Nevin Manimala

Int J Geriatr Psychiatry. 2024 Mar;39(3):e6076. doi: 10.1002/gps.6076.

ABSTRACT

OBJECTIVES: The herbs in Tao Hong Si Wu Decoction (THSWD) are beneficial in the treatment of cognitive impairment. However, the underlying mechanisms of THSWD in treating diabetes-associated cognitive dysfunction (DACD) are not entirely explored. This study is aimed to investigate the therapeutic effects of THSWD in DACD model rats and the underlying mechanism.

METHODS: Ultra-high-phase liquid chromatography was employed to identify the main compounds contained in the THSWD extract. DACD rat model was induced by feeding with a high-sugar and high-fat diet and injecting streptozotocin (35 mg/kg). DACD rats were gavaged with THSWD for 1 week. The learning and memory abilities of the rats were measured by using the Morris water maze. Western blotting was used to detect the changes in DACD rat targets. Statistical methods were used to evaluate the correlation between proteins.

RESULTS: The results show that THSWD effectively reduced the escape latency, hippocampal neuron damage, glycosylated hemoglobin, type A1C, and blood lipid levels in DACD rats. Furthermore, DACD rats showed significantly increased amyloid precursor protein, β-secretase, Aβ_1-40 , Aβ_1-42 , Tau phosphorylation, and advanced glycation end products (AGEs) expression. However, THSWD treatment can reverse this phenomenon.

CONCLUSIONS: THSWD can improve the learning and memory abilities of DACD rats by inhibiting the expression of AEGs-AGE receptors pathway, which provides an experimental basis for the clinical application of THSWD. In addition, the experiment combines pharmacological and statistical methods, which offers a new perspective for the study of Chinese herbal medicine.

PMID:38488826 | DOI:10.1002/gps.6076

JAMA Netw Open. 2024 Mar 4;7(3):e242546. doi: 10.1001/jamanetworkopen.2024.2546.

ABSTRACT

IMPORTANCE: Clinician specialization in the care of nursing home (NH) residents or patients in skilled nursing facilities (SNFs) has become increasingly common. It is not known whether clinicians focused on NH care, often referred to as SNFists (ie, physicians, nurse practitioners, and physician assistants concentrating their practice in the NH or SNF setting), are associated with a reduced likelihood of burdensome transitions in the last 90 days of life for residents, which are a marker of poor-quality end-of-life (EOL) care.

OBJECTIVE: To quantify the association between receipt of care from an SNFist and quality of EOL care for NH residents.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed Medicare fee-for-service claims for a nationally representative 20% sample of beneficiaries to examine burdensome transitions among NH decedents at the EOL from January 1, 2013, through December 31, 2019. Statistical analyses were conducted from December 2022 to June 2023.

EXPOSURE: Receipt of care from an SNFist, defined as physicians and advanced practitioners who provided 80% or more of their evaluation and management visits in NHs annually.

MAIN OUTCOMES AND MEASURES: This study used augmented inverse probability weighting in analyses of Medicare fee-for-service claims for a nationally representative 20% sample of beneficiaries. Main outcomes included 4 measures of burdensome transitions: (1) hospital transfer in the last 3 days of life; (2) lack of continuity in NHs after hospitalization in the last 90 days of life; (3) multiple hospitalizations in the last 90 days of life for any reason or any hospitalization for pneumonia, urinary tract infection, dehydration, or sepsis; and (4) any hospitalization in the last 90 days of life for an ambulatory care-sensitive condition.

RESULTS: Of the 2 091 954 NH decedents studied (mean [SD] age, 85.4 [8.5] years; 1 470 724 women [70.3%]), 953 722 (45.6%) received care from SNFists and 1 138 232 (54.4%) received care from non-SNFists; 422 575 of all decedents (20.2%) experienced a burdensome transition at the EOL. Receipt of care by an SNFist was associated with a reduced risk of (1) hospital transfer in the last 3 days of life (-1.6% [95% CI, -2.5% to -0.8%]), (2) lack of continuity in NHs after hospitalization (-4.8% [95% CI, -6.7% to -3.0%]), and (3) decedents experiencing multiple hospitalizations for any reason or any hospitalization for pneumonia, urinary tract infection, dehydration, or sepsis (-5.8% [95% CI, -10.1% to -1.7%]). There was not a statistically significant association with the risk of hospitalization for an ambulatory care-sensitive condition in the last 90 days of life (0.0% [95% CI, -14.7% to 131.7%]).

CONCLUSIONS AND RELEVANCE: This study suggests that SNFists may be an important resource to improve the quality of EOL care for NH residents.

PMID:38488792 | DOI:10.1001/jamanetworkopen.2024.2546

JAMA Netw Open. 2024 Mar 4;7(3):e242609. doi: 10.1001/jamanetworkopen.2024.2609.

ABSTRACT

IMPORTANCE: The lack of standardized genetics training in pediatrics residencies, along with a shortage of medical geneticists, necessitates innovative educational approaches.

OBJECTIVE: To compare pediatric resident recognition of Kabuki syndrome (KS) and Noonan syndrome (NS) after 1 of 4 educational interventions, including generative artificial intelligence (AI) methods.

DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study used generative AI to create images of children with KS and NS. From October 1, 2022, to February 28, 2023, US pediatric residents were provided images through a web-based survey to assess whether these images helped them recognize genetic conditions.

INTERVENTIONS: Participants categorized 20 images after exposure to 1 of 4 educational interventions (text-only descriptions, real images, and 2 types of images created by generative AI).

MAIN OUTCOMES AND MEASURES: Associations between educational interventions with accuracy and self-reported confidence.

RESULTS: Of 2515 contacted pediatric residents, 106 and 102 completed the KS and NS surveys, respectively. For KS, the sensitivity of text description was 48.5% (128 of 264), which was not significantly different from random guessing (odds ratio [OR], 0.94; 95% CI, 0.69-1.29; P = .71). Sensitivity was thus compared for real images vs random guessing (60.3% [188 of 312]; OR, 1.52; 95% CI, 1.15-2.00; P = .003) and 2 types of generative AI images vs random guessing (57.0% [212 of 372]; OR, 1.32; 95% CI, 1.04-1.69; P = .02 and 59.6% [193 of 324]; OR, 1.47; 95% CI, 1.12-1.94; P = .006) (denominators differ according to survey responses). The sensitivity of the NS text-only description was 65.3% (196 of 300). Compared with text-only, the sensitivity of the real images was 74.3% (205 of 276; OR, 1.53; 95% CI, 1.08-2.18; P = .02), and the sensitivity of the 2 types of images created by generative AI was 68.0% (204 of 300; OR, 1.13; 95% CI, 0.77-1.66; P = .54) and 71.0% (247 of 328; OR, 1.30; 95% CI, 0.92-1.83; P = .14). For specificity, no intervention was statistically different from text only. After the interventions, the number of participants who reported being unsure about important diagnostic facial features decreased from 56 (52.8%) to 5 (7.6%) for KS (P < .001) and 25 (24.5%) to 4 (4.7%) for NS (P < .001). There was a significant association between confidence level and sensitivity for real and generated images.

CONCLUSIONS AND RELEVANCE: In this study, real and generated images helped participants recognize KS and NS; real images appeared most helpful. Generated images were noninferior to real images and could serve an adjunctive role, particularly for rare conditions.

PMID:38488790 | DOI:10.1001/jamanetworkopen.2024.2609

Stat Med. 2024 Apr 15;43(8):1527-1548. doi: 10.1002/sim.10029. Epub 2024 Feb 6.

ABSTRACT

When analyzing multivariate longitudinal binary data, we estimate the effects on the responses of the covariates while accounting for three types of complex correlations present in the data. These include the correlations within separate responses over time, cross-correlations between different responses at different times, and correlations between different responses at each time point. The number of parameters thus increases quadratically with the dimension of the correlation matrix, making parameter estimation difficult; the estimated correlation matrix must also meet the positive definiteness constraint. The correlation matrix may additionally be heteroscedastic; however, the matrix structure is commonly considered to be homoscedastic and constrained, such as exchangeable or autoregressive with order one. These assumptions are overly strong, resulting in skewed estimates of the covariate effects on the responses. Hence, we propose probit linear mixed models for multivariate longitudinal binary data, where the correlation matrix is estimated using hypersphere decomposition instead of the strong assumptions noted above. Simulations and real examples are used to demonstrate the proposed methods. An open source R package, BayesMGLM, is made available on GitHub at https://github.com/kuojunglee/BayesMGLM/ with full documentation to produce the results.

PMID:38488782 | DOI:10.1002/sim.10029

Immunol Med. 2024 Mar 15:1-10. doi: 10.1080/25785826.2024.2328918. Online ahead of print.

ABSTRACT

Anti-aminoacyl-tRNA synthetase (ARS) antibodies are myositis-specific antibodies associated with anti-synthetase syndrome (ASSD). Some patients are positive for anti-ARS antibodies on enzyme-linked immunosorbent assay (ELISA) but negative on RNA-immunoprecipitation (RNA-IP) (the gold standard method). Whether these patients should be considered truly positive for anti-ARS antibodies remains unclear. Therefore, we investigated the clinical characteristics of these patients and verified the authenticity of their anti-ARS positivity. Patients who were positive for anti-ARS antibodies on ELISA were divided into the non-discrepant (positive on RNA-IP, n = 52) and discrepant (negative on RNA-IP, n = 8) groups. Patient clinical characteristics were compared between the groups. For each positive individual, the authenticity of anti-ARS antibody positivity on ELISA was cross-examined using protein-IP and western blotting. All patients in the discrepant group had lung involvement, including five (63%) with interstitial lung disease. The overall survival time was significantly lower in the discrepant group than in the non-discrepant group (p < 0.05). Validation tests confirmed the presence of anti-ARS antibodies in the sera of the discrepant group but indicated different reactivity from typical anti-ARS antibodies. In conclusion, some anti-ARS antibodies are detected by ELISA but not RNA-IP. Such anti-ARS antibody discrepancies need further elucidation to attain validation of the diagnostic process in ASSD.

PMID:38488763 | DOI:10.1080/25785826.2024.2328918

Ann Hum Genet. 2024 Mar 15. doi: 10.1111/ahg.12555. Online ahead of print.

ABSTRACT

BACKGROUND: Dyslipidemia is becoming prevalent in Africa, where malaria is endemic. Observational studies have documented the long-term protective effect of malaria on dyslipidemia; however, these study designs are prone to confounding. Therefore, we used Mendelian randomization (MR, a method robust to confounders and reverse causation) to determine the causal effect of severe malaria (SM) and the recurrence of non-severe malaria (RNM) on lipid traits.

METHOD: We performed two-sample MR using genome wide association study (GWAS) summary statistics for recurrent non-severe malaria (RNM) from a Benin cohort (N = 775) and severe malaria from the MalariaGEN dataset (N = 17,000) and lipid traits from summary-level data of a meta-analyzed African lipid GWAS (MALG, N = 24,215) from the African Partnership for Chronic Disease Research (APCDR) (N = 13,612) and the Africa Wits-IN-DEPTH partnership for genomics studies (AWI-Gen) dataset (N = 10,603).

RESULT: No evidence of significant causal association was obtained between RNM and high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol and triglycerides. However, a notable association emerged between severe malarial anaemia (SMA) which is a subtype of severe malaria and reduced HDL-C levels, suggesting a potential subtype-specific effect. Nonetheless, we strongly believe that the small sample size likely affects our estimates, warranting cautious interpretation of these results.

CONCLUSION: Our findings challenge the hypothesis of a broad causal relationship between malaria (both severe and recurrent non-severe forms) and dyslipidemia. The isolated association with SMA highlights an intriguing area for future research. However, we believe that conducting larger studies to investigate the connection between malaria and dyslipidemia in Africa will enhance our ability to better address the burden posed by both diseases.

PMID:38488696 | DOI:10.1111/ahg.12555

Ear Hear. 2024 Mar 15. doi: 10.1097/AUD.0000000000001499. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine if blood prestin level changes after exposure to music at high sound pressure levels, and if this change is associated with temporary threshold shift (TTS) and/or changes in distortion product (DP) amplitude.

DESIGN: Participants were exposed to pop-rock music at 100 dBA for 15 min monaurally through headphones. Pure-tone audiometry, DP amplitude, and blood prestin level were measured before and after exposure.

RESULTS: Fourteen adults (9 women; age range: 20 to 54 years, median age = 31 [Interquartile ratio = 6.75]) with normal hearing were included in the study. Mean prestin level increased shortly after exposure to music, then returned to baseline within 1 week, although this trend was not observed in all participants. All participants presented TTS or a decrease in DP amplitude in at least one frequency after music exposure. There was a statistically significant average threshold elevation at 4 min postexposure. Statistically significant DP amplitude shifts were observed at 4 and 6 kHz, 2 min following exposure. Mean baseline serum prestin level (mean: 140.00 pg/mL, 95% confidence interval (CI): 125.92 to 154.07) progressively increased following music exposure, reaching a maximum at 2 hr (mean: 158.29 pg/mL, 95% CI: 130.42 to 186.66) and returned to preexposure level at 1 week (mean: 139.18 pg/mL, 95% CI: 114.69 to 163.68). However, after correction for multiple comparisons, mean prestin level showed no statistically significant increase from baseline at any timepoint. No correlation between maximum blood prestin level change and average TTS or distortion product otoacoustic emission amplitude shift was found. However, in an exploratory analysis, TTS at 6 kHz (the frequency at which maximum TTS occurred) decreased significantly as baseline blood prestin level increased.

CONCLUSIONS: The results suggest that blood prestin level may change after exposure to music at high sound pressure levels, although statistical significance was not reached in this relatively small sample after correction. Baseline serum prestin level may also predict the degree of TTS. These findings thus suggest that the role of baseline serum prestin level as a proxy marker of cochlear susceptibility to intense music exposure should be further explored.

PMID:38488693 | DOI:10.1097/AUD.0000000000001499

Cornea. 2024 Mar 15. doi: 10.1097/ICO.0000000000003493. Online ahead of print.

ABSTRACT

PURPOSE: This study addresses the growing concern of Dry Eye Disease (DED), which has become increasingly prevalent due to modern lifestyles characterized by prolonged screen usage, global warming, polypharmacy, and extended life expectancy.

METHODS: Grounded in the Dry Eye Workshop II (DEWSII) diagnosis framework, the study focuses on DED as a multifactorial condition affecting the ocular surface’s tear film homeostasis. The study evaluates the short-term impact of 5 commercially available ocular lubricants on disrupting the hyperosmolar environment and determine whether these lubricants can offer potential treatment benefits for DED.

RESULTS: Conducted on 300 eyes (from 150 patients) with 5 preservative-free lubricants compared to a control group, the study reveals that all lubricants effectively reduced tear film osmolarity within 15 minutes of application. Notably, the control group exhibited an increase in average osmolarity (+0.98 mOsm/L) without lubricant use. Siccafluid demonstrated the most substantial osmolarity reduction after 15 minutes, with an average decrease of 11.54 mOsm/L. Statistical significance was observed for Siccafluid, Optive Fusion unique dose (UD), and Systane Ultra UD, while Hyabak and Freegen preservative free (PF) showed lower significance.

CONCLUSIONS: Emphasizing the importance of disrupting the hyperosmolar environment to break the cycle of inflammation, the study concludes that ocular lubricants, at least as an immediate post-application effect, can interrupt this cycle and improve the hyperosmolar environment of the ocular surface.

PMID:38488642 | DOI:10.1097/ICO.0000000000003493

JMIR Pediatr Parent. 2024 Mar 6;7:e51574. doi: 10.2196/51574.

ABSTRACT

BACKGROUND: Children (aged 0-14 years) living with HIV often experience lower rates of HIV diagnosis, treatment, and viral load suppression. In Haiti, only 63% of children living with HIV know their HIV status (compared to 85% overall), 63% are on treatment (compared to 85% overall), and 48% are virally suppressed (compared to 73% overall). Electronic medical records (EMRs) can improve HIV care and patient outcomes, but these benefits are largely dependent on providers having access to quality and nonmissing data.

OBJECTIVE: We sought to understand the associations between EMR data missingness and interruption in antiretroviral therapy treatment by age group (pediatric vs adult).

METHODS: We assessed associations between patient intake record data missingness and interruption in treatment (IIT) status at 6 and 12 months post antiretroviral therapy initiation using patient-level data drawn from iSanté, the most widely used EMR in Haiti. Missingness was assessed for tuberculosis diagnosis, World Health Organization HIV stage, and weight using a composite score indicator (ie, the number of indicators of interest missing). Risk ratios were estimated using marginal parameters from multilevel modified Poisson models with robust error variances and random intercepts for the facility to account for clustering.

RESULTS: Data were drawn from 50 facilities and comprised 31,457 patient records from people living with HIV, of which 1306 (4.2%) were pediatric cases. Pediatric patients were more likely than adult patients to experience IIT (n=431, 33% vs n=7477, 23.4% at 6 months; P<.001). Additionally, pediatric patient records had higher data missingness, with 581 (44.5%) pediatric records missing at least 1 indicator of interest, compared to 7812 (25.9%) adult records (P<.001). Among pediatric patients, each additional indicator missing was associated with a 1.34 times greater likelihood of experiencing IIT at 6 months (95% CI 1.08-1.66; P=.008) and 1.24 times greater likelihood of experiencing IIT at 12 months (95% CI 1.05-1.46; P=.01). These relationships were not statistically significant for adult patients. Compared to pediatric patients with 0 missing indicators, pediatric patients with 1, 2, or 3 missing indicators were 1.59 (95% CI 1.26-2.01; P<.001), 1.74 (95% CI 1.02-2.97; P=.04), and 2.25 (95% CI 1.43-3.56; P=.001) times more likely to experience IIT at 6 months, respectively. Among adult patients, compared to patients with 0 indicators missing, having all 3 indicators missing was associated with being 1.32 times more likely to experience IIT at 6 months (95% CI 1.03-1.70; P=.03), while there was no association with IIT status for other levels of missingness.

CONCLUSIONS: These findings suggest that both EMR data quality and quality of care are lower for children living with HIV in Haiti. This underscores the need for further research into the mechanisms by which EMR data quality impacts the quality of care and patient outcomes among this population. Efforts to improve both EMR data quality and quality of care should consider prioritizing pediatric patients.

PMID:38488632 | DOI:10.2196/51574

Hypertens Pregnancy. 2024 Dec;43(1):2329068. doi: 10.1080/10641955.2024.2329068. Epub 2024 Mar 15.

ABSTRACT

BACKGROUND: Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality.

METHODS: This network meta-analysis was registered with PROSPERO. We searched the PubMed, ClinicalTrials.gov. and Embase databases for studies published from inception to the 31^st of March 2023. RevMan5.3 software provided by the Cochrane Collaboration was used for direct meta-analysis (DMA) statistical analysis. Funnel maps, network meta-analysis (NMA), the surface under the cumulative ranking curve (SUCRA) to rank the different interventions and publication bias were generated by STATA 17.0 software.

RESULTS: We included eight randomized controlled trials (RCTs) involving a total of 1192 women with PE; two studies were of high quality and six were of moderate quality. Eight interventions were addressed in the NMA. In the DMA, we found that blood pressure in the Ketanserin group were significantly higher than those in the Nicardipine group. NMA showed that blood pressure in the Dihydralazine group was significantly higher than that in the Methyldopa, Labetalol, Nicardipine and Diltiazem groups. And the blood pressure in the Labetalol group was significantly lower than that in the Nicardipine group. SUCRA values showed that Diltiazem was more effective in lowering blood pressure than other drugs looked at in this study.

CONCLUSION: According to the eight RCTs included in this study, Diltiazem was the most effective in reducing blood pressure in PE patients; Labetalol and Nicardipine also had good effects. Diltiazem is preferred for the treatment of patients with severe PE and high blood pressure.

PMID:38488570 | DOI:10.1080/10641955.2024.2329068