Tag: nevin manimala

Twin Res Hum Genet. 2024 Mar 18:1-11. doi: 10.1017/thg.2024.4. Online ahead of print.

ABSTRACT

In this cohort profile article we describe the lifetime major depressive disorder (MDD) database that has been established as part of the BIObanks Netherlands Internet Collaboration (BIONIC). Across the Netherlands we collected data on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lifetime MDD diagnosis in 132,850 Dutch individuals. Currently, N = 66,684 of these also have genomewide single nucleotide polymorphism (SNP) data. We initiated this project because the complex genetic basis of MDD requires large population-wide studies with uniform in-depth phenotyping. For standardized phenotyping we developed the LIDAS (LIfetime Depression Assessment Survey), which then was used to measure MDD in 11 Dutch cohorts. Data from these cohorts were combined with diagnostic interview depression data from 5 clinical cohorts to create a dataset of N = 29,650 lifetime MDD cases (22%) meeting DSM-5 criteria and 94,300 screened controls. In addition, genomewide genotype data from the cohorts were assembled into a genomewide association study (GWAS) dataset of N = 66,684 Dutch individuals (25.3% cases). Phenotype data include DSM-5-based MDD diagnoses, sociodemographic variables, information on lifestyle and BMI, characteristics of depressive symptoms and episodes, and psychiatric diagnosis and treatment history. We describe the establishment and harmonization of the BIONIC phenotype and GWAS datasets and provide an overview of the available information and sample characteristics. Our next step is the GWAS of lifetime MDD in the Netherlands, with future plans including fine-grained genetic analyses of depression characteristics, international collaborations and multi-omics studies.

PMID:38497097 | DOI:10.1017/thg.2024.4

Saudi Pharm J. 2024 Apr;32(4):102022. doi: 10.1016/j.jsps.2024.102022. Epub 2024 Mar 6.

ABSTRACT

BACKGROUND: Single nucleotide polymorphisms in the gene encoding proteins involved in mercaptopurine metabolism can influence drug efficacy and safety. This study aims to assess clinical pharmacists’ knowledge about mercaptopurine-related genes and their polymorphisms and investigate their attitudes, perceptions, and beliefs about the need for and importance of pharmacogenetic testing for mercaptopurine.

METHODS: A cross-sectional descriptive study was conducted among oncology/hematology clinical pharmacists in Saudi Arabia using an online-questionnaire developed by experts in the field. The questionnaire consists of four-sections exploring clinical pharmacists’ knowledge, attitudes, perceptions, and beliefs about the importance of gene testing and genes polymorphism when prescribing mercaptopurine. Descriptive statistics were used to analyze the data in the study.

RESULTS: A total of 41 oncology/hematology clinical pharmacists responded to the survey invitation. Almost half of them had more than 10 years of work experience, but only 17 % of them received formal training in pharmacogenetics. The overall level of knowledge about pharmacogenetics among participants was low, with a mean score of 2.8 points (1.7) out of 8 items. However, around 76 % agreed that it is important to perform pharmacogenetic screening prior to prescribing mercaptopurine, and almost 93 % state that it will influence their dosage recommendation. Most of the participants had a good perception (95.1 %) of their role in genetic testing for medication selection, dosing, and monitoring; however, about 10 % of surveyed pharmacists reported not being completely responsible about recommending pharmacogenetic testing. The surveyed pharmacists had a good belief in the importance of pharmacogenetic testing and their overall attitude was positive toward the use of pharmacogenetic testing, with emphasis on the importance of training on the proper assessment and interpretation of pharmacogenetic tests.

CONCLUSIONS: Pharmacists demonstrated good perception and positive attitude toward pharmacogenetic testing, despite the low level of knowledge and limited formal training. Thus, more attention to developing national guidelines on pharmacogenetic testing is warranted to ensure successful pharmacogenetic testing implementation.

PMID:38497085 | PMC:PMC10940172 | DOI:10.1016/j.jsps.2024.102022

Sex Med Rev. 2024 Mar 17:qeae012. doi: 10.1093/sxmrev/qeae012. Online ahead of print.

ABSTRACT

INTRODUCTION: Erectile dysfunction (ED) is a common condition that affects millions worldwide. Patients and urologists alike are seeking alternative therapies that can provide long-lasting results in the treatment of ED. This review provides a comprehensive overview of restorative treatments available for ED, such as platelet-rich plasma, stem cell therapy, and shockwave therapy.

OBJECTIVE: The aim of this narrative review is to provide a primer for urologists and general practitioners on the basics of implementing ED restorative therapies in their practice.

METHODS: The PubMed, MEDLINE, and Google Scholar databases were searched for articles in the English language through August 31, 2023, that included key terms such as “erectile dysfunction,” “restorative therapy,” “shockwave therapy,” “platelet-rich plasma,” “stem cell therapy,” and “stromal vascular fraction.” Reference lists of selected studies were manually reviewed to find articles not identified by the initial database search.

RESULTS: Shockwave therapy has demonstrated effectiveness in treating ED, with devices like the Medispec ED1000 and Storz Duolith showing statistically significant improvements in patient scores for International Index of Erectile Function (IIEF)-Erectile Function scores in clinical trials. In reported studies of platelet-rich plasma injections, a substantial percentage of patients reached a minimal clinically important difference in the IIEF-Erectile Function scale after treatment. Studies of ED treatment with stem cell therapy, while limited and with small sample sizes, have demonstrated encouraging improvements in patient scores for the abridged 5-item version of the IIEF after treatment.

CONCLUSION: Shockwave, platelet-rich plasma, and stem cell therapies are important, novel, noninvasive restorative treatments for ED that can provide relief for patients wishing to avoid a more invasive approach. While these therapies have shown promising results in clinical trials, more research is required to establish them as standardized and efficacious options in the management of ED.

PMID:38494449 | DOI:10.1093/sxmrev/qeae012

Hematol Transfus Cell Ther. 2024 Mar 14:S2531-1379(24)00056-7. doi: 10.1016/j.htct.2024.02.013. Online ahead of print.

ABSTRACT

BACKGROUND: Sickle cell disease (SCD) comprises a heterogeneous group of inherited hemolytic disorders that increases the risk of maternal and perinatal complications due to chronic systemic inflammatory response, endothelial damage and vaso-occlusion. The contribution of genotypes to the severity of outcomes during pregnancy is not completely established.

METHODS: A retrospective study of medical charts was performed to compare maternal and perinatal outcomes in Hb SS, Hb SC disease and sickle-beta thalassemia (Hb Sβ) pregnancies followed at a high-risk antenatal care unit over a 6-year period. A descriptive analysis of morphological findings was performed of the placenta when pathology reports were available.

RESULTS: Sixty-two SCD pregnant women [25 Hb SS (40 %), 29 Hb SC (47 %) and 8 Hb Sβ (13 %)] were included. Overall, SCD was associated with maternal complications (77 %), preterm birth (30 %), cesarean section (80 %) and a need of blood transfusion. In general there were no statistically significant differences between genotypes. The only significant difference was the hemoglobin level at first antenatal care visit which was lower for the homozygous genotype (7.7 g/dL) compared to Hb SC and Hb Sβ (9.7 g/dL and 8.4 g/dL, respectively; p-value = 0.01). Ten of 15 evaluated placentas showed abnormal morphological findings CONCLUSION: SCD, regardless of the underlying genotype, is associated with increased adverse maternal and perinatal outcomes and placental abnormalities associated with maternal vascular malperfusion.

PMID:38494406 | DOI:10.1016/j.htct.2024.02.013

Parkinsonism Relat Disord. 2024 Mar 9:106076. doi: 10.1016/j.parkreldis.2024.106076. Online ahead of print.

ABSTRACT

INTRODUCTION: Progressive supranuclear palsy (PSP) is characterized by pathology prominently in the basal ganglia, the tegmentum of the brainstem, and the frontal cortex. However, pathology varies according to clinical features. This study aimed to statistically verify the correspondence between the clinical and pathological subtypes of PSP.

METHODS: We identified patients with a pathological diagnosis of PSP and classified the eight clinical subtypes of the Movement Disorders Society criteria for the clinical diagnosis of PSP (MDS-PSP criteria) into the Richardson, Akinesia, and Cognitive groups. We used anti-phosphorylated tau antibody immunostaining to semi-quantitatively evaluate neurofibrillary tangles (NFTs) and coiled bodies/threads (CB/Ths) in the globus pallidus, subthalamic nucleus, and midbrain tegmentum. In the frontal cortex, tufted astrocytes (TAs) and CB/Ths were assessed on a 3-point scale. We compared the pathology among the three groups, recorded the phenotypes ranked the second and lower in the multiple allocation extinction rule and examined whether the pathology changed depending on applying each phenotype.

RESULTS: The Richardson group exhibited severe NFTs and CB/Ths in the midbrain tegmentum. The Akinesia group showed severe NFTs in the globus pallidus. The Cognitive group had severe TAs and CB/Ths in the frontal cortex. TAs and CB/Ths in the frontal cortex correspond to behavioral variant frontotemporal dementia, and supranuclear vertical oculomotor palsy.

CONCLUSION: These clinical symptoms may reflect the distribution of tau pathologies in PSP.

PMID:38494398 | DOI:10.1016/j.parkreldis.2024.106076

Burns. 2024 Mar 1:S0305-4179(24)00066-4. doi: 10.1016/j.burns.2024.02.029. Online ahead of print.

ABSTRACT

BACKGROUND: Studies suggest increased occurrence of cancer in persons who have experienced a burn injury with hospital admission.

OBJECTIVE: To determine the incidence of cancer among those hospitalised for burn injuries in Scotland compared with a similar group without a history of burn injury hospitalisation.

METHOD: A retrospective cohort design was used to compare cancer (ICD10 C00-97, excluding C44) incidence in two groups: 6805 burn injury patients discharged from Scottish hospitals between 2009 and 2019, and 25,946 subjects from the general population who were matched to burn patients by sex, year of birth, and degree of social deprivation. Cancer incidence was identified from the Scottish cancer registry. Cox proportional hazard regression was used to model time to cancer incidence adjusting for age, sex, degree of deprivation and presence of a comorbidity. Cancer risk was presented as standardised incidence ratios (SIRs) and hazard ratios (HR).

RESULTS: We found a higher prevalence of pre-existing conditions, particularly alcohol abuse among patients with burns. Pre-existing cancers were more common in the burn cohort (3.5%) than the comparison group (1.7%) and were excluded from further analysis. Over a median follow-up of 4-5 years, a total of 236 (3.5%) burn patients and 969 (3.7%) persons in the comparison group were diagnosed with cancer. At 0-6 months the cancer SIR for burn patients was 1.88 95% CI (1.40-2.52). After excluding the first six months of follow-up, the overall incidence of cancer was marginally elevated in burn patients (SIR 1.04, 95% CI 0.90-1.19, p = 0.62) and not statistically different from the incidence in comparison subjects (adjusted HR 1.03, 95% CI 0.88-1.21, p = 0.71).

CONCLUSIONS: Patients that suffer burn injury have a higher incidence of cancer than the general population and a group matched by age, sex and degree of deprivation. A higher incidence of adverse health-related behaviours such as smoking, alcohol use and pre-existing health conditions among many patients that suffer a burn most likely explain this observed increase. Any persisting inflammatory or immune dysfunction following burn injury is unlikely to account for the increase in cancers in this study.

PMID:38494397 | DOI:10.1016/j.burns.2024.02.029

Burns. 2024 Mar 2:S0305-4179(24)00063-9. doi: 10.1016/j.burns.2024.02.034. Online ahead of print.

ABSTRACT

The main objective of this study is to analyse the association between Quality of Life (QOL), Emotional Symptomology and perceived Emotional Intelligence (EI) in burn patients. Additionally, it is intended determine the predictor models of QOL, and confirm the mediating effect of emotional symptomology between QOL and perceived EI. This is a transversal study developed in the Hospital da Prelada, Porto, Portugal, with a sample of 92 patients that were hospitalized in the Burn Unit and the Reconstructive Plastic Surgery Service. The assessment protocol consisted of a sociodemographic and clinical data sheet. To assess the perception of QOL of the burn patient it was used the Burn Specific Health Scale – Revised (BSHS-R), the emotional symptomology was measured by the Brief Symptom Inventory (BSI) and Trait Met-Mood Scale-24 (TMMS) was used to assess Emotional Intelligence (EI). The cross-sectional and correctional data were analysed through descriptive statistics, correlations, regressions and simple mediations. The results obtained suggest significant associations between QOL, perceived EI and Emotional Symptomology in burn patients. The results of the predictor models of the QOL domains encompass the Positive Symptom Distress Index (PSDI of Emotional Symptomology), where the total variance is explained mainly by the models of QOL Affect and Body Image 46% and Treatment 31%. The mediating effect of the PSDI in the relationship between QOL in the Affect and Body Image dimension and the Mood Repairs (MR) was also tested, having proved to have a total mediation (the Mood Repairs loses its contribution in the QOL model when the PSDI variable is introduced). This study underscores the importance of perceived Emotional Intelligence and its association with the burn impact in the different dimensions of QOL of the patients. The intention of this study is to alert health professionals for patient support in the search for strategies that aim for positive adaptation which promotes QOL and emotional adjustment of burn patients to their new condition.

PMID:38494394 | DOI:10.1016/j.burns.2024.02.034

Eur Urol. 2024 Mar 16:S0302-2838(24)00058-7. doi: 10.1016/j.eururo.2024.01.021. Online ahead of print.

ABSTRACT

Nearly all men with metastatic hormone-sensitive prostate cancer treated with intermittent androgen deprivation therapy (ADT) experience recurrence within 6 mo of testosterone recovery. We conducted a single-arm phase 2 trial to evaluate whether addition of dual androgen receptor pathway inhibitors (ARPIs) and metastasis-directed stereotactic body radiotherapy (SBRT) to intermittent ADT improves recurrence rates for men with between one and five nonvisceral, extrapelvic metastases on prostate-specific membrane antigen positron emission tomography/computed tomography after prior radical prostatectomy. Patients received 6 mo of androgen annihilation therapy (AAT; leuprolide, abiraterone acetate plus prednisone, and apalutamide) and metastasis-directed SBRT. The primary endpoint was the percentage of patients with prostate-specific antigen (PSA) <0.05 ng/ml 6 mo after testosterone recovery (≥150 ng/dl), with the study powered to detect an improvement from 1% to 12%. We enrolled 28 men between March 2021 and June 2022. Median follow-up was 20 mo (interquartile range 16-22). Twenty-six patients (93%) completed SBRT with 6 mo of hormone therapy, of whom six discontinued at least one ARPI; two patients withdrew prematurely. At 6 mo after testosterone recovery, PSA was maintained at <0.05 ng/ml in 13/26 patients (50%, 95% confidence interval 32-67%). Rates of grade 2 and 3 AAT toxicity were 21% and 21%. The results confirm that addition of metastasis-directed SBRT to highly potent systemic therapy can maintain low PSA after testosterone recovery, although further studies are needed to clarify the optimal systemic therapy regimen. PATIENT SUMMARY: We tested a combination of intensified hormone therapy (called androgen annihilation therapy) and radiotherapy targeted at metastases in men with recurrence of metastatic prostate cancer. We found that half of patients were recurrence-free 6 months after their testosterone level recovered, and that less than a quarter of patients experienced a severe drug-related side effect. Overall, this appears to be an effective therapy with acceptable side effects. This trial is registered on ClinicalTrials.gov as NCT03902951.

PMID:38494380 | DOI:10.1016/j.eururo.2024.01.021

Pain Manag Nurs. 2024 Mar 16:S1524-9042(24)00011-0. doi: 10.1016/j.pmn.2024.02.002. Online ahead of print.

ABSTRACT

OBJECTIVES: Comparison of the effects of dry heat versus moist heat therapy modalities on the intensity of pain and wound healing of episiotomies among postnatal women.

DESIGN: A Systematic review and meta-analysis of controlled trials.

DATA SOURCES: Six databases searched for original articles using relevant keywords until September 10, 2023, without time or language restrictions.

REVIEW/ANALYSIS METHODS: All analyses employed Comprehensive Meta-Analysis (CMA) V.2. The measure of heterogeneity was computed using Cochran’s Q-value. The I² index was employed to quantitatively demonstrate heterogeneity. Statistical significance was reported for P-values <0.05 and I²>50%.

RESULTS: Four quasi-experimental and three randomized controlled trials (RCTs) studies with moderate-to-good quality evidence met inclusion criteria. On the third to fifth day after the intervention in the dry heat group, the amount of pain was significantly lower than in the group that used moist heat [MD (95% CI) =-1.395 (-2.374, -0.416), P=0.005]. The use of a hair dryer significantly reduced pain (P=0.029), but an infrared lamp did not significantly reduce pain compared to moist heat (P=0.064). As compared to the moist heat group, the women using dry heat experienced better wound healing to the extent of 2.002 units of the REEDA (Redness, Edema, Ecchymosis, Discharge, Approximation) scale, which was statistically significant [MD (95% CI) = -2.002 (-2.785, -1.219), P<0.001].

CONCLUSION: Compared to sitz baths, dry heat reduced pain and improved episiotomy site healing in postnatal women. Therefore, dry heat, especially hair dryers, is suggested as a non-pharmacological strategy inside maternity hospitals, but additional targeted, high-quality trials are needed.

PMID:38494347 | DOI:10.1016/j.pmn.2024.02.002

Clin Neuropsychol. 2024 Mar 17:1-23. doi: 10.1080/13854046.2024.2328881. Online ahead of print.

ABSTRACT

Objective: The present study aimed to examine the impact of lifetime blast exposure (LBE) on neuropsychological functioning in service members and veterans (SMVs). Method: Participants were 282 SMVs, with and without history of traumatic brain injury (TBI), who were prospectively enrolled in a Defense and Veterans Brain Injury Center (DVBIC)-Traumatic Brain Injury Center of Excellence (TBICoE) Longitudinal TBI Study. A cross-sectional analysis of baseline data was conducted. LBE was based on two factors: Military Occupational Speciality (MOS) and SMV self-report. Participants were divided into three groups based on LBE: Blast Naive (n = 61), Blast + Low Risk MOS (n = 96), Blast + High Risk MOS (n = 125). Multivariate analysis of variance (MANOVA) was used to examine group differences on neurocognitive domains and the Minnesota Multiphasic Personality Inventory-2 Restructured Form. Results: There were no statistically significant differences in attention/working memory, processing speed, executive functioning, and memory (Fs < 1.75, ps > .1, η_p²s < .032) or in General Cognition (Fs < 0.95, ps > .3, η_p²s < .008). Prior to correction for covariates, lifetime blast exposure was related to Restructured Clinical (F(18,542) = 1.77, p = .026, η_p² = .055), Somatic/Cognitive (F(10,550) = 1.99, p = .033, η_p² = .035), and Externalizing Scales (F(8,552) = 2.17, p = .028, η_p² = .030); however, these relationships did not remain significant after correction for covariates (Fs < 1.53, ps > .145, η_p²s < .032). Conclusions: We did not find evidence of a relationship between LBE and neurocognitive performance or psychiatric symptoms. This stands in contrast to prior studies demonstrating an association between lifetime blast exposure and highly sensitive blood biomarkers and/or neuroimaging. Overall, findings suggest the neuropsychological impact of lifetime blast exposure is minimal in individuals remaining in or recently retired from military service.

PMID:38494345 | DOI:10.1080/13854046.2024.2328881