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Daily Archives: June 26, 2023

Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050

26 Jun, 2023 | 01:00h | UTC

Summary: This systematic review analyzed the global burden of diabetes, including trends, projections, and attributions to risk factors. It considered data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), covering 204 countries and territories.

In 2021, an estimated 529 million people worldwide were living with diabetes. Regionally, the highest rates were observed in North Africa, the Middle East, and Oceania. Type 2 diabetes accounted for 96% of diabetes cases and 95.4% of diabetes DALYs (disability-adjusted life-years). More than half of global type 2 diabetes DALYs were attributable to high body mass index (BMI).

Predictions suggest that more than 1.31 billion people will have diabetes by 2050, with high prevalence rates in North Africa, the Middle East, and Latin America. The study notes the ongoing challenge of preventing and controlling type 2 diabetes, largely driven by increasing obesity. An understanding of disparities in risk profiles and disease burdens can inform strategies to control diabetes risk factors.

Article: Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021 – The Lancet

Editorial: Diabetes: a defining disease of the 21st century – The Lancet

News Release: Global diabetes cases to soar from 529 million to 1.3 billion by 2050 – Institute for Health Metrics and Evaluation

 

Commentary on Twitter (thread – click for more)

 

Phase 2 RCT | Orforglipron, an oral GLP-1 receptor agonist, significantly reduces weight in adults with obesity

26 Jun, 2023 | 00:58h | UTC

Summary: The article reports a phase 2, randomized, double-blind trial investigating the efficacy of the GLP-1 receptor agonist, orforglipron, as an oral weight loss treatment for adults with obesity or overweight plus at least one weight-related condition. The study involved 272 participants, who were administered orforglipron at varying doses or a placebo over a 36-week period.

The key findings of the study indicated significant weight reduction in individuals who were administered orforglipron. At 26 weeks, weight changes in the orforglipron group ranged from -8.6% to -12.6% compared to -2.0% in the placebo group. At 36 weeks, these figures were -9.4% to -14.7% for the orforglipron group and -2.3% for the placebo group. Furthermore, 46-75% of orforglipron recipients experienced a weight reduction of at least 10% by week 36, compared to 9% in the placebo group.

Improvements were also observed in all prespecified weight-related and cardiometabolic measures among orforglipron users. However, the treatment was associated with some mild to moderate gastrointestinal side effects, leading to discontinuation in 10-17% of participants. The safety profile was in line with other GLP-1 receptor agonists. These findings suggest that orforglipron could potentially be an effective oral treatment for weight reduction in adults with obesity, though further research is needed to corroborate these results and assess long-term effects.

Article: Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity – New England Journal of Medicine (link to abstract – $ for full-text)

 

Phase 2 RCT | Oral GLP-1 agonist Orforglipron outperforms dulaglutide and placebo in type 2 diabetes control

26 Jun, 2023 | 00:54h | UTC

Summary: In a 26-week, phase 2, double-blind, randomized trial spanning multiple centers in the USA, Hungary, Poland, and Slovakia, researchers examined the efficacy and safety of orforglipron, a non-peptide GLP-1 receptor agonist. The sample comprised 383 adults aged 18 and older with type 2 diabetes treated with diet and exercise, with or without metformin, and with a glycated hemoglobin (HbA1c) of 7.0–10.5%.

The study’s primary efficacy outcome revealed that orforglipron achieved a significantly higher mean reduction in HbA1c compared to both the placebo and dulaglutide (-2.10% vs -0.43% and -1.10%, respectively). Furthermore, orforglipron induced a change in mean body weight at week 26 of -10.1 kg, outperforming both the placebo and dulaglutide. Adverse events mostly encompassed mild to moderate gastrointestinal issues.

The study concluded that orforglipron at doses of 12 mg or higher could potentially serve as an effective alternative to injectable GLP-1 receptor agonists and oral semaglutide, for type 2 diabetes treatment. While the drug’s safety profile was consistent with other GLP-1 receptor agonists, there is a need for larger confirmatory studies and dose regimen optimization.

Article: Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study – The Lancet (link to abstract – $ for full-text)

Commentary: Orforglipron Shows Promise as Weight Loss, Diabetes Agent in Phase 2 Trials – HCP Live

 

Phase 2 RCT | Comparative study on CagriSema, Semaglutide, and Cagrilintide in type 2 diabetes

26 Jun, 2023 | 00:52h | UTC

Summary: The study, a 32-week multicentre, randomized, double-blind, phase 2 trial, evaluated the combined effect of cagrilintide and semaglutide (CagriSema) on individuals with type 2 diabetes. 92 adults with type 2 diabetes and a BMI of 27 kg/m2 or higher were randomly assigned to one of three treatment groups: CagriSema, semaglutide, or cagrilintide.

The results indicated that the mean reduction in HbA1c was more pronounced with CagriSema than cagrilintide, but not semaglutide. The CagriSema group also showed greater weight loss versus both semaglutide and cagrilintide. In terms of safety, the most common adverse events were mild to moderate gastrointestinal events, with no fatal adverse events reported.

These findings suggest that CagriSema presents as a viable treatment option for type 2 diabetes, offering significant benefits in terms of weight loss and glycemic control. A potential limitation is the short duration of the study, which may not account for long-term effects and safety of the intervention. The authors conclude that these results support further investigation of CagriSema in larger, longer phase 3 trials.

Article: Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial – The Lancet (link to abstract – $ for full-text)

 

WHO outlines 40 research priorities on antimicrobial resistance

26 Jun, 2023 | 00:50h | UTC

News release: WHO outlines 40 research priorities on antimicrobial resistance – World Health Organization

Report: Global research agenda for antimicrobial resistance in human health – World Health Organization

 

Commentary on Twitter

 

Secondary analysis of a RCT | Bempedoic acid reduces CV events in statin-intolerant patients with high CV risk

26 Jun, 2023 | 00:49h | UTC

Summary: This secondary analysis of a Randomized Clinical Trial (RCT) evaluated the efficacy of bempedoic acid in primary prevention of cardiovascular events among statin-intolerant patients at high cardiovascular risk. From a total of 13,970 participants, 4206 met the criteria for primary prevention and were analyzed in this study. Those allocated to receive bempedoic acid showed a significant reduction in major cardiovascular events, reflected in a hazard ratio of 0.70.

The average age of this patient cohort was 68 years, and most participants (66%) were diagnosed with diabetes. Treatment with bempedoic acid also led to a significant 21.3% reduction in low-density lipoprotein cholesterol (LDL-C) levels and a 21.5% decrease in high-sensitivity C-reactive protein levels, suggesting improved cardiovascular health.

This study underscores the potential benefits of lipid-modulating therapy for primary prevention in high-risk patients, who are often undertreated. However, it is important to note the inherent limitations of this secondary analysis. The analysis was performed on a subgroup within a larger clinical trial, which could potentially lead to false-positive findings due to multiple testing. Furthermore, the results may not generalize to younger populations, those with lower pretreatment LDL-C levels, those without diabetes, or those with a lower baseline cardiovascular risk.

Article: Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients – JAMA (free for a limited period)

Editorial: Bempedoic Acid for High-Risk Primary Prevention of Cardiovascular Disease: Not a Statin Substitute but a Good Plan B – JAMA (free for a limited period)

See also: Visual Abstract

Commentary: Study Suggests Bempedoic Acid Could Find Role in Primary Prevention – HCP Live

Original Study: RCT | Bempedoic acid shows modest reduction in cardiovascular events for statin-intolerant patients

 

RCT | High-dose dual-antibiotic cement doesn’t lower infection rates in hip hemiarthroplasty

26 Jun, 2023 | 00:47h | UTC

Summary: This randomized superiority trial studied the effect of high-dose dual-antibiotic loaded cement versus standard care single-antibiotic loaded cement on deep surgical site infection (SSI) rates in hip hemiarthroplasty patients. This large-scale study, conducted in 26 UK hospitals, included people aged 60 and older with a hip fracture.

The trial randomly allocated 4936 participants to either treatment group. The primary outcome was deep SSI at 90 days post-randomisation. Notably, no significant difference was found between the groups. About 1.7% of participants in the single-antibiotic group and 1.2% in the dual-antibiotic group experienced a deep SSI (adjusted odds ratio 1.43; 95% CI 0.87–2.35; p=0.16). This result contradicts previous findings suggesting that high-dose dual-antibiotic cement could reduce infection rates.

Article: High-dose dual-antibiotic loaded cement for hip hemiarthroplasty in the UK (WHiTE 8): a randomised controlled trial – The Lancet

News release: Antibiotic bone cement found not to reduce infection after hip replacement – University of Oxford

 

Cohort Study | Association of preterm birth with increased asthma and COPD risk in adulthood

26 Jun, 2023 | 00:45h | UTC

Summary: This population-based register study investigated the correlation between gestational ages (GA) and obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) in adulthood. The study used registry data from 706,717 individuals born between 1987-1998 in Finland (4.8% preterm), and 1,669,528 individuals born from 1967-1999 in Norway (5.0% preterm). The study observed care episodes of asthma and COPD using nationwide healthcare registers.

The results showed an increased risk of obstructive airway disease in adulthood for those born at <28 or 28–31 completed weeks of gestation. Even after adjustments, the risk remained 2-3 times greater compared to those who were born full term (at 39-41 completed weeks). Additionally, the risk for COPD at age 30–50 was significantly higher for those born at <28 weeks, with an odds ratio (OR) of 7.44. The study also identified that bronchopulmonary dysplasia (BPD) in infancy increased the odds of obstructive airway disease for those born at <28 and 28–31 weeks.

These findings suggest that preterm birth is a notable risk factor for asthma and COPD in adulthood, and this risk was observed across all gestational ages before full term. The study recommends diagnostic vigilance for adults born very preterm presenting with respiratory symptoms. However, the researchers also noted the potential limitations of using registry data, which might include residual confounding from unmeasured confounders and lack of data on certain prenatal or early life factors.

Article: Preterm birth and asthma and COPD in adulthood: a nationwide register study from two Nordic countries – European Respiratory Journal (free for a limited period)

 

Commentary on Twitter

 

RCT | Shortened head-up tilt test is non-inferior to traditional method for suspected vasovagal syncope

26 Jun, 2023 | 00:42h | UTC

Summary: The randomized clinical trial compared a short-duration head-up tilt test (HUTT) with the traditional longer-duration test for diagnosing suspected vasovagal syncope (VVS). The study involved 554 patients, half of which underwent the Fast protocol and the other half the Traditional protocol. The Fast protocol consisted of a 10-minute passive phase followed by a 10-minute nitroglycerin (NTG) phase if the passive phase yielded negative results, while the Traditional protocol included a 20-minute passive phase and a 15-minute NTG phase.

The findings showed no significant difference in the diagnostic value between the two protocols. Positive responses, identified by syncope induction amid hypotension or bradycardia, were seen in 60.3% of patients in the Fast protocol and 58.5% in the Traditional. However, there was a trend of less vasodepressor response in the Fast protocol during the passive phase.

This study suggests that the Fast HUTT protocol could replace the Traditional one, reducing test duration from 40 to 25 minutes without compromising diagnostic efficacy. However, the research didn’t assess the specificity of the Fast HUTT protocol in patients without a history of syncope, which serves as a limitation.

Article: Short-duration head-up tilt test potentiated with sublingual nitroglycerin in suspected vasovagal syncope: the fast Italian protocol – European Heart Journal (free for a limited period)

 

Commentary on Twitter

 

Review | Differentiating infection, colonization, and sterile inflammation in critical illness

26 Jun, 2023 | 00:41h | UTC

Differentiating infection, colonisation, and sterile inflammation in critical illness: the emerging role of host-response profiling – Intensive Care Medicine (free for a limited period)

 

Commentary on Twitter

 

M-A | Lifetime burden of psychological symptoms, disorders, and suicide due to cancer in childhood, adolescent, and young adult years

26 Jun, 2023 | 00:39h | UTC

Lifetime Burden of Psychological Symptoms, Disorders, and Suicide Due to Cancer in Childhood, Adolescent, and Young Adult Years: A Systematic Review and Meta-analysis – JAMA Pediatrics (free for a limited period)

Editorial: Poor Mental Health Among Survivors of Childhood Cancer—Risk Factors and a Call for Intervention – JAMA Pediatrics (free for a limited period)

 

Perspective | Early-stage lung cancer: using circulating tumor DNA to get personal

26 Jun, 2023 | 00:38h | UTC

Early-Stage Lung Cancer: Using Circulating Tumor DNA to Get Personal – Journal of Clinical Oncology

 

Review | Update on the management of patients with HIV infection in anesthesia and critical care

26 Jun, 2023 | 00:36h | UTC

Update on the management of patients with HIV infection in anaesthesia and critical care – BJA Education

 

Review | The antibiotic bead pouch – A useful technique for infection prevention and therapy in trauma surgery

26 Jun, 2023 | 00:35h | UTC

The antibiotic bead pouch – a useful technique for temporary soft tissue coverage, infection prevention and therapy in trauma surgery – Journal of Bone and Joint Infection

 

Review | How to treat diffuse large B-cell lymphoma: oncologic and cardiovascular considerations

26 Jun, 2023 | 00:33h | UTC

How to Treat Diffuse Large B-Cell Lymphoma: Oncologic and Cardiovascular Considerations – JACC: CardioOncology

 

Commentary on Twitter

 

Clinical insights into small cell lung cancer: tumor heterogeneity, diagnosis, therapy, and future directions

26 Jun, 2023 | 00:31h | UTC

Clinical insights into small cell lung cancer: Tumor heterogeneity, diagnosis, therapy, and future directions – CA: A Cancer Journal for Clinicians

 

Review | Therapeutic drug monitoring of antimicrobials in critically ill obese patients

26 Jun, 2023 | 00:29h | UTC

Therapeutic Drug Monitoring of Antimicrobials in Critically Ill Obese Patients – Antibiotics

 

Commentary on Twitter

 

Review | Treatment options in HER2-low breast cancer and proposed treatment sequencing algorithm

26 Jun, 2023 | 00:27h | UTC

A review of treatment options in HER2-low breast cancer and proposed treatment sequencing algorithm – Cancer

 

Consensus Paper | Gut microbiota and fecal microbiota transplantation in inflammatory bowel disease

26 Jun, 2023 | 00:26h | UTC

The first international Rome consensus conference on gut microbiota and faecal microbiota transplantation in inflammatory bowel disease – Gut

 

M-A | Effect of resistance exercise dose components for tendinopathy management

26 Jun, 2023 | 00:22h | UTC

Effect of resistance exercise dose components for tendinopathy management: a systematic review with meta-analysis – British Journal of Sports Medicine

 

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