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RCT | Cyclophosphamide-based regimen enhances GVHD-free survival after hematopoietic stem-cell transplantation

27 Jun, 2023 | 13:54h | UTC

Summary: 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

 

RCT | Dolutegravir is noninferior as a replacement for ritonavir-boosted protease inhibitor in HIV therapy

27 Jun, 2023 | 13:52h | UTC

Summary: 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

 

RCT | Evaluating the viability of dolutegravir monotherapy in primary HIV infection

27 Jun, 2023 | 13:50h | UTC

Summary: 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.

Article: Sustained viral suppression with dolutegravir monotherapy over 192 weeks in patients starting combination antiretroviral therapy during primary HIV infection (EARLY-SIMPLIFIED): a randomized, controlled, multi-site, non-inferiority trial – Clinical Infectious Diseases

 

Cohort Study | Increased revision rates seen in shoulder replacement surgeries by surgeons with less than 10 procedures annually

27 Jun, 2023 | 13:48h | UTC

Summary: 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.

Article: Association between surgeon volume and patient outcomes after elective shoulder replacement surgery using data from the National Joint Registry and Hospital Episode Statistics for England: population based cohort study – The BMJ

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

Assessing and managing frailty in emergency laparotomy: a WSES position paper – World Journal of Emergency Surgery

 

SR | Medically assisted hydration in palliative care: uncertain effects on quality of life and survival

27 Jun, 2023 | 13:47h | UTC

Summary: 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 | UTC

Contemporary 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

Step by step daily management of short-term mechanical circulatory support for cardiogenic shock in adults in the intensive cardiac care unit: a clinical consensus statement of the Association for Acute CardioVascular Care of the European Society of Cardiology SC, the European Society of Intensive Care Medicine, the European branch of the Extracorporeal Life Support Organization, and the European Association for Cardio-Thoracic Surgery – European Heart Journal. Acute Cardiovascular Care

 

Special Series | Emergencies in vascular surgery

27 Jun, 2023 | 13:41h | UTC

Homepage – Seminars in Vascular Surgery

Descending thoracic aortic emergencies: Past, present, and future

Thoracic aortic emergencies involving the aortic arch: An integrated cardiovascular surgical treatment approach

Ruptured abdominal aorto-iliac aneurysms: Diagnosis, treatment, abdominal compartment syndrome, and role of simulation-based training

Contemporary multimodal approach to diagnosis and treatment of vascular graft and endograft infections

Acute management of mesenteric emergencies: Tailoring the solution to the problem

Resuscitative balloon occlusion of the aorta in the modern era: Expanding indications, optimal techniques, unresolved issues, and current results

Acute perioperative complications after arterial and venous femoral access in major vascular and cardiac procedures: Ischemic or hemorrhagic patterns and how to solve them

 

Review | Hypertension management in patients with cardiovascular comorbidities

27 Jun, 2023 | 13:39h | UTC

Hypertension management in patients with cardiovascular comorbidities – European Heart Journal

 

Commentary on Twitter

 

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

EULAR points to consider for the definition of clinical and imaging features suspicious for progression from psoriasis to psoriatic arthritis – Annals of the Rheumatic Diseases

 

Commentary on Twitter

 

Review | Renal thrombotic microangiopathy

27 Jun, 2023 | 13:34h | UTC

Renal Thrombotic Microangiopathy: A Review – American Journal of Kidney Diseases

 

Commentary on Twitter

 

Review | Functional coronary angiography for the assessment of the epicardial vessels and the microcirculation

27 Jun, 2023 | 13:33h | UTC

Functional coronary angiography for the assessment of the epicardial vessels and the microcirculation – EuroIntervention

 

Commentary on Twitter

 

The exposome in respiratory diseases: multiple preventable risk factors from early life to adulthood

27 Jun, 2023 | 13:32h | UTC

The exposome in respiratory diseases: multiple preventable risk factors from early life to adulthood – Breathe

 

Commentary on Twitter

 

M-A | Effectiveness of physical therapy in axillary web syndrome after breast cancer

27 Jun, 2023 | 13:28h | UTC

Effectiveness of physical therapy in axillary web syndrome after breast cancer: a systematic review and meta-analysis – Supportive Care in Cancer

 

M-A | Risk factors for non-tuberculous mycobacterial pulmonary disease

27 Jun, 2023 | 13:27h | UTC

Risk Factors for Non-tuberculous Mycobacterial Pulmonary Disease (NTM-PD) A systematic literature review and meta-analysis – Chest

Commentary: 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 | 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

 

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