Tag: nevin manimala

Cartilage. 2024 Oct 18:19476035241288660. doi: 10.1177/19476035241288660. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to comprehensively analyze the landscape of osteoarthritis (OA) biomarker research through the citation analysis of top-cited articles, identifying trends and gaps in this field.

METHODS: The Web of Science Core Collection was utilized to retrieve the top 50 cited articles on OA biomarkers. Data extraction included publication characteristics, citation metrics, and biomarker categorization. Statistical analyses were conducted to discern correlations and assess significance.

RESULTS: The top 50 cited articles spanned the years 1999 to 2020, and collectively cited 4849 articles, accumulating a total of 6177 citations, resulting in an average of 123.5 citations per document. Citations per article varied between 78 and 359, with a citation density ranging from 3.9 to 23.93. Analysis of the top 50 cited articles revealed comparable impact between recent and older publications. Predominant trends included cartilage-related and blood-based biomarkers, while inflammation-related, radiomics, and multi-omics emerged as potential future research directions. In BIPEDS classification, gaps were identified in biomarkers evaluating intervention efficacy and safety.

CONCLUSION: Despite significant advancements, there is no universally acknowledged biomarker for OA. Addressing gaps in biomarker exploration is crucial for enhancing OA management strategies. This study provides insights into prevailing trends and future research directions in OA biomarkers, guiding future investigations and therapeutic development.

PMID:39422972 | DOI:10.1177/19476035241288660

J Alzheimers Dis. 2024;101(s1):S79-S93. doi: 10.3233/JAD-231126.

ABSTRACT

BACKGROUND: Varoglutamstat is a first-in-class, small molecule being investigated as a treatment for early Alzheimer’s disease (AD). It is an inhibitor of glutaminyl cyclase (QC), the enzyme that post-translationally modifies amyloid-β (Aβ) peptides into a toxic form of pyroglutamate Aβ (pGlu-Aβ) and iso-QC which post-translationally modifies cytokine monocyte chemoattractant protein-1 (CCL2) into neuroinflammatory pGlu-CCL2. Early phase clinical trials identified dose margins for safety and tolerability of varoglutamstat and biomarker data supporting its potential for clinical efficacy in early AD.

OBJECTIVE: Present the scientific rationale of varoglutamstat in the treatment of early AD and the methodology of the VIVA-MIND (NCT03919162) trial, which uses a seamless phase 2A-2B design. Our review also includes other pharmacologic approaches to pGlu-Aβ.

METHODS: Phase 2A of the VIVA-MIND trial will determine the highest dose of varoglutamstat that is safe and well tolerated with sufficient plasma exposure and a calculated target occupancy. Continuous safety evaluation using a pre-defined safety stopping boundary will help determine the highest tolerated dose that will carry forward into phase 2B. An interim futility analysis of cognitive function and electroencephalogram changes will be conducted to inform the decision of whether to proceed with phase 2B. Phase 2B will assess the efficacy and longer-term safety of the optimal selected phase 2A dose through 72 weeks of treatment.

CONCLUSIONS: Varoglutamstat provides a unique dual mechanism of action addressing multiple pathogenic contributors to the disease cascade. VIVA-MIND provides a novel and efficient trial design to establish its optimal dosing, safety, tolerability, and efficacy in early AD.

PMID:39422941 | DOI:10.3233/JAD-231126

JAMA Netw Open. 2024 Oct 1;7(10):e2439332. doi: 10.1001/jamanetworkopen.2024.39332.

ABSTRACT

IMPORTANCE: The effect of montelukast in reducing symptom duration among outpatients with mild to moderate COVID-19 is uncertain.

OBJECTIVE: To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial (Accelerating COVID-19 Therapeutic Interventions and Vaccines [ACTIV]-6) was conducted from January 27 through June 23, 2023, during the circulation of Omicron subvariants. Participants aged 30 years or older with confirmed SARS-CoV-2 infection and 2 or more acute COVID-19 symptoms for less than 7 days were included across 104 US sites.

INTERVENTIONS: Participants were randomized 1:1 to receive montelukast, 10 mg once daily, or matched placebo for 14 days.

MAIN OUTCOMES AND MEASURES: The primary outcome was time to sustained recovery (defined as ≥3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of health care utilization events (hospitalization, urgent care clinic visit, emergency department visit, or death); COVID-19 clinical progression scale score; and difference in mean time unwell. A modified intention-to-treat approach was used for the analysis.

RESULTS: Among 1250 participants who were randomized and received the study drug or placebo, the median age was 53 years (IQR, 42-62 years), 753 (60.2%) were female, and 704 (56.3%) reported receiving 2 or more doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [AHR], 1.02; 95% credible interval [CrI], 0.92-1.12; P = .63 for efficacy). Unadjusted median time to sustained recovery was 10 days (95% CI, 10-11 days) in both groups. No deaths occurred, and hospitalizations were reported for 2 participants (0.3%) in each group; the composite of health care utilization events was reported for 18 participants (2.9%) in the montelukast group and 18 (2.9%) in the placebo group (AHR, 1.01; 95% CrI, 0.45-1.84; P = .48 for efficacy). Five participants (0.4%) experienced serious adverse events (3 [0.5%] in the montelukast group and 2 [0.3%] in the placebo group).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of outpatients with mild to moderate COVID-19, treatment with montelukast did not reduce duration of COVID-19 symptoms. These findings do not support the use of montelukast for the treatment of mild to moderate COVID-19.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04885530.

PMID:39422912 | DOI:10.1001/jamanetworkopen.2024.39332

JAMA Netw Open. 2024 Oct 1;7(10):e2439846. doi: 10.1001/jamanetworkopen.2024.39846.

ABSTRACT

IMPORTANCE: Liver disease is a leading cause of mortality in the US. Liver transplant can be a lifesaving procedure for patients with severe liver disease.

OBJECTIVE: To assess temporal trends and geographic variance in liver-related mortality (LRM) and liver transplant in the US.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, the frequencies and geographic variance of LRM in 2018 and 2021 were obtained in a cross-sectional analysis of the Underlying Cause of Death data available on the Centers for Disease Control and Prevention’s Epidemiologic Research database. The number of livers donated and transplanted according to the state of residence of each donor and recipient were obtained from the United Network for Organ Sharing.

MAIN OUTCOMES AND MEASURES: Liver-related mortality in 2018 and 2021, overall and by state, as well as the liver transplant rate according to state of residence of recipient and donor.

RESULTS: Overall LRM in the US was 93 418 in 2021, with a crude rate of 28.1 per 100 000 individuals, an increase of 19.1% compared with rates seen immediately prior to the COVID-19 pandemic in 2018 (77 282 [23.6 per 100 000 individuals]). Liver-related mortality in 2021 varied several-fold between states, from 18.4 per 100 000 individuals per year in Utah to 65.9 per 100 000 individuals per year in New Mexico. The mean number of liver-related deaths per transplant from all donor sources (in state and out of state) was 7.2 in the lowest LRM quintile compared with 21.5 in the highest (95% CI, 12.1-16.6; SE, 1.1; P < .001). Ten states had no liver transplant center. Paradoxically, residents of states with the highest LRM had a much lower rate of liver transplant (at any location) from organs procured from in-state residents than states with the lowest LRM quintile (13.0% vs 35.2% in-state donors; 95% CI, 14.1%-30.3%; SE, 3.9%; P < .001).

CONCLUSIONS AND RELEVANCE: This study suggests that rates of LRM have increased dramatically since the COVID-19 pandemic and vary several-fold between states. Rates of liver transplant are paradoxically lowest among residents living in states with the highest LRM. These findings highlight apparent geographic disparities in access to liver transplant that allocation policy cannot address.

PMID:39422910 | DOI:10.1001/jamanetworkopen.2024.39846

JAMA Netw Open. 2024 Oct 1;7(10):e2440295. doi: 10.1001/jamanetworkopen.2024.40295.

ABSTRACT

IMPORTANCE: Maternal prenatal cannabis use is associated with adverse neonatal health effects, yet little is known about its association with child developmental outcomes.

OBJECTIVE: To evaluate associations between maternal prenatal cannabis use in early pregnancy and child early developmental delays.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 119 976 children born to 106 240 unique individuals between January 2015 and December 2019 and followed up to aged 5.5 years or younger (through December 31, 2021) at Kaiser Permanente Northern California. Individuals were screened for prenatal cannabis use via self-report and urine toxicology at entrance into prenatal care (approximately 8- to 10-weeks’ gestation). Data were analyzed from February 2023 to March 2024.

EXPOSURE: Maternal prenatal cannabis use defined as any use (self-reported or by urine toxicology testing) and use frequency.

MAIN OUTCOMES: Early developmental delays (speech and language disorders, motor delays, global delays) in children up to age 5.5 years defined by International Statistical Classification of Diseases and Related Health Problems, Ninth Revision and Tenth Revision diagnoses codes ascertained from electronic health records.

RESULTS: In this cohort of 119 976 pregnancies among 106 240 unique pregnant individuals, there were 29 543 Hispanic pregnancies (24.6%), 6567 non-Hispanic Black pregnancies (5.5%), 46 823 non-Hispanic White pregnancies (39.0%), 12 837 pregnancies (10.7%) to individuals aged 24 years or younger, and 10 365 pregnancies (8.6%) to individuals insured by Medicaid. Maternal prenatal cannabis use was documented for 6778 pregnancies (5.6%). Daily maternal prenatal cannabis use was reported for 618 pregnancies (0.5%), weekly for 722 pregnancies (0.6%), and monthly or less for 1617 pregnancies (1.3%). No association was observed between maternal prenatal cannabis use and child speech and language disorders (HR, 0.93; 95% CI, 0.84-1.03), global developmental delays (HR, 1.04; 95% CI, 0.68-1.59), or motor delays (HR, 0.86; 95% CI, 0.69-1.06). No association was detected between the frequency of maternal prenatal cannabis use and child early developmental delays.

CONCLUSIONS AND RELEVANCE: In this cohort study, maternal prenatal cannabis use was not associated with an increased risk of child early developmental delays. Future research is needed to assess different patterns of cannabis use throughout pregnancy. Given the association between maternal prenatal cannabis use and other adverse outcomes, pregnant individuals should be educated on those risks.

PMID:39422907 | DOI:10.1001/jamanetworkopen.2024.40295

JAMA Netw Open. 2024 Oct 1;7(10):e2440301. doi: 10.1001/jamanetworkopen.2024.40301.

ABSTRACT

IMPORTANCE: Despite an increase in maternal prenatal cannabis use and associations with adverse neonatal outcomes, research on child neurodevelopmental outcomes is limited.

OBJECTIVE: To evaluate the association between maternal cannabis use in early pregnancy and child autism spectrum disorder (ASD).

DESIGN, SETTING, AND PARTICIPANTS: This population-based retrospective birth cohort study included children born between 2011 and 2019 to pregnant Kaiser Permanente Northern California members screened for prenatal cannabis use during pregnancy. Statistical analysis was conducted February 2023 to March 2024.

EXPOSURES: Maternal prenatal cannabis use was assessed at entrance to prenatal care (approximately 8- to 10-weeks’ gestation) via self-report and/or positive urine toxicology test. Use frequency was assessed.

MAIN OUTCOMES AND MEASURES: Child ASD was defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes ascertained from the electronic health record. Associations between maternal prenatal cannabis use and child ASD were modeled using Cox proportional hazards regression adjusted for maternal sociodemographic, other substance use and disorders, prenatal care initiation, comorbidities, and clustering among maternal siblings.

RESULTS: The study cohort included 178 948 singleton pregnancies among 146 296 unique pregnant individuals, including 48 880 (27.3%) Asian or Pacific Islander, 42 799 (23.9%) Hispanic, 9742 (5.4%) non-Hispanic Black, and 70 733 (39.5%) non-Hispanic White pregnancies. The median (IQR) maternal age at pregnancy onset was 31 (6) years; 8486 (4.7%) screened positive for cannabis use, 7054 (3.9%) via urine toxicology testing and 3662 (2.0%) by self-report. In the total study population, the frequency of self-reported use was monthly or less for 2003 pregnancies (1.1%), weekly for 918 pregnancies (0.5%), daily for 741 pregnancies (0.4%), and unknown for 4824 pregnancies (2.7%). ASD was diagnosed in 3.6% of children. After adjustment for maternal characteristics, maternal prenatal cannabis use was not associated with child ASD (hazard ratio [HR], 1.05; 95% CI, 0.84-1.32). When self-reported frequency of use was assessed, no statistically significant associations were observed after confounder adjustment. No sex-specific associations were documented (males: HR, 1.01; 95% CI, 0.77-1.32; and females: HR, 1.19; 95% CI, 0.77-1.85).

CONCLUSIONS AND RELEVANCE: In this cohort study, maternal cannabis use assessed in early pregnancy was not associated with child ASD. Additional studies are needed to evaluate different patterns of use throughout pregnancy. Given the known adverse neonatal health effects of maternal prenatal cannabis use, clinicians should follow national guidelines and advise against use.

PMID:39422906 | DOI:10.1001/jamanetworkopen.2024.40301

Transl Vis Sci Technol. 2024 Oct 1;13(10):28. doi: 10.1167/tvst.13.10.28.

ABSTRACT

PURPOSE: In the past few decades, the prevalence of myopia, where the eye grows too long, has increased dramatically. The visual environment appears to be critical to regulating the eye growth. Thus, it is very important to determine the properties of the environment that put children at risk for myopia. Researchers have suggested that the intensity of illumination and range of distances to which a child’s eyes are exposed are important, but this has not been confirmed.

METHODS: We designed, built, and tested an inexpensive, child-friendly, head-mounted device that can measure the intensity and spectral content of illumination approaching the eyes and can also measure the distances to which the central visual field of the eyes are exposed. The device is mounted on a child’s bicycle helmet. It includes a camera that measures distances over a substantial range and a six-channel spectral sensor. The sensors are hosted by a light-weight, battery-powered microcomputer. We acquired pilot data from children while they were engaged in various indoor and outdoor activities.

RESULTS: The device proved to be comfortable, easy, and safe to wear, and able to collect very useful data on the statistics of illumination and distances.

CONCLUSIONS: The designed device is an ideal tool to be used in a population of young children, some of whom will later develop myopia and some of whom will not.

TRANSLATIONAL RELEVANCE: Such data would be critical for determining the properties of the visual environment that put children at risk for becoming myopic.

PMID:39422897 | DOI:10.1167/tvst.13.10.28

Ophthalmol Ther. 2024 Oct 18. doi: 10.1007/s40123-024-01051-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Our aim in this work was to investigate the macular choroidal thickness (ChT) changes in 6-12-year-old Danish children with myopia during 2 years of low-dose atropine treatment and 1-year wash-out vs. placebo in an investigator-initiated, placebo-controlled, double-blind randomized clinical trial.

METHODS: Ninety-seven participants were randomized to either 0.01% for 2 years, 0.1% loading dose for 6 months followed by 0.01% for 18 months, or placebo, then a 1-year wash-out. The primary outcome was ChT in the sub-foveal and inner and outer superior, nasal, inferior, and temporal sectors. The secondary outcome was axial length (AL). Outcomes were measured at baseline and 6, 12, 24, and 36 months. One-way analysis of variance was used to detect baseline ChT differences between AL-stratified groups (< 24 mm, 24-25 mm, or > 25 mm). To determine the longitudinal changes in ChT and its effect on AL, all eyes were included in linear mixed modeling with individual eyes nested in the study ID as a random effect.

RESULTS: Longer eyes had significantly thinner ChT in all choroidal sectors (adj-P < 0.01) at baseline. There was no statistically significant change in any ChT sector after 3 years in the placebo group. Sub-foveal and nasal ChT in the 0.1% loading dose and 0.01% group were not significantly different from placebo after 2-year treatment. In the placebo group, a 1-mm increase in AL was significantly associated with a 47-µm thinner nasal ChT after 3 years (95% confidence interval (CI): – 55; – 38, adj-P < 0.001). A 10-µm thicker nasal choroid at baseline was associated with 0.13 mm (95% CI: 0.009; 0.017, adj-P < 0.001) less 3-year axial elongation.

CONCLUSIONS: The ChT in Danish children with myopia remained stable over the 3-year follow-up. A thinner choroid at myopia onset might predispose to increased axial elongation. Treatment with 0.01% atropine did not change the ChT. We speculate that low-dose atropine does not primarily reduce myopia progression via a choroidal mechanism.

TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03911271.

PMID:39422837 | DOI:10.1007/s40123-024-01051-5

Int Urol Nephrol. 2024 Oct 18. doi: 10.1007/s11255-024-04240-0. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the clinical characteristics of the current diagnostic and therapeutic approaches for renal tuberculosis.

METHODS: Clinical diagnosis and treatment data from 765 patients definitively diagnosed with renal tuberculosis between January 2013 and December 2022 were retrospectively analyzed to identify optimal diagnostic and treatment modalities guiding clinical practice.

RESULTS: The number of patients with clinically atypical renal tuberculosis has fluctuated in the last decade, but the changes are not statistically different. T-SPOT, CT, and endoscopy are still commonly used tests with high diagnostic value in clinical practice. The efficacy of anti-tuberculosis drugs was suboptimal, resulting in a cure rate of only 15.43% and a progression rate of only 68.55%. Ureteral stent placement, although effective in relieving hydronephrosis, does not reverse renal impairment and has a 21.43% cure rate and a 57.14% progression rate. Surgical resection was necessary for the majority of patients, with a nephrectomy rate of 76.34% and a cure rate of 81.12%.

CONCLUSION: The prognosis for renal tuberculosis is generally poor, particularly in cases of bilateral involvement. Accurate diagnosis and surgical resection of the tuberculous kidney are essential for preventing complications associated with advanced renal tuberculosis.

PMID:39422827 | DOI:10.1007/s11255-024-04240-0

J Cancer Surviv. 2024 Oct 18. doi: 10.1007/s11764-024-01694-0. Online ahead of print.

ABSTRACT

PURPOSE: Studies looking into the concordance between late effects reported by physicians vs. those reported by Hodgkin lymphoma (HL) survivors are missing.

METHODS: A Life Situation Questionnaire focusing on late effects collected data from 1230 HL survivors (median follow-up 14.3 years). Twenty-six disease- and treatment-related late effects from various organ systems were matched with physician-recorded data. The concordance between physicians and survivors was systematically evaluated using percentage agreement and kappa statistics. Potential non-responder biases and associations with patient and disease characteristics were also investigated.

RESULTS: Agreement levels (indicated by kappa statistics) varied from none to moderate agreement, with the highest Kappa values observed for myocardial infarction (kappa = 0.55, 95% CI 0.43-0.66) and pulmonary embolism (kappa = 0.55, 95% CI 0.35-0.75). HL survivors consistently reported a higher prevalence of late effects compared with physicians. Notably, the prevalence of subjective symptoms such as persistent fatigue and xerostomia was repeatedly underreported by physicians. A trend towards higher concordance was observed in survivors with higher clinical stage, higher education level, and treatment initiated at younger ages. Additionally, findings indicated that survivors who did not respond to the questionnaire experienced fewer late effects compared to those who did respond.

CONCLUSIONS: Substantial discrepancies were noted in the reported prevalence of late effects between survivors and physicians, especially for outcomes which are not easily quantified.

IMPLICATIONS FOR CANCER SURVIVORS: It is therefore essential to integrate outcomes reported by both physicians and survivors to achieve a comprehensive assessment of the long-term consequences of HL treatment.

PMID:39422824 | DOI:10.1007/s11764-024-01694-0