Category: Nevin Manimala

Clin Transl Sci. 2024 Feb;17(2):e13687. doi: 10.1111/cts.13687.

ABSTRACT

Co-administration of clesacostat (acetyl-CoA carboxylase inhibitor, PF-05221304) and ervogastat (diacylglycerol O-acyltransferase inhibitor, PF-06865571) in laboratory models improved non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) end points and mitigated clesacostat-induced elevations in circulating triglycerides. Clesacostat is cleared via organic anion-transporting polypeptide-mediated hepatic uptake and cytochrome P450 family 3A (CYP3A); in vitro clesacostat is identified as a potential CYP3A time-dependent inactivator. In vitro ervogastat is identified as a substrate and potential inducer of CYP3A. Prior to longer-term efficacy trials in participants with NAFLD, safety and pharmacokinetics (PK) were evaluated in a phase I, non-randomized, open-label, fixed-sequence trial in healthy participants. In Cohort 1, participants (n = 7) received clesacostat 15 mg twice daily (b.i.d.) alone (Days 1-7) and co-administered with ervogastat 300 mg b.i.d. (Days 8-14). Mean systemic clesacostat exposures, when co-administered with ervogastat, decreased by 12% and 19%, based on maximum plasma drug concentration and area under the plasma drug concentration-time curve during the dosing interval, respectively. In Cohort 2, participants (n = 9) received ervogastat 300 mg b.i.d. alone (Days 1-7) and co-administered with clesacostat 15 mg b.i.d. (Days 8-14). There were no meaningful differences in systemic ervogastat exposures when administered alone or with clesacostat. Clesacostat 15 mg b.i.d. and ervogastat 300 mg b.i.d. co-administration was overall safe and well tolerated in healthy participants. Cumulative safety and no clinically meaningful PK drug interactions observed in this study supported co-administration of these two novel agents in additional studies exploring efficacy and safety in the management of NAFLD.

PMID:38362827 | DOI:10.1111/cts.13687

Riv Psichiatr. 2024 Jan-Feb;59(1):28-34. doi: 10.1708/4205.41946.

ABSTRACT

AIMS: This study aims to present an overview of the clinical experience of the counseling service “Sportello Studenti”. The service offers free diagnostic and therapeutic psychological assistance to all Tor Vergata University of Rome students.

METHODS: Preliminary findings on the prevalence of anxious, depressive, and prodromal symptoms in a subset of participants recruited during the initial three-year period of the service’s operation (2019-2022) are presented. Beck’s Depression Inventory II (BDI-II), Symptom Checklist-90-Revised (SCL-90-R), Prodromal Questionnaire 16 (PQ-16) and Aberrant Salience Inventory (ASI) have been used to investigate principle psychopathological dimensions.

RESULTS: 261 students aged 18 to 35 completed the assessment (180 female – 69%). Mild widespread depressive symptoms (35.5%) and mild to severe suicide ideation (5.1%) were highlighted. Ninety students (37.2%) result at a higher risk condition for psychosis. A significant statistical correlation between negative psychopathological indicators, such as suicidal thoughts and age, suggests that younger students exhibit higher susceptibility and vulnerability to mental health issues.

DISCUSSION AND CONCLUSIONS: The increasing prevalence of distress among young individuals represents an urgent public health concern that necessitates immediate intervention. It is crucial for countries to adopt a comprehensive approach to promoting psychological and mental health. University counseling services serve as an effective initial intervention to address the negative impact of mental illness on academic performance, social interactions, and emotional well-being in young individuals. They also play a pivotal role in the early identification of individuals at risk of developing severe psychiatric disorders. Sportello Studenti has proven to be a valuable initiative addressing the mental health needs of University of Tor Vergata students, underscoring the significance of promoting psychological well-being.

PMID:38362786 | DOI:10.1708/4205.41946

Riv Psichiatr. 2024 Jan-Feb;59(1):20-27. doi: 10.1708/4205.41945.

ABSTRACT

AIM: To evaluate the effectiveness of the Falloon Psychoeducational Family Intervention (PFI), originally developed for the management of schizophrenia, afterwards adapted for early psychosis, in terms of adherence to the treatment, low relapse rate, improvement social functioning and stress management.

METHODS: This is a one-year, pragmatic, real-world observational study with subjects consecutively recruited at the Campobasso psychiatry ward (SPDC) or Mental Health Center (MHC) starting in November 2020 over an 18 month period. Patients recruited were asked for consent for family members’ participation. The effectiveness of the intervention was evaluated in terms of treatment adherence, discontinuity, relapse rates, clinical symptoms assessed by BPRS and PANSS, improvement in social functioning and stress management.

RESULTS: 13 subjects were recruited; 10 males and 3 females, all singles, with a DUP inferior to one year. At the end of the intervention, significant improvements in treatment adherence, absence of drop-outs and relapses, statistically significant improvements in clinical symptoms, social functioning and stress management were found.

DISCUSSION AND CONCLUSIONS: The results clearly show that family psychoeducational intervention according to the adapted Falloon model, specifically focused on crisis and early stress management, is effective in improving treatment adherence, clinical outcome and social life of first-episode psychotic patients. The limit is the lack of a control and randomization.

PMID:38362785 | DOI:10.1708/4205.41945

Riv Psichiatr. 2024 Jan-Feb;59(1):4-12. doi: 10.1708/4205.41943.

ABSTRACT

INTRODUCTION: The epidemiological studies on Huntington’s disease (HD) in the Asian population suggest that prevalence rates are significantly lower than in the Western population. We conducted a systematic review of epidemiological studies of HD in Asia to compare the level of impact of the disease on the Asian population.

METHODS: Original articles and reviews about HD prevalence in the Asian population were found through databases such as Embase, Medline, and PsychInfo. Relevant articles were analysed by scrutinising of references, including specific key words. A meta-analysis was performed on prevalence rates to find the degree of similarities with I2. Point Prevalence was measured as the number of people affected by HD in a 100,000 population and expressed as Point Prevalence (PP)= Number of people affected/100,000 with 95% Confidence Intervals (CI95).

RESULTS: Results from the random-effect meta-analysis show the highest point prevalence of HD in the Middle East with PP=4.0 (CI95=2.90-5.30). The lowest point prevalence was found in the Chinese population with PP=0.25 (CI95=0.16-0.36). Europe remains at a high prevalence compared to Asian countries with PP=1.00 (CI95=0.82-1.19). The overall prevalence in Asia is PP=0.70 (CI95=0.44-1.0).

CONCLUSION: Our study reveals that HD disease affects the population of Asia to a lesser extent than in Europe. The plausible explanation for differences in prevalence is that in some countries, the affected individuals will not self-refer to HD screening for fear of social stigma, negative influence in marriage, and lack of genetic and neurological testing. Another explanation is that studies that used genetic testing exclusively were able to identify the CAG repeats, subgroups of CAG repeat A1 & A2, and haplogroup C, which has less predisposition to high HD prevalence in Asians compared to the Caucasian population.

PMID:38362783 | DOI:10.1708/4205.41943

Ann R Coll Surg Engl. 2024 Feb 16. doi: 10.1308/rcsann.2023.0044. Online ahead of print.

ABSTRACT

INTRODUCTION: The utilisation of laparoscopic appendicectomy (LA) in children remains contentious despite the well-recognised advantages of laparoscopic surgery. The purpose of this study was to compare intraoperative and postoperative outcomes in LA and open appendicectomy (OA) when performed by adult general surgeons outside specialist paediatric practice in younger children.

METHODS: A retrospective review of all patients under the age of 13 who underwent LA for suspected appendicitis over a two-year period was conducted. These were case-matched with an equivalent number of patients who underwent OA during the same period. Intraoperative and postoperative outcomes were compared.

RESULTS: Fifty-one patients underwent LA during the study period. Patient demographics were statistically equivalent with the OA cohort. A statistically significant longer median operating time (58 vs 49min) was noted in the LA group, but intraoperative outcomes were otherwise comparable. LA, when compared with OA, was associated with a significant improvement in postoperative length of stay (2 vs 3 days, p < 0.001), postoperative complication rate (0% vs 6%, p = 0.01), negative appendicectomy rate (3.9% vs 17.6%, p < 0.001) and 30-day readmission rate (0% vs 5.9%, p = 0.03). No patients in the LA group required conversion to open surgery.

CONCLUSION: LA can be safely delivered by adult general surgeons to younger paediatric populations outside the setting of paediatric specialist practice, with statistically significant improvements in postoperative outcomes noted when compared with OA. These findings are of importance in the current healthcare context where adult general surgeons continue to perform the majority of paediatric appendicectomies.

PMID:38362753 | DOI:10.1308/rcsann.2023.0044

Eur J Psychotraumatol. 2024;15(1):2314913. doi: 10.1080/20008066.2024.2314913. Epub 2024 Feb 16.

ABSTRACT

Background: Stressful events increase the risk for treatment-resistant depression (TRD), and trauma-focused psychotherapy can be useful for TRD patients exposed to early life stress (ELS). Epigenetic processes are known to be related to depression and ELS, but there is no evidence of the effects of trauma-focused psychotherapy on methylation alterations.Objective: We performed the first epigenome-wide association study to investigate methylation changes related to trauma-focused psychotherapies effects in TRD patients.Method: Thirty TRD patients assessed for ELS underwent trauma-focused psychotherapy, of those, 12 received trauma-focused cognitive behavioural therapy, and 18 Eye Movement Desensitization and Reprocessing (EMDR). DNA methylation was profiled with Illumina Infinium EPIC array at T0 (baseline), after 8 weeks (T8, end of psychotherapy) and after 12 weeks (T12 – follow-up). We examined differentially methylated CpG sites and regions, as well as pathways analysis in association with the treatment.Results: Main results obtained have shown 110 differentially methylated regions (DMRs) with a significant adjusted p-value area associated with the effects of trauma-focused psychotherapies in the entire cohort. Several annotated genes are related to inflammatory processes and psychiatric disorders, such as LTA, GFI1, ARID5B, TNFSF13, and LST1. Gene enrichment analyses revealed statistically significant processes related to tumour necrosis factor (TNF) receptor and TNF signalling pathway. Stratified analyses by type of trauma-focused psychotherapy showed statistically significant adjusted p-value area in 141 DMRs only for the group of patients receiving EMDR, with annotated genes related to inflammation and psychiatric disorders, including LTA, GFI1, and S100A8. Gene set enrichment analyses in the EMDR group indicated biological processes related to inflammatory response, particularly the TNF signalling pathway.Conclusion: We provide preliminary valuable insights into global DNA methylation changes associated with trauma-focused psychotherapies effects, in particular with EMDR treatment.

PMID:38362742 | DOI:10.1080/20008066.2024.2314913

Quintessence Int. 2024 Feb 16;0(0):0. doi: 10.3290/j.qi.b4984249. Online ahead of print.

ABSTRACT

The evidence base for the use of space maintainers (SMs) is relatively sparce despite being used for decades after the premature loss of primary molars. Thus, this study aims to increase the dental evidence base via investigating retrospectively the success rates of prefabricated fixed and removable space maintainers inserted from 2019 to 2021 and followed up until 02/2023 at a specialized university clinic and to identify reasons of any reported minor and major failure. Authors hypothesized that there is no significant difference in failure rates between fixed and removable SMs inserted after the premature loss of a single primary molar per quadrant. Patient’s digital records were searched yielding 645 space maintainers. After the application of inclusion criteria, 157 (67%) fixed prefabricated SMs in 112 children and 77 (33%) removable SMs in 61 children were analyzed for an average of 18.4 months (±9.5). Kaplan-Meier survival analysis with Mantel- Cox statistics showed an overall cumulative survival time of 31.6 months (SE=1.15, 95% CI=29.4-33.9). Major failure occurred significantly more in removable maintainers (n=40/67, 59.7%) mostly due to loss of the appliance compared to fixed space maintainers (n=27/67, 40.3%; P<0.001). The present study indicates that space maintainers were mainly placed in young children with high caries experience, where treatment was mostly possible using advanced behavior management. Fixed Space maintainers had a significantly lower failure rate than their removable counterpart. However, both require continual repairs, preservation or even replacement till the eruption of the permanent tooth.

PMID:38362703 | DOI:10.3290/j.qi.b4984249

Quintessence Int. 2024 Feb 16;0(0):0. doi: 10.3290/j.qi.b4984231. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate polymerization efficiency of different bulk-fill resin-based composites (BFRBCs) cured by monowave and polywave light curing units (LCUs), by assessment the degree of conversion (DC) and Vickers microhardness (VMH) at different depths.

METHOD AND MATERIALS: Two commercially available BFRBCs were used; Filtek One Bulk Fill Restorative (3M ESPE) (FOBF) and Tetric N-Ceram Bulk Fill (Ivoclar Vivadent) (TNBF). LCUs utilized were two light-emitting diodes (LEDs) LCUs; a monowave LED LCU (BlueLEX LD-105, Monitex) and a polywave LED LCU (Twin Wave GT-2000, Monitex). For each test, twenty cylindrical specimens (4 mm diameter, 4 mm thickness) were prepared from each BFRBC using a split Teflon mold. Ten specimens were light cured by monowave LCU and the other ten were light cured by polywave LCU according manufacturer’s recommendations. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) was used to assess DC. VMH tester was used to assess VMH. Statistical analysis was performed using three-way ANOVA and Tukey’s post-hoc tests (P <.05).

RESULTS: DC and VMH in BFRBC containing only camphorquinone as photo-initiator were similar when cured with either monowave or polywave LCU. However, BFRBC containing a combination of photo-initiators exhibited significantly higher DC and VMH when cured with polywave LCU. Although all groups showed statistically significant differences between top and bottom surfaces regarding DC and VMH, all of them showed bottom/top ratios >80% regarding DC and VMH.

CONCLUSION: Polywave LCU enhances polymerization efficiency of BFRBCs especially when the later containing a combination of photo-initiators, but does not prevent the use of monowave LCU.

PMID:38362702 | DOI:10.3290/j.qi.b4984231

Curr Rheumatol Rev. 2024 Feb 15. doi: 10.2174/0115733971290285240207080745. Online ahead of print.

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease. It has been identified that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids can be essential risk factors for developing complications such as upper gastrointestinal bleeding (UGIB).

OBJECTIVE: This study aimed to describe the safety profile of drugs used to treat RA focused in UGIB.

METHODS: A cross-sectional study of patients with RA between 2015 and 2021, a description of the population, and an evaluation of the relationship with UGIB through bivariate analysis and logistic regression.

RESULTS: Of 405 individuals, 16 presented UGIB (93.8% women, mean age was 65±13.6 years). No statistically significant differences were found regarding UGIB and medication use, except for the mean dose of corticosteroids. In the multivariate analysis, it was found that the presence of anemia in the last three months had an adjusted OR (ORA) of 16.1 (95% CI 2.74- 24.23) and higher HAQ values during the previous three months had an ORA of 6.17 (95% CI 1.79- 21.24).

CONCLUSION: This study found a low frequency of UGIB in patients with RA. More significant disability and anemia in the previous months were independently associated with UGIB. The low frequency of NSAID use in this population is noteworthy. In general, reasonable medication use related to this complication is recommended.

PMID:38362696 | DOI:10.2174/0115733971290285240207080745

Pharmacoepidemiol Drug Saf. 2024 Feb;33(2):e5750. doi: 10.1002/pds.5750.

ABSTRACT

PURPOSE: Outcome variables that are assumed to follow a negative binomial distribution are frequently used in both clinical and epidemiological studies. Epidemiological studies, particularly those performed by pharmaceutical companies often aim to describe a population rather than compare treatments. Such descriptive studies are often analysed using confidence intervals. While precision calculations and sample size calculations are not always performed in these settings, they have the important role of setting expectations of what results the study may generate. Current methods for precision calculations for the negative binomial rate are based on plugging in parameter values into the confidence interval formulae. This method has the downside of ignoring the randomness of the confidence interval limits. To enable better practice for precision calculations, methods are needed that address the randomness.

METHODS: Using the well-known delta-method we develop a method for calculating the precision probability, that is, the probability of achieving a certain width. We assess the performance of the method in smaller samples through simulations.

RESULTS: The method for the precision probability performs well in small to medium sample sizes, and the usefulness of the method is demonstrated through an example.

CONCLUSIONS: We have developed a simple method for calculating the precision probability for negative binomial rates. This method can be used when planning epidemiological studies in for example, asthma, while correctly taking the randomness of confidence intervals into account.

PMID:38362649 | DOI:10.1002/pds.5750