[Posted 30/Oct/2023]

AUDIENCE: Family Medicine

KEY FINDINGS: Severe erythrocytosis (hematocrit >54%) is a rare outcome of gender-affirming testosterone therapy. Clinical recommendations should reconsider the need for routine frequent erythrocytosis screening within the first year of testosterone therapy for patients who prefer to minimize laboratory draws.

BACKGROUND: Gender-affirming hormone therapy (GAHT) is safe overall, with few adverse effects. One potential effect from using testosterone for GAHT is an increase in hemoglobin and/or hematocrit, known as secondary erythrocytosis. Current guidelines recommend monitoring hemoglobin or hematocrit routinely in the first year, some as frequently as every 3 months, which can create barriers to care. The study explored the incidence of erythrocytosis in the first 20 months of testosterone therapy among people receiving gender-affirming care.

DETAILS: This is a descriptive fixed cohort study of hematocrit and hemoglobin data from the charts of 282 people taking testosterone for GAHT. During the first 20 months of testosterone therapy, the cumulative incidence of hematocrit >50.4% was 12.6%, hematocrit >52% was 1.0%, and hematocrit >54% was 0.6%. All people were taking injectable testosterone cypionate, with a median dose of 100 mg weekly.

Copyright © Annals of Family Medicine, Inc. All rights reserved.

Source: Porat, A. T., Ellwood, M., Rodina, M., et al. (2023). Erythrocytosis in Gender-Affirming Care With Testosterone. Ann Fam Med. 2023; 21(5): 403-407. Published: September/October, 2023. DOI: 10.1370/afm.3018.

A Systematic Review and Individual Patient Data Meta-Analysis

[Posted 15/Sep/2025]

AUDIENCE: Infectious Disease, Pediatric

KEY FINDINGS: Regardless of malaria transmission intensity and age group, a single dose of 0.25 mg/kg primaquine is safe and efficacious for reducing P falciparum transmission. These findings underscore the need for primaquine formulations suitable for young children, and also provide supportive evidence to expand the use of single low-dose primaquine in regions with a moderate-to-high transmission rate that are threatened by artemisinin partial resistance.

BACKGROUND: Adding a single dose of primaquine to artemisinin-based combination therapy (ACT) for the treatment of falciparum malaria can reduce the transmission of Plasmodium falciparum and could limit the spread of artemisinin partial resistance, including in Africa, where the disease burden is greatest. Authors aimed to compare the safety and efficacy of single-dose primaquine plus ACT between young children (aged <5 years) and older children (aged 5 years to <15 years) and adults (aged >=15 years), and between low and moderate-to-high transmission areas.

DETAILS: For this systematic review and individual patient data meta-analysis, authors searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, WHO Global Index Medicus, OpenGrey.eu, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform, from database inception to April 3, 2024, with no language restrictions. Authors included prospective studies on efficacy against falciparum malaria that enrolled at least one child younger than 15 years and involved a study group given a single dose of primaquine (<=0.75 mg/kg) plus ACT. Studies involving mass drug administration, healthy volunteers, or patients with severe malaria or mixed (with non-falciparum) infections were excluded. For inclusion in the efficacy analysis, data on transmission potential (as determined by gametocytaemia, infectivity, or both) at enrolment and follow-up (day 3, day 7, or day 14) were required; the safety analysis required data on haemoglobin concentrations or haematocrit values at enrolment and at one or more follow-up visits by day 7, any data on adverse events, or both. After independent screening of the search results by two reviewers, the investigators of eligible studies were invited to contribute individual patient data. Authors quantified day 7 gametocyte carriage, probability of infecting a mosquito, decreases (>25%) in haemoglobin concentration associated with anaemia, and adverse events until day 28 using regression analyses, with random study-site intercepts to account for clustered data. These analyses were registered with PROSPERO, CRD42021279363 (safety) and CRD42021279369 (efficacy). Of 5697 records identified by the search, 30 studies were eligible for analysis. Of these, individual patient data were shared for 23 studies, including 6056 patients from 16 countries: 1171 (19.3%) young children (aged <5 years), 2827 (46.7%) older children (aged 5 years to <15 years), and 2058 (34.0%) adults (aged >=15 years). Adding a single low dose of primaquine (0.2-0.25 mg/kg) to ACTs reduced day 7 gametocyte positivity (adjusted odds ratio [aOR] 0.34, 95% CI 0.22-0.52; p<0.001) and infectivity to mosquitoes over time (aOR per day 0.02, 0.01-0.07, p<0.001). No difference was found in the effect of single low-dose primaquine both on gametocyte positivity in young children compared with older children (1.08, 0.52-2.23; p=0.84) and adults (0.50, 0.20-1.25; p=0.14) and between low-transmission and moderate-to-high transmission settings (1.07, 0.46-2.52; p=0.86), and on infectivity to mosquitoes in young children compared with older children (1.36, 0.07-27.71; p=0.84) and adults (0.31, 0.01-8.84; p=0.50) and between low-transmission and moderate-to-high transmission settings (0.18, 0.01-2.95; p=0.23). Gametocyte clearance was also similar for different ACTs (dihydroartemisinin-piperaquine vs artemether-lumefantrine) when combined with a primaquine target dose of 0.25 mg/kg (1.56, 0.65-3.79; p=0.32 at day 7). However, patients given a primaquine dose of less than 0.2 mg/kg with dihydroartemisinin-piperaquine were more likely to have gametocytaemia than those treated with artemether-lumefantrine (5.68, 1.38-23.48; p=0.016 at day 7). There was no increase in anaemia-associated declines in haemoglobin concentration (>25%) at a primaquine dose of 0.25 mg/kg, regardless of age group, transmission setting, and glucose-6-phosphate dehydrogenase status. The risks of adverse events of grade 2 or higher and of serious adverse events were similar between primaquine and no-primaquine groups, including in young children.

Copyright © The Author(s). Published by Elsevier Ltd. All rights reserved.

Source: Yilma, D., Stepniewska, K., Bousema, T., et al. (2024). Safety and Efficacy of Single-Dose Primaquine to Interrupt Plasmodium Falciparum Malaria Transmission in Children Compared With Adults: A Systematic Review and Individual Patient Data Meta-Analysis. The Lancet Infectious Diseases. 2025; 25(9): 965-976. Published: September, 2025. DOI: 10.1016/S1473-3099(25)00078-7.

A Quantitative Susceptibility Mapping MRI and PET Study

[Posted 12/Sep/2025]

AUDIENCE: Psychiatry, Family Medicine

KEY FINDINGS: The findings suggest that lower levels of non-neuromelanin-bound iron in the SN-VTA contribute to striatal hyperdopaminergia in schizophrenia. Further investigation is warranted to understand the role of low iron in schizophrenia and its potential as a treatment target.

BACKGROUND: Neuroimaging studies have independently associated schizophrenia with low iron and elevated dopamine synthesis. While preclinical research demonstrates that midbrain iron deficiency leads to striatal hyperdopaminergia, this relationship has not been studied in schizophrenia. The authors conducted a case-control study to examine differences in tissue magnetic susceptibility, a marker of brain iron, and correlated these with striatal dopamine synthesis capacity.

DETAILS: Magnetic susceptibility in the substantia nigra and ventral tegmental area (SN-VTA) was measured using quantitative susceptibility mapping (QSM) MRI in 159 participants (control subjects, N=80; early-course schizophrenia, N=79, including patients who were antipsychotic-naïve or antipsychotic-free). Because magnetic susceptibility is increased by neuromelanin and reduced by myelin, neuromelanin-sensitive MRI (NM-MRI) and diffusion tensor imaging (DTI) were employed to investigate the influence of neuromelanin and myelin on the QSM findings in 99 participants (control subjects, N=38; schizophrenia patients, N=61). Dopamine synthesis capacity (K_i ^cer) was then assessed with [¹⁸F]-DOPA positron emission tomography in 40 people from the schizophrenia group to test whether low SN-VTA magnetic susceptibility was related to high striatal K_i ^cer. SN-VTA magnetic susceptibility was lower in patients with schizophrenia than in control subjects (d=-0.66, 95% CI=-0.98, -0.34). This difference remained significant in analyses controlling for mean diffusivity (a DTI measure inversely correlating with myelin concentration) and NM-MRI contrast-to-noise ratios. SN-VTA magnetic susceptibility was significantly inversely correlated with striatal K_i ^cer, independent of mean diffusivity and NM-MRI contrast-to-noise ratios (r=-0.44). In both analyses, the strongest effects were observed in the ventral SN-VTA.

Copyright © American Psychiatric Association. All rights reserved.

Source: Vano, L. J., McCutcheon, R. A., Sedlacik, J., et al. (2024). Reduced Brain Iron and Striatal Hyperdopaminergia in Schizophrenia: A Quantitative Susceptibility Mapping MRI and PET Study. American Journal of Psychiatry. 2025; 182(9): 830–839. Published: September, 2025. DOI: 10.1176/appi.ajp.20240512.

[Posted 11/Sep/2025]

AUDIENCE: Geriatric, Family Medicine

KEY FINDINGS: Plasma %p-tau217 was associated with progression from CU to MCI in both cohorts, although differences in biomarker associations may be related to differences in the two cohorts.

BACKGROUND: Plasma biomarkers' utility for predicting incident mild cognitive impairment (MCI) remains unclear. Authors evaluated associations of plasma Alzheimer's disease (AD) biomarkers and amyloid positron emission tomography (PET) with transitions from cognitively unimpaired (CU) to MCI in the Mayo Clinic Study of Aging (MCSA) and BioFINDER-2 studies.

DETAILS: Associations of continuous baseline plasma biomarker levels and amyloid PET Centiloid with progression to MCI, adjusting for age, sex, and education, were evaluated with Cox proportional hazards models. The study included 381 MCSA and 584 BioFINDER-2 participants. Amyloid PET and percent phosphorylated to non-phosphorylated tau217 (%p-tau217) were strong predictors of progression to MCI in both cohorts: hazard ratios of 1.49 and 1.23 in the MCSA and 1.72 and 1.65 in BioFINDER, respectively. Amyloid beta 42/40 was a significant predictor in BioFINDER-2 only (hazard ratio 2.20).

Copyright © John Wiley & Sons, Inc. All rights reserved

Source: Cogswell, P. M., Wiste, H. J., Therneau, T. M., et al. (2024). Association of Plasma Alzheimer's Disease Biomarkers With Cognitive Decline in Cognitively Unimpaired Individuals. Alzheimers Dement.. 2025; Published: September, 2025. DOI: 10.1002/alz.70625.

Results From the BE BRIGHT Open-Label Extension Trial

[Posted 10/Sep/2025]

AUDIENCE: Dermatology, Family Medicine

KEY FINDINGS: Almost two-thirds of bimekizumab-treated patients achieved and maintained complete skin clearance through 4 years, making bimekizumab an effective, rapid, and durable long-term treatment option.

BACKGROUND: Patients with moderate to severe psoriasis experience significant burden on quality of life. Long-term management with latest-generation biologics can facilitate sustained complete skin clearance and improved patient well-being. Aim of this study is to report 4-year end-of-study bimekizumab efficacy and safety in patients with moderate to severe psoriasis.

DETAILS: Data were pooled from 3 phase 3 trials (BE VIVID, BE READY, and BE SURE) and their open-label extension (OLE; BE BRIGHT). Efficacy is reported for patients who received bimekizumab continuously from baseline into the OLE. Safety is reported for patients who received >=1 bimekizumab dose. Seven hundred seventy-one patients received bimekizumab from baseline into the OLE. A high proportion achieved complete skin clearance (100% improvement from baseline in Psoriasis Area and Severity Index) at Week 52 (76.2%) and maintained this to Week 196 (64.7%). The rate of treatment-emergent adverse events over 4 years was 169.8/100 patient-years (N = 1495) and did not increase with longer exposure. The most common treatment-emergent adverse events were nasopharyngitis, oral candidiasis, and upper respiratory tract infection, consistent with bimekizumab's known safety profile.

Copyright © Elsevier Ltd. All rights reserved.

Source: Blauvelt, A., Langley, R. G., Lebwohl, M., et al. (2024). Bimekizumab Durability of Efficacy Through 196 Weeks and Safety Through 4 Years in Patients With Moderate to Severe Plaque Psoriasis: Results From the BE BRIGHT Open-Label Extension Trial. Journal of the American Academy of Dermatology. 2025; 93: 644-653. Published: September, 2025. DOI: 10.1016/j.jaad.2025.04.038.

[Posted 9/Sep/2025]

AUDIENCE: Hospice & Palliative Nursing, Emergency Nursing

KEY FINDINGS: Despite the challenging environment of the emergency department, nurses who recognize their important role in the process of life-sustaining treatment withdrawal are more likely to provide high-quality EOL care. The perception of nurses' roles is especially influential on psychological care performance, and alternative approaches may be necessary for spiritual care.

BACKGROUND: This study aimed to identify predictors of end-of-life (EOL) care provided by emergency nurses in South Korea.

DETAILS: A cross-sectional survey was conducted using a structured questionnaire. Data were collected using Google Forms between June 21 and 30, 2022. A total of 154 emergency nurses from 10 tertiary hospitals in a metropolitan area were recruited using convenience sampling, and 139 completed surveys were analyzed. Multiple linear regression was employed to examine the effects of nurses' knowledge of life-sustaining treatment withdrawal (knowledge), their perceptions of their role in the withdrawal process (role perception), and job stress on EOL care. The mean scores for knowledge, role perception, job stress, and EOL care were 13.09±1.75 (max 6), 4.18±0.44 (max 5), 3.55±0.32 (max 4), and 2.48±0.40 (max 4), respectively. Among the EOL care subdomains, psychological domain scores were the highest. Multiple linear regression analysis indicated that nurses' role perception significantly predicted EOL care performance, particularly in the psychological (F=3.924, P=0.001) and spiritual (F=2.171, P=0.020) domains.

Copyright © Journal of Hospice and Palliative Care. All rights reserved.

Source: Park, H. J., Hong, E. A., Min, S. H., et al. (2024). Effects of Emergency Nurses' Life-Sustaining Treatment Withdrawal Knowledge, Role Perception, and Job Stress on Providing End-of-Life Care. J Hosp Palliat Care. 2025; 28(3): 89-98. Published: September 1, 2025. DOI: 10.14475/jhpc.2025.28.3.89.