Tag: nevin manimala

Clin Pharmacol Drug Dev. 2023 Mar 7. doi: 10.1002/cpdd.1232. Online ahead of print.

ABSTRACT

In the 10-week, phase 2 CLARITY study of patients with major depressive disorder, adjunctive therapy to antidepressants with pimavanserin 34 mg once daily statistically significantly improved the Hamilton Depression Rating Scale (HAMD-17) total score (primary endpoint) and Sheehan Disability Scale (SDS) score (secondary endpoint) versus placebo. This analysis characterized the exposure-response (E-R) relationships of pimavanserin in this CLARITY patient population. Exposure measures were estimated for each patient based on population-pharmacokinetic empirical Bayesian estimates. E-R models were developed to describe exposure-efficacy (HAMD-17, SDS, and Clinical Global Impression-Improvement [CGI-I] scale) and exposure-safety relationships (Karolinska Sleepiness Scale [KSS], Massachusetts General Hospital Sexual Functioning Inventory [MGH-SFI], and adverse events [AEs] of headache, sedation, and somnolence) relationships. For the primary efficacy endpoint (HAMD-17 scores), a sigmoid maximum-effect model described the time course of response, and a linear function of pimavanserin exposure was statistically significant. HAMD-17 scores decreased steadily over time following placebo and pimavanserin treatment; separation from placebo increased as peak pimavanserin plasma concentration (C_max ) increased. At median pimavanserin C_max (34-mg dose), the reduction from baseline in HAMD-17 scores was -11.1 and -13.5 at weeks 5 and 10, respectively. Relative to placebo, the model predicted comparable reductions in HAMD-17 scores at weeks 5 and 10. Similar improvements in favor of pimavanserin were detected with SDS, CGI-I, MGH-SFI, and KSS scores. No E-R relationship was found for AEs. E-R modeling predicted a relationship between higher pimavanserin exposure and improvement in HAMD-17 score and improvement across multiple secondary efficacy endpoints.

PMID:36880278 | DOI:10.1002/cpdd.1232

J Clin Endocrinol Metab. 2023 Mar 6:dgad122. doi: 10.1210/clinem/dgad122. Online ahead of print.

ABSTRACT

BACKGROUND: Stress triggers a cascade of reactions that alter the organism’s dynamic steady state. There is a scarcity of interventional studies that show cortisol variability on stress over time in groups of patients with chronic noncommunicable diseases and comorbidities.

PURPOSE: In this research, we aimed to examine salivary cortisol changes in the cognitive stress response of patients with Hypertension and Diabetes Mellitus (HT & DM) and patients with Hypertension (HT) and to determine the differences between them.

METHODS: The research was conducted by solving an arithmetic task as a stress test in 62 patients with HT&DM and HT that are being treated in the outpatient clinic of Medical Pharmacology and Clinical Pharmacology Department in Istanbul University, Istanbul Medical Faculty Hospital.

RESULTS: There was no statistically significant difference among HT&DM and HT groups on systolic and diastolic blood pressure (BP) values (p = 0.331 and p = 0.058). When measured by repeated ANOVA, salivary cortisol level [F (1.842, 60) = 8.771, p < 0.0001], systolic blood pressure [F (2.185, 60) = 12.080, p < 0.0001], diastolic blood pressure [F (2.793, 60) = 6.043, p = 0.001] and the heart rate [F (2.073, 60) = 13.259, p < 0.0001] were statistically significant for the main effect (time), while the effect of the group*time interaction factor was statistically not significant (p = 0.773; p = 0.751; p = 0.713 and p = 0.506, respectively).

MAIN CONCLUSIONS: In conclusion, the arithmetic problem-solving task used in the HT&DM and HT patients were found to be useful as an acute stress test in the laboratory environment. There was no statistically significant difference was found in terms of group*time interaction factor between the HT&DM and HT groups, however the salivary cortisol and BP values increased significantly after acute stress within each group.

PMID:36880261 | DOI:10.1210/clinem/dgad122

J Fish Biol. 2023 Mar 7. doi: 10.1111/jfb.15369. Online ahead of print.

ABSTRACT

Otolith shape analysis has been one of the most used approaches to study population structure in the last decades. Currently, two sets of shape descriptors are used to perform otolith shape analysis, namely Elliptic Fourier descriptor (EFd), which focuses on the overall otolith shape differences, and Discrete Wavelet descriptor (DWd), which is sensible to local differences along the otolith contour. Here, we conduct a comparative analysis of the performance of both descriptors in reconstructing the population structure and connectivity patterns in a small pelagic fish species with a wide geographical distribution and fast growth rate, the European sardine Sardina pilchardus (Walbaum, 1792), for the first time. A combination of each otolith shape descriptor and shape indices was explored using multivariate statistical methods. The two otolith shape descriptors showed similar, although limited overall classification success associated with the population dynamic characteristics of the species. Both descriptors point to migration among adjacent areas, such as northern Atlantic locations, eastern Mediterranean, and even across well-defined physical obstacles, such as the Strait of Gibraltar, among Atlantic and western Mediterranean locations. Both descriptors supported the division of the populations of Mediterranean waters into three main groups but slightly differed in the Atlantic waters groups limits. A comparison of present results with those from previous otolith shape analysis studies using EFd on a decadal time scale revealed differences in the population structure and connectivity patterns compared to the earlier period. These differences may be attributed to changes in environmental variables leading to changes in population dynamics but can also be the result of the sardine biomass sharp decrease that occurred in the last decade.

PMID:36880257 | DOI:10.1111/jfb.15369

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Jan;35(1):77-81. doi: 10.3760/cma.j.cn121430-20220624-00600.

ABSTRACT

OBJECTIVE: To investigate the prognostic value of the ratio of veno-arterial carbon dioxide partial pressure difference to arterio-venous oxygen content difference (Pv-aCO₂/Ca-vO₂) in children with primary peritonitis-related septic shock.

METHODS: A retrospective study was conducted. Sixty-three children with primary peritonitis-related septic shock admitted to department of intensive care unit of the Children’s Hospital Affiliated to Xi’an Jiaotong University from December 2016 to December 2021 were enrolled. The 28-day all-cause mortality was the primary endpoint event. The children were divided into survival group and death group according to the prognosis. The baseline data, blood gas analysis, blood routine, coagulation, inflammatory status, critical score and other related clinical data of the two groups were statistics. The factors affecting the prognosis were analyzed by binary Logistic regression, and the predictability of risk factors were tested by the receiver operator characteristic curve (ROC curve). The risk factors were stratified according to the cut-off, Kaplan-Meier survival curve analysis compared the prognostic differences between the groups.

RESULTS: A total of 63 children were enrolled, including 30 males and 33 females, the average age (5.6±4.0) years old, 16 cases died in 28 days, with mortality was 25.4%. There were no significant differences in gender, age, body weight and pathogen distribution between the two groups. The proportion of mechanical ventilation, surgical intervention, vasoactive drug application, and procalcitonin, C-reactive protein, activated partial thromboplastin time, serum lactate (Lac), Pv-aCO₂/Ca-vO₂, pediatric sequential organ failure assessment, pediatric risk of mortality III in the death group were higher than those in the survival group. Platelet count, fibrinogen, mean arterial pressure were lower than those in the survival group, and the differences were statistically significant. Binary Logistic regression analysis showed that Lac and Pv-aCO₂/Ca-vO₂ were independent risk factors affecting the prognosis of children [odds ratio (OR) and 95% confidence interval (95%CI) were 2.01 (1.15-3.21), 2.37 (1.41-3.22), respectively, both P < 0.01]. ROC curve analysis showed that the area under curve (AUC) of Lac, Pv-aCO₂/Ca-vO₂ and their combination were 0.745, 0.876 and 0.923, the sensitivity were 75%, 85% and 88%, and the specificity were 71%, 87% and 91%, respectively. Risk factors were stratified according to cut-off, and Kaplan-Meier survival curve analysis showed that the 28-day cumulative probability of survival of Lac ≥ 4 mmol/L group was lower than that in Lac < 4 mmol/L group [64.29% (18/28) vs. 82.86% (29/35), P < 0.05]. Pv-aCO₂/Ca-vO₂ ≥ 1.6 group 28-day cumulative probability of survival was less than Pv-aCO₂/Ca-vO₂ < 1.6 group [62.07% (18/29) vs. 85.29% (29/34), P < 0.01]. After a hierarchical combination of the two sets of indicator variables, the 28-day cumulative probability of survival of Pv-aCO₂/Ca-vO₂ ≥ 1.6 and Lac ≥ 4 mmol/L group significantly lower than that of the other three groups (Log-rank test, χ² = 7.910, P = 0.017).

CONCLUSIONS: Pv-aCO₂/Ca-vO₂ combined with Lac has a good predictive value for the prognosis of children with peritonitis-related septic shock.

PMID:36880243 | DOI:10.3760/cma.j.cn121430-20220624-00600

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Jan;35(1):23-27. doi: 10.3760/cma.j.cn121430-20220114-00063.

ABSTRACT

OBJECTIVE: To systematically evaluate the distribution characteristics of traditional Chinese medicine (TCM) syndromes in adult influenza patients and to provide a basis for the TCM syndrome differentiation of influenza.

METHODS: The CNKI, CBM, Wanfang, VIP, PubMed, Embase, Cochrane Library databases were searched to collect cross-sectional studies on the distribution pattern of TCM syndromes in adult patients with influenza. The risk of bias assessment tool for cross-sectional studies developed by the Joanna Briggs Institute (JBI) evidence-based health care center was used to evaluate the literature quality, and the Stata 15.1 software was used to conduct a Meta-analysis of the pooled effect sizes of the included studies.

RESULTS: A total of 11 studies with 4 367 influenza patients were included. Quality assessment results of JBI showed that the risk bias was higher in the sample size calculation, and the description of sampling modalities and response rate was unclear. There were 17 influenza syndromes after specification, and a single group rate Meta-analysis was performed of the syndromes with ≥ 50 incident cases showed that there were 9 syndromes with an incidence ≥ 10% and statistical significance, the top 5 syndromes were syndrome of wind and heat invading the defense [n = 1 583, RATE = 34.3%, 95% confidence interval (95%CI) was 22.2%-46.3%], syndrome of exterior cold and interior heat (n = 1 122, RATE = 36.1%, 95%CI was 21.2%-51.1%), syndrome of wind-cold fettering the exterior (n = 860, RATE = 19.4%, 95%CI was 10.7%-28.0%), syndrome of heat and toxin in the lung (n = 217, RATE = 17.1%, 95%CI was 9.1%-25.0%), and syndrome of disease involving both defense phase and qi phase (n = 184, RATE = 38.8%, 95%CI was 14.2%-63.5%). The results of the subgroup analysis in different geographical regions showed that the frequency of distribution of syndrome of wind and heat invading the defense and heat and toxin in the lung was higher in the South (RATE: 36.5%, 18.6%) than in the North (RATE: 30.9%, 15.4%), and the frequency of distribution of syndrome of wind-cold fettering the exterior and exterior cold and interior heat in the North (RATE: 23.8%, 40.1%) was higher than that in the South (RATE: 15.7%, 32.3%).

CONCLUSIONS: There are 9 common TCM syndromes of influenza, including wind and heat invading the defense syndrome, exterior cold and interior heat syndrome, wind-cold fettering the exterior syndrome, heat and toxin in the lung syndrome, disease involving both defense phase and qi phase syndrome, wind and heat complicated by dampnessinvading the surface syndrome, wind and cold complicated by dampnessinvading the surface syndrome, defense phase syndrome and dampness and heatinvading the surface syndrome, which can provide a reference for the TCM syndrome differentiation and treatment of influenza.

PMID:36880233 | DOI:10.3760/cma.j.cn121430-20220114-00063

Cancer Med. 2023 Mar 7. doi: 10.1002/cam4.5702. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer threatening the public health globally. Although HCC has been associated with the telomere length (TL), the causal relationship between them is not well understood. Therefore, we attempted to explore the linear causal relationship between TL and HCC through Mendelian randomization (MR) analysis among Asian and European populations.

METHODS: The summary statistics of TL-associated single nucleotide polymorphisms (SNPs) were obtained from a genome-wide association study (GWAS) in the Asian population (N = 23,096). The data of TL-associated SNPs in the European population (N = 472,174) and the GWAS summary statistics of HCC in the Asian population (1866 cases, 195,745 controls) as well as the European population (168 cases, 372,016 controls) were downloaded from the public GWAS database. Two-sample MR was performed using inverse variance weighting (IVW), weighted median estimate, MR-Egger regression, weighted-mode estimate, and simple-mode estimate methods. Sensitivity analysis was performed to text the primary results’ robustness.

RESULTS: Nine SNPs associated with TL in Asian populations and 98 SNPs in European populations were selected as instrumental variables. No linear causal relationship between heritable TL and the HCC risk was recorded in the Asian (IVW analysis odds ratio [OR] = 1.023, 95% confidence interval [CI] 0.745, 1.405, p = 0.887) and European populations (IVW analysis OR = 0.487, 95% CI 0.180, 1.320, p = 0.157). Other methods also achieved similar outcomes. Sensitivity analysis was performed and revealed no heterogeneity and horizontal pleiotropy.

CONCLUSIONS: No linear causal association was recorded between heritable TL and HCC in Asian and European populations.

PMID:36880214 | DOI:10.1002/cam4.5702

Orbit. 2023 Mar 7:1-8. doi: 10.1080/01676830.2023.2186435. Online ahead of print.

ABSTRACT

PURPOSE: To assess whether transcutaneous retrobulbar amphotericin B injections (TRAMB) reduce exenteration rate without increasing mortality in rhino-orbital-cerebral mucormycosis (ROCM).

METHODS: In this retrospective case-control study, 46 patients (51 eyes) with biopsy-proven ROCM were evaluated at 9 tertiary care institutions from 1998 to 2021. Patients were stratified by radiographic evidence of local orbital versus extensive involvement at presentation. Extensive involvement was defined by MRI or CT evidence of abnormal or loss of contrast enhancement of the orbital apex with or without cavernous sinus, bilateral orbital, or intracranial extension. Cases (+TRAMB) received TRAMB as adjunctive therapy while controls (-TRAMB) did not. Patient survival, globe survival, and vision/motility loss were compared between +TRAMB and -TRAMB groups. A generalized linear mixed effects model including demographic and clinical covariates was used to evaluate the impact of TRAMB on orbital exenteration and disease-specific mortality.

RESULTS: Among eyes with local orbital involvement, exenteration was significantly lower in the +TRAMB group (1/8) versus -TRAMB (8/14) (p = 0.04). No significant difference in mortality was observed between the ±TRAMB groups. Among eyes with extensive involvement, there was no significant difference in exenteration or mortality rates between the ±TRAMB groups. Across all eyes, the number of TRAMB injections correlated with a statistically significant decreased rate of exenteration (p = 0.048); there was no correlation with mortality.

CONCLUSIONS: Patients with ROCM with local orbital involvement treated with adjunctive TRAMB demonstrated a lower exenteration rate and no increased risk of mortality. For extensive involvement, adjunctive TRAMB does not improve or worsen these outcomes.

PMID:36880205 | DOI:10.1080/01676830.2023.2186435

Public Health Nurs. 2023 Mar 6. doi: 10.1111/phn.13182. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore in a sample of school nurses (SN) in California the impact of the COVID-19 pandemic on school nurse health services, how school nurses mitigated the impact of COVID-19, and moral distress levels among school nurses.

DESIGN AND METHODS: Nineteen (N = 19) school nurses who work in K-12 schools in California, USA participated in a mixed-methods approach involving qualitative descriptive design, inductive content analysis, and descriptive statistics. Interviews were conducted in August and September 2021.

RESULTS: Five themes emerged: (1) role of the SN during the COVID-19 pandemic, (2) coordination with school administration, (3) COVID-19 related challenges and disruptions to care, (4) moral distress, and (5) coping during the pandemic.

CONCLUSION: The pandemic had a profound impact on school nurses. This study provides school nurse perspectives of the impact of COVID-19 on services they delivered, the unique skills of school nurses essential to mitigation strategies, and moral distress school nurses encountered during the pandemic. Understanding the important role school nurses had during the pandemic is paramount to fully contextualize the contributions they made within public health nursing practice and inform preparedness for future pandemics.

PMID:36880197 | DOI:10.1111/phn.13182

Ann Rehabil Med. 2023 Feb;47(1):4-10. doi: 10.5535/arm.23020. Epub 2023 Feb 28.

ABSTRACT

Spinal cord injury (SCI) has been recognized as a medically complex and life-disrupting condition. As the aging of the population accelerates, the trend of SCI has changed. This review aimed to provide comprehensive statistics and recent epidemiological changes in SCI and rehabilitation in Korea. All three insurance databases (National Health Insurance Service [NHIS], automobile insurance [AUI], and industrial accident compensation insurance [IACI]) were considered. These nationwide databases provide data on the current trends in term of incidence, etiology, and rehabilitation of SCI. Traumatic spinal cord injury (TSCI) was more frequent among the elderly in the NHIS compared to working age individuals in the AUI and IACI. In all three trauma-related insurance databases, male with TSCI outnumbered female. TSCI incidence per year was approximately 17 times higher among males than females, on average, in IACI. In all three insurances, the cervical level of TSCI was the most frequent. Although the ratio of SCI patients receiving rehabilitation treatment at primary and secondary hospitals increased for nine years, the increase in training on activities of daily living (ADL training) was found to be relatively small. This review provides a broader and comprehensive understanding of the incidence, etiology, and rehabilitation treatment of SCI in Korea.

PMID:36880194 | DOI:10.5535/arm.23020

Curr Radiopharm. 2023 Mar 7. doi: 10.2174/1874471016666230307113045. Online ahead of print.

ABSTRACT

OBJECTIVE: Previously, the 99mTc inhalation was used for pneumonia treatment that decreases inflammation and disease severity. We aimed to investigate the safety and effectiveness of carbon nanoparticles labeled with Technetium isotope (99mTc) in a form of ultradispersed aerosol in combination with standard COVID-19 therapy. The study was a randomized phase 1 and phase 2 clinical trial of low-dose radionuclide inhalation therapy for patients with COVID-19 related pneumonia.

METHOD: We enrolled 47 patients with confirmed COVID-19 infection and early laboratory signs of cytokine storm and randomized them into the Treatment and Control groups. We analyzed blood parameters reflecting the COVID-19 severity and inflammatory response.

RESULTS: Low-dose 99mTc-labeled inhalation showed a minimal accumulation of radionuclide in lungs in healthy volunteers. We observed no significant differences between the groups before treatment in WBC-count, D-dimer, CRP, Ferritin or LDH levels. We found that Ferritin and LDH levels significantly raised after the 7th day follow-up only in the Control group (p<0.0001 and p=0.0005, respectively), while mean values of the same indicators did not change in patients in the Treatment group after the radionuclide treatment. D-dimer values also lowered in the radionuclide treated group, however, this effect was not statistically significant. Furthermore, we evaluated a significant decrease in CD19+ cell counts in patients of the radionuclide-treated group.

CONCLUSION: Inhaled low-dose radionuclide therapy of 99mTc aerosol affects the major prognostic indicators of COVID-19-related pneumonia restraining inflammatory response. Overall, we identified no evidence of major adverse events in the group receiving radionuclide.

PMID:36880188 | DOI:10.2174/1874471016666230307113045