Tag: nevin manimala

J Biopharm Stat. 2025 Mar 13:1-22. doi: 10.1080/10543406.2024.2444242. Online ahead of print.

ABSTRACT

The restricted mean survival time has been widely used in the field of medical research because of its clear physical and simple clinical interpretation. In this paper, we propose an efficient estimation that incorporates the auxiliary restricted mean survival information into the estimation of the proportional hazard (PH) model. Compared to conventional models that do not incorporate available auxiliary information, the proposed method improves efficiency in estimating regression parameters by utilizing the double empirical likelihood method. We prove that the estimator asymptotically follows a multivariate normal distribution with a covariance matrix that can be consistently estimated. To address scenarios where the PH assumption is violated, we also extended the method to the stratified Cox model. In addition, simulation studies show that the proposed estimators are more efficient than those derived from the conventional partial likelihood approach. A type 2 diabetes dataset is then used to evaluate the risk of antidiabetic drugs and demonstrate the proposed method.

PMID:40079137 | DOI:10.1080/10543406.2024.2444242

Psychol Med. 2025 Mar 13;55:e85. doi: 10.1017/S0033291725000455.

ABSTRACT

BACKGROUND: Population-level preventive interventions are urgently needed and may be effective for psychosis due to social determinants. We tested three syndemic models along pathways from childhood adversity (CA) to psychotic spectrum disorder (PSD) and their implications for prevention.

METHODS: Cross-sectional data from 7461 British men surveyed in 5 population subgroups. We tested interactions on both additive and multiplicative scales for a syndemic of violence/criminality (VC), sexual behavior (SH), and substance misuse (SM) according to the presence of CA and adult traumatic life events; mediation analysis of path models; and partial least squares path modeling, with PSD as outcome.

RESULTS: Multiplicative synergistic interactions were found between VC, SH, and SM among men, who experienced CA and traumatic adult life events. However, when disaggregated, only SM mediated the pathway from CA to PSD. Path modeling showed traumatic life events acted on PSD through the syndemic and had no direct effect on PSD. Higher syndemic scores and living in areas of deprivation characterized men with PSD and CA.

CONCLUSIONS: Our findings support a broad division of PSD into cases due to (i) biological/inherent causes, and (ii) social determinants, the latter including a syndemic pathway determined by CA. Preventive strategies should focus primarily on preventing adverse effects of CA on developmental pathways which result in PSD. Single component prevention strategies may prevent triggering effects of SM on PSD during adolescence/early adulthood among vulnerable individuals due to CA. Future research should determine applicability and transferability of interventions based on these findings to different populations, specifically those experiencing syndemics.

PMID:40079091 | DOI:10.1017/S0033291725000455

Curr Med Res Opin. 2025 Mar 13:1-17. doi: 10.1080/03007995.2025.2478160. Online ahead of print.

ABSTRACT

BACKGROUND: Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder that significantly impacts renal function. Despite conventional treatments, morbidity and mortality remain high, necessitating the exploration of safer and more effective therapies, including the potential benefits of Traditional Chinese Medicine (TCM) for improving kidney health and survival rates.

METHODS: Patients with newly diagnosed with SLE with catastrophic illness certificate were retrospectively enrolled from CGRD between 2005 and 2020. Patients were stratified into groups based on TCM treatment post-diagnosis. Outcomes measured included end-stage renal disease (ESRD) incidence and all-cause mortality, using Cox proportional hazard models and Kaplan-Meier analysis for statistical evaluation.Results Among 10462 newly diagnosed SLE patients, 1831 had received at least 28 days of TCM treatment, while 7966 had not received TCM treatment. After propensity score matching, there were equally 1831 individuals in each group, with no significant baseline differences in age, sex, biochemical profiles and comorbidities. TCM usage was associated with a significantly reduced rate of ESRD over a 0.5-year follow-up (adjusted hazard ratio (aHR): 0.24; 95% confidence interval (CI): 0.07-0.80, p = 0.02), with a trend that persisted over five years. TCM group’s proteinuria was significantly lower than that of the non-TCM group at various time points post-index date, including 6 months (174.98 mg vs. 248.09 mg, p < 0.001), 1 year (161.05 mg vs. 303.03 mg, p < 0.001), 3 years (150.26 mg vs. 250 mg, p = 0.03), and 10 years (147.06 mg vs. 190.75 mg, p = 0.03). After adjusting for confounding covariates, TCM users had a significantly decreased risk of mortality (aHR 0.70, 95% CI 0.58-0.83).

CONCLUSION: Integrating TCM with conventional treatment could lower risk of ESRD and mortality, highlighting the potential for a more holistic approach to patient care for SLE.

PMID:40079084 | DOI:10.1080/03007995.2025.2478160

J Biopharm Stat. 2025 Mar 13:1-6. doi: 10.1080/10543406.2025.2473612. Online ahead of print.

ABSTRACT

Conventionally, the product quality specification and control chart limits are determined as the mean plus and minus 3 sample standard deviations with the assumption that the quality data is normally distributed. These limits correspond to an interval centered at the mean, covering approximately 97.3% of the population. The estimate of such an interval is called the $\beta$-content tolerance interval. It has been proposed to use a two one-sided $\beta$-content tolerance interval approach for determining drug product quality specifications. For a given confidence level, $1–\alpha ,$ and a coverage percentage p, the $\beta$-content tolerance interval is not precise when the sample size is small. For the derivation of a precise $\beta$-content tolerance interval, Faulkenberry and Daly proposed a “goodness” criterion for sample size determination. In order to avoid overestimating the $\beta$-content tolerance interval when p is large, we propose to define the precision requirement as the probability of the tolerance interval covering more than $\frac{\left(1+p\right)}{2}$ is restricted to a pre-specified significance level ${\alpha }^{‘}$. Quality specification studies are often not planned with proper sample sizes. To obtain precise $\beta$-content tolerance intervals for quality specification studies, the proper coverage p satisfying the “goodness” criterion and the minimum sample sizes were also determined with the pre-specified significance level ${\alpha }^{‘}$. With this approach, one may properly set the product specificationwhile avoiding over-specifying the quality limits.

PMID:40079049 | DOI:10.1080/10543406.2025.2473612

Front Pediatr. 2025 Feb 26;13:1444471. doi: 10.3389/fped.2025.1444471. eCollection 2025.

ABSTRACT

BACKGROUND: With advances in perinatal medicine, there has been a rise in the preterm birth rate, especially the rate of very low birth weight (VLBW) and extremely low birth weight infants. Studies have shown that maternal age during pregnancy and at the time of delivery is associated with pregnancy complications and poor neonatal outcomes. Little is known about the effect of maternal age on the outcome of very low birth weight infants.

OBJECTIVES: To investigate the effects of maternal age on the adverse outcomes of singleton very low birth weight neonates.

METHODS: We used data of VLBW infants from the neonatal database of our hospital. Maternal age was categorized as 20-24, 25-34 (reference group), 35-39 and ≥40 years. Statistical analyses included univariate and multivariate logistic regression analysis.

RESULTS: The study ultimately included 603 singleton, very low birth weight infants. After adjustment, neonatal outcomes in the group of older mothers were similar to those of the reference group for bronchopulmonary dysplasia, necrotizing enterocolitis, respiratory distress syndrome, severe asphyxia, retinopathy of prematurity and intraventricular hemorrhage grades 3-4. In the 20-24 year age group higher odds were present for sepsis [Odds ratio (OR) = 6.021; 95% confidence interval (CI), 1.741-20.818, p < 0.05] and for mortality (OR = 7.784; 95% CI, 2.198-27.568, p < 0.05). Higher odds for asphyxia (OR = 1.891; 95% CI, 1.238-2.890, p < 0.05) and death (OR = 2.101, 95% CI, 1.004-4.395, p < 0.05) were observed in infants of mothers in the 35-39 year age group. The incidence of sepsis was significantly higher in the age group of ≥40 years (OR = 2.873; 95% CI, 1.186-6.958, p < 0.05).

CONCLUSIONS: In singleton very low birth weight neonates, neonatal outcomes were associated with maternal age, and adverse outcomes were more pronounced in infants of advanced maternal age (AMA) mothers.

PMID:40079033 | PMC:PMC11897033 | DOI:10.3389/fped.2025.1444471

Front Immunol. 2025 Feb 26;16:1521299. doi: 10.3389/fimmu.2025.1521299. eCollection 2025.

ABSTRACT

BACKGROUND AND AIMS: Autoantibodies against apolipoprotein A-1 (AAA1) are elicited by SARS-CoV-2 infection and predict COVID-19 symptoms persistence at one year in adults, but whether this applies to children is unknown. We studied the association of SARS-CoV-2 exposure with AAA1 prevalence in children and the association of AAA1 seropositivity with symptom persistence.

METHODS: Anti-SARS-CoV-2 and AAA1 serologies were examined in 1031 participants aged 6 months to 17 years old from the prospective SEROCOV-KIDS cohort and recruited between 12.2021 and 02.2022. Four SARS-CoV-2 serology-based groups were defined: “Infected-unvaccinated (I+/V-)”, “Uninfected-vaccinated (I-/V+)”, “Infected-Vaccinated (I+/V+)”, and “Naïve (I-/V-)”. Reported outcomes were collected using online questionnaires. Associations with study endpoints were assessed using logistic regression.

RESULTS: Overall, seropositivity rates for anti-RBD, anti-N, and AAA1 were 71% (736/1031), 55% (568/1031), and 5.8% (60/1031), respectively. AAA1 showed an inverse association with age but not with any other characteristics. The I+/V- group displayed higher median AAA1 levels and seropositivity (7.9%) compared to the other groups (p ≤ 0.011), translating into a 2-fold increased AAA1 seroconversion risk (Odds ratio [OR]: 2.11, [95% Confidence Interval (CI)]: 1.22-3.65; p=0.008), unchanged after adjustment for age and sex. AAA1 seropositivity was independently associated with a 2-fold odds of symptoms persistence at ≥ 4 weeks (p ≤ 0.03) in the entire dataset and infected individuals, but not ≥ 12 weeks.

CONCLUSIONS: Despite the limitations of the study (cross-sectional design, patient-related outcomes using validated questionnaires), the results indicate that SARS-CoV-2 infection could elicit an AAA1 response in children, which could be independently associated with short-time symptoms persistence.

PMID:40079006 | PMC:PMC11897246 | DOI:10.3389/fimmu.2025.1521299

Front Immunol. 2025 Feb 26;16:1526443. doi: 10.3389/fimmu.2025.1526443. eCollection 2025.

ABSTRACT

This study evaluated the efficacy and safety of camrelizumab combined with platinum-based chemotherapy (taxanes [T] or fluorouracil agents [F] plus platinum [P] drugs) as the first-line treatment in advanced esophageal squamous cell carcinoma (ESCC), using immune repertoire sequencing (IRS) to explore treatment response mechanism. In this multi-center, prospective cohort study, 88 patients received camrelizumab plus TP or FP, achieving a 1-year progression-free survival of 56.8% and overall survival of 68.2%. The objective response rate (ORR) was 64.8%, with a disease control rate of 91.1%. While most treatment-related adverse events were mild, 12.5% of patients experienced grade ≥3 toxicities. IRS showed significant differences in T-cell receptor (TCR) β-chain and immunoglobulin heavy chain between patients with (ORR group) or without ORR (non-ORR group), particularly in the distribution and expression of some genes. Specifically, we found the significant differences in the amino acid composition of complementarity determining region 3 (CDR3) polypeptide sequences in TCR and B-cell receptor (BCR) between the ORR and non-ORR groups. For TCR, we observed substantial oligoclonal enrichment and differences in the abundance of specific V and J genes. Similarly, for BCR, we detected differences in the clonotype abundance of CDR3 polypeptide segments and identified several differential V genes. Camrelizumab combined with platinum-based chemotherapy is effective and well-tolerated as the first-line treatment for ESCC, and IRS may reveal mechanism influencing treatment response.

PMID:40079001 | PMC:PMC11897899 | DOI:10.3389/fimmu.2025.1526443

Biosaf Health. 2024 Nov 19;6(6):361-368. doi: 10.1016/j.bsheal.2024.11.005. eCollection 2024 Dec.

ABSTRACT

Recently, there has been a continuous stream of reports on emerging tick-borne pathogens affecting humans. Qinghai Province, located in the northweastern region, is one of China’s major pastoral areas, providing a suitable environment for ticks’ survival and transmitting tick-borne pathogens. Here, we collected 560 free-living and parasitic ticks from 11 locations in Qinghai Province using the flag-drag method or tweezers, identifying them as belonging to 4 species of ticks. The overall positivity rate for tick-borne pathogens was 51.61 %, comprising Rickettsia (34.64 %), Anaplasma (5.00 %), Ehrlichia (2.14 %), Borrelia burgdorferi sensu lato (BBSL) (7.50 %), Babesia (0.18 %), and Theileria (5.89 %). Sequencing revealed the presence of 7 species of Rickettsia, 4 species of Anaplasma, 2 species of Ehrlichia, 2 species of BBSL, 1 species of Babesia, and 3 species of Theileria. Among the ticks, 6.43 % were co-infected with 2 pathogens, while 0.36 % exhibited co-infection with 3 pathogens. Significant correlations (P < 0.05) were observed between the prevalence of tick-borne pathogens and factors including tick species, sex, developmental stages, parasitic status, and blood-feeding status. The results highlight the diverse distribution of tick-borne pathogens in Qinghai Province, posing a significant threat to both local animal husbandry and human health. It underscores the need to enhance systematic monitoring of tick-borne pathogens in the local population and livestock.

PMID:40078982 | PMC:PMC11894961 | DOI:10.1016/j.bsheal.2024.11.005

AAS Open Res. 2020 Jan 14;1:10. doi: 10.12688/aasopenres.12848.2. eCollection 2018.

ABSTRACT

Background: A number of studies have investigated transgenerational effects of parental post-traumatic stress disorder (PTSD) and its repercussions for offspring. Few studies however, have looked at this issue in the African context. Methods: The present study addresses this gap by utilizing a Pearson correlation matrix to investigate symptom severity within the three Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) PTSD symptom domains in mothers exposed to the genocide against the Tutsi in Rwanda (n=25) and offspring (n=25), and an ethnically matched set of controls (n=50) who were outside of Rwanda during the 1994 genocide. All mothers were pregnant with the offspring included in the study during the time of the genocide. Results: Total PTS score was significantly (p<0.01) correlated with each of the three symptom domains at various strengths in both cases and controls. No significant differences in association of total PTS score and PTSD symptom domains were observed between exposed mothers and offspring, suggesting that each symptom domain contributed equivalently to both exposed mothers and offspring distress. In contrast, the re-experiencing symptom domain showed a significant difference in correlation to overall PTS score in non-exposed mothers compared to their offspring (p<0.05), with mothers showing a significantly higher correlation. Furthermore, the correlation between avoidance/numbing symptoms to overall PTS was significantly different (p≤0.01) across exposed and non-exposed mothers. As a secondary analysis, we explored the relationship between DNA methylation in the glucocorticoid receptor (NR3C1) locus, an important stress modulating gene, and PTSD symptom domains, finding an association between DNA methylation and re-experiencing among genocide-exposed mothers that exceeded any other observed associations by approximately two-fold. Conclusions: This is the first report, to our knowledge, of a symptom-based analysis of transgenerational transmission of PTSD in sub-Saharan Africa. These findings can be leveraged to inform further mechanistic and treatment research for PTSD.

PMID:40078965 | PMC:PMC11231627 | DOI:10.12688/aasopenres.12848.2

Front Toxicol. 2025 Feb 26;7:1517970. doi: 10.3389/ftox.2025.1517970. eCollection 2025.

ABSTRACT

BACKGROUND: Poisoning is a global public health problem that has more unfavorable outcomes in developing countries. This study aimed to assess treatment outcomes and associated factors among poisoned patients treated at Saint Peter Specialized Hospital Toxicology Center.

METHODS: An institutional-based retrospective cohort study was employed by reviewing medical chart records of acutely poisoned patients who had been admitted at St. Peter Specialized Hospital Toxicology Center on 01/01/2017 to 30/12/2023 and the medical chart records review was employed from 01/01/2024 to 30/01/2024. This study analyzed records of 553 poisoned patients. A systematic random sampling technique was used to select the study unit. Data were entered and analyzed using Statistical Package for Social Sciences (SPSS) Windows version 26. A binary logistic regression model was used to identify associated factors for treatment outcomes of poisoned patients. A p-value <0.05 was considered statistically significant.

RESULT: A total of 553 documents of poisoned patients were assessed. The overall mortality rate was 18 (3.25%), and four patients developed chronic complications. Factor analyses show that arrival to the center before 4 h (AOR = 0.43, P = 0.008) predicted recovery, whereas arrival at the toxicology center after 8 h (AOR = 2.21, P = 0.004), being hypotensive (AOR = 1.85, P = 0.002), needing intubation (AOR = 2.52, P = 0.014), and the presence of two or more complication (AOR = 3.3, P < 0.001) at admission were predictors of mortality.

CONCLUSION AND RECOMMENDATION: The mortality rate for poisoned patients was 18 (3.25%). In this study, delayed arrival to the toxicology center, being hypotensive, needing intubation, and the presence of two or more complications at admission were factors associated with the mortality and morbidity of the patients. Establishing a strong referral link between the toxicology center and regional health institutions, ensuring the availability of possible advanced clinical setup early recognition, and aggressively resuscitating critically ill patients will help minimize unfavorable outcomes.

PMID:40078956 | PMC:PMC11897292 | DOI:10.3389/ftox.2025.1517970