Nature Medicine最新文献

Distressing voices are a core symptom of psychosis, for which existing treatments are currently suboptimal; as such, new effective treatments for distressing voices are needed. AVATAR therapy involves voice-hearers engaging in a series of facilitated dialogues with a digital embodiment of the distressing voice. This randomized phase 2/3 trial assesses the efficacy of two forms of AVATAR therapy, AVATAR-Brief (AV-BRF) and AVATAR-Extended (AV-EXT), both combined with treatment as usual (TAU) compared to TAU alone, and conducted an intention-to-treat analysis. We recruited 345 participants with psychosis; data were available for 300 participants (86.9%) at 16 weeks and 298 (86.4%) at 28 weeks. The primary outcome was voice-related distress at both time points, while voice severity and voice frequency were key secondary outcomes. Voice-related distress improved, compared with TAU, in both forms at 16 weeks but not at 28 weeks. Distress at 16 weeks was as follows: AV-BRF, effect −1.05 points, 96.5% confidence interval (CI) = −2.110 to 0, P = 0.035, Cohen’s d = 0.38 (CI = 0 to 0.767); AV-EXT −1.60 points, 96.5% CI = −3.133 to −0.058, P = 0.029, Cohen’s d = 0.58 (CI = 0.021 to 1.139). Distress at 28 weeks was: AV-BRF, −0.62 points, 96.5% CI = −1.912 to 0.679, P = 0.316, Cohen’s d = 0.22 (CI = −0.247 to 0.695); AV-EXT −1.06 points, 96.5% CI = −2.700 to 0.586, P = 0.175, Cohen’s d = 0.38 (CI = −0.213 to 0.981). Voice severity improved in both forms, compared with TAU, at 16 weeks but not at 28 weeks whereas frequency was reduced in AV-EXT but not in AV-BRF at both time points. There were no related serious adverse events. These findings provide partial support for our primary hypotheses. AV-EXT met our threshold for a clinically significant change, suggesting that future work should be primarily guided by this protocol. ISRCTN registration: ISRCTN55682735.

Correction to: Nature Medicine https://doi.org/10.1038/s41591-024-03264-4, published online 1 September 2024.

Semaglutide reduces albuminuria and the risk of kidney disease progression in patients with type 2 diabetes and chronic kidney disease (CKD). We conducted a randomized placebo-controlled double-blind clinical trial in adults with CKD (estimated glomerular filtration rate (eGFR) ≥25 ml min⁻¹ 1.73 m⁻² and urine albumin-to-creatinine ratio (UACR) ≥30 and <3,500 mg g⁻¹) and body mass index ≥27 kg m⁻². Participants were randomized to semaglutide 2.4 mg per week or placebo. The primary endpoint was percentage change from baseline in UACR at week 24. Safety was monitored throughout. Overall, 125 participants were screened, of whom 101 were randomized to semaglutide (n = 51) or placebo (n = 50). Mean age was 55.8 (s.d. 12) years; 40 participants (39.6%) were female; median UACR was 251 mg g⁻¹ (interquartile range 100, 584); mean eGFR was 65.0 (s.d. 25) ml min⁻¹ 1.73 m⁻²; and mean body mass index was 36.2 (s.d. 5.6) kg m⁻². Chronic glomerulonephritis (n = 25) and hypertensive CKD (n = 27) were the most common CKD etiologies. Treatment for 24 weeks with semaglutide compared to placebo reduced UACR by −52.1% (95% confidence interval −65.5, −33.4; P < 0.0001). Gastrointestinal adverse events were more often reported with semaglutide (n = 30) than with placebo (n = 15). Semaglutide treatment for 24 weeks resulted in a clinically meaningful reduction in albuminuria in patients with overweight/obesity and non-diabetic CKD. ClinicalTrials.gov registration: NCT04889183.

Obesity and cardiometabolic disease often, but not always, coincide. Distinguishing subpopulations within which cardiometabolic risk diverges from the risk expected for a given body mass index (BMI) may facilitate precision prevention of cardiometabolic diseases. Accordingly, we performed unsupervised clustering in four European population-based cohorts (N ≈ 173,000). We detected five discordant profiles consisting of individuals with cardiometabolic biomarkers higher or lower than expected given their BMI, which generally increases disease risk, in total representing ~20% of the total population. Persons with discordant profiles differed from concordant individuals in prevalence and future risk of major adverse cardiovascular events (MACE) and type 2 diabetes. Subtle BMI-discordances in biomarkers affected disease risk. For instance, a 10% higher probability of having a discordant lipid profile was associated with a 5% higher risk of MACE (hazard ratio in women 1.05, 95% confidence interval 1.03, 1.06, P = 4.19 × 10⁻¹⁰; hazard ratio in men 1.05, 95% confidence interval 1.04, 1.06, P = 9.33 × 10⁻¹⁴). Multivariate prediction models for MACE and type 2 diabetes performed better when incorporating discordant profile information (likelihood ratio test P < 0.001). This enhancement represents an additional net benefit of 4−15 additional correct interventions and 37−135 additional unnecessary interventions correctly avoided for every 10,000 individuals tested.

Monkeypox virus (MPXV) is endemic in Western and Central Africa and, in May 2022, a clade IIb lineage (B.1) caused a global outbreak outside Africa, resulting in its detection in 116 countries/territories. To understand the global phylogenetics of MPXV, we analysed all available MPXV sequences, including 10,670 sequences from 65 countries collected between 1958 and 2024. Our analysis reveals high mobility of clade I viruses within Central Africa, sustained human-to-human transmission of clade IIb lineage A viruses within the Eastern Mediterranean region, and distinct mutational signatures that can distinguish sustained human-to-human from animal-to-animal transmission. Moreover, distinct clade I sequences from Sudan suggest local MPXV circulation in areas of Eastern Africa over the past four decades. Our study underscores the importance of genomic surveillance in tracking spatiotemporal dynamics of MXPV clades and the need to strengthen such surveillance, including in some parts of Eastern Africa.