A Systematic Review

[Posted 5/Nov/2024]

AUDIENCE: Family Medicine

KEY FINDINGS: Different anticoagulation-related perioperative management strategies achieve different outcomes following elective arthroplasty in patients with therapeutic chronic anticoagulation. There is contradictory evidence regarding the need for the discontinuation of therapeutic warfarin. Retrospective data showed that individual risk stratification with multi-modal prophylaxis resulted in minimal complications.

BACKGROUND: There are currently different management guidelines for patients undergoing elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) that are on long-term anticoagulation. The timing of discontinuation and restarting the anticoagulation is challenging during the postoperative care, which often involves general practitioners and physiotherapists.

DETAILS: The systematic review followed the PRISMA guidelines and included 3 databases: PubMed/MEDLINE, EMBASE, and Web of Science Core Collection. The risk of bias assessment was performed using the Methodological index for non-randomized studies (MINORS) criteria. Six retrospective studies involving 727 patients with therapeutic anticoagulation (1,540 controls) for elective THA, TKA and revision arthroplasty have been included. The follow-up ranged from 30 days to 1 year postoperatively. All studies evaluated outcomes of warfarin therapeutic anticoagulation versus prophylactic dosages of one or more of the following: warfarin, aspirin, low-molecular-weight heparin (LMWH) and unfractionated low-dose heparin (UFH). One study did not discontinue therapeutic anticoagulation. Two studies reported no significant differences in complications between groups, whilst 3 studies had significantly higher rates of superficial wound infections, revision surgeries, postoperative haematomas, and prosthetic joint infections (PJI).

Copyright © Oxford University Press. All rights reserved.

Source: Andronic, D., Andronic, O., Ammann, E., et al. (2024). Outcomes of Different Perioperative Management Strategies of Patients on Chronic Anticoagulation in Elective Total Hip and Knee Arthroplasty: A Systematic Review. Family Practice. 2024; 41(5): 629–637. Published: October, 2024. DOI: 10.1093/fampra/cmae020.

A Systematic Review and Meta-Analysis

[Posted 5/Mar/2025]

AUDIENCE: Family Medicine

KEY FINDINGS: Prophylactic iron supplementation likely results in a large reduction in maternal anaemia during pregnancy. Future research should qualify the impact of this benefit on women's quality of life and determine which subpopulations benefit most. Evidence surrounding the harms of iron supplementation in the non-anaemic population is poor quality and inconsistent. Randomized controlled trials quantifying the risk of gastrointestinal (GI) disturbance and iron overload are essential to inform iron supplement use and reduce unwarranted variations in international guidelines.

BACKGROUND: Iron deficiency during pregnancy poses a significant risk to both maternal and foetal health. Current international guidelines provide discrepant advice on antenatal iron supplementation for non-anaemic women. Study was aimed to quantify the benefits and harms of routine antenatal supplementation in non-anaemic women.

DETAILS: The Cochrane Library, MEDLINE, Embase, and clinical trial registries were searched for randomized controlled trials and observational studies comparing oral iron supplementation with placebo or no supplement in non-anaemic pregnant women. Risk of bias was assessed for each study and the results were synthesized via meta-analysis. Twenty-three eligible studies were identified with 4492 non-anaemic pregnant women. Supplemented groups had higher haemoglobin [mean difference = 6.95 g/l, 95% confidence interval (CI): 4.81-9.09, P < .001, moderate certainty, I2 = 91%] and ferritin (mean difference = 12.22 ng/ml, 95% CI: 6.92-17.52, P < .001, moderate certainty, I2 = 87%) and were at lower risk of anaemia (relative risk = 0.50, 95% CI: 0.34-0.74, P < .001, high certainty, I2 = 42%, number needed to treat (NNT) = 10). There was no difference in birth weight, preterm birth, and rate of caesarean section. Reporting on harms was inconsistent and there was insufficient evidence to determine an association between iron supplements and any negative outcome.

Copyright © Oxford University Press. All rights reserved.

Source: Watt, A., Eaton, H., Eastwick-Jones, K., et al. (2024). The Benefits and Harms of Oral Iron Supplementation in Non-Anaemic Pregnant Women: A Systematic Review and Meta-Analysis. Family Practice . 2024; 42(1): cmae079. Published: February, 2025. DOI: 10.1093/fampra/cmae079.

A Multicentre, Single-Arm, Phase 2 Trial

[Posted 4/Mar/2025]

AUDIENCE: Hematology, Oncology

KEY FINDINGS: Isatuximab, weekly bortezomib, and lenalidomide with limited dexamethasone was active and safe as initial therapy for older patients with multiple myeloma ineligible for autologous HSCT. A modified quadruplet regimen in which dexamethasone is omitted after two cycles can be used in this patient population.

BACKGROUND: Adding anti-CD38 monoclonal antibodies to standard therapies can improve outcomes in patients with multiple myeloma. Long-term treatment with corticosteroids increases the risk of infection. We aimed to evaluate the safety and activity of isatuximab, weekly bortezomib, lenalidomide, and limited dexamethasone in patients with newly diagnosed multiple myeloma ineligible for autologous haematopoietic stem-cell transplantation (HSCT).

DETAILS: REST is an academic, multicentre, single-arm, phase 2 trial of adults with newly diagnosed multiple myeloma and measurable disease as defined by International Myeloma Working Group criteria, ineligible for high-dose melphalan and autologous HSCT, Eastern Cooperative Oncology Group performance status of 0-3 (with 3 only allowed if related to myeloma). In 28-day cycles, patients received isatuximab (10 mg/kg intravenously on days 1, 8, 15, and 22 of cycle 1, and days 1 and 15 of cycles 2-18), bortezomib (1.3 mg/m² subcutaneously on days 1, 8, and 15 of cycles 1-8), and lenalidomide (25 mg orally on days 1-21, until progressive disease). Dexamethasone was given 20 mg orally on days 1, 8, 15 and 22, limited to the two first cycles only. The primary endpoint was measurable residual disease (MRD)-negative complete response, assessed by next-generation flow cytometry (sensitivity 1.0 x 10-5), during or after 18 cycles of study treatment. MRD was tested in all patients who had at least complete response before cycle 19 and in all patients who had at least very good partial response at cycle 19. All patients enrolled initiated treatment and were included in the analyses. Between June 30, 2021 and Jan 19, 2023, we assessed for eligibility and recruited 51 patients (27 [53%] females and 24 [47%] males), with a median age of 77 years (IQR 73.5-80). 39 participants completed 18 cycles of treatment on protocol, of whom two had discontinued treatment but not protocol. At a median follow-up of 27.0 months (IQR 23.0-33.7), MRD-negative complete response was observed in 19 (37% [95% CI 25.3-51.0]) patients, with a median treatment duration of 22 months (IQR 15.2-28.8; range 1.4-35.1). Disease progression or death had occurred in 18 (35%) of 51 patients, and eight (16%) patients had died. During the first 18 cycles of study treatment, the most common adverse events of grade 3 or 4 were neutropenia (28 [55%] patients), infections (21 [41%] patients), and thrombocytopenia (11 [22%] patients). 48 serious adverse events of grade 3 or higher were reported in 27 (53%) patients. A total of 14 (27%) patients discontinued treatment before cycle 19, most commonly because of progressive disease (eight [16%]) and adverse events (four [8%]). Two deaths (one due to pneumonia and one due to sepsis) were assessed as possibly related to study treatment.

Copyright © Elsevier Ltd. All rights reserved.

Source: Askeland, F. B., Haukas, E., Slordahl, T. S., et al. (2024). Isatuximab, Bortezomib, Lenalidomide, and Limited Dexamethasone in Patients With Transplant-Ineligible Multiple Myeloma (REST): A Multicentre, Single-Arm, Phase 2 Trial. The Lancet Haematology. 2025; 12(2): e120-e127. Published: February, 2025. DOI: 10.101/FS2352-3026.

[Posted 4/Mar/2025]

AUDIENCE: Nursing

KEY FINDINGS:

BACKGROUND: Diaper rash is a frequent diagnosis among neonates in the Neonatal Intensive Care Unit (NICU). It is characterized by an acute inflammatory eruption of the skin in the diaper area.

DETAILS: This study aimed to investigate the effect of colloid oatmeal and colloid cream on diaper rash among preterm neonates in the NICU. This study took place in the NICU of El-Raml Children's Hospital at Wengat in Alexandria, Egypt. Using a randomized control trial pre-posttest design with three parallel groups. Ninety preterm neonates with diaper rash were randomly assigned to three equal groups. Diaper Dermatitis Scale attached with demographic and clinical data was used. The outcome was assessed for four consecutive days for each group. Preterm neonates who received colloid oatmeal had significantly declined in the total mean score of severity of diaper rash in 3rd and 4th days with mean 0.833 ± 1.234 and 0.000 ± 0.000 compared to 2.333 ± 0.844 and 1.500 ± 1.224 in colloid group and 2.566 ± 0.817 and 1.966 ± 1.325 in the control group (p₁ = 0.027 in the 4th day, and p₂ and p₃ < 0.001 for each day).

Copyright © Neonatal Nurses Association. Published by Elsevier Ltd. All rights reserved.

Source: Saleh. S. E., Ismail, E.M., Fathy, H. M. A. E., et al. (2024). The Effect of Colloid Oatmeal Compared to Colloid Cream on Diaper Rash Among Preterm Neonates in the Neonatal Intensive Care Unit. J. Neonatal Nurs.. 2025; 31(1): 135-145. Published: February, 2025. DOI: 10.1016/j.jnn.2024.07.017.

A Population-Based Cohort Study in Sweden

[Posted 3/Mar/2025]

AUDIENCE: Cardiology, Emergency Medicine, Rheumatology

KEY FINDINGS: In patients with gout and without CHD, long-term allopurinol use protects against first-ever ACS compared with non-users. In contrast, allopurinol initiators, possibly having more systemic inflammation, had a higher risk of first-ever ACS compared with long-term users.

BACKGROUND: Purpose of this study is to investigate the impact of allopurinol use on the risk of first-ever acute coronary syndrome (ACS) event in patients with gout.

DETAILS: Using national and regional register data, we included all patients with a gout diagnosis at primary or specialised care in Western Sweden in the period 2007-2017 (n=18,862; 67% male patients). Patients with a prior history of coronary heart disease (CHD) were excluded. Follow-up started at the first gout diagnosis and ended at the first-ever ACS event, death or study end. The main outcome was the risk of first-ever ACS in: (1) allopurinol users versus non-users, by defining three categories of allopurinol exposure: exposed to 100 mg, >100 mg and no exposure (reference) and (2) allopurinol initiators (within 125 days) versus long-term users (reference). Multivariable logistic regression analysis was used to calculate ORs and 95% CIs. In analysis 1 (n=18,862), 15.3% (n=2892) were exposed to 100 mg, 9.1% (n=1717) to >100 mg and 75.6% (n=14,253) were not exposed. Allopurinol users were older and had more comorbidities compared with non-users. Allopurinol exposure (100 mg and >100 mg) was associated with significantly lower odds of first-ever ACS (OR 0.77; 95% CI 0.63 to 0.94, and OR 0.61; 95% CI 0.47 to 0.81, respectively). In Analysis 2, allopurinol initiators (n=489) had significantly higher odds of first-ever ACS compared with long-term users (n=2916) (OR 1.68; 95% CI 1.03 to 2.75).

Copyright © BMJ Publishing Group Ltd.. All rights reserved.

Source: Drivelegka, P., Jacobsson, L., Sandstrom, T. Z., et al. (2025). Allopurinol Use and Risk of Acute Coronary Syndrome in Gout Patients: A Population-Based Cohort Study in Sweden. BMJ Open. 2025; 15(2): e092522. Published: February 27, 2025. DOI: 10.1136/bmjopen-2024-092522.

[Posted 3/Mar/2025]

AUDIENCE: Endocrinology, Family Medicine

KEY FINDINGS: The FDA has resolved the shortage of semaglutide injection products, a glucagon-like peptide 1 (GLP-1) medication, meeting US demand, ending a nearly 3-year shortage. Patients and prescribers may still see intermittent and limited localized supply disruptions as the products move through the supply chain from the manufacturer and distributors to local pharmacies.

BACKGROUND: FDA has determined the shortage of semaglutide injection products, a glucagon-like peptide 1 (GLP-1) medication, is resolved. Semaglutide injection products have been in shortage since 2022 due to increased demand.

DETAILS: FDA confirmed with the drug's manufacturer that their stated product availability and manufacturing capacity can meet the present and projected national demand. Patients and prescribers may still see intermittent and limited localized supply disruptions as the products move through the supply chain from the manufacturer and distributors to local pharmacies.

To avoid unnecessary disruption to patient treatment, the agency does not intend to take action against compounders for violations of the FD&C Act arising from conditions that depend on semaglutide injection products’ inclusion on FDA’s drug shortage list:

• For a state-licensed pharmacy or physician compounding under section 503A of the FD&C Act: compounding, distributing or dispensing semaglutide injection products that are essentially a copy of an FDA-approved product within 60 calendar days from today's announcement, until April 22, 2025.
• For outsourcing facilities under section 503B of the FD&C Act: compounding, distributing or dispensing semaglutide injection products that are essentially a copy of an FDA-approved drug product within 90 calendar days from today’s announcement, until May 22, 2025. FDA may still take action regarding violations of any other statutory or regulatory requirements, such as to address findings that a product may be of substandard quality or otherwise unsafe.

Current shortage status of other GLP-1 products (as of February 21, 2025):

FDA continues to actively monitor drug availability and is currently working to determine whether the demand or projected demand for each drug in shortage exceeds the available supply.

• Dulaglutide injection: In shortage. Manufacturer has reported all presentations are available.
• Liraglutide injection: In shortage. Manufacturer has reported two presentations are available, and three have limited availability.

Source: FDA cLarifies Policies for Compounders as National GLP-1 Supply Begins to Stabilize. FDA. Published: February, 21, 2025.