Category: Nevin Manimala

CNS Drugs. 2024 Jan 8. doi: 10.1007/s40263-023-01056-x. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Identifying key factors for a successful transition from once-monthly paliperidone palmitate (PP1M) to three-monthly paliperidone palmitate (PP3M) is crucial for improving treatment outcomes, enhancing patient adherence, and reducing relapse risk in patients with schizophrenia. Providing region-specific insights for evidence-based clinical decisions can aid clinicians in optimizing transition strategies for Chinese patients with schizophrenia. Therefore, the objective of this post hoc analysis of a double-blind parallel-group multicenter phase 3 study (NCT01515423) was to identify factors related to the disease stabilization that may allow for a successful transition from PP1M to PP3M in the treatment of Chinese patients with schizophrenia.

METHODS: Adults (18-70 years) diagnosed with schizophrenia using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition text revision, for over 1 year and with a baseline Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120 were entered into an open-label (OL) phase receiving PP1M for 17 weeks. After the 17-week OL phase, patients who met the criteria necessary for stabilization were randomized (1:1) to PP1M (fixed-dose, 50, 75, 100, or 150 mg eq.) or PP3M (fixed-dose, 175, 263, 350, or 525 mg eq.) in a 48-week double-blind phase. Stabilization was defined as a PANSS total score < 70, PANSS item (P1, P2, P3, P6, P7, G8, G14) scores ≤ 4, and a reduction in Clinical Global Impression Severity (CGI-S) score of ≥ 1 from OL baseline. This post hoc analysis evaluated changes and trends in symptom severity using PANSS, changes in mental states using CGI-S, and changes in personal and social functioning using Personal and Social Performance (PSP) scores from baseline to the endpoint of the OL phase in patients who either met or did not meet the stabilization criteria (stabilized versus non-stabilized group). Comparison of changes and trends in the clinical scores between the stabilized group and non-stabilized group were conducted using linear mixed model and Mann-Kendall trend analysis, respectively. Univariate and multivariate logistic regression analyses were conducted to explore factors associated with stabilization status for transition.

RESULTS: Of 296 patients enrolled, 210 achieved disease stabilization (106 patients and 104 patients were randomized to PP1M and PP3M, respectively). Significant downward trends in the PANSS and CGI-S scores were detected in the stabilized patients (n = 210, Z_PANSS = -2.21, p = 0.028; Z_CGI-S = -2.21, p = 0.028) but not in the non-stabilized patients (n = 86). No significant trends in the PSP scores were observed in either group. The factors significantly associated with disease stabilization were the CGI-S score at baseline [odds ratio (OR) = 0.22, 95% confidence interval (CI): 0.09, 0.5), reduction of the PANSS score at week 13 (OR = 1.11, 95% CI: 1.06, 1.17), and reduction of CGI-S score at week 13 (OR = 2.27, 95% CI: 1.03, 5.02).

CONCLUSION: A lower CGI-S total score at baseline and greater reductions in PANSS and CGI-S scores at week 13 were associated with patients achieving disease stabilization, that may allow for a successful transition. Evidence from this study indicates that better disease condition at baseline, early functional improvement and symptomatic relief were the key factors associated with disease stabilization. The findings may guide clinicians to identify suitable patients for transition from PP1M to PP3M and further optimize the use of PP3M in China.

CLINICAL TRIALS REGISTRATION: EudraCT number: 2011-004889-15 and ClinicalTrials.gov (identifier: NCT01515423) for the original double-blind randomized study.

PMID:38190077 | DOI:10.1007/s40263-023-01056-x

J Epidemiol Glob Health. 2024 Jan 8. doi: 10.1007/s44197-023-00175-4. Online ahead of print.

ABSTRACT

Maternal and paternal age at birth is increasing globally. Maternal age may affect perinatal outcomes, but the effect of paternal age and its joint effect with maternal age are not well established. This prospective, multicenter, cohort analysis used data from the University Hospital Advanced Age Pregnant Cohort Study in China from 2016 to 2021, to investigate the separate association of paternal age and joint association of paternal and maternal age with adverse perinatal outcomes. Of 16,114 singleton deliveries, mean paternal and maternal age (± SD) was 38.0 ± 5.3 years and 36.0 ± 4.1 years. In unadjusted analyses, older paternal age was associated with increased risks of gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy, preeclampsia, placenta accreta spectrum disorders, placenta previa, cesarean delivery (CD), and postpartum hemorrhage, preterm birth (PTB), large-for-gestational-age, macrosomia, and congenital anomaly, except for small-for-gestational-age. In multivariable analyses, the associations turned to null for most outcomes, and attenuated but still significant for GDM, CD, PTB, and macrosomia. As compare to paternal age of < 30 years, the risks in older paternal age groups increased by 31-45% for GDM, 17-33% for CD, 32-36% for PTB, and 28-31% for macrosomia. The predicted probabilities of GDM, placenta previa, and CD increased rapidly with paternal age up to thresholds of 36.4-40.3 years, and then plateaued or decelerated. The risks of GDM, CD, and PTB were much greater for pregnancies with younger paternal and older maternal age, despite no statistical interaction between the associations related to paternal and maternal age. Our findings support the advocation that paternal age, besides maternal age, should be considered during preconception counseling.Trial Registration NCT03220750, Registered July 18, 2017-Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/NCT03220750 .

PMID:38190051 | DOI:10.1007/s44197-023-00175-4

Biometals. 2024 Jan 8. doi: 10.1007/s10534-023-00563-0. Online ahead of print.

ABSTRACT

There is limited experimental evidence on the biochemical consequences of aluminium (Al) and cadmium (Cd) co-exposures during pregnancy and postnatal life.This study investigated the impacts of perinatal Al chloride (AlCl₃) and Cd chloride (CdCl₂) co-exposures on neuroendocrine functions in mice offspring during postnatal life. The study comprised of four pregnant experimental groups. Group 1 received AlCl₃ (10 mg/kg), group 2 were administered CdCl₂ (1.5 mg/kg), while group 3 received both AlCl₃ (10 mg/kg) and CdCl₂ (1.5 mg/kg) (AlCl₃+CdCl₂), and group 4 received saline (10 mL/kg) only and served as control group. All experimental animals were chemically exposed once daily from gestation days 7-20. Upon delivery, male pups were regrouped based on maternal chemical exposure on postnatal day 21 (PND 21) and allowed to grow to adulthood until PND 78, after which they were sacrificed for assessment of neuroendocrine markers and histological investigations. There was no statistical significance (p > 0.05) on follicle stimulating hormone, testosterone, estrogen and progesterone, thyroid stimulating hormone, thyroxine (T4) in all treatment groups relative to controls|. However, AlCl₃ and AlCl₃-CdCl₂ significantly (p < 0.05) reduced triiodothyronine (T3) levels, with a profound increase in T3:T4 ratio by AlCl₃, and AlCl₃+CdCl₂ compared to control. Furthermore, pups from pregnant mice treated with CdCl₂ and AlCl₃+CdCl₂ demonstrated increased testicular malondialdehyde concentration with increased catalase activity relative to controls, suggesting oxidative imbalance. In addition, AlCl₃, CdCl₂, and AlCl₃+CdCl₂ exposures induced testicular and hypothalamic architectural disruption compared to controls, with marked architectural derangement in the AlCl₃+CdCl₂ group. Our findings suggest that prenatal co-exposures to Alcl₃ and CdCl₂ induce testicular and hypothalamic alterations in offspring via a testicular oxidative stress and thyrotoxicosis-dependent mechanisms.

PMID:38190032 | DOI:10.1007/s10534-023-00563-0

Endocrine. 2024 Jan 8. doi: 10.1007/s12020-023-03669-0. Online ahead of print.

ABSTRACT

PURPOSE: The study aimed to investigate the potential effect of Antithrombin III (ATIII) between chronic renal insufficiency and chronic coronary artery disease (chronic CAD) in type 2 diabetes mellitus (T2DM) patients.

METHODS: T2DM patients hospitalized in ZhongDa Hospital from 2013 to 2018 were enrolled. Relationships between renal function, ATIII, and chronic CAD risk were explored using multivariate regression models. Multiplicative and additive interactions were investigated between ATIII and renal function for CAD risk, and the role of ATIII was determined by bootstrap mediation analysis in patients with chronic renal dysfunction.

RESULTS: A total of 4197 patients were included in the study, with a chronic CAD prevalence of 23.02%. Low ATIII level was statistically associated with chronic renal insufficiency and elevated CAD risk even after adjustments (P < 0.05). A positive correlation between renal function and ATIII was demonstrated, and each 1 SD increase in renal function, ATIII increased by 2.947% (2.406-3.488%, P < 0.001) and 0.969% (0.297-1.642%, P < 0.001) in crude and adjusted models respectively. Patients with decreased renal function and ATIII were at the highest chronic CAD risk (OR = 1.51, 95%CI:1.15-1.98, P < 0.05), while no multiplicative and additive interaction effects were significant. Bootstrap mediation analysis estimated that ATIII mediated approximately 4.27% of the effect of chronic renal insufficiency on chronic CAD risk.

CONCLUSION: ATIII may serve as a mediator between chronic renal insufficiency and chronic CAD, providing mechanistic clues for renal-heart association and new insight into clinical therapies.

PMID:38190026 | DOI:10.1007/s12020-023-03669-0

Psychometrika. 2024 Jan 8. doi: 10.1007/s11336-023-09945-2. Online ahead of print.

ABSTRACT

Most measures of agreement are chance-corrected. They differ in three dimensions: their definition of chance agreement, their choice of disagreement function, and how they handle multiple raters. Chance agreement is usually defined in a pairwise manner, following either Cohen’s kappa or Fleiss’s kappa. The disagreement function is usually a nominal, quadratic, or absolute value function. But how to handle multiple raters is contentious, with the main contenders being Fleiss’s kappa, Conger’s kappa, and Hubert’s kappa, the variant of Fleiss’s kappa where agreement is said to occur only if every rater agrees. More generally, multi-rater agreement coefficients can be defined in a g-wise way, where the disagreement weighting function uses g raters instead of two. This paper contains two main contributions. (a) We propose using Fréchet variances to handle the case of multiple raters. The Fréchet variances are intuitive disagreement measures and turn out to generalize the nominal, quadratic, and absolute value functions to the case of more than two raters. (b) We derive the limit theory of g-wise weighted agreement coefficients, with chance agreement of the Cohen-type or Fleiss-type, for the case where every item is rated by the same number of raters. Trying out three confidence interval constructions, we end up recommending calculating confidence intervals using the arcsine transform or the Fisher transform.

PMID:38190018 | DOI:10.1007/s11336-023-09945-2

Eur J Epidemiol. 2024 Jan 8. doi: 10.1007/s10654-023-01080-7. Online ahead of print.

ABSTRACT

To explore to which extent neurodegeneration and cerebral small vessel disease (SVD) could mediate the association between type-2 diabetes and higher dementia risk. The analytical sample consisted in 2228 participants, out of the Three-City study, aged 65 and older, free of dementia at baseline who underwent brain MRI. Diabetes was defined by medication intake or fasting or non-fasting elevated glucose levels. Dementia status was assessed every 2 to 3 years, during up to 12 years of follow-up. Brain parenchymal fraction (BPF) and white matter hyperintensities volume (WMHV) were selected as markers of neurodegeneration and cerebral SVD respectively. We performed a mediation analysis of the effect of baseline BPF and WMHV (mediators) on the association between diabetes and dementia risk using linear and Cox models adjusted for age, sex, education level, hypertension, hypercholesterolemia, BMI, smoking and alcohol drinking status, APOE-ε4 status, and study site. At baseline, 8.8% of the participants had diabetes. Diabetes (yes vs. no) was associated with higher WMHV (β_diab = 0.193, 95% CI 0.040; 0.346) and lower BPF (β_diab = -0.342, 95% CI -0.474; -0.210), as well as with an increased risk of dementia over 12 years of follow-up (HR_diab = 1.65, 95% CI 1.04; 2.60). The association between diabetes status and dementia risk was statistically mediated by higher WMHV (HRdiab=1.05, 95% CI 1.01; 1.11, mediated part = 10.8%) and lower BPF (HR_diab = 1.12, 95% CI 1.05; 1.20, mediated part = 22.9%). This study showed that both neurodegeneration and cerebral SVD statistically explained almost 30% of the association between diabetes and dementia.

PMID:38190014 | DOI:10.1007/s10654-023-01080-7

Sports Med Open. 2024 Jan 8;10(1):5. doi: 10.1186/s40798-023-00671-8.

ABSTRACT

BACKGROUND: Patellofemoral pain (PFP) is among the most common injuries in runners. While multiple risk factors for patellofemoral pain have been investigated, the interactions of variables contributing to this condition have not been explored. This study aimed to classify runners with patellofemoral pain using a combination of factors including biomechanical, anthropometric, and demographic factors through a Classification and Regression Tree analysis.

RESULTS: Thirty-eight runners with PFP and 38 healthy controls (CON) were selected with mean (standard deviation) age 33 (16) years old and body mass index 22.3 (2.6) kg/m². Each ran at self-selected speed, but no between-group difference was identified (PFP = 2.54 (0.2) m/s x CON = 2.55 (0.1) m/s, P = .660). Runners with patellofemoral pain had different patterns of interactions involving braking ground reaction force impulse, contact time, vertical average loading rate, and age. The classification and regression tree model classified 84.2% of runners with patellofemoral pain, and 78.9% of healthy controls. The prevalence ratios ranged from 0.06 (95% confidence interval: 0.02-0.23) to 9.86 (95% confidence interval: 1.16-83.34). The strongest model identified runners with patellofemoral pain as having higher braking ground reaction force impulse, lower contact times, higher vertical average loading rate, and older age. The receiver operating characteristic curve demonstrated high accuracy at 0.83 (95% confidence interval: 0.74-0.93; standard error: 0.04; P < .001).

CONCLUSIONS: The classification and regression tree model identified an influence of multiple factors associated with patellofemoral pain in runners. Future studies may clarify whether addressing modifiable biomechanical factors may address this form of injury.

PMID:38190013 | DOI:10.1186/s40798-023-00671-8

J Opioid Manag. 2023 Nov-Dec;19(6):533-541. doi: 10.5055/jom.0838.

ABSTRACT

OBJECTIVE: This study evaluated the opioid sparing and pain relief effect of erector spinae plane block (ESPB) for radiofrequency ablation (RFA) of hepatic focal lesions under conscious sedation.

DESIGN: A randomized controlled trial.

SETTING: Tanta University Hospitals.

PATIENTS: Fifty patients aged 30-60 years old and eligible for RFA of hepatic focal lesions were included.

INTERVENTIONS: Patients randomized to receive either local anesthetic infiltration (group I) or ESPB (group II). Both groups received sedation by propofol infusion.

MAIN OUTCOME MEASURE(S): The primary outcome was total fentanyl consumption. Secondary outcomes were nonverbal pain score (NVPS), time to first analgesic request post-procedure, radiologist’s satisfaction, and complications.

RESULTS: In group I, NVPS was significantly increased at 10, 15, 25, and 30 minutes during RFA compared to group II (p = 0.008, <0.001, 0.018, and 0.001, respectively) with no significant differences on arrival to post-anesthesia care unit (PACU) and after 1 hour. Total fentanyl consumption during the procedure was significantly increased in group I compared to group II (160.9 ± 38.2 and 76 ± 21 µg, respectively; p < 0.001) with prolonged time to first analgesia request post-procedure in group II compared to group I (392.7 ± 38.8 and 101.1 ± 13.6 minutes, respectively; p < 0.001). The level of radiologist’s satisfaction was significantly increased in the group II (p = 0.010). Three patients in group I and one patient in group II needed general anesthesia. Lower incidence of complications in group II occurred with statistical insignificance.

CONCLUSIONS: The ESPB provided adequate analgesia and reduced opioids consumption during the hepatic RFA, with high radiologist’s satisfaction.

PMID:38189195 | DOI:10.5055/jom.0838

J Opioid Manag. 2023 Nov-Dec;19(6):523-532. doi: 10.5055/jom.0837.

ABSTRACT

OBJECTIVE: The primary objective of this study is to assess factors that influence opioid prescribing by dentists and the role of these factors in the practice of dental pain control.

DESIGN: A 25-question survey instrument was distributed to the study population for anonymous responses, covering dentist and practice demographics and opioid prescribing characteristics.

SETTING: Private solo and group practice settings, including general practitioners and dental specialists.

PARTICIPANTS: Potential participants included all active members of a large state dental professional association.

MAIN OUTCOME MEASURES: They were practitioner and practice demographic traits, types of opioids prescribed, and statistical correlations. Outcome variables included practice type, practitioner gender, practice location, practice model, and years in practice. Categorical covariates were summarized statistically by frequencies and percentages, and continuous covariates were summarized by means, medians, ranges, and standard deviations.

RESULTS: Strongest correlations with opioid prescribing included general practitioner (vs specialist) and male gender. The coronavirus disease 2019 pandemic was confirmed as having exerted a significant impact on opioid prescribing among the survey respondents.

CONCLUSIONS: Further research is warranted to assess post-pandemic opioid prescribing patterns, and additional educational strategies regarding limitations of opioid prescriptions should be applied to general, rather than specialty, dental practitioners.

PMID:38189194 | DOI:10.5055/jom.0837

J Opioid Manag. 2023 Nov-Dec;19(6):515-521. doi: 10.5055/jom.0836.

ABSTRACT

BACKGROUND: The epidemic of opioid misuse and abuse is rampant in the United States. A large percentage of patients who go on to misuse or abuse opioids were initially legally prescribed an opioid medication by their physician. One of the most common reasons patients of reproductive age seek medical care is for pregnancy and delivery. These patients are frequently prescribed opioids. Greater than one in 10 Medicaid-enrolled women fill an opioid prescription after vaginal delivery.

OBJECTIVE: To assess the opioid prescribing patterns of obstetric providers following vaginal deliveries.

STUDY DESIGN: Obstetric physicians and certified nurse midwives (CNMs) from different practice backgrounds were administered a questionnaire regarding opioid prescribing practices for patients who undergo vaginal delivery. Providers were contacted via email and completed survey via REDCap.

RESULTS: Ninety-nine providers completed the survey between October 2018 and January 2019. Eight percent of all providers reported prescribing opioids at discharge after vaginal deliveries. There was a statistically significant difference in the proportion of physicians who provided opioid prescriptions at discharge compared to CNMs (16.7 percent vs 1.8 percent, respectively, p < .05). Common reasons for prescribing opioids at discharge included post-partum tubal ligation (56.4 percent), third- and fourth-degree lacerations (59.6 and 73.4 percent, respectively), and operative deliveries (26.6 percent). Physicians were significantly more likely to prescribe an opioid after a second-degree laceration than CNMs (19.1 percent vs 5.3 percent, p < 0.05).

CONCLUSIONS: Practice patterns for opioid prescription vary by provider type as well as by delivery characteristics. Further study is necessary to delineate the optimal care while minimizing unnecessary opioid prescriptions.

PMID:38189193 | DOI:10.5055/jom.0836