Day: October 4, 2023

Categories : New Compounds and Treatments OphthalmologyTags : 3 Comments

Eyedrops instead of Injections for Age-related Macular Degeneration

On By ModernMedia
Retina showing reticular pseudodrusen. Although they can infrequently appear in individuals with no other apparent pathology, their highest rates of occurrence are in association with age-related macular degeneration (AMD), for which they hold clinical significance by being highly correlated with end-stage disease sub-types, choroidal neovascularisation and geographic atrophy. Credit: National Eye Institute

A new compound potentially could offer an alternative to injections for the millions of people who suffer from wet age-related macular degeneration (AMD). The condition causes vision loss due to the uncontrolled growth and leakage of blood vessels in the back of the eye. A new paper in Cell Reports Medicine finds that a small-molecule inhibitor can reverse damage from AMD and promote regenerative and healing processes.

The drug can also be delivered via eyedrops – an improvement over current treatments for AMD, which require repeated injections into the eye.

“The idea was to develop something that can be more patient-friendly and doesn’t require a visit to the doctor’s office,” said lead researcher Yulia Komarova, associate professor of pharmacology at University of Illinois Chicago.

Komarova’s compound targets the protein End Binding-3 in endothelial cells, which line the inside of blood vessels. In the new study, the researchers looked at whether inhibiting EB3 function could stop the damaging leakage associated with wet AMD.

Using computational drug design methods, the team developed a small molecule drug, End Binding-3 inhibitor (EBIN), that could be delivered externally via eyedrops instead of by injection. They then tested its effectiveness in animal models of wet AMD, finding that twice-daily treatment reduced eye damage within 2–3 weeks.

Further investigation found that the inhibitor worked by rolling back aging-related genetic modifications. Aging causes inflammation and hypoxia in the eye that leads to changes in gene expression associated with the cellular effects and symptoms of wet AMD. Komarova and colleagues found that the EB3 inhibitor they developed reversed these epigenetic changes, restoring gene expression to a normal, healthy state.

“We reduce the effects of the stressor on endothelial cells and we improve regenerative processes, accelerating healing,” Komarova said. “That can be tremendous for the function of the cells.”

Because blood vessel leakage and hypoxic stress also drive many other medical conditions, Komarova’s group is interested in testing the inhibitor in models of acute lung injury, diabetic retinopathy, stroke, heart disease and even the general effects of aging on the brain. They are also exploring whether an implantable lens, similar to a contact lens, could deliver the drug to the eye more effectively than eyedrops.

Source: University of Illinois Chicago

Categories : COVIDTags :

New SARS-CoV-2 Variant BA.2.86 not as Resistant to Antibodies as First Feared

On By ModernMedia
Image by Fusion Medical on Unsplash

Researchers studying the new SARS-CoV-2 variant BA.2.86 have found that the new variant was not significantly more resistant to antibodies than several other circulating variants. Their study, published in The Lancet Infectious Diseases, also showed that antibody levels to BA.2.86 were significantly higher after a wave of XBB infections compared to before, suggesting that the vaccines based on XBB should provide some cross-protection to BA.2.86.

The recently emerged BA.2.86 is very different from any other currently circulating variants. It includes many mutations in the spike gene, reminiscent of the emergence of Omicron.  The virus uses the viral spike to infect cells and is the main target for our antibodies.  When the spike mutates, it comes with the risk that our antibodies are less effective against this new ‘variant’, and therefore that our protection from infection is reduced and that vaccines may need to be updated.

“We engineered a spike gene that matches that of the BA.2.86 variant and tested the blood of Stockholm blood donors (specifically those donations made very recently) to see how effective their antibodies are against this new variant. We found that although BA.2.86 was quite resistant to neutralising antibodies, it wasn’t significantly more resistant than a number of other variants that are also circulating”, says Daniel Sheward, lead author of the study and Postdoctoral researcher in Benjamin Murrell’s team at Karolinska Institutet.

An important question is whether upcoming updated vaccines that are based on the XBB variant will boost protection against BA.2.86.  To determine whether antibodies triggered by infection with XBB may be effective against this new variant, Ben Murrell’s team also compared samples taken before and after XBB spread in Sweden.

“We also found that antibody levels to BA.2.86 were significantly higher after a wave of XBB infections compared to before, suggesting that the vaccines based on XBB should provide some cross-protection to BA.2.86. However, BA.2.86 was resistant to all available monoclonal antibody therapeutics that we tested,” says Daniel Sheward.

Public health agencies need to know what the current level of immunity to this new variant is, and whether the vaccines are sufficient must be updated.  Monoclonal antibodies also represent an important option for some patient groups, such as the immunocompromised – for the clinicians, it’s important to know which if any, monoclonal antibody therapeutics will be effective against the variants that are circulating.  

“I think the main message is that there is currently no reason to be alarmed over this new variant and that it’s probably a good idea to get a booster vaccine when they are offered.  However, another ‘omicron-like’ event is also a reminder that we shouldn’t get complacent”, says Benjamin Murrell, Principal researcher at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet.

Source: Karolinska Institutet

Categories : Cancer PaediatricsTags :

The Urgent Need for Early Detection Emphasised this Bone Marrow & Leukaemia Awareness Month

On By ModernMedia
Credit: National Cancer Institute

Leukaemia has been identified as the most prevalent cancer among the country’s youth, according to the latest report from the National Cancer Registry (NCR) of South Africa (2021). However, approximately half of children with cancer remain undiagnosed, with the majority of cases only being detected during the advanced stages of the illness. This is partly attributed to a lack of awareness of the early warning signs of childhood cancer.

As the world observes Bone Marrow & Leukaemia Awareness Month until the 15th of October, Dr Candice Hendricks, Paediatric Haematologist and Medical Spokesperson for DKMS Africa shares that leukaemia can be categorised as acute leukaemias or chronic leukaemias, each with varying symptoms. “Acute leukaemias are far more common in children and can further be divided into acute lymphoblastic- (ALL) and acute myeloid leukaemia (AML). Among children, especially those aged between two and 10, Acute Lymphoblastic Leukaemia (ALL) is the most common blood cancer in this age group.

“This disease arises from genetic mutations in immature lymphocytes called lymphoblasts which are located in the bone marrow. The mutations lead to uncontrolled growth of these lymphoblasts,” she explains. “Lymphoblasts are abnormal blood stem cells that lose the ability to make mature blood cells. The uncontrolled growth of these cells in the bone marrow displaces normal blood cell development and leads to a decrease in properly functioning red blood cells, white blood cells, and platelets. Patients may potentially present with an elevated white blood cell count on blood results, however, their impaired function leaves the body vulnerable to infections.”

Aligned with the NCR, Dr Hendricks emphasises that early symptoms often go unnoticed, as they mimic common, mild conditions, causing many patients and those who care for them to overlook them. “However, the severity of these symptoms escalates rapidly with acute leukaemias and persist even after standard treatment for infections. A high index of suspicion is required in diagnosing patients, and if any symptom persists, an immediate full blood count test is necessary, followed by additional tests if irregularities are detected.”

Prominent symptoms indicating the disease include:

  • Blood clotting disorders or blood diathesis characterised by easy bruising from minor impacts and the appearance of small reddish spots on the skin. Other signs encompass blood in urine, as well as uncontrollable gum and nose bleeding.
  • Muscle and joint pain, particularly in the limbs, along with frequent limb numbness.
  • Fever and night sweats.
  • Anaemia caused by a deficiency of red blood cells, leading to constant fatigue, reduced exercise capacity, lethargy, sleepiness, and pale skin.
  • Recurrent infections that persist despite antibiotic treatment due to cancer cells impairing the immune system. Pathological cancer cells displace healthy leukocytes, rendering the body susceptible to various viral, bacterial, and fungal infections.
  • Loss of appetite and weight loss.
  • Enlarged lymph nodes.
  • Stomach pain resulting from spleen and/or liver enlargement.

In support of Bone Marrow & Leukaemia Awareness Month, DKMS Africa continues to raise awareness and funds to cover the registration costs for as many potential stem cell donors as possible. Stem cell donations offer the best chance of survival for children afflicted by high-risk leukaemia which does not respond to or recurs after standard treatment. Answer the call! If you’re aged between 17 and 55 and in good general health, please register at https://www.dkms-africa.org/register-now. Registration is entirely free and takes less than five minutes.

For further information, get in touch with DKMS Africa at 0800 12 10 82.

About DKMS
DKMS is an international non-profit organisation dedicated to saving the lives of patients with blood cancer and blood disorders. Founded in Germany in 1991 by Dr. Peter Harf, DKMS and organisations of over 1,000 employees have since relentlessly pursued the aim of giving as many patients as possible a second chance at life. With over 11 million registered donors, DKMS has succeeded in doing this 100,000 times to date by providing blood stem cell donations to those in need. This accomplishment has led to DKMS becoming the global leader in the facilitation of unrelated blood stem cell transplants. The organisation has offices in Germany, the US, Poland, the UK, Chile and South Africa. In India, DKMS has founded the joint venture DKMS-BMST together with the Bangalore Medical Services Trust. International expansion and collaboration are key to helping patients worldwide because, like the organisation itself, blood cancer knows no borders.

DKMS is also heavily involved in the fields of medicine and science, with its own research unit focused on continually improving the survival and recovery rate of patients. In its high-performance laboratory, the DKMS Life Science Lab, the organisation sets worldwide standards in the typing of potential blood stem cell donors.

Categories : Gender Metabolic DisordersTags :

Study Suggests Lowering Type 2 Diabetes Diagnosis Threshold in Women under 50

On By ModernMedia
Photo by National Cancer Institute on Unsplash

New research published in the journal Diabetes Therapy suggests that the diagnosis threshold for type 2 diabetes (T2D) should be lowered in women aged under 50 years, since natural blood loss through menstruation could be affecting their blood sugar management.

Analysis of the national diabetes audit results has shown that women of younger age with type 2 diabetes mellitus (T2D) seem to have a higher mortality rate than men. The underlying mechanisms remain unclear. However, it is known that women are on average diagnosed with T2D at a later age than men. In this new study, the authors investigated whether a contributing factor to this late diagnosis may be a sex difference in the levels of glycated haemoglobin (HbA1c) due to haemoglobin replacement linked to menstrual blood loss.

This mechanism behind this could be shorter erythrocyte (red blood cell) survival which results in shorter exposure of haemoglobin to glucose compared with individuals who do not menstruate. Given that the diagnosis of T2D is also based on HbA1c, the use of the same reference range irrespective of age and sex, when a slightly lower point for T2D for premenopausal women may be appropriate, could potentially lead to under diagnosis of T2D in women and missed opportunities for intervention.

The study, by Dr Adrian Heald, Salford Royal Hospital, UK, and colleagues, examined HbA1c testing across seven UK laboratory sites (representing 5% of UK population). They conducted an exploratory analysis in two cohorts: cohort 1 was from one laboratory tested between 2012 and 2019 (146 907 participants). They assessed the sex and age differences of HbA1c in individuals who underwent single testing only, that had not been diagnosed with diabetes and had an HbA1c result of equal to or less than 48mmol/mol (the cutoff for diagnosing diabetes). The process was replicated in cohort 2 results from six laboratories with individuals tested between 2019 and 2021 (total people included 938 678). The possible national impact was estimated by extrapolating findings based on the Office of National Statistics (ONS) England population data and National Diabetes Audit published T2D prevalence and related excess mortality.

At age 50 years, average HbA1c levels in women lag by approximately five years compared to men. The data also show women aged under 50 years old had an HbA1c distribution that was lower than that of men by an average of 1.6mmol/mol (4.7% of the overall mean) while the difference in the distribution of HbA1c for individuals aged 50 years and over was less pronounced.  Further analysis showed that, at HbA1c of 48mmol/mol, 50% fewer women could be diagnosed with T2D than men under the age of 50, whilst only 20% fewer women could be diagnosed with T2D than men over or equal to the age of 50. These findings were consistent with those in cohort 2.

Based on these observations, the authors estimated the effects of lowering the threshold for diagnosis of diabetes from HbA1c (48mmol/mol) by 4.2% to 46mmol/mol for women under the age of 50. This analysis showed that an additional 35 345 currently undiagnosed women in England would be reclassified as being diagnosed with T2D (17% more than the current 208 000 recorded women with T2D aged under 50 years). Lifestyle changes and treatment for diabetes would then be initiated for these women enabling improvement in health outcomes over both the short and longer term.

The authors also highlight that sex and gender difference in adverse cardiovascular risk factors are known to be present prior to the development of T2D. Once diagnosed, the prevalence of atherosclerotic cardiovascular disease is twice as high in patients with diabetes mellitus compared to those without diabetes mellitus. For women, diabetes mellitus is a stronger risk factor for cardiovascular disease than for men: women with diabetes aged 35–59 years have the highest relative cardiovascular death risk across all age and sex groups.

Furthermore, there is disparity in cardiovascular risk factor management between men and women, including in high-risk groups such as women with T2D.  Women are less likely than men to receive treatment and cardiovascular risk reduction interventions that are recommended by international guidelines on diabetes. In addition, concordance with medication or prescription treating cardiovascular risk factors is lower in women than men with T2D, with less use of statins, aspirin and beta blockers. The authors say taken together, these factors mean “timely diagnosis of type 2 diabetes and initiation of preventative treatment has the potential to improve cardiovascular risk profile over lifetime and facilitate longer life quality and expectancy in women. Our findings provide evidence that the HbA1c threshold for this group should be re-evaluated.”

Source: EurekAlert!

Categories : HospitalsTags :

Department of Health in Last-minute Bid to Avoid Stand-off with Nurses over Uniforms

On By ModernMedia
Photo by Jeshoots Com on Unsplash

By Marecia Damons for GroundUp

The Department of Health is scrambling to avoid a stand-off with nurses who have threatened to work in their own clothes if a dispute over the provision of uniforms is not resolved.

Since 2005, nurses had received an annual allowance to buy their uniforms. But this ended on 31 March this year, after a new agreement was signed in the Public Health and Social Development Sectoral Bargaining Council in terms of which they would get uniforms instead.

As a result, nurses did not get the usual allowance in April – R2600 a year, according to Spokesperson for the Democratic Nursing Association of SA (DENOSA) Sibongiseni Delihlazo.

Instead, they were supposed to be provided with uniforms by 1 October 2023. The agreement stated that in the first year, government must provide nurses with four sets of uniforms, one pair of shoes, and one jersey. In the second year, government must provide three sets of uniforms, one belt, and one jacket.

The plan was that the procurement process would be centralised. But at another bargaining council meeting, in June 2023, the health department said it would be difficult to provide the uniforms on time.

Then on 12 July, Sandile Buthelezi, director-general for the DOH, issued a circular to all provincial health departments notifying them that the uniforms would be provided from January 2024 to January 2025.

The circular stated that the DOH would use a decentralised approach to providing uniforms by using provincial tenders.

“Provincial heads are responsible for participating and facilitating in tender processes through the bid specification in terms of colour, fabric composition and garment, development, review of the policy and monitoring and evaluation,” Buthelezi wrote.

Until January 2026, the circular said, nurses would be expected to wear the new uniform from Monday to Thursday and wear their old uniform from Friday to Sunday. From January 2026, when they would have both years’ issue, nurses would be expected to wear the new uniforms every day.

DENOSA responded to this a week later, and said the department’s circular went against the bargaining agreement.

Delihlazo said they proposed that if the department is unable to supply the uniform by 1 October, they must pay nurses an allowance as previously.

If the department failed to provide uniforms or pay an allowance, DENOSA said, its 84 000 members would embark on an indefinite protest action by wearing their own clothes to work from 1 October.

Delihlazo said the yearly allowance did not cover the cost of a full uniform. “Their uniforms are tearing and the colour is fading. So how can you expect nurses to wear uniforms if you don’t pay them a uniform allowance?”

He said the tender process meant the colour of the nurses’ uniforms and the quality of the fabrics might differ from one province to the next. The process also “opens a window of opportunity for corruption,” Delihlazo said. “Money may be given for uniforms but the tender process is porous.”.

Then, at a last-minute meeting of the bargaining council last Thursday, the department proposed to put on hold the supply of uniforms until 2024, according to a DENOSA statement. Meanwhile the health department would pay nurses an allowance of R3,153 by 30 November.

DENOSA said the agreement should be signed by the end of the week. If not, the union said, nurses would work in their own clothes.

The health department did not respond to GroundUp’s questions.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp