Tag: pubmed

JAMA Netw Open. 2024 Jan 2;7(1):e2350630. doi: 10.1001/jamanetworkopen.2023.50630.

ABSTRACT

IMPORTANCE: Xylazine is increasingly reported in street drugs and fatal overdoses in the US, yet state-level data are limited, hampering local public health responses.

OBJECTIVE: To gather available state-level data on xylazine involvement in overdose deaths and in forensic drug reports.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was a secondary analysis of 2019 to 2022 data from the National Forensic Laboratory Information System (NFLIS), National Center for Health Statistics, and individual states’ medical examiner or public health agency reports. Data were analyzed from August to October 2023.

EXPOSURE: State.

MAIN OUTCOMES AND MEASURES: Yearly xylazine-related overdose deaths per 100 000 residents; xylazine NFLIS drug reports, both per 100 000 residents and as a percentage of all NFLIS drug reports (from samples of drugs seized by law enforcement and analyzed by NFLIS-participating laboratories).

RESULTS: A total of 63 state-years were included in analyses of mortality rates, while 204 state-years were included in analyses of NFLIS reports. According to the publicly available data compiled in this study, at least 43 states reported at least 1 xylazine-related overdose death from 2019 to 2022, yet yearly totals of xylazine-related deaths were available for only 21 states. Of states with data available, xylazine-involved overdose death rates were highest in Vermont (10.5 per 100 000 residents) and Connecticut (9.8 per 100 000 residents) in 2022. In 2019, 16 states had zero xylazine reports included in NFLIS reports; in 2022, only 2 states had zero xylazine reports and all but 3 states had recorded an increase in xylazine’s representation in NFLIS reports. In 2022, xylazine represented 16.17% of all NFLIS reports in Delaware and between 5.95% and 7.00% of NFLIS reports in Connecticut, Maryland, District of Columbia, New Jersey, and Rhode Island, yet less than 1.0% of NFLIS reports in 35 different states.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of publicly available data on fatal overdoses and drugs analyzed by forensic laboratories, xylazine’s reported presence in overdose deaths and forensic reports was concentrated in the eastern US yet extended across the country to encompass nearly all states. In spite of xylazine’s geographic reach, yearly state-level numbers of xylazine-related overdose deaths were publicly available for less than half of all states.

PMID:38180756 | DOI:10.1001/jamanetworkopen.2023.50630

J Acquir Immune Defic Syndr. 2024 Jan 1;95(1S):e89-e96. doi: 10.1097/QAI.0000000000003326. Epub 2024 Jan 4.

ABSTRACT

INTRODUCTION: Mortality rates for people living with HIV (PLHIV) on antiretroviral therapy (ART) in high-income countries continue to decline. We compared mortality rates among PLHIV on ART in Europe for 2016-2020 with Spectrum’s estimates.

METHODS: The AIDS Impact Module in Spectrum is a compartmental HIV epidemic model coupled with a demographic population projection model. We used national Spectrum projections developed for the 2022 HIV estimates round to calculate mortality rates among PLHIV on ART, adjusting to the age/country distribution of PLHIV starting ART from 1996 to 2020 in the Antiretroviral Therapy Cohort Collaboration (ART-CC)’s European cohorts.

RESULTS: In the ART-CC, 11,504 of 162,835 PLHIV died. Between 1996-1999 and 2016-2020, AIDS-related mortality in the ART-CC decreased from 8.8 (95% CI: 7.6 to 10.1) to 1.0 (0.9-1.2) and from 5.9 (4.4-8.1) to 1.1 (0.9-1.4) deaths per 1000 person-years among men and women, respectively. Non-AIDS-related mortality decreased from 9.1 (7.9-10.5) to 6.1 (5.8-6.5) and from 7.0 (5.2-9.3) to 4.8 (4.3-5.2) deaths per 1000 person-years among men and women, respectively. Adjusted all-cause mortality rates in Spectrum among men were near ART-CC estimates for 2016-2020 (Spectrum: 7.02-7.47 deaths per 1000 person-years) but approximately 20% lower in women (Spectrum: 4.66-4.70). Adjusted excess mortality rates in Spectrum were 2.5-fold higher in women and 3.1-3.4-fold higher in men in comparison to the ART-CC’s AIDS-specific mortality rates.

DISCUSSION: Spectrum’s all-cause mortality estimates among PLHIV are consistent with age/country-controlled mortality observed in ART-CC, with some underestimation of mortality among women. Comparing results suggest that 60%-70% of excess deaths among PLHIV on ART in Spectrum are from non-AIDS causes.

PMID:38180742 | DOI:10.1097/QAI.0000000000003326

J Acquir Immune Defic Syndr. 2024 Jan 1;95(1S):e34-e45. doi: 10.1097/QAI.0000000000003340. Epub 2024 Jan 4.

ABSTRACT

BACKGROUND: Previously, The Joint United Nations Programme on HIV/AIDS estimated proportions of adult new HIV infections among key populations (KPs) in the last calendar year, globally and in 8 regions. We refined and updated these, for 2010 and 2022, using country-level trend models informed by national data.

METHODS: Infections among 15-49 year olds were estimated for sex workers (SWs), male clients of female SW, men who have sex with men (MSM), people who inject drugs (PWID), transgender women (TGW), and non-KP sex partners of these groups. Transmission models used were Goals (71 countries), AIDS Epidemic Model (13 Asian countries), Optima (9 European and Central Asian countries), and Thembisa (South Africa). Statistical Estimation and Projection Package fits were used for 15 countries. For 40 countries, new infections in 1 or more KPs were approximated from first-time diagnoses by the mode of transmission. Infection proportions among nonclient partners came from Goals, Optima, AIDS Epidemic Model, and Thembisa. For remaining countries and groups not represented in models, median proportions by KP were extrapolated from countries modeled within the same region.

RESULTS: Across 172 countries, estimated proportions of new adult infections in 2010 and 2022 were both 7.7% for SW, 11% and 20% for MSM, 0.72% and 1.1% for TGW, 6.8% and 8.0% for PWID, 12% and 10% for clients, and 5.3% and 8.2% for nonclient partners. In sub-Saharan Africa, proportions of new HIV infections decreased among SW, clients, and non-KP partners but increased for PWID; elsewhere these groups’ 2010-to-2022 differences were opposite. For MSM and TGW, the proportions increased across all regions.

CONCLUSIONS: KPs continue to have disproportionately high HIV incidence.

PMID:38180737 | DOI:10.1097/QAI.0000000000003340

Neurol Ther. 2024 Jan 5. doi: 10.1007/s40120-023-00571-9. Online ahead of print.

ABSTRACT

INTRODUCTION: The objective of this study is to develop a clinical tool for the evaluation and follow-up of adolescent and adult patients with 5q spinal muscular atrophy (SMA) and to design its validation.

METHODS: This prospective, non-interventional study will be carried out at five centres in Spain and will include patients aged 16 years or older with a confirmed diagnosis of 5q SMA (biallelic mutation of the survival motor neuron 1 [SMN1] gene). A panel of experts made up of neurologists, physiatrists and Spanish patients’ association (FundAME), participated in the design of the clinical tool. Physicians will administer the tool at three time points (baseline, 12 months and 24 months). Additionally, data from other questionnaires and scales will be collected. Once recruitment is achieved, an interim statistical analysis will be performed to assess its psychometric properties by applying Rasch analysis and classical statistical tests.

RESULTS: The tool will consist of up to 53 items to assess functional status from a clinical perspective in seven key dimensions (bulbar, respiratory, axial, lower, upper, fatigability and other symptoms), which will be collected together with objective clinical measures (body mass index, forced vital capacity, pinch strength and 6-minute walk test).

CONCLUSIONS: The validation of this tool will facilitate the clinical evaluation of adult and adolescent patients with SMA and the quantification of their response to new treatments in both clinical practice and research.

PMID:38180726 | DOI:10.1007/s40120-023-00571-9

Pain Ther. 2024 Jan 5. doi: 10.1007/s40122-023-00570-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Chronic low back pain (cLBP) is a problem globally, creating a tremendous economic burden. Since conventional treatments often fail, various forms of electrical stimulation have been proposed to improve function and decrease pain. Patient-reported outcome measures (PROMs) have not been adequately reported in the electrical stimulation literature.

METHODS: A retrospective independent statistical analysis was conducted on PROMs data for users of H-Wave^® device stimulation (HWDS) collected by the device manufacturer over a period of 4 years. Final surveys for 34,192 pain management patients were filtered for pain chronicity limited to 3-24 months and device use of 22-365 days, resulting in 11,503 patients with “all diagnoses”; this number was then reduced to 2711 patients with nonspecific cLBP, sprain, or strain.

RESULTS: Reported pain was reduced by 3.12 points (0-10 pain scale), with significant (≥ 20%) relief in 85.28%. Function/activities of daily living (ADL) improved in 96.36%, while improved work performance was reported in 81.61%. Medication use decreased or stopped in 64.41% and sleep improved in 59.76%. Over 96% reported having expectations met or exceeded, service satisfaction, and confidence in device use, while no adverse events were reported. Subgroup analyses found positive associations with longer duration of device use, home exercise participation, and working, whereas older age and longer pain chronicity resulted in reduced benefit. Similar analysis of the larger all-diagnoses cohort demonstrated near-equivalent positive outcomes.

CONCLUSION: Treatment outcomes directly reported by cLBP HWDS patients demonstrated profound positive effects on function and ADL, robust improvement in pain perception, and additional benefits like decreased medication use, better sleep, and improved work performance, representing compelling new evidence of treatment efficacy.

PMID:38180725 | DOI:10.1007/s40122-023-00570-6

Gen Thorac Cardiovasc Surg. 2024 Jan 5. doi: 10.1007/s11748-023-01990-z. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the influence of prolonged cardiopulmonary resuscitation (CPR) on outcomes in heart transplantation with higher risk donor hearts (HRDHs).

METHODS: Patients transplanted in our hospital between May 2006 and December 2019 were divided into 2 groups, HRDH recipients and non HRDH recipients. HRDH was defined as meeting at least one of the following criteria: (1) donor left ventricular ejection fraction ≤ 50%, (2) donor-recipient predicted heart mass ratio < 0.8 or > 1.2, (3) donor age ≥ 55 years, (4) ischemic time > 4 h and (5) catecholamine index > 20. Recipients of HRDHs were divided into 3 groups according to the time of CPR (Group1: non-CPR, Group 2: less than 30 min-CPR, and Group 3: longer than 30 min CPR).

RESULTS: A total of 125 recipients were enrolled in this study, composing of HRDH recipients (n = 97, 78%) and non HRDH recipients (n = 28, 22%). Overall survival and the rate of freedom from cardiac events at 10 years after heart transplantation were comparable between two groups. Of 97 HRDH recipients, 54 (56%) without CPR, 22 (23%) with CPR < 30 min, and 21 (22%) with CPR ≥ 30 min were identified. One-year survival rates were not significantly different among three groups. The 1-year rate of freedom from cardiac events was not also statistically different, excluding the patients with coronary artery disease found in early postoperative period, which was thought to be donor-transmitted disease. Multivariate logistics regression for cardiac events identified that the CPR duration was not a risk factor even in HRDH-recipients.

CONCLUSION: The CPR duration did not affect the outcomes after heart transplantation in HRDH recipients.

PMID:38180694 | DOI:10.1007/s11748-023-01990-z

Inflammopharmacology. 2024 Jan 5. doi: 10.1007/s10787-023-01404-9. Online ahead of print.

ABSTRACT

Depression is linked with oxidative stress and inflammation, where key players include nitric oxide (NO), nuclear factor erythroid 2-related factor 2 (Nrf2), Brain-Derived Neurotrophic Factor (BDNF), and Heme Oxidase-1 (HO-1). Augmenting the efficacy of antidepressants represents a compelling avenue of exploration. We explored the potential of vitamins C and D as adjuncts to escitalopram (Esc) in a lipopolysaccharide (LPS)-induced depression model focusing on the aforementioned biomarkers. Male Swiss albino mice were stratified into distinct groups: control, LPS, LPS + Esc, LPS + Esc + Vit C, LPS + Esc + Vit D, and LPS + Esc + Vit C + Vit D. After a 7-day treatment period, a single LPS dose (2 mg/kg), was administered, followed by comprehensive assessments of behavior and biochemical parameters. Notably, a statistically significant (p < 0.05) alleviation of depressive symptoms was discerned in the Esc + Vit C + Vit D group versus the LPS group, albeit with concomitant pronounced sedation evident in all LPS-treated groups (p < 0.05). Within the cortex, LPS reduced (p < 0.05) the expression levels of NO_x, Nrf2, BDNF, and HO-1, with only HO-1 being reinstated to baseline in the LPS + Esc + Vit D and the LPS + Esc + Vit C + Vit D groups. Conversely, the hippocampal NO_x, Nrf2, and HO-1 levels remained unaltered following LPS administration. Notably, the combination of Esc, Vit C, and Vit D effectively restored hippocampal BDNF levels, which had been diminished by Esc alone. In conclusion, vitamins C and D enhance the therapeutic effects of escitalopram through a mechanism independent of Nrf2. These findings underscore the imperative need for in-depth investigations.

PMID:38180676 | DOI:10.1007/s10787-023-01404-9

Metabolomics. 2024 Jan 5;20(1):13. doi: 10.1007/s11306-023-02081-z.

ABSTRACT

INTRODUCTION: The burden of stroke in patients with hypertension is very high, and its prediction is critical.

OBJECTIVES: We aimed to use plasma lipidomics profiling to identify lipid biomarkers for predicting incident stroke in patients with hypertension.

METHODS: This was a nested case-control study. Baseline plasma samples were collected from 30 hypertensive patients with newly developed stroke, 30 matched patients with hypertension, 30 matched patients at high risk of stroke, and 30 matched healthy controls. Lipidomics analysis was performed by ultrahigh-performance liquid chromatography-tandem mass spectrometry, and differential lipid metabolites were screened using multivariate and univariate statistical methods. Machine learning methods (least absolute shrinkage and selection operator, random forest) were used to identify candidate biomarkers for predicting stroke in patients with hypertension.

RESULTS: Co-expression network analysis revealed that the key molecular alterations of the lipid network in stroke implicate glycerophospholipid metabolism and choline metabolism. Six lipid metabolites were identified as candidate biomarkers by multivariate statistical and machine learning methods, namely phosphatidyl choline(40:3p)(rep), cholesteryl ester(20:5), monoglyceride(29:5), triglyceride(18:0p/18:1/18:1), triglyceride(18:1/18:2/21:0) and coenzyme(q9). The combination of these six lipid biomarkers exhibited good diagnostic and predictive ability, as it could indicate a risk of stroke at an early stage in patients with hypertension (area under the curve = 0.870; 95% confidence interval: 0.783-0.957).

CONCLUSIONS: We determined lipidomic signatures associated with future stroke development and identified new lipid biomarkers for predicting stroke in patients with hypertension. The biomarkers have translational potential and thus may serve as blood-based biomarkers for predicting hypertensive stroke.

PMID:38180633 | DOI:10.1007/s11306-023-02081-z

Int J Comput Assist Radiol Surg. 2024 Jan 5. doi: 10.1007/s11548-023-03044-4. Online ahead of print.

ABSTRACT

PURPOSE: Standardized uptake values (SUVs) derived from ¹⁸F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography are a crucial parameter for identifying tumors or abnormalities in an organ. Moreover, exploring ways to improve the identification of tumors or abnormalities using a statistical measurement tool is important in clinical research. Therefore, we developed a fully automatic method to create a personally normalized Z-score map of the liver SUV.

METHODS: The normalized Z-score map for each patient was created using the SUV mean and standard deviation estimated from blood-test-derived variables, such as alanine aminotransferase and aspartate aminotransferase, as well as other demographic information. This was performed using the least absolute shrinkage and selection operator (LASSO)-based estimation formula. We also used receiver operating characteristic (ROC) to analyze the results of people with and without hepatic tumors and compared them to the ROC curve of normal SUV.

RESULTS: A total of 7757 people were selected for this study. Of these, 7744 were healthy, while 13 had abnormalities. The area under the ROC curve results indicated that the anomaly detection approach (0.91) outperformed only the maximum SUV (0.89). To build the LASSO regression, sets of covariates, including sex, weight, body mass index, blood glucose level, triglyceride, total cholesterol, γ-glutamyl transpeptidase, total protein, creatinine, insulin, albumin, and cholinesterase, were used to determine the SUV mean, whereas weight was used to determine the SUV standard deviation.

CONCLUSION: The Z-score normalizes the mean and standard deviation. It is effective in ROC curve analysis and increases the clarity of the abnormality. This normalization is a key technique for effective measurement of maximum glucose consumption by tumors in the liver.

PMID:38180621 | DOI:10.1007/s11548-023-03044-4

Metabolomics. 2024 Jan 5;20(1):12. doi: 10.1007/s11306-023-02078-8.

ABSTRACT

INTRODUCTION: Alzheimer’s Disease (AD) is complex and novel approaches are urgently needed to aid in diagnosis. Blood is frequently used as a source for biomarkers; however, its complexity prevents proper detection. The analytical power of metabolomics, coupled with statistical tools, can assist in reducing this complexity.

OBJECTIVES: Thus, we sought to validate a previously proposed panel of metabolic blood-based biomarkers for AD and expand our understanding of the pathological mechanisms involved in AD that are reflected in the blood.

METHODS: In the validation cohort serum and plasma were collected from 25 AD patients and 25 healthy controls. Serum was analysed for metabolites using nuclear magnetic resonance (NMR) spectroscopy, while plasma was tested for markers of neuronal damage and AD hallmark proteins using single molecule array (SIMOA).

RESULTS: The diagnostic performance of the metabolite biomarker panel was confirmed using sparse-partial least squares discriminant analysis (sPLS-DA) with an area under the curve (AUC) of 0.73 (95% confidence interval: 0.59-0.87). Pyruvic acid and valine were consistently reduced in the discovery and validation cohorts. Pathway analysis of significantly altered metabolites in the validation set revealed that they are involved in branched-chain amino acids (BCAAs) and energy metabolism (glycolysis and gluconeogenesis). Additionally, strong positive correlations were observed for valine and isoleucine between cerebrospinal fluid p-tau and t-tau.

CONCLUSIONS: Our proposed panel of metabolites was successfully validated using a combined approach of NMR and sPLS-DA. It was discovered that cognitive-impairment-related metabolites belong to BCAAs and are involved in energy metabolism.

PMID:38180611 | DOI:10.1007/s11306-023-02078-8