Category: Nevin Manimala

JAMA Ophthalmol. 2024 Mar 14. doi: 10.1001/jamaophthalmol.2024.0151. Online ahead of print.

ABSTRACT

IMPORTANCE: Primary open-angle glaucoma (POAG) is a highly heritable disease, with 127 identified risk loci to date. Polygenic risk score (PRS) may provide a clinically useful measure of aggregate genetic burden and improve patient risk stratification.

OBJECTIVE: To assess whether a PRS improves prediction of POAG onset in patients with ocular hypertension.

DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc analysis of the Ocular Hypertension Treatment Study. Data were collected from 22 US sites with a mean (SD) follow-up of 14.0 (6.9) years. A total of 1636 participants were followed up from February 1994 to December 2008; 1077 participants were enrolled in an ancillary genetics study, of which 1009 met criteria for this analysis. PRS was calculated using summary statistics from the largest cross-ancestry POAG meta-analysis, with weights trained using 8 813 496 variants from 449 186 cross-ancestry participants in the UK Biobank. Data were analyzed from July 2022 to December 2023.

EXPOSURES: From February 1994 to June 2002, participants were randomized to either topical intraocular pressure-lowering medication or close observation. After June 2002, both groups received medication.

MAIN OUTCOMES AND MEASURES: Outcome measures were hazard ratios for POAG onset. Concordance index and time-dependent areas under the receiver operating characteristic curve were used to compare the predictive performance of multivariable Cox proportional hazards models.

RESULTS: Of 1009 included participants, 562 (55.7%) were female, and the mean (SD) age was 55.9 (9.3) years. The mean (SD) PRS was significantly higher for 350 POAG converters (0.24 [0.95]) compared with 659 nonconverters (-0.12 [1.00]) (P < .001). POAG risk increased 1.36% (95% CI, 1.08-1.64) with each higher PRS decile, with conversion ranging from 9.52% (95% CI, 7.09-11.95) in the lowest PRS decile to 21.81% (95% CI, 19.37-24.25) in the highest decile. Comparison of low-risk and high-risk PRS tertiles showed a 2.0-fold increase in 20-year POAG risk for participants of European and African ancestries. In the subgroup randomized to delayed treatment, each increase in PRS decile was associated with a 0.52-year (95% CI, 0.01-1.03) decrease in age at diagnosis (P = .047). No significant linear association between PRS and age at POAG diagnosis was present in the early treatment group. Prediction models significantly improved with the addition of PRS as a covariate (C index = 0.77) compared with the Ocular Hypertension Treatment Study baseline model (C index = 0.75) (P < .001). Each 1-SD higher PRS conferred a mean hazard ratio of 1.25 (95% CI, 1.13-1.44) for POAG onset.

CONCLUSIONS AND RELEVANCE: Higher PRS was associated with increased risk for POAG in patients with ocular hypertension. The inclusion of a PRS improved the prediction of POAG onset.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00000125.

PMID:38483402 | DOI:10.1001/jamaophthalmol.2024.0151

Oral Health Prev Dent. 2024 Jan 15;22(1):139-144. doi: 10.3290/j.ohpd.b5081283.

ABSTRACT

PURPOSE: To examine the clinical efficacy of a chlorhexidine gargle combined with recombinant bovine basic fibroblast growth factor (rb-bFGF) gel in the treatment of recurrent oral ulcers and its effects on inflammatory factors, immune function, and recurrence rate.

MATERIALS AND METHODS: Ninety-six patients with recurrent oral ulcers were randomly assigned to two groups: experimental (treatment with chlorhexidine gargle plus rb-bFGF gel) and control (treatment with chlorhexidine gargle alone) (n = 48 cases). The therapeutic efficacy, clinical improvement of symptoms, and recurrence rate within 3 months were compared between the two groups. Serum inflammatory factor and immune factor levels of patients in the two groups were measured before and after treatment.

RESULTS: A statistically significantly higher total effective rate was found in patients of the experimental group (95.83%) versus the control group (81.25%) (p < 0.05). The time to onset of pain relief was shortened, the duration of pain relief was prolonged, and VAS scores for pain level were lower in the experimental than the control group (p < 0.05). Among patients in the experimental group, the number of oral ulcers and ulcer area decreased, and faster onset of pain relief and time until normal eating improved in comparison to the control group (p < 0.05). Reduced levels of IL-2, IL-6, IL-8, and TNF-α were observed in the experimental vs the control group (p < 0.05). Elevated levels of CD3+, CD4+, and NKT and reduced levels of CD8+ were found in the experimental group compared to the control group (p < 0.05). The ulcer recurrence rate of patients in the experimental group (8.33%) was notably lower in comparison to the control group (29.17%).

CONCLUSION: Chlorhexidine gargle plus rb-bFGF gel can improve the clinical outcome of patients with recurrent oral ulcers. It can reduce the levels of inflammatory factors, improve immune function, and reduce the recurrence rate.

PMID:38483398 | DOI:10.3290/j.ohpd.b5081283

JAMA Netw Open. 2024 Mar 4;7(3):e240087. doi: 10.1001/jamanetworkopen.2024.0087.

ABSTRACT

IMPORTANCE: Lack of timely follow-up of cancer-related abnormal test results can lead to delayed or missed diagnoses, adverse cancer outcomes, and substantial cost burden for patients. Care delivery models, such as the Veterans Affairs’ (VA) Patient-Aligned Care Team (PACT), which aim to improve patient-centered care coordination, could potentially also improve timely follow-up of abnormal test results. PACT was implemented nationally in the VA between 2010 and 2012.

OBJECTIVE: To evaluate the long-term association between PACT implementation and timely follow-up of abnormal test results related to the diagnosis of 5 different cancers.

DESIGN, SETTING, AND PARTICIPANTS: This multiyear retrospective cohort study used 14 years of VA data (2006-2019), which were analyzed using panel data-based random-effects linear regressions. The setting included all VA clinics and facilities. The participants were adult patients who underwent diagnostic testing related to 5 different cancers and had abnormal test results. Data extraction and statistical analyses were performed from September 2021 to December 2023.

EXPOSURE: Calendar years denoting preperiods and postperiods of PACT implementation, and the PACT Implementation Progress Index Score denoting the extent of implementation in each VA clinic and facility.

MAIN OUTCOME AND MEASURE: Percentage of potentially missed timely follow-ups of abnormal test results.

RESULTS: This study analyzed 6 data sets representing 5 different types of cancers. During the initial years of PACT implementation (2010 to 2013), percentage of potentially missed timely follow-ups decreased between 3 to 7 percentage points for urinalysis suggestive of bladder cancer, 12 to 14 percentage points for mammograms suggestive of breast cancer, 19 to 22 percentage points for fecal tests suggestive of colorectal cancer, and 6 to 13 percentage points for iron deficiency anemia laboratory tests suggestive of colorectal cancer, with no statistically significant changes for α-fetoprotien tests and lung cancer imaging. However, these beneficial reductions were not sustained over time. Better PACT implementation scores were associated with a decrease in potentially missed timely follow-up percentages for urinalysis (0.3-percentage point reduction [95% CI, -0.6 to -0.1] with 1-point increase in the score), and laboratory tests suggestive of iron deficiency anemia (0.5-percentage point reduction [95% CI,-0.8 to -0.2] with 1-point increase in the score).

CONCLUSIONS AND RELEVANCE: This cohort study found that implementation of PACT in the VA was associated with a potential short-term improvement in the quality of follow-up for certain test results. Additional multifaceted sustained interventions to reduce missed test results are required to prevent care delays.

PMID:38483392 | DOI:10.1001/jamanetworkopen.2024.0087

J Adolesc Health. 2024 Mar 13:S1054-139X(24)00060-0. doi: 10.1016/j.jadohealth.2024.01.024. Online ahead of print.

ABSTRACT

PURPOSE: This national prospective multicohort study examined the relationship between US adolescents’ use of stimulant therapy for attention-deficit/hyperactivity disorder (ADHD) and subsequent risk of nonmedical stimulant use (i.e., nonmedical use of prescription stimulants and cocaine use) during young adulthood, relative to nonstimulant therapy and population controls.

METHODS: Nationally representative multicohort panels of 11,905 US 12th-grade students were surveyed via self-administered questionnaires at baseline (age 18) and followed prospectively over six years into young adulthood (ages 19‒24).

RESULTS: There were no statistically significant differences between adolescents who used stimulant therapy for ADHD compared to those who used only nonstimulant medications and population controls in their adjusted odds of nonmedical stimulant use incidence or prevalence during young adulthood, after adjusting for baseline covariates.

DISCUSSION: The findings offer preliminary support that adolescents who use prescription stimulant or nonstimulant medications for ADHD when clinically indicated are not at greater risk for nonmedical stimulant use during young adulthood.

PMID:38483378 | DOI:10.1016/j.jadohealth.2024.01.024

J Adolesc Health. 2024 Mar 11:S1054-139X(24)00058-2. doi: 10.1016/j.jadohealth.2024.01.022. Online ahead of print.

ABSTRACT

PURPOSE: The everyday experience of safety promotes health and successful development during adolescence. To date, few studies have examined racial variation in the spatial determinants of in-the-moment perceived safety.

METHODS: Drawing on data from the Columbus, Ohio-based Adolescent Health and Development in Context study (N = 1,405), we consider the influence of intraindividual variability in Global Positioning System-based exposure to both high-proportion White urban neighborhoods and neighborhood violence for the everyday location-based safety perceptions of Black and White youth (ages 11-17) as captured by ecological momentary assessment.

RESULTS: Exposure to higher area-level violence reduces youths’ safety perceptions. Momentary exposure to residentially White-dominated neighborhoods also reduces perceived safety, but only for Black youth who spend more time, on average, in White areas. In contrast, we observe some limited evidence that White youth perceive greater safety when in White neighborhoods if they spend more time in white neighborhoods on average.

DISCUSSION: These findings point to the need for greater attention to in situ experiences in understanding the origins of racial disparities in health and wellbeing. For Black youth, a restricted focus on the consequences of residing in Black segregated neighborhoods may obscure potentially health consequential exposures beyond these areas.

PMID:38483377 | DOI:10.1016/j.jadohealth.2024.01.022

JAMA Otolaryngol Head Neck Surg. 2024 Mar 14. doi: 10.1001/jamaoto.2024.0133. Online ahead of print.

ABSTRACT

IMPORTANCE: Patients with induced laryngeal obstruction (ILO) present with a variety of behavioral health profiles. Identifying these profiles is crucial in that behavioral health conditions may affect treatment duration and outcomes.

OBJECTIVE: To characterize the prevalence of anxiety, depression, posttraumatic stress disorder (PTSD), and physical somatic symptoms in adult and pediatric patients with ILO and determine the factors associated with anxiety, depression, PTSD, and physical somatic symptoms in patients with ILO?

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included a nonprobability sample of 83 adult and 81 pediatric patients diagnosed with ILO at outpatient adult and pediatric otolaryngology clinics between 2021 and 2023. Exclusion criteria included a comorbid respiratory diagnosis other than asthma, head or neck cancer, or neurological impairments. Recruitment took place between September 2021 and March 2023. The analyses were run in January 2024.

MAIN OUTCOME MEASURES: Patients were prospectively screened for anxiety, depression, PTSD, and somatic physical symptoms. In addition, any past behavioral health diagnoses were extracted from the medical record. Comorbidities, ILO symptoms triggers, and onset details were gathered from ILO evaluations. Adult patients completed the Screen for Adult Anxiety Related Disorders (SCAARED), depression (Patient Health Questionnaire [PHQ]-9), and somatic physical symptoms portions of the Patient Health Questionnaires (PHQ-15), and the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5). Pediatric patients completed the Screen for Child Anxiety Related Disorders (SCARED), depression (PHQ-9A) and somatic physical symptoms portions of the Patient Health Questionnaires for Adolescents (PHQ-15A), and the UCLA PTSD Reaction Index brief screeners.

RESULTS: Eighty-three adult patients participated in this study (mean [SD] age, 45.8 [14.3] years; 64 female, 19 male). Eighty-one pediatric patients participated (mean [SD] age, 13.83 [2.55] years; 67 female, 14 male). Adult and pediatric patients with ILO screened positive for elevated rates of anxiety (53 adults [63%]; 49 children [60%]), depression (27 adults [32%]; 25 children [30%]), and PTSD (29 adults [34%]; 13 children [16%]). Most of the patients with anxiety and depression symptoms were formally diagnosed prior to ILO evaluation, with rates of previously diagnosed anxiety, depression, and PTSD also above published norms. Adults were twice as likely as children to present with PTSD (odds ratio, 2.1; 95% CI, 0.05-4.48). Elevated rates of physical somatic symptoms were also evident, with 38 adults (45%) and 32 children (39%) scoring in the moderate to severe range.

CONCLUSIONS AND RELEVANCE: This study found high rates of adult and pediatric patients with ILO screened positive for anxiety, depression, and PTSD symptoms. Future work should investigate how behavioral health and ILO treatments can best be coordinated to maximize treatment outcomes.

PMID:38483372 | DOI:10.1001/jamaoto.2024.0133

Neuromodulation. 2024 Mar 11:S1094-7159(24)00055-2. doi: 10.1016/j.neurom.2024.01.006. Online ahead of print.

ABSTRACT

BACKGROUND: Adults with refractory, mechanical chronic low back pain associated with impaired neuromuscular control of the lumbar multifidus muscle have few treatment options that provide long-term clinical benefit. This study hypothesized that restorative neurostimulation, a rehabilitative treatment that activates the lumbar multifidus muscles to overcome underlying dysfunction, is safe and provides relevant and durable clinical benefit to patients with this specific etiology.

MATERIALS AND METHODS: In this prospective five-year longitudinal follow-up of the ReActiv8-B pivotal trial, participants (N = 204) had activity-limiting, moderate-to-severe, refractory, mechanical chronic low back pain, a positive prone instability test result indicating impaired multifidus muscle control, and no indications for spine surgery. Low back pain intensity (10-cm visual analog scale [VAS]), disability (Oswestry Disability Index), and quality of life (EuroQol’s “EQ-5D-5L” index) were compared with baseline and following the intent-to-treat principle, with a supporting mixed-effects model for repeated measures that accounted for missing data.

RESULTS: At five years (n = 126), low back pain VAS had improved from 7.3 to 2.4 cm (-4.9; 95% CI, -5.3 to -4.5 cm; p < 0.0001), and 71.8% of participants had a reduction of ≥50%. The Oswestry Disability Index improved from 39.1 to 16.5 (-22.7; 95% CI, -25.4 to -20.8; p < 0.0001), and 61.1% of participants had reduction of ≥20 points. The EQ-5D-5L index improved from 0.585 to 0.807 (0.231; 95% CI, 0.195-0.267; p < 0.0001). Although the mixed-effects model attenuated completed-case results, conclusions and statistical significance were maintained. Of 52 subjects who were on opioids at baseline and had a five-year visit, 46% discontinued, and 23% decreased intake. The safety profile compared favorably with neurostimulator treatments for other types of back pain. No lead migrations were observed.

CONCLUSION: Over a five-year period, restorative neurostimulation provided clinically substantial and durable benefits with a favorable safety profile in patients with refractory chronic low back pain associated with multifidus muscle dysfunction.

CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354; registration date: October 15, 2016; principal investigator: Christopher Gilligan, MD, Brigham and Women’s Hospital, Boston, MA, USA. The study was conducted in Australia (Broadmeadow, New South Wales; Noosa Heads, Queensland; Welland, South Australia; Clayton, Victoria), Belgium (Sint-Niklaas; Wilrijk), The Netherlands (Rotterdam), UK (Leeds, London, Middlesbrough), and USA (La Jolla, CA; Santa Monica, CA; Aurora, CO; Carmel, IN; Indianapolis, IN; Kansas City, KS; Boston, MA; Royal Oak, MI; Durham, NC; Winston-Salem, NC; Cleveland, OH; Providence, RI; Spartanburg, SC; Spokane, WA; Charleston, WV).

PMID:38483366 | DOI:10.1016/j.neurom.2024.01.006

Cytotherapy. 2024 Mar 2:S1465-3249(24)00071-9. doi: 10.1016/j.jcyt.2024.02.022. Online ahead of print.

ABSTRACT

BACKGROUND AIMS: Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, offer groundbreaking therapeutic potential for degenerative diseases and cellular repair. Despite their significance, a comprehensive bibliometric analysis in this field, particularly in relation to age-related macular degeneration (AMD), is yet to be conducted. This study aims to map the foundational and emerging areas in stem cell and AMD research through bibliometric analysis.

METHODS: This study analyzed articles and reviews on stem cells and AMD from 2000 to 2022, sourced from the Web of Science Core Collection. We used VOSviewer and CiteSpace for analysis and visualization of data pertaining to countries, institutions, authors, journals, references and key words. Statistical analyses were conducted using R language and Microsoft Excel 365.

RESULTS: In total, 539 publications were included, indicating an increase in global literature on stem cells and AMD from 2000 to 2022. The USA was the leading contributor, with 239 papers and the highest H-index, also the USA had the highest average citation rate per article (59.82). Notably, 50% of the top 10 institutions were from the USA, with the University of California system being the most productive. Key authors included Masayo Takahashi, Michiko Mandai, Dennis Clegg, Pete J. Coffey, Boris Stanzel, and Budd A. Tucker. Investigative Ophthalmology & Visual Science published the majority of relevant papers (n = 27). Key words like “clinical trial,” “stem cell therapy,” “retinal organoid,” and “retinal progenitor cells” were predominant.

CONCLUSIONS: Research on stem cells and AMD has grown significantly, highlighting the need for increased global cooperation. Current research prioritizes the relationship between “ipsc,” “induced pluripotent stem cell,” “cell culture,” and “human embryonic stem cell.” As stem cell culture and safety have advanced, focus has shifted to prognosis and complications post-transplantation, signifying the movement of stem cell research from labs to clinical settings.

PMID:38483361 | DOI:10.1016/j.jcyt.2024.02.022

Clin Pharmacol Ther. 2024 Mar 14. doi: 10.1002/cpt.3248. Online ahead of print.

ABSTRACT

Concurrent use of skeletal muscle relaxants (SMRs) and opioids has been linked to an increased risk of injury. However, it remains unclear whether the injury risks differ by specific SMR when combined with opioids. We conducted nine retrospective cohort studies within a US Medicaid population. Each cohort consisted exclusively of person-time exposed to both an SMR and one of the three most dispensed opioids-hydrocodone, oxycodone, and tramadol. Opioid users were further divided into three cohorts based on the initiation order of SMRs and opioids-synchronically triggered, opioid-triggered, and SMR-triggered. Within each cohort, we used Cox proportional hazard models to compare the injury rates for different SMRs compared to methocarbamol, adjusting for covariates. We identified 349,543, 139,458, and 218,967 concurrent users of SMRs with hydrocodone, oxycodone, and tramadol, respectively. In the oxycodone-SMR-triggered cohort, the adjusted hazard ratios (HRs) were 1.86 (95% CI, 1.23-2.82) for carisoprodol and 1.73 (1.09-2.73) for tizanidine. In the tramadol-synchronically triggered cohort, the adjusted HRs were 0.69 (0.49-0.97) for metaxalone and 0.62 (0.42-0.90) for tizanidine. In the tramadol-SMR-triggered cohort, the adjusted HRs were 1.51 (1.01-2.26) for baclofen and 1.48 (1.03-2.11) for cyclobenzaprine. All other HRs were statistically nonsignificant. In conclusion, the relative injury rate associated with different SMRs used concurrently with the three most dispensed opioids appears to vary depending on the specific opioid and the order of combination initiation. If confirmed by future studies, clinicians should consider the varying injury rates when prescribing SMRs to individuals using hydrocodone, oxycodone, and tramadol.

PMID:38482733 | DOI:10.1002/cpt.3248

J Econ Entomol. 2024 Mar 14:toae047. doi: 10.1093/jee/toae047. Online ahead of print.

ABSTRACT

The maize weevil, Sitophilus zeamais Motschulsky, is a hidden pest that presents serious risk to grain quality during postharvest storage. Lipid-derived volatile detection is considered a key reference for early prediction of S. zeamais infestation. However, the exact compositions of fatty acids and volatile organic compounds (VOCs) in S. zeamais-infested wheat are yet to be determined. In this study, we aimed to explore the effect of S. zeamais infestation on lipid metabolism in wheat infested with S. zeamais eggs (4 days), larvae (20 days), pupae (35 days), and adults (45 days). Compared to those in the control group, the activities of lipid oxidation enzymes, such as lipase, lipoxygenase, and alcohol dehydrogenase, increased by 82.73%, 105.12%, and 487.86%, respectively, during the storage period of 1 life cycle of S. zeamais. Additionally, the fatty acid composition of S. zeamais-infested wheat was significantly altered (palmitic acid [1.10-fold], oleic acid [1.07-fold], and linoleic acid [0.95-fold]). Furthermore, 91 VOCs were identified in all wheat samples; then, multivariate statistical analyses categorized these samples into 4 groups: uninfested, longer storage, lightly infested, and heavily infested. Moreover, 31, 26, and 45 potential VOCs were identified to distinguish uninfested wheat from those in the other 3 groups. These results demonstrated that S. zeamais infestation induces an elevation in lipid-related enzymatic activities, which potentially leads to a decrease in lipid content alongside the production of specific VOCs (undecan-4-olide, heptaldehyde, and 2-nonenal). These findings provide novel insights for rapidly identifying grains infested by hidden pests and effectively managing these pests during grain storage.

PMID:38482708 | DOI:10.1093/jee/toae047