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Podcast | Wisely ordering autoantibodies
28 Jun, 2023 | 13:09h | UTC#399 Wisely Ordering Autoantibodies – ACP IM2023 – The Curbsiders
KDOQI US commentary on the 2021 KDIGO clinical practice guideline for the management of glomerular diseases
28 Jun, 2023 | 13:07h | UTCOriginal Guideline: KDIGO 2021 clinical practice guideline for the management of glomerular diseases – Kidney Disease: Improving Global Outcomes
Position Statement | Prehospital hemorrhage control and treatment by clinicians
27 Jun, 2023 | 14:02h | UTC
EASL Clinical Practice Guidelines on acute-on-chronic liver failure
27 Jun, 2023 | 14:00h | UTCEASL Clinical Practice Guidelines on acute-on-chronic liver failure – Journal of Hepatology
Commentary on Twitter
?NEW@EASLnews Clinical Practice Guidelines on acute-on-chronic liver failure
Available here: https://t.co/GCNg1AIX9X pic.twitter.com/aKd0DUJBkL
— Journal of Hepatology (@JHepatology) June 24, 2023
RCT | Oral Semaglutide at 25mg and 50mg improves glycemic control in overweight T2DM patients compared to standard 14mg dose
27 Jun, 2023 | 13:58h | UTCSummary: The study was a global, multicenter, randomized, double-blind, phase 3b trial involving 1606 adults with inadequately controlled type 2 diabetes. The mean HbA1c in the study population was 9.0% and the mean BMI was 33.8 kg/m2. Participants were assigned to receive either 14mg, 25mg, or 50mg of once-daily oral semaglutide for 68 weeks. The trial aimed to investigate the effectiveness of a new formulation of semaglutide at higher investigational doses against the standard 14mg dose.
The primary endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 52. Results showed that at week 52, changes in HbA1c levels were significantly more substantial with the 25mg (-1.8 percentage points) and 50mg (-2.0 percentage points) doses compared to the 14mg dose (-1.5 percentage points). During the trial, ten deaths occurred, but none were considered treatment-related. No new safety concerns were identified, though adverse events, primarily mild to moderate gastrointestinal disorders, were slightly more frequent in the 25mg and 50mg groups.
The study limitations include a relatively short exposure to the higher doses due to the up to 16 weeks of dose-escalation period, non-adjustable doses due to masking requirements, and a cohort predominantly of White ethnicity, considering the high prevalence of type 2 diabetes in other racial groups. The study was unable to assess differences in efficacy and tolerability between the 25mg and 50mg doses, raising the question of whether the 50mg dosage is necessary if similar effects can be achieved with the 25mg dose.
The implications for further research highlight the need for real-world studies to investigate the clinical impact and safety of these higher doses of oral semaglutide. The superior glycemic control and bodyweight loss with oral semaglutide 25mg and 50mg suggest that these higher doses might help individualize treatment goals and intensify treatment by increasing the dose of a single oral agent. Future studies could consider comparing the 25mg and 50mg doses more directly to determine the most effective and tolerable dose for patients.
Article: Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial – The Lancet (free registration required)
RCT | Once-daily oral Semaglutide 50mg outperforms placebo in obesity treatment
27 Jun, 2023 | 13:57h | UTCSummary: The referenced study is a phase 3, superiority, randomized, double-blind, placebo-controlled trial that investigated the effectiveness of oral semaglutide 50mg in treating overweight and obese adults without type 2 diabetes. The trial was conducted in 50 outpatient clinics across Asia, Europe, and North America, with a total of 667 participants randomly allocated to receive either the treatment or a placebo.
The primary outcome measured was the percentage change in bodyweight from baseline to week 68. Results showed a significant reduction in bodyweight among participants receiving semaglutide – a mean change of -15.1% compared to -2.4% for placebo recipients. Additionally, a higher percentage of semaglutide recipients achieved weight reductions of at least 5%, 10%, 15%, and 20% compared to placebo recipients.
However, it’s important to note that adverse events were more frequently observed in the semaglutide group. Specifically, 80% of participants receiving oral semaglutide 50 mg experienced gastrointestinal adverse events, mostly mild to moderate, compared to 46% in the placebo group. This highlights the need for careful patient monitoring during treatment.
The findings indicate that oral semaglutide 50mg, when taken once daily, can lead to a clinically meaningful decrease in bodyweight among overweight and obese adults without type 2 diabetes. Despite the higher occurrence of gastrointestinal adverse events, the significant weight loss potential positions oral semaglutide as a promising treatment option. Further research is recommended to establish long-term safety and efficacy.
Article: Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial – The Lancet (link to abstract – $ for full-text)
RCT | Cyclophosphamide-based regimen enhances GVHD-free survival after hematopoietic stem-cell transplantation
27 Jun, 2023 | 13:54h | UTCSummary: The article details a phase 3 trial comparing the efficacy of two graft-versus-host disease (GVHD) prophylactic regimens in hematologic cancer patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT). The experimental group received cyclophosphamide–tacrolimus–mycophenolate mofetil, and the standard group received tacrolimus–methotrexate. The patients, a total of 431, underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched unrelated donor.
The primary end point was GVHD-free, relapse-free survival at 1 year. Results indicated a significantly higher incidence of this outcome in the experimental group (hazard ratio, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P=0.001). At 1 year, adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) in the experimental group, compared to 34.9% (95% CI, 28.6 to 41.3) in the standard group.
Notably, patients in the experimental-prophylaxis group appeared to have less severe acute or chronic GVHD and a higher incidence of immunosuppression-free survival at 1 year. Overall survival, disease-free survival, relapse, transplantation-related death, and engraftment did not show a substantial difference between the groups. These results suggest that cyclophosphamide–tacrolimus–mycophenolate mofetil may offer a more effective prophylaxis against GVHD in HSCT patients.
Article: Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis – New England Journal of Medicine (link to abstract – $ for full-text)
News Release: Study Sets New Standard for Graft-Versus-Host Disease Prevention After Stem Cell Transplant – Johns Hopkins Medicine
Commentary on Twitter
In this trial, 1-year GVHD-free, relapse-free survival after stem-cell transplantation was 52.7% in the cyclophosphamide–tacrolimus–mycophenolate mofetil group and 34.9% in the tacrolimus–methotrexate group. https://t.co/wCdvP1LChu
— NEJM (@NEJM) June 21, 2023
RCT | Dolutegravir is noninferior as a replacement for ritonavir-boosted protease inhibitor in HIV therapy
27 Jun, 2023 | 13:52h | UTCSummary: This randomized clinical trial (RCT) assessed the switch from ritonavir-boosted protease inhibitor (PI) to dolutegravir in HIV patients without genotype information but with viral suppression. The multicenter, open-label trial, involving 795 participants across four sites in Kenya, compared those who switched to dolutegravir (398) with those continuing with their current ritonavir-boosted PI regimen (397). The primary end point was an HIV type 1 RNA level of at least 50 copies per milliliter at week 48.
At the end of the trial period, the number of patients in both groups who met the primary end point was nearly the same (5.0% in the dolutegravir group and 5.1% in the ritonavir-boosted PI group). This indicates the noninferiority of dolutegravir, within a 4% margin. Additionally, no mutations conferring resistance to either drug were detected. The incidence of treatment-related adverse events of grade 3 or 4 was similar in both groups (5.7% for dolutegravir and 6.9% for ritonavir-boosted PI).
The study concludes that dolutegravir is a noninferior alternative to ritonavir-boosted PI for previously treated, virally suppressed HIV patients lacking drug-resistance mutation data. The similar safety profiles also support the switch. However, further research may provide valuable insights on the long-term implications of the switch.
Article: Second-Line Switch to Dolutegravir for Treatment of HIV Infection – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary: Second-Line Switch to Dolutegravir Noninferior in HIV – HealthDay
Commentary on Twitter
In an open-label, multicenter trial in Kenya, HIV-infected patients following a ritonavir-boosted protease inhibitor regimen were assigned to switch to dolutegravir or continue the regimen. The dolutegravir-based regimen was noninferior. https://t.co/jL70h5ejnV
— NEJM (@NEJM) June 21, 2023
RCT | Evaluating the viability of dolutegravir monotherapy in primary HIV infection
27 Jun, 2023 | 13:50h | UTCSummary: The study in focus is a randomized, controlled, non-inferiority trial spanning over 192 weeks, titled “EARLY-SIMPLIFIED”. It evaluated the effect of simplifying combination antiretroviral therapy (cART) to dolutegravir (DTG) monotherapy in patients with early-stage HIV-1 infection. The trial recruited 101 people who had begun cART within 180 days of a documented primary HIV-1 infection with suppressed viral load.
The patients were randomly divided into two groups: DTG monotherapy (n=68) and continued cART (n=33). The primary endpoints were viral failure rates at 48, 96, 144, and 192 weeks. Results revealed no difference in viral response between the two groups at 96 weeks, suggesting non-inferiority of DTG monotherapy. At the end of the trial (192 weeks), no virological failures were recorded in either group.
The study indicates that early initiation of cART during primary HIV infection might permit sustained virological suppression after switching to DTG monotherapy. However, the study was limited by its highly selected patient population and the transition to an observational design after 96 weeks. It provides insight into the potential for minimizing ART toxicity by stratifying patients according to the latent reservoir size or duration of active infection before starting therapy.
Cohort Study | Increased revision rates seen in shoulder replacement surgeries by surgeons with less than 10 procedures annually
27 Jun, 2023 | 13:48h | UTCSummary: This prospective cohort study investigated the correlation between surgeon volume and patient outcomes after elective shoulder replacement surgeries. Utilizing data from 39,281 procedures performed by 638 surgeons in UK public and private hospitals between 2012-20, the study focuses on adults aged 18 years or older.
The results indicate a significant connection between a surgeon’s mean annual volume and risk of adverse patient outcomes. Surgeons performing fewer than 10.4 procedures per year demonstrated a significantly increased risk of revision surgery, with the hazard ratio being almost twice as high as that of the lowest risk surgeons. Higher mean annual surgical volume correlated with lower risks of reoperations, fewer serious adverse events, and shorter hospital stays.
These findings suggest the need for strategic resource planning in surgical services, with considerations given to surgeon’s annual procedure volume to improve patient outcomes after shoulder replacement surgery. It should be noted that the study was limited in scope to surgeries performed within the NHS and private hospitals in England. Furthermore, potential confounding factors like patients’ social circumstances, carer availability, or body mass index were not considered.
Editorial: Surgeon volume and patient outcomes in shoulder replacement surgery – The BMJ
News Release: Patients do better when surgeon averages 10 + annual shoulder ops – BMJ Newsroom
Position Paper | Assessing and managing frailty in emergency laparotomy
27 Jun, 2023 | 13:45h | UTC
SR | Medically assisted hydration in palliative care: uncertain effects on quality of life and survival
27 Jun, 2023 | 13:47h | UTCSummary: The Cochrane Review analyzed Randomized Controlled Trials (RCTs) to evaluate the impact of Medically Assisted Hydration (MAH) on the Quality of Life (QoL) and survival of adults receiving palliative care. A total of four studies involving 422 participants, all diagnosed with advanced cancer, were considered. Two studies compared MAH with placebo, and two compared it with standard care.
The primary outcome was QoL, assessed through validated scales, with survival and adverse events being secondary outcomes. Mean differences (MD) and risk ratios (RR) were calculated for continuous and dichotomous outcomes, respectively. However, results were inconclusive due to a very low certainty of evidence. Hence, it is unclear whether MAH improves QoL, prolongs survival, or leads to adverse events when compared to placebo or standard care.
The findings are only applicable to inpatients with advanced cancer at the end of life and do not transfer to other adults in palliative care with non-cancer, dementia, or neurodegenerative diseases, or those with an extended prognosis. The lack of high-quality evidence leaves clinicians to make decisions based on perceived benefits and harms for individual circumstances.
Article: Medically assisted hydration for adults receiving palliative care – Cochrane Library
Review | Contemporary artery-first approaches in pancreatoduodenectomy
27 Jun, 2023 | 13:43h | UTCContemporary artery-first approaches in pancreatoduodenectomy – British Journal of Surgery
Review | Management of short-term mechanical circulatory support for cardiogenic shock in adults in the intensive cardiac care unit
27 Jun, 2023 | 13:42h | UTC
Special Series | Emergencies in vascular surgery
27 Jun, 2023 | 13:41h | UTCHomepage – Seminars in Vascular Surgery
Descending thoracic aortic emergencies: Past, present, and future
Acute management of mesenteric emergencies: Tailoring the solution to the problem
Review | Hypertension management in patients with cardiovascular comorbidities
27 Jun, 2023 | 13:39h | UTCHypertension management in patients with cardiovascular comorbidities – European Heart Journal
Commentary on Twitter
Hypertension management in patients with cardiovascular comorbidities. A State-of-the-Art review just published in #EHJ.@escardio @ESC_Journals #CardioTwitter #hypertensionhttps://t.co/esgOEkxlta pic.twitter.com/xDRHSWn6sZ
— EHJ Editor-in-Chief (@ehj_ed) June 21, 2023
EULAR points to consider for the definition of clinical and imaging features suspicious for progression from psoriasis to psoriatic arthritis
27 Jun, 2023 | 13:37h | UTC
Commentary on Twitter
Have you checked the latest recommendations? @eular_org points to consider for the definition of clinical and imaging features suspicious for progression from PsO to PsA
▶️ 3 stages relevant to PsA prevention
▶️ 5 OP and 10 points to consider? https://t.co/Kr9akTjNC6 pic.twitter.com/cHsg0ZTlb6
— ARD & RMD Open (@ARD_BMJ) June 21, 2023
Review | Renal thrombotic microangiopathy
27 Jun, 2023 | 13:34h | UTCRenal Thrombotic Microangiopathy: A Review – American Journal of Kidney Diseases
Commentary on Twitter
Renal Thrombotic Microangiopathy: A Review https://t.co/YabUm18t4q (FREE)@CPQMD @ReichHeather @UofTNephrology pic.twitter.com/Y9rSnuTFBo
— AJKD (@AJKDonline) June 24, 2023
Review | Functional coronary angiography for the assessment of the epicardial vessels and the microcirculation
27 Jun, 2023 | 13:33h | UTC
Commentary on Twitter
? STATE OF THE ART: Functional coronary angiography for the assessment of the epicardial vessels and the microcirculation by Faria D, et al. https://t.co/gMUMILNCdc angiography-for-the-assessment-of-the-epicardial-vessels-and-the-microcirculation pic.twitter.com/mSUihEZf78
— EuroIntervention (@EuroInterventio) June 20, 2023
The exposome in respiratory diseases: multiple preventable risk factors from early life to adulthood
27 Jun, 2023 | 13:32h | UTC
Commentary on Twitter
The increasing global burden of respiratory diseases over recent decades raises questions about the lifelong impact of environmental factors during industrialisation and urbanisation. There is a clear need for action in primary and secondary prevention. https://t.co/MFzkETBr2X pic.twitter.com/jp9LYSiSAR
— ERS publications (@ERSpublications) June 20, 2023
M-A | Effectiveness of physical therapy in axillary web syndrome after breast cancer
27 Jun, 2023 | 13:28h | UTC
M-A | Risk factors for non-tuberculous mycobacterial pulmonary disease
27 Jun, 2023 | 13:27h | UTCCommentary: Comorbid respiratory disease key predictor of NTM-PD – MDedge
Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050
26 Jun, 2023 | 01:00h | UTCSummary: 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.
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)
Today: More than 529 million people across the globe have diabetes
In the next 30 years: 1.3 billion people are projected to have diabetes
https://t.co/gh2O0K7RY0— Institute for Health Metrics and Evaluation (IHME) (@IHME_UW) June 22, 2023
Phase 2 RCT | Orforglipron, an oral GLP-1 receptor agonist, significantly reduces weight in adults with obesity
26 Jun, 2023 | 00:58h | UTCSummary: 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 | UTCSummary: 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