Which factors are significantly associated with impairment of GFR in adults with type 2 diabetes?

Spain: A recent study published in Endocrinología, Diabetes y Nutrición has shed light on the risk factors associated with glomerular filtration rate (GFR) in Mexican adults with type 2 diabetes mellitus (T2DM).

The researchers showed male sex, older age, longer duration of type 2 diabetes, and arterial hypertension were associated with a decrease in the GFR; waist circumference (WC), and body mass index (BMI) were directly associated. There was no impact of glucose and HbA1c on the glomerular filtration rate.

Type 2 diabetes mellitus is related to GFR impairment, which is one of the leading causes of chronic kidney disease (CKD). CKD is defined as the permanent loss of kidney function and is characterized by a GFR below 60 ml/min/1.73 m2. Approximately 10% of the world’s adult population is affected by this disorder, which is why it is considered a serious public health problem.

Against the above background, Gloria Mendoza López and colleagues from Spain aimed to identify the risk factors related to GFR in Mexican adults with type 2 diabetes using a validated multiple linear regression model (MLRM), with emphasis on glycemic control, body adiposity, duration of diabetes and other relevant risk factors.

For this purpose, the researchers conducted a cross-sectional, analytical, and observational study on 252 adults with a previous diagnosis of T2DM. Body mass index and waist circumference were determined, and a fasting blood sample was collected for creatinine, glucose, and HbA1c determinations.

Cockcroft–Gault equation adjusted for body surface area was used for GFR calculation. Four MLRMs were performed to determine the factors related to the GFR; it was evaluated whether these models complied with the statistical assumptions of the linear regression model.

The participants’ average age was 60 ± 12 years, and 62.3% were women.

The study led to the following findings:

  • GFR correlated with BMI and WC; age and duration of the diabetes were associated inversely.
  • Model 4 of the MLRM reported a coefficient of determination of 53.5% where the variables BMI (β = 1.31), duration of T2DM (β = −0.57), male sex (β = −6.01), age (β = −1.45), and arterial hypertension (β = −6.53) were simultaneously and significantly related to the GFR.

In conclusion, the factors related to GFR reduction in Mexican adults with T2DM were being male, age, duration of type 2 diabetes, and the presence of hypertension. WC and BMI were related to an increase in GFR. The researchers found no significant effect of glucose or HbA1c levels on this.

One of the study limitations is the lack of measurement of other biochemical parameters (such as urine albumin or blood urea nitrogen), which would have enabled a more sensitive diagnosis of the patient’s kidney function. In addition to the relatively small sample size, another weakness is the lack of information on smoking habits and physical activity in the patients studied.

Reference:

Mendoza López G, Morales Villar AB, Tejada Bueno AP, Lozada Hernández J, García Cortes LR, Maldonado Hernández J. Factores de riesgo asociados con la tasa de filtración glomerular en adultos mexicanos con diabetes mellitus tipo 2. Endocrinol Diabetes Nutr. 2024. https://doi.org/10.1016/j.endinu.2023.12.002

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Oral Minocycline fails to arrest progression of Macular Degeneration: JAMA

A recent study published in the Journal of American Medical Association investigated the potential of oral minocycline in slowing down the progression of geographic atrophy (GA) in age-related macular degeneration (AMD). GA is a leading cause of irreversible vision loss among the elderly which makes effective treatments crucial.

Existing therapies for GA enlargement in AMD are limited in efficacy and often require invasive intravitreal administration by raising concerns about safety and patient compliance. Thus, Tiarnan Keenan and team evaluate the safety and efficacy of oral minocycline, a microglial inhibitor, as an alternative therapeutic approach.

The phase 2 clinical trial was conducted over 45 months and included 37 participants with GA in one or both eyes. After a 9-month run-in phase, the participants received oral minocycline (100 mg, twice daily) for 3 years. However, despite the treatment, this research found no significant reduction in the rate of GA enlargement when compared to the run-in phase.

The National Institutes of Health (NIH) and Bristol Eye Hospital expressed disappointment at the results by underlining that oral minocycline did not show the desired efficacy in slowing down GA progression. The difference in rate of change of GA area on fundus autofluorescence was the primary outcome measure which remained largely unaffected by the treatment.

Also, secondary outcome measures included visual acuity and subfoveal retinal thickness showed no significant improvement with oral minocycline treatment. Despite some adverse events related to minocycline, like the elevated thyrotropin levels, skin hyperpigmentation and no severe ocular complications were reported.

Reference:

Keenan, T. D. L., Bailey, C., Abraham, M., Orndahl, C., Menezes, S., Bellur, S., Arunachalam, T., Kangale-Whitney, C., Srinivas, S., Karamat, A., Nittala, M., Cunningham, D., Jeffrey, B. G., Wiley, H. E., Thavikulwat, A. T., Sadda, S., Cukras, C. A., Chew, E. Y., & Wong, W. T. (2024). Phase 2 Trial Evaluating Minocycline for Geographic Atrophy in Age-Related Macular Degeneration. In JAMA Ophthalmology. American Medical Association (AMA). https://doi.org/10.1001/jamaophthalmol.2024.0118

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Guselkumab improves physical function in patients with active psoriatic arthritis: Study

A recent study published in the ACR Open Rheumatology journal explored the effectiveness of guselkumab in treating patients with psoriatic arthritis (PsA). The study evaluated patient-reported outcomes after 6 months of on-label guselkumab use and provided valuable insights into its real-world effectiveness.

Psoriatic arthritis is a chronic inflammatory disease that affects the joints and skin that causes pain, stiffness and swelling. Despite advancements in treatment, many patients continue to struggle with symptoms that leads to decreased quality of life.

The study included participants from the CorEvitas Registry who initiated and persisted with guselkumab treatment and focused on key patient-reported outcomes such as pain, patient global assessment of arthritis and psoriasis and physical function.

The results from the analysis revealed that of the patients who persisted with on-label guselkumab treatment for 6 months, a significant proportion experienced clinically meaningful improvements in pain and physical function. Approximately 40% of patients reported at least a 15-mm reduction in pain scores while around 30% achieved improvements in physical function scores.

The study population consisted mainly of patients with treatment-resistant PsA by indicating the potential of guselkumab as a viable treatment option for those who have not responded well to previous therapies. This unveiled the importance of exploring alternative treatment options for PsA patients who may have limited choices due to treatment resistance.

The study also emphasized that pain and physical function are crucial factors which impact the overall quality of life for PsA patients. The outcomes demonstrate that guselkumab holds promise in addressing these key aspects of the disease which could improve outcomes and management of PsA symptoms.

Source:

Mease, P. J., Ogdie, A., Tesser, J., Shiff, N. J., Zhao, R. S., Chakravarty, S. D., Kelleman, M., Dodge, R., McLean, R. R., Broadwell, A., Kavanaugh, A., & Merola, J. F. (2024). Improvements in Patient‐Reported Outcomes Through Six Months of Guselkumab Treatment in Patients With Active Psoriatic Arthritis: Real‐World Data From the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. In ACR Open Rheumatology. Wiley. https://doi.org/10.1002/acr2.11657

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Omega 3 may arrest memory dysfunction due to high-fat diet intake before surgery: Study

USA: Consuming a high-fat diet can increase the risk of persistent postoperative cognitive dysfunction-associated memory impairments following surgery in a TLR4-dependent manner, a recent study published in Brain, Behavior, and Immunity has found. 

The study, building upon previous research from the same lab at Ohio State University, also showed that taking a DHA omega-3 fatty acid supplement for a month before the unhealthy eating and surgical procedure prevented the effects on memory linked to both the high-fat diet and the surgery in aged and young adult rats.

“Eating fatty food in the days leading up to surgery may prompt a heightened inflammatory response in the brain that interferes for weeks with memory-related cognitive function in older adults, research in animals suggests, even in young adults,” the study stated. 

Three days on a high-fat diet alone was detrimental to a specific type of fear-related memory in aged rats for as long as two weeks later – the same type of impairment seen in younger rats that ate fatty food and had a surgical procedure. The team has traced the brain inflammation behind these effects to a protein that activates the immune response.

“These data suggest that these multiple insults have a compounding effect,” said senior author Ruth Barrientos, an investigator in Ohio State’s Institute for Behavioral Medicine Research and associate professor of psychiatry and behavioral health and neuroscience in the College of Medicine.

“We’ve shown that an unhealthy diet, even in the short term, especially when it’s consumed so close to a surgery, which in and of itself will cause an inflammatory response, can have damaging results,” Barrientos said. “The high-fat diet alone might increase inflammation in the brain just a little bit, but then you have surgery that does the same thing, and when put together in a short amount of time you get a synergistic response that can set things in motion toward a longer-term memory issue.”

The study was published recently in the journal Brain, Behavior, and Immunity.

Barrientos’ lab studies how everyday life events might trigger inflammation in the aging brain as the nervous system responds to signals from the immune system reacting to a threat. Decades of research has suggested that with aging comes long-term “priming” of the brain’s inflammatory profile and a loss of brain-cell reserve to bounce back.

Researchers fed young adult and aged rats a diet high in saturated fat for three days before a procedure resembling exploratory abdominal surgery – an event already known to cause about a week of cognitive issues in an older brain. Control rats ate regular food and were anesthetized, but had no surgery. (Barrientos’ lab has determined anesthesia alone does not cause memory problems in rats.)

In this study, as in previous research on aged rats treated with morphine after surgery, the team showed that an immune system receptor called TLR4 was the culprit behind the brain inflammation and related memory problems generated by both surgery and the high-fat diet, said first author Stephanie Muscat, assistant clinical professor of neuroscience at Ohio State.

“Blocking the TLR4 signaling pathway prior to the diet and surgery completely prevented that neuroimmune response and memory impairments, which confirmed this specific mechanism,” Muscat said. “And as we had found before in another model of an unhealthy diet, we showed that DHA supplementation did mitigate those inflammatory effects and prevent memory deficits after surgery.”

There were some surprising memory findings in the new work. Different behavioral tasks are used to test two types of memory: contextual memory based in the hippocampus and cued-fear memory based in the amygdala. In contextual memory tests, rats with normal memory freeze when they re-enter a room in which they had an unpleasant experience. Cued-fear memory is evident when rats freeze in a new environment when they hear a sound connected to that previous bad experience.

For aged rats in this study, as expected, the combination of a high-fat diet and surgery led to problems with both contextual and cued-fear memory that persisted for at least two weeks-a longer-lasting effect than the researchers had seen before.

The high-fat diet alone also impaired the aging rats’ cued-fear memory. And in young adult rats, the combination of the high-fat diet and surgery led to only cued-fear memory deficits, but no problems with memory governed by the hippocampus.

“What this is telling us in aged animals, along with the fact we’re seeing this same impairment in young animals after the high-fat diet and surgery, is that cued-fear memory is uniquely vulnerable to the effects of diet. And we don’t know why,” Barrientos said. “One of the things we’re hoping to understand in the future is the vulnerability of the amygdala to these unhealthy diet challenges.”

With increasing evidence suggesting that fatty and highly processed foods can trigger inflammation-related memory problems in brains of all ages, the consistent findings that DHA – one of two omega-3 fatty acids in fish and other seafood and available in supplement form – has a protective effect are compelling, Barrientos said.

“DHA was effective at preventing these changes,” she said. “And that’s amazing – it suggests that this could be a potential pretreatment, especially if people know they’re going to have surgery and their diet is unhealthy.”

Reference:

Stephanie M. Muscat, Michael J. Butler, Menaz N. Bettes, James W. DeMarsh, Emmanuel A. Scaria, Nicholas P. Deems, Ruth M. Barrientos, Post-operative cognitive dysfunction is exacerbated by high-fat diet via TLR4 and prevented by dietary DHA supplementation, Brain, Behavior, and Immunity, Volume 116, https://doi.org/10.1016/j.bbi.2023.12.028.

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Not placing drain may reduce rates of pancreatic leaks and hospital stay after distal pancreatectomy: Study

Research led by Amsterdam UMC across ten Dutch hospitals and two Italian hospitals has found that not placing a drain during surgery improves outcomes in patients undergoing a left-sided pancreatic resection, also known as ‘distal pancreatectomy’. The study, today published in Lancet Gastroenterology & Hepatology, set out to confirm the safety of drainless surgery, as compared to the current routine practice of leaving a surgical drain. Ultimately, the study not only confirmed the safety of ‘drainless surgery’ but, in addition, demonstrated that this approach reduced the rates of postoperative pancreatic leaks and overall morbidity and hospital stay.

“This study is expected to close a longstanding debate among surgeons” says Marc Besselink, professor of surgery at Amsterdam UMC and principal investigator of the study, “in an era where medicine is increasingly becoming more complex and costly, this study actually shows that omitting an intervention actually improves outcome. Sometimes, less is more”.

Surgeons traditionally place a drain to facilitate the removal of fluids such pancreatic juice, that could build-up after surgery, in patients undergoing distal pancreatectomy. This is routine practice due to the high (25%) risk of postoperative leaks which may have serious consequences. However, an increasingly large group of surgeons have argued that many of these leaks stop spontaneously and that leaving a percutaneous surgical drain actually increases the risk of complications as it may facilitate leaks and increase the risk of infection.

The PANDORINA trial set out to investigate this and included 282 patients undergoing distal pancreatectomy. The primary goal was to demonstrate that drainless surgery was safe in terms of major complications. This succeeded. Secondarily, the study showed that the rates of detected postoperative leaks decreased by 15% (from 27% to 12%) in patients undergoing drainless surgery and the rate of overall complications also reduced (from 51% to 33%).

“The benefit of drainless surgery is much larger than we anticipated before the trial,” adds Professor Roberto Salvia from the Pancreas Institute in Verona, and for our colleagues this is very compelling evidence”. In order to facilitate this, the researchers have already shared their findings at several international symposia. “We expect that drainless surgery for distal pancreatectomy will now enter the international guidelines and become part of daily practice for pancreatic surgeons across the world” says Ward van Bodegraven, researcher at Amsterdam UMC and coordinator of the trial.  

Reference:

Eduard A van Bodegraven, Alberto Balduzzi, Tess M E van Ramshorst, Prof Giuseppe Malleo,  Frederique L Vissers, Jony van Hilst, Prophylactic abdominal drainage after distal pancreatectomy (PANDORINA): an international, multicentre, open-label, randomised controlled, non-inferiority trial, The Lancet Gastroenterology & Hepatology, https://doi.org/10.1016/S2468-1253(24)00037-2.

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CDSCO Panel Rejects Akum Pharma’s Clonazepam-Duloxetine Combination Drug

New Delhi: Reviewing the justification provided by the drug major Akum Pharmaceutical concerning the fixed-dose combination (FDC) Clonazepam plus Duloxetine Hydrochloride, the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has rejected approval for the proposed FDC.

This came after the drug maker Akum Pharmaceutical presented the proposal along with justification and rationality before the committee.

Clonazepam is a benzodiazepine drug used for the acute treatment of panic disorder, epilepsy, and nonconvulsive status epilepticus. The drug also has many off-label indications, including restless leg syndrome, acute mania, insomnia, and tardive dyskinesia.

Its primary mode of action is to facilitate GABAergic transmission in the brain by a direct effect on benzodiazepine receptors. GABA receptors lie on the cell bodies of dorsal raphe neurons, and GABA acts to inhibit raphe cell firing, an action potentiated by benzodiazepines.

Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor antidepressant (SSNRI). Duloxetine affects chemicals in the brain that may be unbalanced in people with depression.

Duloxetine is used to treat major depressive disorder in adults. It is also used to treat general anxiety disorder in adults and children who are at least 7 years old. Duloxetine is also used in adults to treat nerve pain caused by diabetes (diabetic neuropathy), or chronic muscle or joint pain (such as low back pain and osteoarthritis pain).

In line with the fixed-dose combination (FDC) Clonazepam plus Duloxetine Hydrochloride (Gastro-resistant pellets), at an earlier SEC meeting held on 12.10.2023, the expert panel suggested, ‘The firm should present the justification on the rationality of the combination and its significant benefits’.

The expert panel also said that the proposed FDC was not approved anywhere in the world and that the firm should provide current, peer-reviewed scientific research to support the proposed indication of the FDC.

In continuation, at the recent SEC meeting for Neurology and Psychiatry held on 23rd February 2024, the expert panel reviewed the proposal along with justification and rationality of the FDC Clonazepam IP (as uncoated tablet) 0.5mg plus Duloxetine Hydrochloride IP eq. to Duloxetine (as Gastro-resistant pellets) 20mg capsule provided by Akum Pharmaceutical.

Following extensive consideration, the committee restated its previous recommendation that it not be approved by the FDC.

Also Read: AstraZeneca Gets CDSCO Panel Nod to Study anticancer drug Volrustomig

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DCI invites applications from dental colleges for renewal permissions for MDS course, details

New Delhi- Through a recent notice, the Dental Council of India (DCI) has invited applications for renewal of permission for postgraduate- MDS courses at dental colleges.

This comes as a letter has been issued by Vinay Gupta, Deputy Secretary, Dental Council of India (DCI) to the Principals/Heads of all Dental Colleges in India regarding the application for renewal of permission in Post Graduate courses.

The letter said that as per the provision of the Dental Council of India Regulation, 2006, the institutions which are to be renewed for the PG course, should submit their application for permission of renewal for the PG course to the Dental Council of India by the 30th April.

Also Read: DCI Releases Updated List Of Defaulter Dental Colleges Who Failed To Submit Anti-Ragging Orientation Program Report

Furthermore, all the dental colleges are also hereby directed to apply to DCI without any delay, for the purpose, along with a requisite fee of Rs.1,77,000/- (1,50,000 + 18% GST) per subject as prescribed in the Dental Council of India Regulations, 2006.

Further, all Dental Colleges are also directed to apply to DCI for this purpose without any delay along with the requisite fee of Rs 1,77,000/- (Rs 1,50,000 + 18% GST) per subject, as prescribed in the Dental Council of India Regulations, 2006. Along with this, other necessary documents etc. are also required so that the Council can process the renewal request timely as per DCI Regulations, 2006.

Also Read: DCI Releases List of Defaulter Dental Colleges who failed to submit Anti-Ragging Orientation Program Report

Meanwhile, DCI will not inspect for renewal of MDS courses in the event of non-receipt of application from the concerned Dental College nor will DCI be responsible for the delay and consequences of failure to do so.

The Dental Council of India has been constituted by an Act of Parliament to regulate the profession of dentistry and also to maintain the highest standards of dental education in the country. It is the statutory and bounden duty of the DCI to take such steps which are required to be taken to maintain the highest standards of dental education in the country.

To view the official notice, click the link below

https://medicaldialogues.in/pdf_upload/dci-234408.pdf

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The problem with seeing young sportspeople as athletes first, children second

A recent report commissioned by Swim England, the national governing body for swimming in England, has found evidence of a “culture of fear” in swimming clubs. The report finds that children involved in competitive swimming can be treated like professional athletes, and the importance of sporting performance held above all else.

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Zydus Lifesciences gets USFDA okay for Finasteride and Tadalafil Capsules

Ahmedabad: Zydus Lifesciences Limited has announced that the Company has received final
approval from the United States Food and Drug Administration (USFDA) to market Finasteride and
Tadalafil Capsules USP 5 mg/5 mg. (USRLD: ENTADFI TM).

“Zydus is the “first approved applicant” for Finasteride and Tadalafil Capsules, 5 mg/5 mg, as defined
in section 505(j)(5)(B)(v)(III) of the FD&C Act and therefore is eligible for 180 days of CGT
exclusivity,” the Company stated.

Tadalafil is used to treat benign prostatic hyperplasia.

Benign prostatic hyperplasia is also known as prostate enlargement. In this disease, there is a noncancerous increase in size of the prostate gland. Symptoms may include Weak stream, frequent urination, trouble starting to urinate, inability to urinate, or loss of bladder control. 

The drug will
be manufactured at the group’s formulation manufacturing facility at Ahmedabad SEZ II, India.


The group now has 392 approvals and has so far filed over 460* ANDAs since the commencement
of the filing process in FY 2003-04.

Read also: Zydus Lifesciences bags USFDA tentative nod for Edaravone Injection to treat amyotrophic lateral sclerosis

Medical Dialogues team had earlier reported that the Company had received final approval from the USFDA to market Silodosin Capsules, 4 mg and 8 mg (USRLD: Rapaflo capsules). Silodosin capsules are indicated to treat signs and symptoms of an enlarged prostate gland, which is also known as benign enlargement of the prostate (benign prostatic hyperplasia or BPH).

Read also: Zydus Lifesciences bags USFDA nod for Silodosin, Pregabalin capsules

Headquartered in Ahmedabad, Zydus Lifesciences Limited is an innovative, global lifesciences company that discovers, develops, manufactures, and markets a broad range of healthcare therapies. The group has a significant presence in cancer related therapies and offers a wide range of solutions with cytotoxic, supportive & targeted drugs. The group employs over 26,000 people worldwide, including 1,400 scientists engaged in R & D.

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