens to be a part of the series to answer questions from the stakeholders on the topics that fall under the OTAT umbrella.

The town hall session addressed the factors that should be considered by sponsors when gauging the study population for early phase gene therapy trials, which happens to be the office’s yardstick for allowing single-arm and externally controlled trials so as to provide primary evidence related to effectiveness for approval, and also the guidelines from the agency to determine the gene therapy clinical trial duration.

According to clinical team leader from the general medicine branch of FDA division of clinical evaluation and pharmacology and toxicology, Melanie Blank, They are working hard to fasten the development of gene therapy and it is indeed a very time in this segment. They are witnessing either one or two applications coming in every week pertaining to different diseases’ need for gene therapies.

Trial Duration

Branch Chief in General Medicine 1 at DCEPT, Elizabeth Hart, said that there isn’t any one-size-fits-all approach that determines the necessary clinical trial duration, but instead the time length varies based on the disease type that the therapy is known to treat.

A shorter time is going to be needed for diseases that happen to be rapidly progressive so as to demonstrate their efficacy as compared to those that are known to be more heterogeneous. She added that for such diseases, it can be a possibility to showcase a clinically meaningful effect with biomarkers that are valid.

Study Populations And The Factors That Determine Them

As per Blank, the sponsors must do a benefit-risk analysis to make sure that the patients who happen to be most benefited from the therapy are given the preference of enrolment. When it comes to benefit-risk, they are looking to enrol patients who are most likely to get benefited and that they really want to make sure that whosoever enrols ought to have the greatest potential benefit.

The capacity to give informed consent is another significant factor when it comes to determining the study population, said Blank in response to a question on what elements the sponsors must use when looking into the study population for gene therapy trials across every phase.

According to Blank, the older patients who give consent happen to be more favourable than those who cannot give consent. An adult patient is able to provide consent, while the paediatric population provides assent and for that matter, the youngest of all cannot provide either. Blank adds that when the disease is likely to affect the adult population, they go ahead with adults first just to ensure that some preliminary data on safety is available before going ahead with children and thereafter to go into those who can assent, again in that case older before approaching the younger.

Single-Arm Studies: The Conditions

The officials were asked to specify if the agency is going to allow the single-arm use of externally controlled studies in place of two well-directed randomised studies to gauge the new gene therapies’ efficacy.

The branch chief of General Medicine 2 in the DCEPT, Lei Xu, opined that the regulatory approval of gene therapies hinges on efficacy evidence which is substantial from a study that is well-controlled and adequate.

That said, the agency shall approve the external controls like the history as well as the concurrent controls for the gene therapy in order to treat the conditions that happen to be serious and rare. This includes cases pertaining to well understood underlying pathogeneses of diseases, the course of which is well documented and is also pretty much predictable, and can also be verified and measured objectively.

FDA has recently come up with a guideline based on criteria that will be used to allow external controls that shall substitute for two well-controlled randomised trials, although the guidance does not specify rare diseases. Apparently, it was Wilson Bryan, the outgoing OTAT director, who first announced the idea to have a town hall series during a meeting in 2022 so as to enhance the communication done with sponsors and thereby widen the scope of messaging.

There are evidences which suggest before the pandemic, when telemedicine was operated, it was effective secure, cost effective as well as a patient-centred service. The body of evidence has grown considerably since the pandemic occurred, and it has been brought to light that when telemedicine is not used appropriately, it is not perceived as something that is cost-effective or effective at all.

The idea is to zero-in on what the high quality and value adding features of telemedicines are so that their usage by patients is more widespread. A pragmatic and systematic review of telemedicine that took place between 2020 and 2022 was carried out to gauge its relevance in order to clarify its impact. The evidence that was witnessed came from the data of OCED nations.

The evidence suggested that telemedicines might as well have inequalities when it comes to care access and access among older, poorer as well as rural patients remained a concern as they happen to be among the cohort that is most likely to not gain from the health and digital literacy of telemedicine usage.

There is indeed substantial evidence stating that telemedicine did deliver effective, safe, as well as responsive services, although this contrasted with the views of numerous physicians. In Australia and Canada, a large set of population thought that the quality of care was in fact equivalent to that of in-person consultations. However, in places such as Sweden, Austria, and Norway, there were concerns on if at all remote consultations can replace in-person visits for services ranging from care visits to psychotherapy or also in cases where in-person coordination and bond was not even established in the first place. There were also concerns regarding increased health spending as well as high opportunity costs where serious medical issues were involved.

Emergency physicians as well as other specialists had a concern that the patients who were referred to them never had an in-person consultation and were not even given a proper examination.

When it came to Canada, challenges were raised because there were for-profit services that offered access to care by those with whom the patients had not consulted before, which in fact jeopardised the efficiency of the system.

Besides, telemedicine can also lead to inpatient care, where it would have been more appropriate to initially conduct an in-person consultation. This is especially of relevance in case of certain provider payment scheme that may lead to spending higher with no extra value.

As per a 2021 Canadian survey, 81% individuals who used video consultation revealed that it had helped them avoid doctor in-person or emergency room visits. There have also been instances where mobile health-led integrated care, ehealth interventions, and smartphone app-based models have reduced hospitalisation rates, which has led to lower costs.

On the other hand, teleconsultations can very well increase the patient numbers that are seen by the doctors in one single day, therefore elevating the stress levels because of high workloads.

Two inexpensive and widely available medications could be repurposed as a novel treatment for lacunar stroke, a kind of stroke connected to roughly half of all dementias. A lacunar stroke is a type of ischemic stroke that happens when one of the tiny arteries in the brain gets blocked and stops letting blood flow to it.

Each year, they affect approximately 25,000 people in the UK and, therefore, can cause memory issues as well as movement challenges.

Researchers from the Universities of Nottingham and Edinburgh conducted a clinical experiment that demonstrated that two drugs already used in healthcare could effectively and safely enhance outcomes after a lacunar stroke.

Treatment of lacunar stroke with drug repurposing

Other heart and circulation problems are currently treated with isosorbide mononitrate and cilostazol. If the findings of further trials are positive, they could be available for the treatment of lacunar strokes within five years.

Professor Joanna Wardlaw, the Chair of Applied Neuroimaging at the University of Edinburgh and Foundation Chair at the UK Dementia Research Institute, has stated that, until now, lacunar strokes have received the same care as other kinds of stroke, yet lacunar stroke plainly differs. He has further gone on to say that now that they understand more about what is triggering these strokes to attack the brain, they have been able to focus their efforts on treatments that can put a halt to this damage.

Before recommending either medicine as a treatment, these findings must be confirmed in larger trials. But given that these medications are currently widely used to treat other circulatory conditions and are reasonably priced, it shouldn’t take long to translate our research’s findings into routine clinical practice.

Enhancing patient outcomes

The trial included 363 participants who had suffered a lacunar stroke. For one year, participants received either isosorbide mononitrate or cilostazol alone, both medications combined, or none, in addition to routine stroke preventive care. The researchers looked into cilostazol and isosorbide mononitrate, which are thought to improve blood vessel inner lining function. Endothelial dysfunction is hypothesized to play a part in cerebral small vessel disease (cSVD).

After one year, people who took both medications were roughly 20% less likely to develop issues with their memory and thinking than the control group. They were also more self-sufficient and reported a higher quality of life.

Isosorbide mononitrate was found to be effective in reducing the risk of lacunar strokes, as well as improving thinking and memory skills, and quality of life. Cilostazol was also found to be effective in improving independence and mood. When taken together, these two drugs had even more positive effects.

The team is now planning to test these drugs in a larger, four-year clinical trial, which they are hoping will start by the end of 2023. These promising findings provide a long-awaited positive step towards the first treatments becoming available for lacunar strokes, offering much-needed hope for thousands of people, said Professor Sir Nilesh Samani, Director of the British Heart Foundation, the trial’s financial sponsor.

Notably, lacunar strokes are not the only reason cerebral small vessel disease might affect someone. These discoveries also open up new areas of investigation into other small artery disease-related illnesses, such as vascular dementia.