Mental Disorders as a Risk Factor of Acute Coronary Syndrome
Results of this systematic review and meta-analysis suggest that depressive disorders, anxiety disorders, PTSD, and sleep disorders were associated with an increased risk of ACS. Particularly, PTSD and sleep disorders emerged as significant risk factors for ACS, indicating the potential impact of sleep quality on cardiovascular outcomes. Future research addressing these limitations could provide more nuanced insights into the association between mental health and ACS.
Summary
A Systematic Review and Meta-Analysis.
[Posted 23/Jan/2026]
AUDIENCE: Psychiatry, Family Medicine
KEY FINDINGS: Results of this systematic review and meta-analysis suggest that depressive disorders, anxiety disorders, PTSD, and sleep disorders were associated with an increased risk of ACS. Particularly, PTSD and sleep disorders emerged as significant risk factors for ACS, indicating the potential impact of sleep quality on cardiovascular outcomes. Future research addressing these limitations could provide more nuanced insights into the association between mental health and ACS.
BACKGROUND: Aim of this study is to estimate the association of ACS among patients with mental disorders, as compared with patients without mental disorders.
DETAILS: Study screening was performed in duplicates with conflicts resolved upon consensus. Inclusion criteria were as follows: (1) observational or randomized study, (2) measured association with ACS (incident events, risk ratio, odds ratio, hazard ratio [HR]), and (3) investigated any clinical mental disorder (based on DSM and International Classification of Diseases) before ACS events. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Data extraction was performed in duplicate and resolved on consensus. Data were quantitatively synthesized through random-effects meta-analysis. The National Institutes of Health Study Quality Assessment Tools were used to assess the quality of included studies. Studies were analyzed from January 1966 to October 2021. Among 3616 initially identified studies, 25 full-text articles met inclusion criteria with 22,048,504 participants of median (IQR) age 48.0 (34.5-56.1) years, with 13 019 897 males (59.1%). Depressive disorder (HR, 1.40; 95% CI, 1.11-1.78; P = .01; Grading of Recommendations Assessment, Development, and Evaluation [GRADE] certainty = very low), anxiety disorder (HR, 1.63; 95% CI, 1.40-1.89; P < .001; GRADE certainty = low), sleep disorder (HR, 1.60; 95% CI, 1.22-2.10; P < .001; GRADE certainty = low), and posttraumatic stress disorder (PTSD; HR, 2.73; 95% CI, 1.94-3.84; P < .001; GRADE certainty = moderate) were associated with increased risk of ACS. Bipolar (HR, 1.48; 95% CI, 0.47-4.61; P = .28; GRADE certainty = very low) and psychotic (HR, 0.97; 95% CI, 0.01-178.30; P = .06; GRADE certainty = very low) disorders were not significantly associated with increased risk of acute myocardial infarction, although they had similar point estimates to some other mental disorders.
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Efficacies of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria in children aged 6 months to 10 years in Uganda
Artemether-lumefantrine was associated with a higher risk of recurrent malaria than other antimalarial combinations tested, and K13 mutations were associated with delayed parasite clearance. Changes in first-line therapy for uncomplicated malaria must be considered in response to suboptimal efficacy of artemether-lumefantrine.
Summary
A randomised, open-label, phase 4 clinical trial
[Posted 22/Jan/2026]]
AUDIENCE: Infectious Disease, Family Medicine
KEY FINDINGS: Artemether-lumefantrine was associated with a higher risk of recurrent malaria than other antimalarial combinations tested, and K13 mutations were associated with delayed parasite clearance. Changes in first-line therapy for uncomplicated malaria must be considered in response to suboptimal efficacy of artemether-lumefantrine.
BACKGROUND: Anti-malarial artemisinin-based combination therapies (ACTs) might be losing efficacy in east Africa, with the spread of artemisinin partial resistance and reduced partner drug activity. Our trial aimed to measure the efficacies of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine in three sites in Uganda.
DETAILS: This randomised, open-label, phase 4 clinical trial was carried out at three sites in the Agago, Arua, and Busia districts of Uganda. Children aged 6 months to 10 years with uncomplicated Plasmodium falciparum malaria were randomly assigned to receive either artemether-lumefantrine (20 mg artemether; 120 mg lumefantrine; twice a day for 3 days) in all sites or dihydroartemisinin-piperaquine (40 mg dihydroartemisinin and 320 mg piperaquine, once a day for 3 days) in Agago, artesunate-amodiaquine (25 mg artesunate and 67.5 mg amodiaquine for children <9 kg or 50 mg artesunate and 135 mg amodiaquine for children >=9 kg, once a day for 3 days) in Busia; and artesunate-pyronaridine (60 mg artesunate and 180 mg pyronaridine for children >15 kg or 20 mg artesunate and 60 mg pyronaridine for children <15 kg, once a day for 3 days) in Arua, with follow-up to 42 days. Participants were not blinded to group assignments; however, investigators and those assessing outcome were masked. The primary outcome was parasitaemia, assessed by microscopy, either uncorrected or PCR-corrected to distinguish recrudescence from new infection. All participants who received the treatment per protocol and were not lost to follow-up were included in the primary outcome. All participants who were randomly allocated to treatment groups were included in the safety analyses. This study is registered with the Pan African Clinical Trials Registry, number PACTR202301796134887, and is complete. Between Nov 7, 2022, and March 24, 2023, 808 participants (437 [54%] female) were enrolled and assigned to treatment groups; 15 (2%) were lost to follow-up and 793 (98%) completed follow-up. The uncorrected adequate clinical and parasitological response for artemether-lumefantrine was 87 (51.8%; 95% CI 44.0-59.5) of 168 participants in Arua, 88 (51.8%; 44.0-59.4) of 170 and Busia, and 131 (79.4%; 72.3-85.1) of 165 in Agago. This response for artemether-lumefantrine was lower than that of the other ACTs at all sites: 97 (98.0%; 92.2-99.6) of 99 for dihydroartemisinin-piperaquine in Agago, 95 (99.0%; 93.5-99.9) of 96 for artesunate-amodiaquine in Busia, and 73 (73.7%; 63.8-81.8) of 99 for artesunate-pyronaridine in Arua. PCR-corrected 28-day efficacies were 88 (81.5%; 72.6-88.1) of 108 for artemether-lumefantrine and 95 (100%; 95.2-100.0) of 95 for artesunate-amodiaquine in Busia; 131 (97.0%; 92.1-99.0) of 135 for artemether-lumefantrine and 97 (100%; 95.3-100.0) of 97 for dihydroartemisinin-piperaquine in Agago; and 87 (82.1%; 73.2-88.6) of 106 for artemether-lumefantrine and 73 (92.4%; 83.6-96.9) of 79 for artesunate-pyronaridine in Arua. All regimens were well tolerated. The most common adverse events were upper respiratory tract infection, diarrhoea, and anaemia. None of the reported adverse events were attributed to the study drugs. There were two serious adverse events, both cases of severe malaria in Arua, one in each of the treatment groups. Parasite clearance half-lives were prolonged with parasites carrying the PfK13 Cys469Tyr (median 4.2 h; IQR 3.4-4.9) and Ala675Val (4.9 h; 3.4-5.7) mutations compared with wild-type parasites (2.8 h; 2.3-3.6; p<0.0001).
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Source: Kamya, M. R., Nankabirwa, J. I., Ebong, C., et al. Efficacies of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria in children aged 6 months to 10 years in Uganda: a randomised, open-label, phase 4 clinical trial. The Lancet Infectious Diseases. 2026; 26(1): 67-68. Published: January, 2026. DOI: 10.1016/S1473-3099(25)00407-4.
Medical Management and Revascularization for Asymptomatic Carotid Stenosis
Among patients with high-grade stenosis without recent symptoms, the addition of stenting led to a lower risk of a composite of perioperative stroke or death or ipsilateral stroke within 4 years than intensive medical management alone. Carotid endarterectomy did not lead to a significant benefit.
KEY FINDINGS: Among patients with high-grade stenosis without recent symptoms, the addition of stenting led to a lower risk of a composite of perioperative stroke or death or ipsilateral stroke within 4 years than intensive medical management alone. Carotid endarterectomy did not lead to a significant benefit.
BACKGROUND: Improvements in medical therapy, carotid-artery stenting, and carotid endarterectomy call into question the preferred management of asymptomatic carotid stenosis. Whether adding revascularization to intensive medical management would provide greater benefit than intensive medical management alone is unclear.
DETAILS: Authors conducted two parallel, observer-blinded clinical trials that enrolled patients with high-grade (>=70%) asymptomatic carotid stenosis across 155 centers in five countries. The stenting trial compared intensive medical management alone (medical-therapy group) with carotid-artery stenting plus intensive medical management (stenting group); the endarterectomy trial compared intensive medical management alone (medical-therapy group) with carotid endarterectomy plus intensive medical management (endarterectomy group). The primary outcome was a composite of any stroke or death, assessed from randomization to 44 days, or ipsilateral ischemic stroke, assessed during the remaining follow-up period up to 4 years. A total of 1245 patients underwent randomization in the stenting trial and 1240 in the endarterectomy trial. In the stenting trial, the 4-year incidence of primary-outcome events was 6.0% (95% confidence interval [CI], 3.8 to 8.3) in the medical-therapy group and 2.8% (95% CI, 1.5 to 4.3) in the stenting group (P=0.02 for the absolute difference). In the endarterectomy trial, the 4-year incidence of primary-outcome events was 5.3% (95% CI, 3.3 to 7.4) in the medical-therapy group and 3.7% (95% CI, 2.1 to 5.5) in the endarterectomy group (P=0.24 for the absolute difference). From day 0 to 44, in the stenting trial, no strokes or deaths occurred in the medical-therapy group and seven strokes and one death occurred in the stenting group; in the endarterectomy trial, three strokes occurred in the medical-therapy group and nine strokes occurred in the endarterectomy group.
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UNC Researchers Discover Method to Combat Antibiotic Treatment Failure
In animal models, the selected molecule substantially improved pathogen clearance for S. aureus, M. tuberculosis, and S. enterica when used in combination with existing antibiotics. This finding supports a new therapeutic concept: targeting the host cell environment can potentiate antibiotic activity and overcome intracellular bacterial persistence. The discovery presents an innovative direction for combating infections that evade standard therapy.
KEY FINDINGS: Enhanced antibiotic performance observed in preclinical mouse models. Potential to improve treatment outcomes for multiple intracellular bacterial infections. Ongoing efforts include mechanism elucidation and patent development.
BACKGROUND: Antibiotic resistance has severely limited the effectiveness of conventional treatments against persistent bacterial infections. Some pathogens, such as Staphylococcus aureus, Mycobacterium tuberculosis, and Salmonella enterica, can survive inside immune cells, remaining dormant and shielded from antibiotic action. The increasing prevalence of such infections underscores an urgent need for alternative approaches that do not rely solely on developing stronger antibiotics.
DETAILS: Researchers at the University of North Carolina (UNC) School of Medicine, led by Dr. Brian Conlon and Dr. Kuan-Yi Lu, identified a novel small molecule that modifies immune cell behavior to enhance antibiotic performance. Instead of directly targeting bacteria, the molecule reprograms the host's immune cells to activate dormant pathogens, rendering them more susceptible to antibiotic killing.
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The team screened approximately 5,000 small molecules through the UNC Small Molecule Screening Core. They used luminescent reporter strains of S. aureus to identify compounds that triggered bacterial activation. The most promising compound was subsequently tested in mouse models, where it significantly improved antibiotic efficacy when administered alongside standard treatments.
In animal models, the selected molecule substantially improved pathogen clearance for S. aureus, M. tuberculosis, and S. enterica when used in combination with existing antibiotics. This finding supports a new therapeutic concept: targeting the host cell environment can potentiate antibiotic activity and overcome intracellular bacterial persistence. The discovery presents an innovative direction for combating infections that evade standard therapy.
Copyright © UNC School of Medicine. All rights reserved.
Source: Conlon, B. and Kuan-Yi, L. UNC Researchers Discover Method to Combat Antibiotic Treatment Failure. UNC Health Newsroom. 2025; Published: October 14, 2025.
Antipsychotic Prescriptions in People With Dementia in Primary Care
This study highlights how antipsychotic prescribing in dementia is discordant with current NICE guidelines on both duration and dose. More than half of those who discontinued their treatment then restarted treatment. These findings emphasise a persistent gap between clinical guidelines and real-world prescribing, underscoring the need for interventions that prioritise safety and person-centred dementia care.
Summary
A Cohort Study Investigating Adherence of Dose and Duration to UK Clinical Guidelines
[Posted 14/Oct/2025]
AUDIENCE: Psychiatry, Family Medicine
KEY FINDINGS: This study highlights how antipsychotic prescribing in dementia is discordant with current NICE guidelines on both duration and dose. More than half of those who discontinued their treatment then restarted treatment. These findings emphasise a persistent gap between clinical guidelines and real-world prescribing, underscoring the need for interventions that prioritise safety and person-centred dementia care.
BACKGROUND: In the UK, it is recommended by the National Institute for Health and Care Excellence (NICE) that if antipsychotics are initiated in people living with dementia, treatment should be at the lowest dose for the shortest time possible (1-3 months). In this study, authors aimed to investigate how dose and duration of antipsychotic medication adhere to UK clinical guidelines and explore treatment restart details in those who stop treatment.
DETAILS: Authors did a retrospective cohort study using longitudinal UK primary care data from the IQVIA Medical Research Database. Authors included people living with dementia aged 60-85 years who received their first antipsychotic prescription between Jan 1, 2000, and Dec 31, 2023. Individuals with any previous antipsychotic prescriptions in their records more than 1 year before a dementia diagnosis and those who had missing social deprivation information were excluded from the study. Duration of first and subsequent antipsychotic treatment episodes, medication dosage, and treatment discontinuation and reinitiation rates were investigated. Duration and discontinuation were defined by grouping consecutive prescriptions into treatment episodes using the waiting time distribution method (80% inter-arrival density, 59 days). Daily doses were derived from strength and frequency information and categorised as low or moderate or high based on established minimum effective dose equivalences. People with lived experience of dementia care contributed throughout this project, shaping the research question and advising on interpretation and dissemination strategies. In the dataset search, authors identified 108,910 people with a record indicating dementia at any time. In total, 99,091 cases were excluded (ie, individuals with no antipsychotic prescription between the ages of 60 and 85 years between 2000 and 2023, a previous history of antipsychotics, missing deprivation information, or only one eligible prescription). Authors included 9819 people living with dementia aged 60-85 years who received their first antipsychotic prescription between 2000 and 2023 in the study. 5310 (54.1%) were female and 4509 (45.9%) were male, with a mean age of 77.1 years (SD 5.6 years), and ethnicity data were not available. The first treatment episode lasted a median of 7 months (IQR 6.6-8.7), exceeding NICE guidelines of 1-3 months and 18.1% [95% CI 17.4-18.9]) were initiated on a prescription above the minimum effective dose (ie, low dose). Of the 1781 participants who started on a moderate or high dose, 519 (29.1%) had a moderate or high dose in all quarters of the first year of treatment. 1 year after treatment initiation, 5136 (78.3%) of 6559 eligible individuals remained on medication (48.9% [95% CI 47.7-50.1] on low dose, 14.8% [13.9-15.6] on moderate or high dose of haloperidol, olanzapine, quetiapine or risperidone; and 14.6% [13.8-15.5] on other antipsychotics). Of the 5547 individuals eligible to restart treatment after initial discontinuation, 3106 (56%) restarted with a median treatment duration of 2.6 months (IQR 0.0-9.9).
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Source: Smsith, H. C., Petersen, I., Hayes, J. F., et al. (2024). Antipsychotic Prescriptions in People With Dementia in Primary Care: A Cohort Study Investigating Adherence of Dose and Duration to UK Clinical Guidelines. The Lancet Psychiatry. 2025; 12(10): 758-767. Published: October, 2025. DOI: 10.1016/S2215-0366(25)00261-5.
Association of Family History and Polygenic Risk Score With Longitudinal Prognosis in Parkinson Disease
Having a family history of PD predicts slower progression of cognitive decline and caudate dopaminergic degeneration, and less FOG compared with those without a family history independent of PRS. Taken together, information on family history could be used as a proxy for the clinical heterogeneity of PD.
KEY FINDINGS: Having a family history of PD predicts slower progression of cognitive decline and caudate dopaminergic degeneration, and less FOG compared with those without a family history independent of PRS. Taken together, information on family history could be used as a proxy for the clinical heterogeneity of PD.
BACKGROUND: Evidence suggests that either family history or polygenic risk score (PRS) is associated with developing Parkinson disease (PD). However, little is known about the longitudinal prognosis of PD according to family history and higher PRS.
DETAILS: From the Parkinson's Progression Markers Initiative database, 395 patients with PD who followed up for more than 2 years were grouped into those with family history within first-degree, second-degree, and third-degree relatives (N = 127 [32.2%]) vs those without (N = 268 [67.8%]). The PRS of 386 patients was computed using whole-genome sequencing data. Longitudinal assessment of motor, cognition, and imaging based on dopaminergic degeneration was conducted during the regular follow-up period. Effects of family history, PRS, or both on longitudinal changes of cognition, motor severity, and nigrostriatal degeneration were tested using a linear mixed model. The risk of freezing of gait (FOG) according to family history was assessed using the Kaplan-Meier analysis and Cox regression models. During a median follow-up of 9.1 years, PD with positive family history showed a slower decline of caudate dopamine transporter uptake (ß estimate of family history x time = 0.02, 95% CI = 0.002-0.036, p = 0.027). Family history of PD and higher PRS were independently associated with a slower decline of Montreal Cognitive Assessment (ß estimate of family history x time = 0.12, 95% CI = 0.02-0.22, p = 0.017; ß estimate of PRS x time = 0.09, 95% CI = 0.03-0.16, p = 0.006). In those 364 patients without FOG at baseline, PD with positive family history had a lower risk of FOG (hazard ratio of family history = 0.57, 95% CI = 0.38-0.84, p = 0.005).
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Source: Park, M. and Lee, Y. (2025). Association of Family History and Polygenic Risk Score With Longitudinal Prognosis in Parkinson Disease. Neurology Genetics. 2025; Published: October, 2025. DOI: 10.1212/NXG.0000000000200115.
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