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Systematic Review and Meta-Analysis: Pharmacological and Nonpharmacological Interventions for Disruptive Mood Dysregulation Disorder

J Child Adolesc Psychopharmacol. 2024 Apr 29. doi: 10.1089/cap.2024.0013. Online ahead of print.

ABSTRACT

Objectives: Disruptive mood dysregulation disorder (DMDD) is a relatively new diagnosis that comprises severe, nonepisodic irritability and recurrent outbursts of emotional instability in adolescents. This meta-analysis examined the efficacy of the available pharmacological and nonpharmacological interventions for DMDD. Methods: Literature searches were conducted in July 2023. To determine relevant articles, 330 abstracts were reviewed, and 39 articles were identified for full review. A random-effects model was used for the meta-analysis, and a subgroup analysis was performed to assess the effects of study design and intervention type. Results: Eleven studies were reviewed, including six pharmacological and five nonpharmacological. Despite high heterogeneity in effects (I2 = 85%), we showed statistically significant improvements in irritability symptoms following intervention. We showed statistically significant enhancements in symptoms of irritability following the intervention. The subgroup analysis revealed that, compared with randomized controlled trials (RCTs), open trials showed significant improvements in irritability. In addition, drug intervention significantly improved irritability compared to nondrug interventions. Atomoxetine (ATX), optimized stimulants, and stimulants combined with other drugs and behavioral therapy effectively improved irritability. Conclusions: With research indicating potential benefits for irritability from a combination of pharmacological interventions and therapy, including ATX, stimulants in conjunction with antipsychotic or antidepressant medications, and cognitive-behavioral techniques such as Dialectical Behavior Therapy for Children. Future large-scale RCTs are essential to further explore and refine these treatment approaches, especially focusing on the efficacy of combining pharmacological with effective nonpharmacological to improve irritability and overall outcomes in this population.

PMID:38683583 | DOI:10.1089/cap.2024.0013

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Association of New-Onset Seizures With SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

JAMA Neurol. 2024 Apr 29. doi: 10.1001/jamaneurol.2024.0967. Online ahead of print.

ABSTRACT

IMPORTANCE: Seizures have been reported as an adverse effect of the SARS-CoV-2 vaccine. However, no study has answered the question of whether there is any association between seizures in the general population and COVID-19 vaccination.

OBJECTIVE: To evaluate the seizure incidence among SARS-CoV-2 vaccine recipients compared with those who received a placebo.

DATA SOURCES: A systematic search of MEDLINE (via PubMed), Web of Science, Scopus, Cochrane Library, Google Scholar, review publications, editorials, letters to editors, and conference papers, along with the references of the included studies from December 2019 to July 7, 2023.

STUDY SELECTION: Randomized clinical trials (RCTs) reporting seizure incidence with SARS-CoV-2 vaccination were included.

DATA EXTRACTION AND SYNTHESIS: This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework and used the Mantel-Haenszel method with random- and common-effect models. The risk of bias of the studies was assessed using the Cochrane assessment tool for RCTs.

MAIN OUTCOMES AND MEASURES: The outcome of interest was new-onset seizure incidence proportion compared among (1) SARS-CoV-2 vaccine recipients and (2) placebo recipients.

RESULTS: Six RCTs were included in the study. Results of the pooled analysis comparing the incidence of new-onset seizure between the 63 521 vaccine and 54 919 placebo recipients in the 28-day follow-up after vaccine/placebo injection showed no statistically significant difference between the 2 groups (9 events [0.014%] in vaccine and 1 event [0.002%] in placebo recipients; odds ratio [OR], 2.70; 95% CI, 0.76-9.57; P = .12; I2 = 0%, τ2 = 0, Cochran Q P = .74). Likewise, in the entire blinded-phase period after injection, with a median of more than 43 days, no significant difference was identified between the vaccine and placebo groups regarding incident new-onset seizure (13/43 724 events [0.03%] in vaccine and 5/40 612 [0.012%] in placebo recipients; OR, 2.31; 95% CI, 0.86-3.23, P > .99, I2 = 0%, τ2 = 0, Cochran Q P = .95).

CONCLUSIONS AND RELEVANCE: According to this systematic review and meta-analysis, there was no statistically significant difference in the risk of new-onset seizure incidence between vaccinated individuals and placebo recipients.

PMID:38683573 | DOI:10.1001/jamaneurol.2024.0967

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Perception of risk of HIV infection and knowledge about the use of antiretrovirals in prevention

Medicina (B Aires). 2024;84(2):249-255.

ABSTRACT

INTRODUCTION: Combined prevention (CP) is considered the key strategy against the HIV epidemic. The objective of the study was to evaluate the perception of risk of HIV infection and the knowledge about the use of antiretrovirals (ARV) for prevention, among patients who attend a Sexually Transmitted Infections (STI) clinic.

METHODS: A survey on personal data and perception of risk of HIV infection, knowledge about post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP), was administered to patients at the time of applying doses of penicillin for the treatment of syphilis, or when taking a blood sample for STI diagnosis, between May and December, 2022.

RESULTS: 100 persons were surveyed: 43 were under 25 years of age, 67 reported male sex-gender and 33 females. Thirty of 91 (33%) perceived they had had some risk of infection in their lives, 19 of them in the last year; 77/96 (80%) stated that they had no knowledge about PEP, and 82/100, about PrEP. Only 22 out of 100 responded that antiretrovirals could provide benefit in preventing HIV; 26 (60%) of the 43 patients <25 years of age, and 18 of the 57 ≥ 25 years (31.6%) responded they have had two or more sexual partners in the last year. No statistically significant differences were observed related to gender and age group.

DISCUSSION: The low perception of infection risk and knowledge about the use of antiretrovirals in HIV prevention, show the existing difficulties for the implementation of combined prevention (PEP-PrEP) in this population.

PMID:38683509

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Evaluation of PD-L1 expression and intratumoral lymphocytic infiltration in triple-negative invasive breast carcinoma

Medicina (B Aires). 2024;84(2):227-235.

ABSTRACT

INTRODUCTION: Triple negative breast cancer endophenotype (TNBC) is one of the least frequent and without therapeutic target; therefore we propose to study the correlation of PD-L1 immune checkpoint with the establishment of tumor microenvironment assessed by intratumoral stromal lymphocyte infiltration (TILS) and its importance in clinical practice.

METHODS: A retrospective case-control study was performed, with 31 cases of triple-negative infiltrating breast carcinoma and 57 unmatched controls of Luminal A, Luminal B and HER-2 endophenotype seen in one year. The following variables were evaluated: histologic type and grade, PD-L1 expression with clone 22C3, TILS, lymphovascular invasion, tumor size, lymph node involvement and metastasis. Statistical analysis was performed with the chi-square test and Spearman correlation coefficient test.

RESULTS: a statistically significant negative correlation was found between TILS and PD-L1 (rho – 0.106, p 0.025), indicating that the higher the expression of PD-L1, the lower the intratumoral lymphocytic infiltration. In the TILS B (10-40% TILS) and C (40-90% TILS) groups where there was a marked intratumoral inflammatory infiltrate, a greater number of patients were negative for PD-L1 (CPS <10) with 16 and 10 cases, respectively. For TNBC cases a negative association coefficient was identified (rho -0.378) with statistical significance (p 0.01).

DISCUSSION: The association between TNBC, TILS and PDL1 expression was established, which is important for the establishment of target therapies and the development of precision medicine.

PMID:38683507

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Knowledge and competences in hematological malignancies amongst radiation oncology residents in Germany-results from a national survey

Strahlenther Onkol. 2024 Apr 29. doi: 10.1007/s00066-024-02236-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Radiation oncology is a pivotal modality in the treatment of hematologic malignancies. To enable state-of-the-art patient care, structured education during residency is essential. However, given the lack of detailed data, the scope of educational opportunities available to trainees remains elusive. This prompted our group to perform a national survey amongst radiation oncology residents in Germany assessing the status quo of competences in the treatment of lymphoma and leukemia patients. Furthermore, areas of potential improvement were identified to further the goal of competence-based education for residents.

METHODS: A survey-based analysis was conducted to assess the knowledge and competence of radiation oncology residents in Germany regarding hematological malignancies. A decisive questionnaire covering demographics, self-assessment of competences, and areas for improvement was developed in adaption of a survey by the Association of Residents in Radiation Oncology and distributed amongst 1439 members of the German Society of Radiation Oncology. Responses were collected anonymously via an online survey tool and analyzed using descriptive statistics and chi-square tests.

RESULTS: A total of 59 complete and 22 partial responses were collected, yielding a 5.6% response rate. Participants’ competence varied, with notable experience gaps in pediatric cases, proton therapy, and large-field techniques like total-skin irradiation or pediatric total body irradiation. While participants felt confident in treatment planning and patient counseling, they showed deficiencies in the definition of the planning target volume for modern involved site radiotherapy. Resources for education included national and international guidelines, scientific reviews, and textbooks. Board-certified radiation oncologists and physicians from specialized lymphoma centers demonstrated higher overall competence levels.

CONCLUSION: This survey highlights the diversity of resident education regarding hematological malignancies in German radiation oncology programs. Knowledge gaps exist in key areas, including pediatric cases and specialized techniques. Competence-based education, interactive teaching formats, and rotations to specialized centers are potential strategies to address these gaps. The study contributes to the understanding of the federal educational landscape, underscoring the need for standardized and comprehensive training to ensure optimal patient care in hematological malignancies within the context of radiation oncology. Further research and collaborations are warranted to enhance training and expertise in this critical domain.

PMID:38683476 | DOI:10.1007/s00066-024-02236-4

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Effectiveness of Vortioxetine in Patients with Major Depressive Disorder Associated with Chronic Pain: An Observational Study in a Spanish Population

Pain Ther. 2024 Apr 29. doi: 10.1007/s40122-024-00597-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Chronic pain (CP) and depression/anxiety often coexist, worsening each other’s symptoms. Treating this comorbidity is challenging. Tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors are the first-line treatment options for this comorbidity, although sometimes they are not effective and/or well tolerated by patients, and there is little clinical evidence that selective serotonin reuptake inhibitors are useful for controlling CP. The antidepressant vortioxetine, with a multimodal mechanism that may help reduce pain, has proven clinical efficacy in patients with major depressive disorder (MDD). This study investigated vortioxetine’s effectiveness for MDD and CP in clinical practice.

METHODS: This was a 3-month, multicenter, prospective, open-label, non-interventional pharmacoepidemiologic study. Patients (n = 64) with MDD (9-item Patient Health Questionnaire [PHQ-9] score ≥ 15) and CP (visual analogue scale [VAS] score ≥ 4) were treated with vortioxetine for 3 months (initiated with 10 mg/day, with flexible dosing thereafter [5-20 mg/day]). VAS, Clinical Global Impression (CGI), and Patient Global Impression (PGI) scales were used at baseline and at 1 and 3 months. Brief Pain Inventory (BPI), PHQ-9 scale, and Satisfaction with Medicines Questionnaire (SATMED-Q) were used at baseline and at 3 months. Adverse Events (AEs) were recorded. Descriptive statistics, chi-square tests, and Student’s t-tests were used for paired data.

RESULTS: MDD patients showed a statistically significant improvement in VAS from baseline (mean [standard deviation (SD)]: 7.42 [0.69]) to 1 month (mean [SD]: 6.1 [0.81], P < 0.001) and 3 months (mean [SD]: 5.09 [1.26], P < 0.0001). Similarly, BPI and PHQ-9 scores showed significant improvement from baseline (mean [SD]: 6.20 [0.80] and 16.63 [1.47], respectively) to 3 months (mean [SD]: 4.73 [0.98] and 7.30 [2.60], P < 0.0001, respectively). Patients showed clinical improvement with CGI and PGI scales and reported being satisfied with the treatment in the SATMED-Q. A few mild EAs were registered.

CONCLUSION: Vortioxetine can relieve depressive and pain symptoms, with a good safety profile, in patients with MDD and CP.

PMID:38683448 | DOI:10.1007/s40122-024-00597-3

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Environmentally friendly silver nanoparticles synthesized from Verbascum nudatum var. extract and evaluation of its versatile biological properties and dye degradation activity

Environ Sci Pollut Res Int. 2024 Apr 29. doi: 10.1007/s11356-024-33424-5. Online ahead of print.

ABSTRACT

In the present study, green synthesis of silver nanoparticles (VNE-AgNPs) via Verbascum nudatum extract was carried out for the first time. The synthesized AgNPs were characterized by different spectral methods such as UV-vis, FTIR, XRD, TEM, and EDAX. According to TEM analyses, the average size range of AgNPs was 17-21 nm, and the dominant peaks in the 111°, 200°, 221°, and 311° planes in the XRD pattern indicated the Ag-NPs FCC crystal structure. FTIR data showed that VNE-AgNPs interacted with many reducing, capping, and stabilizing phytochemicals during green synthesis. VNE-AgNPs had higher antibacterial activity against S. aureus and E. coli bacterial strains with a maximum inhibition zone of 21 and 18 mm, respectively, than penicillin 5 IU, used as a positive control in the study. The cytotoxic effect of VNE-AgNPs appeared at a concentration of 50 µg/mL in L929 cells and 5 µg/mL in cancer (A549) cells. When the impact of VNE-AgNPs and C-AgNPs on inflammation was compared, it was found that VNE-AgNPs increased TNF-α levels (333.45 ± 67.20 ng/mg-protein) statistically (p < 0.05) more than TNF-α levels (256.92 ± 27.88 ng/mg-protein) in cells treated with C-AgNPs. VNE-Ag-NPs were found to have a degradation efficiency of 65% against methylene blue (MB) dye within 3 h.

PMID:38683425 | DOI:10.1007/s11356-024-33424-5

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Assessing the possible association between MTHFR (rs1801133) and GPx-1 (rs1050450) polymorphisms with the risk of type 2 diabetes, diabetic neuropathy, and diabetic retinopathy

Mol Biol Rep. 2024 Apr 29;51(1):583. doi: 10.1007/s11033-024-09519-0.

ABSTRACT

PURPOSE: Oxidative stress in chronic hyperglycemia could injure the tissues and onset of diabetes-related complications like retinopathy and neuropathy. This study investigates the association between methylenetetrahydrofolate reductase (MTHFR) and glutathione peroxidase (GPx) genetic variants with these complications.

METHODS: In this case-control study, 400 individuals, including 100 healthy subjects and 300 patients with type 2 diabetes mellitus (T2DM) in three subgroups: with retinopathy(n = 100), with neuropathy(n = 100), and without complication (n = 100) from West Iran, were studied. MTHFR (rs1801133) and GPx-1 (rs1050450) variants were identified by the PCR-RFLP method. The plasma levels of GPx activity, glutathione, malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative stress (TOS) were measured by chemical methods.

RESULTS: Higher BMI, TOS and MDA levels were observed in patients with neuropathy compared to other patients and controls. Diabetic patients with neuropathy had lower levels of glutathione (7.8 ± 4.5; P < 0.001), GPx activity (39.5 ± 8.5; P < 0.001), and TAC (703.1 ± 129.1; P = 0.0001) in comparison with other groups. The patients without complication and retinopathic patients had higher plasma levels of glutathione (12.2 ± 2.4; p = 0.02) and TAC (793.4 ± 124.6; P < 0.001), respectively. MTHFR TT genotype significantly correlated with lower levels of TOS (3.5 ± 1.1; P < 0.001) and OSI (0.0050 ± 0.001; P < 0.001). Subjects with the GPx-1 TT genotype had higher levels of MDA (6.8 ± 2.5; P = 0.02) and lower levels of TOS (3.7 ± 1.6; P < 0.001), which is statistically significant. TT genotype of MTHFR was associated with 3.9 fold (95% CI 1.04-4.76; P = 0.0436) increased risk of neuropathy. Also, GPx-1 CT genotype increased the risk of retinopathy [OR = 2.7 (95% CI = 1.38-5.44; P = 0.0039)].

CONCLUSION: The MTHFR TT genotype increased the risk of neuropathy in diabetic patients significantly. The GPx-1 CT genotype is related to increased retinopathy risk among diabetic patients. Both MTHFR and Gpx-1 TT genotypes were associated with higher BMI levels.

PMID:38683407 | DOI:10.1007/s11033-024-09519-0

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A Randomised Trial on the Effects of the Addition of Uterosacral Ligament Plication to Pectopexy Operation on Anatomical Restoration and Female Sexual Functions

Int Urogynecol J. 2024 Apr 29. doi: 10.1007/s00192-024-05771-x. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: The objective was to determine whether the addition of uterosacral ligament plication to pectopexy for pelvic organ prolapse increases anatomical improvement and female sexual functioning.

METHODS: This is a prospective randomised study. Forty patients who underwent laparoscopic pectopexy (LP) and laparoscopic pectopexy with uterosacral ligament plication (LPUSL) were included in the study. A total of 38 patients were evaluated in the study. Patients were assessed by the Pelvic Organ Prolapse Quantification (POP-Q) system and the patients who had symptomatic apical prolapse POP-Q ≥ II were included in the study. Patients were evaluated preoperatively and postoperatively at the 3rd, 6th and 12th month, with respect to anatomical changes as well as sexual function.

RESULTS: A statistically significant difference was found when the preoperative C points was compared with the C points postoperatively, at 3rd, 6th and 12th months in both the LP and LPUSL groups (p < 0.001). Additionally, there were statistically significant difference between the LP and LPUSL groups in terms of C and Aa points at the 6th and 12th postoperative months in favour of the LPUSL group (p = 0.007, p = 0.005 respectively). There was also a statistically significant difference when Ba points were compared between the two groups at the 12th postoperative month, in favour of the LPUSL group (p = 0.002). There were no statistically significant differences between the groups with respect to the variables of the Female Sexual Function Index. Additionally, all parameters were significantly better in both groups at the 3rd and 12th months than the preoperative values in post hoc analysis; only desire also had a significant improvement between the 3rd and 12th months in the LPUSL group in post hoc analysis.

CONCLUSION: Pectopexy operation seems to be a successful surgical approach as an alternative to sacrocolpopexy. The addition of uterosacral ligament plication to pectopexy operation improves the anatomical restoration more drastically than with LP on its own. Moreover, either LP or LPUSL has improved the majority of sexual function indices.

PMID:38683391 | DOI:10.1007/s00192-024-05771-x

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Exploring the feasibility of robotic liver resection in a limited resource setting

J Robot Surg. 2024 Apr 29;18(1):187. doi: 10.1007/s11701-024-01901-1.

ABSTRACT

The transition from open hepatectomy to minimally invasive techniques has reduced morbidity and mortality. However, laparoscopic liver resection (LLR) requires substantial expertise. Robotic liver resection (RLR) combines minimal invasiveness with open surgical precision. It may facilitate complex procedures without the learning required for LLR. We evaluated RLR outcomes in a limited resource setting and assessed its efficacy and practicality. This retrospective study analyzed 67 robotic hepatectomies conducted from 2020 to 2023. Demographic, perioperative factors, and surgical outcomes were analyzed. Major hepatectomies were required in 46/67 (68.7%) patients who underwent RLR. No open conversions, 30-day mortalities, or readmissions occurred. Complications occurred in 7.4% of patients; major complications occurred in 5.9%. Learning curve analysis showed a negative correlation between operation sequence and operative time. Effective use of robotic technology combined with the expertise of well-trained surgeons facilitates successful execution of RLR with feasible surgical outcomes, even at smaller centers.

PMID:38683380 | DOI:10.1007/s11701-024-01901-1