Health Ministry directs PGI Chandigarh Director to expedite completion of Satellite Centres

Chandigarh: Taking cognizance of the delay in the completion of PGI’s satellite centres in Una and Ferozepur, the Ministry of Health and Family Welfare has issued a
directive to the Postgraduate Institute of Medical Education and Research (PGI) Chandigarh director to ensure regular inspections and monitoring to accelerate the process.

This directive came from the latest meeting of the standing finance committee held in New
Delhi.

The committee emphasized that to ensure cooperation and efficiency of the work process, the tenders for
civil works and medical services need to be combined. Currently, these services are managed separately by the institute and this is creating delays in the completion of the work. The construction of PGI satellite centres in Ferozepur and
Una was initially slated for completion by 2021. However, progress has been
slow, and in 2022, the parliamentary committee of the Rajya Sabha criticized
PGI for the delays, reports Times of India.

Also Read:PGI’s Prof Mandeep Singh Dhillon retires after 37 years of service

In February, the
foundation stone for the Ferozepur satellite centre was laid by Prime Minister Narendra Modi virtually. This centre had an
allocated budget of Rs 490.54 crores and it will feature 100 beds, including 30 for
intensive care and high-dependency units. It will house 10 clinical speciality
departments, five support departments, and multiple operation theatres.
Additionally, the building will be a platinum-rated green hospital, utilizing
modern construction techniques to ensure sustainability.

The Una satellite centre is supposed to be a 300-bed hospital
with the future plans of turning it into a medical college. Spread over 38 acres and costing Rs
491 crores, the facility will include multispeciality outpatient departments
(OPDs), an intensive care unit (ICU), a blood bank, modular operation theatres,
and consultant rooms. The campus will also house residential units for staff,
a shopping complex, and a guest house for visiting faculty, reports the Daily.

PGI received the land for the Una project in 2018, and the
foundation stone was laid in 2019. Despite these early steps, construction has
lagged, prompting the recent directives to accelerate progress. The health ministry’s insistence on regular inspections and
combined tenders aims to eliminate bottlenecks and ensure the timely completion
of these critical healthcare facilities. 

Also Read: 95 faculty members to be recruited for Advanced Mother and Child Centre at PGI Chandigarh

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Breaking the Chain: The Crucial Role of Prediabetes Screening in Preventing Diabetes and Its Complications

Preventing Diabetes -A Stitch in Time Saves Nine:

Diabetes prevention has become extremely critical, necessitating all healthcare stakeholders’ actions. Many diabetes-preventative interventions continue to focus primarily on prediabetes. Data regarding prediabetes prevalence is useful in evaluating and predicting the present and potential future diabetes pandemics(1).

Prediabetes: Indian Scenario

The Indian Council of Medical Research–India Diabetes (ICMR-INDIAB) study emphasises the enormous burden of prediabetes, where the prevalence of prediabetes in India is estimated to be 136 million, higher than the prevalence of diabetes [101 million] (1).

Prediabetes Conversion to Diabetes: The conversion rate from prediabetes to type 2 diabetes (T2D) is very high among Asian Indians (2). Mohan et al. reported more than 40% of Indian prediabetes patients developed T2DM within 8 years of follow-up(3). A recently published paper by K.M. Venkat Narayan et al indicated that among the Indian population, the annual transition probability from isolated impaired fasting glucose (i-IFG) to diabetes is 8.6%, while that from impaired glucose tolerance (IGT) to diabetes is 13.9%. The average time spent by Indians in IFG (impaired fasting glucose) and IGT are 9.7 and 6.1 years, respectively (4).

Prediabetes and Complications: A study from India found that over 10% of people with prediabetes had vascular complications linked to diabetes, indicating that prediabetes is linked to an increased risk of vascular complications. Prediabetes also increases cardiovascular disease [incidence rate per 10,000 person-years: 58.3 for those with normal glucose regulation vs. 67.0 for those with prediabetes] and all-cause mortality [incidence rate per 10,000 person-years: 73.6 for those with normal glucose regulation vs. 81 for those with prediabetes] (5).

Why is Prediabetes Screening Crucial? High insulin resistance is prominent in Asian Indians, which hastens the progression of diabetes (5). The average time spent by Indians with isolated impaired fasting glucose (i-IFG) and IGT is 9.7 and 6.1 years, respectively (4). Early screening, detection, and treatment of prediabetes are essential in the Indian population since they lower the risk of developing diabetes and its complications (2).

Prediabetes Screening & Tools

The RSSDI(Research Society for Study of Diabetes in India) recommends screening of prediabetes in individuals presenting to health care settings for unrelated illnesses, family members of diabetes patients, antenatal care, dental care, overweight children and adolescents at the onset of puberty, and community screening wherever feasible (6). The RSSDI guideline and ADA (American Diabetes Association) 2024 diagnosed prediabetes in an individual having an A1C 5.7–6.4% (39–47 mmol/mol), IFG 100 mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L) and 2-h PG during 75-g OGTT (oral glucose tolerance test) 140 mg/dL (7.8 mmol/L) to 199 mg/dL [11.0 mmol/L] (6,7).

Non-invasive, easy-to-apply ancillary screening tools are needed for identifying and screening individuals with prediabetes (8). Mohan et al. developed a simple screening tool, the Indian Diabetes Risk Score (IDRS), to screen the population for diabetes. IDRS is computed using age, family history of diabetes, waist circumference, and a subject’s physical activity level. The score ranges from 0 to 100; a score ≥60 denotes high risk, 30–60 denotes moderate, and a score <30 in a subject denotes low risk of developing diabetes in the future (9). More recently, the International Diabetes Federation (IDF) has suggested the use of 1-h post-load plasma glucose ≥ 155 mg/dL (8.6 mmol/L) in people with normal glucose tolerance (NGT) during an OGTT to indicate prediabetes (10).

Risk Factors for the Development of Prediabetes

According to Indian Expert Group Consensus, the common risk factors for prediabetes in India include age (45 or older), positive family history of diabetes and gestational diabetes, high HbA1c, physical inactivity, poor high-density lipoprotein cholesterol (HDL-C) below 35 mg/dL, high triglycerides (TG) above 200 mg/dL, hypertension or being on hypertension medications (2).

Early Prediabetes Screening Helps in Early Identification & Management

A meta-analysis of 7 interventional studies involving 26,389 patients assessed the benefits of effective interventions, which included lifestyle (including dietary and exercise recommendations) or drugs (including acarbose and metformin) on microvascular and macrovascular events in prediabetic patients. The results provided that early effective intervention significantly reduced all-cause mortality by 18% in prediabetic patients without a history of cardiovascular disease (95% CI=0.69~0.98, P=0.03) and retinopathy by 38% [95% CI 0.70-0.98] (11). Another cross-sectional study (n=2968) assessed the prevalence of prediabetes and undiagnosed diabetes in patients with cardiovascular disease according to the ADA criteria. The results showed about 32.4% of them had prediabetes, and up to one-third of those with undiagnosed prediabetes had already been diagnosed with cardiovascular complications (12). These suggest that an early diagnosis and interventions can benefit prediabetes patients.

A lifestyle change may reduce the number of prediabetic people who develop diabetes to 20% (13). The Indian Diabetes Prevention Program (IDPP) trial also noted this benefit in Asian Indians. A moderate-intensity exercise, just 150 minutes per week of brisk walking, enhanced insulin sensitivity among prediabetes. However, lifestyle interventions may not be effective and sufficient in all cases of prediabetes. Metformin is the only pharmacologic agent recommended for preventing or postponing T2D. The DCGI (Drug Controller General of India) approved the use of metformin in prediabetes, where lifestyle intervention is insufficiently effective in reducing body weight and improving glucose tolerance (2).

Take Home Messages

  • Prediabetes needs to be the primary target for diabetes prevention. Indian population spends significant years in isolated impaired fasting glucose (i-IFG) and impaired glucose tolerance (IGT).
  • Early screening, detection, and treatment of prediabetes lowers the risk of developing diabetes and its complications.
  • Indian Diabetes Risk Score and 1-h post-load plasma glucose ≥ 155 mg/dL are simple, practical inexpensive screening tools suggested for the Indian population.
  • Early interventions reduced cardiovascular disease by 18% and retinopathy by 38% in prediabetes.
  • Lifestyle changes could delay the onset of diabetes, and Metformin is suggested where lifestyle changes are insufficient. Metformin is DCGI approved treatment for the management of prediabetes.

References:

1. Anjana RM, Unnikrishnan R, Deepa M, Pradeepa R, Tandon N, Das AK, Joshi S, Bajaj S, Jabbar PK, Das HK, Kumar A, Dhandhania VK, Bhansali A, Rao PV, Desai A, Kalra S, Gupta A, Lakshmy R, Madhu SV, Elangovan N, Chowdhury S, Venkatesan U, Subashini R, Kaur T, Dhaliwal RS, Mohan V; ICMR-INDIAB Collaborative Study Group. Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17). Lancet Diabetes Endocrinol. 2023 Jul;11(7):474-489. doi: 10.1016/S2213-8587(23)00119-5.

2. Das AK, Mohan V, Ramachandran A, et al. An Expert Group Consensus Statement on “Approach and Management of Prediabetes in India”. J Assoc Physicians India 2022;70(12):69–78.

3. Mohan V, Deepa M, Anjana RM, Lanthorn H, Deepa R. Incidence of diabetes and pre-diabetes in a selected urban south Indian population (CUPS-19). J Assoc Physicians India. 2008 Mar;56:152-7.

4. Narayan KMV, Kondal D, Chang HH, Mohan D, Gujral UP, Anjana RM, Staimez LR, Patel SA, Ali MK, Prabhakaran D, Tandon N, Mohan V. Natural History of Type 2 Diabetes in Indians: Time to Progression. Diabetes Care. 2024 May 1;47(5):858-863. doi: 10.2337/dc23-1514

5. Madhu SV. Defying the Odds: Conquering Prediabetes for a Diabetes-Free Tomorrow. Indian J Endocrinol Metab. 2023 Jul-Aug;27(4):273-276. doi: 10.4103/2230-8210.388224. Epub 2023 Aug 29.

6. Chawla R, Madhu SV, Makkar BM, Ghosh S, Saboo B, Kalra S; RSSDI-ESI Consensus Group. RSSDI-ESI Clinical Practice Recommendations for the Management of Type 2 Diabetes Mellitus 2020. Indian J Endocrinol Metab. 2020 Jan-Feb;24(1):1-122. doi: 10.4103/ijem.IJEM_225_20.

7. American Diabetes Association Professional Practice Committee; 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes—2024. Diabetes Care 1 January 2024; 47 (Supplement_1): S20–S42. https://doi.org/10.2337/dc24-S002

8. Liu Y, Feng W, Lou J, Qiu W, Shen J, Zhu Z, Hua Y, Zhang M, Billong LF. Performance of a prediabetes risk prediction model: A systematic review. Heliyon. 2023 May 6;9(5):e15529. doi: 10.1016/j.heliyon.2023.e15529.

9. Mohan V, Deepa R, Deepa M, Somannavar S, Datta M. A simplified Indian Diabetes Risk Score for screening for undiagnosed diabetic subjects. J Assoc Physicians India. 2005 Sep;53:759-63.

10. Bergman M, Manco M, Satman I, Chan J, Inês Schmidt M, Sesti G, Vanessa Fiorentino T, Abdul-Ghani M, Jagannathan R, Kumar Thyparambil Aravindakshan P, Gabriel R, Mohan V, Buysschaert M, Bennakhi A, Pascal Kengne A, Dorcely B, Nilsson PM, Tuomi T, Battelino T, Hussain A, Ceriello A, Tuomilehto J. International Diabetes Federation Position Statement on the 1-hour post-load plasma glucose for the diagnosis of intermediate hyperglycemia and type 2 diabetes. Diabetes Res Clin Pract. 2024 Mar;209:111589. doi: 10.1016/j.diabres.2024.111589.

11. An X, Zhang Y, Sun W, Kang X, Ji H, Sun Y, Jiang L, Zhao X, Gao Q, Lian F, Tong X. Early effective intervention can significantly reduce all-cause mortality in prediabetic patients: a systematic review and meta-analysis based on high-quality clinical studies. Front Endocrinol (Lausanne). 2024 Mar 1;15:1294819. doi: 10.3389/fendo.2024.1294819

12. Cosic V, Jakab J, Pravecek MK, Miskic B. The Importance of Prediabetes Screening in the Prevention of Cardiovascular Disease. Med Arch. 2023 Apr;77(2):97-104. doi: 10.5455/medarh.2023.77.97-104.

13. Tuso P. Prediabetes and lifestyle modification: time to prevent a preventable disease. Perm J. 2014 Summer;18(3):88-93. doi: 10.7812/TPP/14-002.

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Doctors at MASSH Super Specialty Hospital treated 50-year-old woman with rare appendix cancer

New Delhi: Doctors at the MASSH Super Specialty Hospital in the national capital have successfully treated a 50-year-old woman suffering from a rare form of appendix cancer, providing her with a new lease on life.

The woman initially sought medical attention due to persistent right lower abdominal pain and nausea lasting for 15 days. Upon examination, doctors discovered a large tubular, thick-walled cystic mass measuring 14.3 x 13.8 x 8.5 cm. This mass extended from the base of the caecum (a pouch connected to the junction of the small and large intestines) to the right adnexa in the pelvis, indicating a condition known as Mucocele of the appendix.

Also Read:Doctors at Apollo Cancer Centre perform Minimally invasive robotic surgery on patient with Pseudomyxoma Peritonei

As per a media report in IANS,”Mucocele of the appendix is a rare clinical entity, and its treatment requires meticulous care and precision, with no spillage technique. Mucocele of the appendix poses diagnostic and therapeutic challenges due to its rarity,” said Dr Sachin Ambekar, Director of Minimal Access Surgery, Surgical Oncology & Medical Director at MASSH, on Monday.

It is so uncommon and occurs in only 0.07-0.63 per cent of all appendectomy cases.

The team resorted to 3D laparoscopy to ensure precise visualisation and meticulous dissection.

During the procedure, adhesions were visualised in 360-degree depth perception not seen in conventional laparoscopy, and meticulous dissection was carried out without any mucinous spill.

A cystic mass of the appendix (14.3 x 13.8 x 8.5 cm), with inflamed walls but without perforation was located in the right iliac fossa. Notably, no lesions were found in the peritoneal cavity, news agency IANS reported.

“3D Laparoscopy played a crucial role in this operation by enabling us to visualise and dissect with never before seen 360-degree in-depth precision. This technology offers significant advantages over conventional laparoscopy, particularly in delicate procedures such as this,” Dr. Ambekar said.

Remarkably, the patient experienced no complications during the postoperative period and was discharged from the hospital on the second day, the doctor said. 

Also Read:Rare case viable amputated part of the appendix after autoamputation: A report

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Persistence with tirzepatide key to effective weight loss, study suggests

USA: In the ever-evolving landscape of diabetes management, promising new findings suggest that persistence with tirzepatide-a novel investigational therapy-may significantly improve glycemic control and cardiovascular outcomes for patients with type 2 diabetes mellitus. This encouraging revelation underscores the importance of perseverance and tailored treatment strategies in optimizing diabetes care.

New post hoc data from Lilly’s SURMOUNT-1 trial of overweight/obese people but without diabetes suggest that the drug will almost always produce at least 5% weight loss eventually, even among slow responders.

The findings presented at the American Association of Clinical Endocrinology (AACE) 2024 conference suggest patience may pay off when using tirzepatide (Zepbound, Eli Lilly) to treat obesity.

“Some obesity treatment guidelines suggest anti-obesity medication (AOM) discontinuation that fails to produce 5% or greater weight reduction within 12 weeks. Newer AOMs may take longer to achieve full weight-loss benefit given their recommended dose titration schedule,” Kimberly Gudzune, MD, director of the Johns Hopkins Healthful Eating, Activity & Weight Program, Baltimore, Maryland.

The analysis showed that among participants who had lost less than 5% of their body weight by week 12 of tirzepatide, nearly all went on to lose 5% or more by week 72. Thus, Gudzune said, “It is reasonable to consider treatment for longer than 12 weeks to determine weight loss response to tirzepatide, which takes at least 20 weeks to reach the highest dose.”

The post hoc analysis included 1545 patients; they were randomly assigned to total tirzepatide doses of 5 mg, 10 mg, or 15 mg, and had data available at weeks 0, 12, 24, and 72. Among those, 1267 had lost at least 5% of their body weight by week 12, defined as “early responders,” and 278 had lost less than 5% of body weight by then, called “slow responders.”

The study led to the following findings:

  • At baseline, slow responders were significantly more likely to be male (44.8% of slow versus 30.1% of early responders), have higher body weight (24.3 kg versus 21.8 kg), and have lower waist circumference (117.5 cm versus 113.4 cm).
  • There were no significant differences by age, body mass index, prediabetes status, or obesity duration.
  • By the end of dose titration at week 24, 70% of slow responders had achieved 5% or more of body weight reduction, as had 100% of early responders.
  • By 72 weeks, 90% of the slow responders had achieved at least 5% of body weight loss, and 30% had achieved at least 15% reduction.
  • Even in the group maintained on the lowest 5-mg dose throughout the trial, 87% had achieved at least 5% weight loss by week 72, with 15% achieving at least 15%. And in the group that had been titrated up to 15 mg tirzepatide, 94% of slow responders achieved at least 5% weight loss.
  • The mean time to reach 5% weight loss for slow responders who went to achieve 5% or greater weight loss was 24.8 weeks.
  • Of the total 1545 participants, there were 28 who had lost less than 5% of their overall body weight on tirzepatide. Of those, four had missed more than three consecutive doses, and 13 were on the lowest 5-mg dose.

“Future studies are warranted for better understanding the variability in weight loss response to tirzepatide treatment,” the researchers concluded.

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Alirocumab addition to statins fails to improve endothelial function in acute MI patients: PACMAN-AMI trial substudy

Switzerland: In a significant development in cardiovascular medicine, findings from a substudy of the PACMAN-AMI randomized clinical trial shed light on the potential benefits of alirocumab in improving endothelial function and reducing coronary atherosclerosis, in patients who have experienced myocardial infarction (MI). This substudy, conducted within the larger PACMAN-AMI trial framework, represents a crucial step forward in understanding the therapeutic potential of alirocumab in post-MI care.

The research, published in the Atherosclerosis journal, found no further improvement of flow-mediated dilation (FMD) with the addition of alirocumab among patients with acute myocardial infarction (AMI) than 52 weeks of secondary preventative medical therapy, including high-intensity statin therapy. FMD was significantly associated with baseline coronary plaque burden, but not lipid pool or fibrous cap thickness.

Myocardial infarction, commonly known as a heart attack, is a life-threatening condition characterized by the interruption of blood flow to the heart muscle, usually due to the obstruction of a coronary artery by a blood clot. Following a heart attack, patients are at increased risk of recurrent cardiovascular events, including further heart attacks and stroke, making effective secondary prevention strategies imperative.

Alirocumab, a monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), has garnered attention as a potential therapeutic agent for reducing low-density lipoprotein cholesterol (LDL-C) levels and lowering the risk of cardiovascular events.

Emrush Rexhaj, Department of Cardiology, Bern University Hospital Inselspital, Freiburgstrasse, Bern, Switzerland, and colleagues aimed to examine the effects of the PCSK9 inhibitor alirocumab added to high-intensity statin on FMD. They also investigated its association with coronary atherosclerosis in non-infarct-related arteries using near-infrared spectroscopy (NIRS), intracoronary intravascular ultrasound (IVUS), and optical coherence tomography (OCT).

For this purpose, the researchers conducted a pre-specified substudy among patients recruited at Bern University Hospital, Switzerland, for the randomized-controlled, double-blind, PACMAN-AMI trial that compared the effects of biweekly alirocumab 150 mg versus placebo added to rosuvastatin. At 4 and 52 weeks, brachial artery FMD was measured, and intracoronary imaging at baseline and 52 weeks.

The researchers reported the following findings:

  • 139/173 patients completed the substudy. There was no difference in FMD at 52 weeks in the alirocumab (n = 68, 5.44 ± 2.24%) versus placebo (n = 71, 5.45 ± 2.19%) group (difference = −0.21%).
  • FMD improved throughout 52 weeks in both groups similarly.
  • There was a significant association between 4 weeks FMD and baseline plaque burden (IVUS) (n = 139, slope = −1.00), but not with lipid pool (NIRS) (n = 139, slope = −7.36), or fibrous cap thickness (OCT) (n = 81, slope = −1.57).

The study revealed improvement in endothelial function as evaluated by brachial artery FMD achieved throughout one year with guideline-based secondary preventative medical therapy, including a high-intensity statin in patients with AMI. However, adding PCSK9 inhibitor alirocumab did not further improve endothelial function.

FMD was significantly inversely related to non-infarct related arteries (non-IRA) intracoronary plaque burden before treatment initiation, but not to lipid pool or fibrous cap thickness.

Reference:

Rexhaj E, Bär S, Soria R, Ueki Y, Häner JD, Otsuka T, Kavaliauskaite R, Siontis GC, Stortecky S, Shibutani H, Spirk D, Engstrøm T, Lang I, Morf L, Ambühl M, Windecker S, Losdat S, Koskinas KC, Räber L; PACMAN-AMI Investigators. Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction: A PACMAN-AMI randomized clinical trial substudy. Atherosclerosis. 2024 May;392:117504. doi: 10.1016/j.atherosclerosis.2024.117504. Epub 2024 Mar 6. PMID: 38513436.

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Semaglutide tied to meaningful weight loss, waist size reduction and CV benefits in non diabetic overweight adults: Study

Researchers have found in latest  research  that Semaglutide can produce clinically meaningful weight loss and reduce waist size for at least 4 years in adults with overweight or obesity who don’t have diabetes, and delivers cardiovascular benefits irrespective of weight lost. 

Two important studies based on the largest and longest clinical trial of the effects of semaglutide on weight in over 17,000 adults with overweight and obesity but not diabetes find patients lost on average 10% of their body weight and over 7cm from their waistline after 4 years.

Clinically meaningful weight loss was achieved by men and women of all races, ages, and body sizes, across all regions, with a lower rate of serious adverse events compared with placebo.

Over half of adults taking semaglutide moved down at least one BMI category after 2 years compared to 16% receiving placebo; and 12% reached a healthy BMI (25 kg/m² or less) compared with 1% in the placebo group.

Importantly, the findings also indicate that semaglutide delivers cardiovascular benefits irrespective of starting weight and the amount of weight lost-suggesting that even patients with mild obesity or those not losing weight are likely to gain some advantage.

Two important studies are being presented at this year’s European Congress on Obesity (ECO) in Venice, Italy (12-15 May), based on the landmark Semaglutide and Cardiovascular Outcomes (SELECT) trial from the same international author group. The first new study, led by Professor Donna Ryan from Pennington Biomedical Research Centre, New Orleans, USA, and being published simultaneously in Nature Medicine, examines the long-term weight effects of semaglutide. The second study led by led by Professor John Deanfield from University College London, UK, investigates whether the cardiovascular benefits are related to starting weight or the amount of weight lost.

Semaglutide is a GLP-1 medication primarily prescribed for adults with type 2 diabetes but is also approved for weight loss in people with obesity or overweight who have at least one other health issue. This class of medications simulate the functions of the body’s natural incretin hormones, which help to lower blood sugar levels after a meal. Adjusting these hormone levels can also make people feel full, and in doing so, helps lower their daily calorie intake.

In 2023, the SELECT trial reported that adults with overweight or obesity but not diabetes taking semaglutide for more than 3 years had a 20% lower risk of heart attack, stroke, or death due to cardiovascular disease, and lost an average 9.4% of their bodyweight [1].

Between October 2018 and June 2023, 17,604 adults (aged 45 or older; 72% male) from 804 sites in 41 countries with overweight or obesity (BMI of 27 kg/m² or higher) were enrolled and treated with Semaglutide (2.4mg) or placebo for an average of 40 months. They had previously experienced a heart attack, stroke and/or had peripheral artery disease, but did not have type 1 or type 2 diabetes when they joined the study.

The researchers examined markers of obesity that include body composition and fat distribution (waist circumference and waist circumference-to-height ratio [WHtR]), rather than just BMI alone, to help clarify the effect of semaglutide on central abdominal fat which has been proven to cause greater cardiovascular risk than general obesity.

Clinically meaningful weight loss in all sexes, races, body sizes, and regions

The first new study shows that once-weekly treatment with semaglutide can produce clinically meaningful and sustained weight loss and decrease waist size for at least 4 years in adults with overweight or obesity who do not have diabetes, with a lower rate of serious adverse events compared with placebo.

Importantly, men and women of all races, ages, and body sizes, across all geographical regions were able to achieve sustained, clinically meaningful weight loss.

“Our long-term analysis of semaglutide establishes that clinically relevant weight loss can be sustained for up to 4 years in a geographically and racially diverse population of adults with overweight and obesity but not diabetes,” says Professor Ryan. “This degree of weight loss in such a large and diverse population suggests that it may be possible to impact the public health burden of multiple obesity-related illnesses. While our trial focused on cardiovascular events, many other chronic diseases including several types of cancer, osteoarthritis, and anxiety and depression would benefit from effective weight management.”

In the semaglutide group, weight loss continued to week 65 and was sustained for 4 years, with participants’ losing on average 10.2% of their body weight and 7.7cm from their waistline, compared with 1.5% and 1.3cm respectively in the placebo group.

Similarly, in the semaglutide group, average WHtR fell by 6.9% compared with 1% in the placebo group.

These improvements were seen across both sexes and all categories of race and age, irrespective of starting blood sugar (glycaemic) status or metabolically unhealthy body fat. However, women taking semaglutide tended to lose more weight on average than men, and Asian patients lost less weight on average than other races.

Interestingly, after 2 years over half (52%) of participants treated with semaglutide had transitioned to a lower BMI category compared with 16% of those given placebo. For example, the proportion of participants with obesity (BMI 30kg/m² or higher) declined from 71% to 43% in the semaglutide group, and from 72% to 68% in the placebo group. Moreover, 12% of adults in the semaglutide group achieved a healthy weight (BMI 25kg/m² or less) compared with 1.2% in the placebo group

For each BMI category (<30, ≤30-<35, ≤35-<40, and ≥40 kg/m2) there were lower rates (events per 100 years of observation) of SAEs with semaglutide (43.23, 43.54, 51.0, 47.06) than with placebo (50.48, 49.66, 52.73, 60.85) respectively.

There were no unexpected safety issues with semaglutide in the SELECT trial. The proportion of participants with serious adverse events (SAEs) was lower in the semaglutide group than the placebo group (33% vs 36%), mainly driven by differences in cardiac disorders (11.5% vs 13.5%). More patients receiving semaglutide discontinued the trial due to gastrointestinal symptoms, including nausea and diarrhoea, mainly during the 20-week dose escalation phase. Importantly, semaglutide did not lead to an increased rate of pancreatitis, but rates of cholelithiasis (stones in gallbladder) were higher in the semaglutide group.

Cardiovascular benefits irrespective of weight loss

The second study examined the relationship between weight measures at baseline, and change in weight during the study with cardiovascular outcomes. These included time to first major adverse cardiovascular event (MACE) and heart failure measures.

The findings showed that treatment with semaglutide delivered cardiovascular benefits, irrespective of the starting weight and the amount of weight lost. This suggests that even patients with relatively mild levels of obesity, or those who only lose modest amount of weight, may have improved cardiovascular outcome.

“These findings have important clinical implications”, says Professor Deanfield. “Around half of the patients that I see in my cardiovascular practice have levels of weight equivalent to those in the SELECT trial and are likely to derive benefit from taking Semaglutide on top of their usual level of guideline directed care.”

He adds, “Our findings show that the magnitude of this treatment effect with semaglutide is independent of the amount of weight lost, suggesting that the drug has other actions which lower cardiovascular risk beyond reducing unhealthy body fat. These alternative mechanisms may include positive impacts on blood sugar, blood pressure, or inflammation, as well as direct effects on the heart muscle and blood vessels, or a combination of one or more of these.”

Despite these important findings, the authors caution that SELECT is not a primary prevention trial so that the data cannot be extrapolated to all adults with overweight and obesity to prevent MACE; and despite being large and diverse, it does not include enough individuals from different racial groups to understand different potential effects.

References:

1. Ryan, D.H., Lingvay, I., Deanfield, J. et al. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med (2024). https://doi.org/10.1038/s41591-024-02996-7

2. Semaglutide can produce clinically meaningful weight loss and reduce waist size for at least 4 years in adults with overweight or obesity who don’t have diabetes, and delivers cardiovascular benefits irrespective of weight lost, European Association for the Study of Obesity, Meeting: European Congress on Obesity (ECO2024).

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Meta-analysis reveals insights into mRNA vaccine-induced thyroid diseases

USA: In a groundbreaking meta-analysis presented at the American Association of Clinical Endocrinology (AACE) conference of 2024, researchers shed light on the rare phenomenon of mRNA vaccine-induced hyperthyroidism, particularly in the context of the SARS-CoV-2 vaccines. This comprehensive study delved into the incidence, risk factors, and outcomes linked to this condition, offering crucial insights for healthcare providers and vaccine recipients.

The meta-analysis revealed that the chance of new-onset thyroid disease following mRNA COVID-19 vaccine administration was rare but still noteworthy.

The researchers found that there were 77 cases of thyroid-related autoimmune diseases among people with no history of autoimmune disease before receiving the COVID-19 vaccine, with 39 cases of subacute thyroiditis (SAT), and 38 cases of Graves’ disease (GD).

Additionally, these autoimmune diseases occurred more frequently in women than in men, “about a 2-1 breakdown, which is what we would expect as women tend to have more autoimmune disease overall than men,” Vikram Gill, MBBS, of St. Peter’s University Hospital/Rutgers University in New Brunswick, New Jersey, said at the poster presentation.

10 men and 28 women were diagnosed with Graves’ disease, while 13 and 26, respectively, were diagnosed with SAT. The average ages of women and men who developed post-vaccination autoimmune diseases were around 44 and 41, respectively.

The emergence of mRNA vaccines, such as those developed against COVID-19, has revolutionized the field of immunization, providing potent protection against infectious diseases. However, as with any medical intervention, rare adverse events can occur. One such complication that has garnered attention is hyperthyroidism, an overactive thyroid gland, which has been reported following mRNA vaccination.

Previous research has revealed links between COVID-19 vaccination and autoimmune disorders, although other research has indicated that having a COVID-19 diagnosis raises the risk for these same disorders, but that vaccination can mitigate that risk.

The researchers searched for articles reporting GD and SAT following COVID-19 mRNA vaccinations from 2019 to November 2023.

The following were the key findings of the study:

  • A GD diagnosis happened about 40 days after the first dose, with SAT emerging sooner, at about 11 days after the first jab.
  • In the group with GD, over half developed hyperthyroidism symptoms after the first dose of the mRNA vaccine, while around 45% showed symptoms after dose 2. Roughly 5% showed signs after the third dose.
  • In the SAT group, almost 54% showed hyperthyroidism symptoms after dose 1, as did about 44% after dose 2, and around 5% after dose 3.
  • Positive anti-TPO [anti-thyroid peroxidase] was only seen in five out of 32 patients who were tested (15.6%), and 32 patients (74.4%) were negative for anti-TPO.
  • Eleven out of 33 patients who were tested (33.3%) were positive for anti-Tg [antithyroglobulin], 22 patients (66.6 %) were negative,

Moving forward, the findings of this meta-analysis will inform clinical practice and public health strategies surrounding mRNA vaccination. Enhanced awareness, coupled with tailored monitoring protocols, will ensure the continued safety and efficacy of these groundbreaking vaccines in combating infectious diseases like COVID-19. As the global vaccination effort progresses, studies like this serve as invaluable tools in optimizing healthcare delivery and promoting vaccine confidence.

Reference:

Gill V and Luo H “mRNA (SARS-CoV-2) vaccine-induced hyperthyroidism — Learnings based on the meta-analysis” AACE 2024.

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Seralutinib effective in managing pulmonary arterial hypertension: Lancet

In the field of pulmonary arterial hypertension (PAH), where morbidity and mortality rates remain alarmingly high, a new inhaled drug can greatly enhance the outcomes in patients. A recent study called as the TORREY trial unveiled promising results regarding the efficacy and safety of a new inhaled drug, the Seralutinib, in managing this life-threatening condition. The findings were published in The Lancet Respiratory Medicine. 

The TORREY trial revealed that Seralutinib, an inhaled kinase inhibitor, targets the crucial pathways involved in PAH progression. Seralutinib disrupts inflammatory, proliferative and fibrotic pathways driving pulmonary vascular remodeling in PAH by inhibiting platelet-derived growth factor receptor, the colony stimulating factor 1 receptor and mast or stem cell growth factor receptor kinases.

This phase 2, randomized, multicenter, double-blind, placebo-controlled study enrolled a total of 86 adult patients with PAH from various hospital and community sites. The participants were randomly assigned to receive either Seralutinib or a placebo via dry powder inhaler over a span of 24 weeks. The patients were already receiving standard background therapy for PAH. The primary endpoint of the trial was the change in pulmonary vascular resistance (PVR) from baseline to 24 weeks.

The results observed that patients treated with Seralutinib expressed a significant reduction in PVR when compared to the patients receiving the placebo. Also, the least squares mean difference in PVR change between the Seralutinib and placebo groups was clinically significant at -96.1 dyne·s/cm5 (p=0.03). While generally well-tolerated, the most common treatment-emergent adverse event in both groups was cough which was reported in 38% of the placebo group and 43% of the Seralutinib group.

These findings hold profound benefits for the management and treatment of PAH. This trial offers hope for patients with this debilitating condition by demonstrating the efficacy of inhaled Seralutinib in reducing PVR. The safety profile of the drug suggests its potential as a valuable addition to existing PAH therapies. Further investigation and development will guide forward this innovative therapy against pulmonary arterial hypertension by offering renewed prospects for patients throughout the globe.

Source:

Frantz, R. P., McLaughlin, V. V., Sahay, S., Escribano Subías, P., Zolty, R. L., Benza, R. L., Channick, R. N., Chin, K. M., Hemnes, A. R., Howard, L. S., Sitbon, O., Vachiéry, J.-L., Zamanian, R. T., Cravets, M., Roscigno, R. F., Mottola, D., Osterhout, R., Bruey, J.-M., Elman, E., … Ghofrani, H.-A. (2024). Seralutinib in adults with pulmonary arterial hypertension (TORREY): a randomised, double-blind, placebo-controlled phase 2 trial. In The Lancet Respiratory Medicine. Elsevier BV. https://doi.org/10.1016/s2213-2600(24)00072-9

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Staged bilateral FUS-STN safely improves motor features in Parkinsonism: JAMA

Staged bilateral FUS-STN safely improves motor features in Parkinsonism suggests a study published in the JAMA Neurology.

Unilateral magnetic resonance imaging (MRI)–guided focused ultrasound subthalamotomy (FUS-STN) improves cardinal motor features among patients with asymmetrical Parkinson’s disease (PD). The feasibility of bilateral FUS-STN is as yet unexplored. A study was done to assess the safety and effectiveness of staged bilateral FUS-STN to treat Parkinson’s disease. This prospective, open-label, case series study was conducted between June 18, 2019, and November 7, 2023, at HM-CINAC, Puerta del Sur University Hospital, Madrid, Spain, and included 6 patients with Parkinson’s disease who had been treated with unilateral FUS-STN contralateral to their most affected body side and whose parkinsonism on the untreated side had progressed and was not optimally controlled with medication.

Primary outcomes were assessed 6 months after the second treatment and included safety (incidence and severity of adverse events after the second treatment) and effectiveness in terms of motor change (measured with the Movement Disorders Society Unified Parkinson’s Disease Rating Scale part III [MDS-UPDRS III]) in the off-medication state (ie, after at least 12 hours of antiparkinsonian drug withdrawal) compared with baseline (ie, prior to the first side ablation). Secondary outcomes included motor change in patients in the on-medication state (ie, after usual antiparkinsonian medication intake), motor complications (measured with the MDS-UPDRS IV), daily living activities (measured with the MDS-UPDRS I-II), quality of life (measured with the 39-item Parkinson’s Disease Questionnaire), change in dopaminergic treatment, patient’s global impression of change (measured with the Global Impression of Change [PGI-C] scale), and long-term (24-month) follow-up. Results: Of 45 patients previously treated with unilateral FUS-STN, 7 were lost to follow-up, and 4 were excluded due to adverse events. Of the remaining 34 patients, 6 (median age at first FUS-STN, 52.6 years [IQR, 49.0-57.3 years]; 3 women [50%]) experienced progression of parkinsonism on the untreated body side and were included. At the time of the first FUS-STN, patients’ median duration of disease was 5.7 years (IQR, 4.7-7.3 years).

The median time between procedures was 3.2 years (IQR, 1.9-3.5 years). After the second FUS-STN, 4 patients presented with contralateral choreic dyskinesia, which resolved by 3 months. Four patients developed speech disturbances, which gradually improved but remained in a mild form for 2 patients at 6 months; 1 patient experienced mild imbalance and dysphagia during the first week after treatment, which subsided by 3 months. No behavioural or cognitive disturbances were found on neuropsychological testing. For patients in the off-medication state, MDS-UPDRS III scores improved by 52.6% between baseline and 6 months after the second FUS-STN (from 37.5 [IQR, 34.2-40.0] to 20.5 [IQR, 8.7-24.0]; median difference, 23.0 [95% CI, 7.0-33.7]; P = .03). The second treated side improved by 64.3% (MDS-UPDRS III score, 17.0 [IQR, 16.0-19.5] prior to the second treatment vs 5.5 [IQR, 3.0-10.2]; median difference, 9.5 [95% CI, 3.2-17.7]; P = .02). After the second procedure, all self-reported PGI-C scores were positive. Findings of this pilot study suggest that staged bilateral FUS-STN was safe and effective for the treatment of PD, although mild but persistent speech-related adverse events were observed among a small number of patients.

Reference:

Martínez-Fernández R, Natera-Villalba E, Rodríguez-Rojas R, et al. Staged Bilateral MRI-Guided Focused Ultrasound Subthalamotomy for Parkinson Disease. JAMA Neurol. Published online May 13, 2024. doi:10.1001/jamaneurol.2024.1220

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Use of restorations on vertically prepared teeth suitable option to classical horizontal preparations: Study

The use of restorations on vertically prepared teeth suitable for classical horizontal preparations suggests a study published in the Journal of Dentistry.

A study was done to evaluate the clinical conditions of single-unit posterior restorations on teeth prepared without a finishing line, after 5.6 years of clinical service. 50 crowns (25 zirconia-based (Zr) and 25 porcelain-fused-to-metal (PFM)) were selected from 34 patients. The restorations were evaluated according to the California Dental Association (CDA) Quality Criteria, and periodontal variables were studied in the abutment teeth compared with the unrestored contralateral teeth. Variables were examined using Mann-Whitney and Pearson´s Chi-Square tests (α = 0.05). The success of the prosthesis was calculated using the Kaplan-Meier test. Results: CDA Quality Criteria was considered satisfactory- excellent in all restorations except for one of them, due to chipping on a PFM crown. At, 66 months, the success rates for PFM and Zr crowns were 85.7% and 100%, respectively. The plaque index (PI) showed that the restored abutment teeth accumulated significantly less plaque than the control teeth, but the gingival index (GI) was statistically higher in the abutment teeth. In 80% of cases, the probing depth (PB) was ≤ 3mm. In addition, in 21% of the cases, gingival recession was less than 2mm. The restoration material had a statistically significant effect on GI and PB, with Zr crowns showing less inflammation and fewer deep pockets than PFM restorations. On the contrary, greater gingival recession was found at the margins of the Zr crowns when compared to the PFM. No statistical differences were found between the two materials in the GI. Cemented crowns on vertical preparations show good clinical behavior after 5 years. The periodontal parameters (PI, GI, PD) of the Zr restorations are significantly better than those of PFM, with the exception of gingival recession. The use of restorations on vertically prepared teeth is a suitable alternative to classical horizontal preparations.

Reference:

M Gonzalez-Bonilla, S Berrendero, B Moron-Conejo, F Martinez-Rus, MP Salido,

Clinical evaluation of posterior zirconia-based and porcelain-fused-to-metal crowns with a vertical preparation technique: an up to 5-year retrospective cohort study.,

Journal of Dentistry, 2024, 104953, ISSN 0300-5712, https://doi.org/10.1016/j.jdent.2024.104953.

(https://www.sciencedirect.com/science/article/pii/S0300571224001234)

Keywords:

Use, restorations, vertically, prepared, teeth, suitable, option, classical, horizontal, preparations, study, Journal of Dentistry, M Gonzalez-Bonilla, S Berrendero, B Moron-Conejo, F Martinez-Rus, MP Salido,Vertical preparation; Crown; Zirconia; Porcelain-fused-to-metal; Periodontal parameters

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