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Nevin Manimala Statistics

Systemic and Tumor-directed Therapy for Oligorecurrent Metastatic Prostate Cancer (SATURN): Primary Endpoint Results from a Phase 2 Clinical Trial

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

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Effectiveness of Dry Heat Versus Moist Heat Modalities on Pain Intensity and Wound Healing of Episiotomies Among Postnatal Women: A Systematic Review and Meta-Analysis

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

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Lifetime blast exposure is not related to cognitive performance or psychiatric symptoms in US military personnel

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, ηp2s < .032) or in General Cognition (Fs < 0.95, ps > .3, ηp2s < .008). Prior to correction for covariates, lifetime blast exposure was related to Restructured Clinical (F(18,542) = 1.77, p = .026, ηp2 = .055), Somatic/Cognitive (F(10,550) = 1.99, p = .033, ηp2 = .035), and Externalizing Scales (F(8,552) = 2.17, p = .028, ηp2 = .030); however, these relationships did not remain significant after correction for covariates (Fs < 1.53, ps > .145, ηp2s < .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

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Nevin Manimala Statistics

EXPRESS: The relationship of the methylation status and polymorphism of glucocorticoid receptor gene (NR3C1) with attempted suicide or non-suicidal self-injury patients in schizophrenia

J Investig Med. 2024 Mar 17:10815589241242715. doi: 10.1177/10815589241242715. Online ahead of print.

ABSTRACT

We aim to investigate the methylation of NR3C1 gene promotor and NR3C1 BclI polymorphism in schizophrenia (SCZ) patients with attempted suicide or non-suicidal self-injury (NSSI). A sample of 112 patients with SCZ were included in the study. SCID-I was used to confirm the diagnosis according to DSM-IV-TR criteria. The patients were evaluated by data forms that had sociodemographic, suicidal behavior, and NSSI information. Methylation-specific PCR was used to identify the methylation of the NR3C1 gene. The analysis of the BclI polymorphism of the NR3C1 gene was evaluated by using the PCR-RFLP. Our results revealed that although the NR3C1 gene methylation was not statistically significantly different, there was a significant difference in NR3C1 genotype distribution between the SCZ groups with and without attempted suicide. SCZ patients carrying the CC genotype had a lower risk of attempted suicide (OR: 0.421; 95% Cl: 0.183-0.970; p=.040), while having the GG genotype in SCZ patients was associated with a higher risk of attempted suicide (OR: 3.785; 95% Cl: 1.107-12.945; p=.042). Additionally, due to NSSI in SCZ patients, there were no significant differences in NR3C1 gene methylation and NR3C1 genotype distribution between the groups. We propose that the NR3C1 BclI polymorphism may be associated with attempted suicide in Turkish patients diagnosed with SCZ.

PMID:38494341 | DOI:10.1177/10815589241242715

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Elucidating the evolution of monkeypox virus genomes through phylo-geo-network and haplogroup analysis

J Genet Eng Biotechnol. 2024 Mar;22(1):100346. doi: 10.1016/j.jgeb.2023.100346. Epub 2024 Jan 28.

ABSTRACT

BACKGROUND: As the world settles down from the COVID-19 pandemic, many countries are faced with an unexpected outbreak of monkeypox infection. Monkeypox is a zoonotic disease caused by monkeypox virus (MPXV), which is an enveloped, double stranded DNA virus belonging to the Poxviridae family. Presently, we construct and analyze the phylo-geo-network and the corresponding haplogroups. Presently, we performed the haplogroup analysis with their defining mutations and phylogenetic lineage study along with geographical distributions with the aim to understand the evolutionary path of the MPXV across the world.

RESULTS: Information about 719 full length genomes of MPXV were collected from GISAID repository and the sequences extracted from NCBI. The alignment of 719 MPXV genomes and their subsequent analysis revealed a total of 1530 segregating sites of which 330 were parsimony informative (PI) sites. The variations had a positive value of Tajima’s D statistic indicating some mutations being prevalent and hence balancing selection. A total of 39 haplogroups were observed in the phylo-geo-network and their defining mutations along with the evolutionary path has been discussed. The phylo-geo-network revealed the nodal haplogroup is represented by GISAID ID 13889450, haplogroup A1, an isolate from Germany, having a total of 296 identical sequences in the study incident across 22 countries. The localized evolution is highlighted by country specific sequences and haplogroups. USA had a total of 58 genomes and 13 haplogroups as compared to Peru (89 genomes, 7 haplogroups) and Germany (26 genomes, 6 haplogroups).

CONCLUSIONS: The evolution of MPXV can be happening in a localized manner and hence accumulation of variations in the MPXV genomes needs to be monitored in order to be prepared for any possible threats.

PMID:38494259 | DOI:10.1016/j.jgeb.2023.100346

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Assessment of vitamin D status and vitamin D receptor polymorphism in Egyptian children with Type 1 diabetes

J Genet Eng Biotechnol. 2024 Mar;22(1):100343. doi: 10.1016/j.jgeb.2023.100343. Epub 2024 Jan 22.

ABSTRACT

BACKGROUND: The endocrine system of vitamin D regulates about 3 % of the human genome. Vitamin D exerts its actions via a nuclear vitamin D receptor (VDR) which in turn regulates insulin secretion from the pancreas. VDR gene polymorphisms could have an impact on how autoimmune illnesses like Type 1 diabetes mellitus (T1DM) develop. We aimed to explore the relation between T1DM and VDR gene polymorphisms in Egyptian diabetic children and their siblings.

METHODS: Enzyme-linked immunosorbent assay was used to quantify 25(OH) vitamin D in the study, which had 179 participants (group 1 = 85 diabetic children, group 2 = 57 siblings of the patients, group 3 = 37 healthy controls). Real-time polymerase chain reaction (RT-PCR) was used to analyze the genotyping of the VDR gene polymorphisms Apa-I (rs7975232), Fok-I (rs2228570), Taq-I (rs731236) and Bsm-I (rs1544410).

RESULTS: The mean serum 25(OH) vitamin D levels was significantly lower in T1DM patients (14.99 ± 9.24 ng/mL) and siblings (16.31 ± 7.96 ng/mL) compared to the controls (19.48 ± 7.42 ng/mL) (p = 0.031). The genotypes distribution of VDR Fok-I (rs2228570) and Bsm-I (rs1544410) polymorphisms showed a significant difference between patients, siblings and controls as P = 0.001 and 0.026 respectively, while the VDR ApaI and TaqI polymorphisms did not. FokI-A allele frequency was significantly lower in T1DM patients and siblings than in controls (p < 0.001). FokI-AA genotype had a statistical significant higher vitamin D levels than other genotypes with p value of 0.024.

CONCLUSION: Our study found that T1DM children had lower vitamin D levels, and VDR FokI and BsmI gene polymorphisms were linked to T1DM in Egyptian children. Determining the relationship between vitamin D levels and VDR polymorphisms, particularly the FokI and other genetic analyses may aid in the early diagnosis of T1DM in children.

PMID:38494252 | DOI:10.1016/j.jgeb.2023.100343

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Ramadan fasting following laparoscopic sleeve gastrectomy: a prospective online survey cohort study in Egypt

J Minim Invasive Surg. 2024 Mar 15;27(1):33-39. doi: 10.7602/jmis.2024.27.1.33.

ABSTRACT

PURPOSE: This study aims to explore the feasibility and implications of Ramadan fasting for patients who have undergone laparoscopic sleeve gastrectomy (LSG), assessing impacts on hydration, nutrient intake, weight management, and gastrointestinal symptoms.

METHODS: A prospective online survey was conducted among 218 LSG patients and 83 control individuals with obesity who had not undergone surgery. Participants were surveyed before and after Ramadan, providing data on fasting practices, hunger and satiety levels, fluid and nutrient intake, and the occurrence of gastrointestinal symptoms. Statistical analysis was used to compare outcomes between fasting and non-fasting periods and between LSG patients and control participants.

RESULTS: A total of 70.2% of LSG patients completed the entire month of Ramadan fasting, with a significant correlation found between the duration post-surgery and the ability to fast. Fasting LSG patients reported decreased hunger, increased satiety, and significant reductions in fluid and nutrient intake during Ramadan. Weight loss was reported in 90.8% of fasting patients, with an average total weight loss of 7.2%. Gastrointestinal symptoms were mild and manageable.

CONCLUSION: The majority of LSG patients can successfully fast during Ramadan with appropriate precautions, including adequate fluid and protein intake. The study highlights the need for patient education and tailored nutritional guidance to ensure safe and effective fasting post-LSG. In order to fast for the entire month, patients may be advised to consider postponing surgery for a few months after Ramadan, avoid overeating during non-fasting hours, and ensure sufficient fluid consumption and protein intake during fasting.

PMID:38494184 | DOI:10.7602/jmis.2024.27.1.33

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Comparison between liquid skin adhesive and wound closure strip for skin closure after subcuticular suturing in single-port laparoscopic appendectomy: a single-center retrospective study in Korea

J Minim Invasive Surg. 2024 Mar 15;27(1):14-22. doi: 10.7602/jmis.2024.27.1.14.

ABSTRACT

PURPOSE: This study was performed to evaluate the safety and feasibility of skin adhesives and to compare postoperative and cosmetic outcomes after wound closure in single-port laparoscopic appendectomy (SPLA) between skin adhesives and steri-strips.

METHODS: This was a single-center retrospective study. We included 22 and 47 patients in whom skin adhesive and steri-strips were used respectively, for skin closure after subcuticular suturing in SPLA between August 2014 and 2020. The patient scar assessment questionnaire (PSAQ) was completed postoperatively to assess postoperative cosmetic outcomes.

RESULTS: On the postoperative day, patients in whom skin adhesive was used had significantly lower numeric rating scores than in whom steri-strips were used (2.8 ± 0.8 vs. 3.9 ± 0.8, p < 0.001). The frequency of analgesic administration within 24 hours and between 24 and 48 hours after surgery was significantly lower in the skin adhesive group compared to the wound closure strip group (1.4 ± 0.8 vs. 2.7 ± 1.2, p = 0.013 and 0.2 ± 0.4 vs. 0.7 ± 0.9, p = 0.002, respectively). In the PSAQ, “satisfaction with appearance” and “satisfaction with symptoms” subitem scores were significantly lower in patients in whom skin adhesive was used (11.3 ± 3.0 vs. 15.1 ± 4.5, p = 0.006 and 6.5 ± 1.8 vs. 9.5 ± 3.3, p = 0.003), whereas, “appearance” and “consciousness” subitems revealed no statistically significant differences between the groups.

CONCLUSION: Liquid skin adhesive closures seem to be safe and feasible and cause less postoperative pain, resulting in greater patient satisfaction with postoperative scars than wound closure strip closure after subcuticular suturing in SPLA.

PMID:38494182 | DOI:10.7602/jmis.2024.27.1.14

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Association between hypertension and pressure ulcer: A systematic review and meta-analysis

Int Wound J. 2024 Mar;21(3):e14829. doi: 10.1111/iwj.14829.

ABSTRACT

This review aims to systematically evaluate the association between hypertension and pressure ulcer (PU). PubMed, Embase, Web of Science, and Cochrane Library were searched for studies from their inception until September 12, 2023. Literature search, data extraction, and quality assessment were conducted independently by two researchers. The random-effects model was used to calculate the combined odds ratio (OR) and corresponding 95% confidence interval (CI) of hypertension in patients with PU; subgroup analyses were performed to explore the source of between-study heterogeneity; sensitivity analysis was used to test the robust of the combined result; and funnel plot and Egger’s test were used to assess the publication bias. Finally, a total of 19 studies with 564 716 subjects were included; the overall pooled result showed no significant association between hypertension and risk of developing PU (OR = 1.15, 95% CI = 0.90-1.47, p = 0.27); and the sensitivity analysis and publication bias analysis showed robust of the combined result. Subgroup analysis indicated a significant association between hypertension and PU when the primary disease was COVID-19 (OR = 1.73, 95% CI = 1.35-2.22, p < 0.0001). No association between hypertension and PU was seen in subgroup analysis on the patient source and study design. In sum, there is no significantly statistical association between hypertension and the occurrence of PU in most cases, while the risk of PU significantly elevates among COVID-19 patients combined with hypertension regardless of patient source and study design.

PMID:38494175 | DOI:10.1111/iwj.14829

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Peripartum Interventions for People with Class III Obesity: A Systematic Review and Meta-Analysis

Am J Obstet Gynecol MFM. 2024 Mar 15:101354. doi: 10.1016/j.ajogmf.2024.101354. Online ahead of print.

ABSTRACT

OBJECTIVE: To identify evidenced-based peripartum interventions for people with a body mass index (BMI) ≥40kg/m2.

DATA SOURCES: PubMed, MEDLINE, EMBASE, Cochrane, CINAHL and ClinicalTrials.gov were searched from inception to 2022 without date, publication type, or language restrictions.

STUDY ELIGIBILITY CRITERIA: Cohort and randomized controlled trials (RCT) that implemented an intervention and evaluated peripartum outcomes of people with a BMI≥40kg/m2 were included. The primary outcome depended on the intervention but commonly related to wound morbidity after cesarean delivery (i.e., infection, separation, hematoma).

STUDY APPRAISAL AND SYNTHESIS METHODS: Meta-analysis was completed for interventions with at least 2 studies. Pooled risk ratios (RR) with 95% confidence intervals (CI) and heterogeneity (I2 statistics) were reported.

RESULTS: Of 20,301 studies screened, 30 studies (17 cohort, 13 RCT) encompassing 10 types of interventions were included. Interventions related to delivery planning (induction of labor, planned cesarean delivery), antibiotics during labor induction or for surgical prophylaxis, six types of cesarean delivery techniques, and anticoagulation dosing after a cesarean delivery. Planned cesarean delivery compared to planned vaginal delivery did not improve outcomes based on 3 cohort studies. One cohort study compared 3g to 2g of cephazolin prophylaxis for cesarean delivery and found no differences in surgical site infections. According to 3 cohort studies and 2 RCTs, there was no improvement in outcomes with a non-low transverse skin incision. Ten studies (4 cohort, 6 RCT) met inclusion criteria for the meta-analysis. Two RCTs compared subcuticular closure with suture vs. staples after cesarean delivery and found no differences in wound morbidity within 6 weeks of cesarean delivery (n=422; RR 1.09, 95% CI [0.75-1.59], I2=9%). Prophylactic negative pressure wound therapy was compared to standard dressing in 4 cohort and 4 RCTs and found no differences in wound morbidity (cohort n=2200; RR 1.19, 95% CI [0.88-1.63], I2=66.1%) or surgical site infections (RCT n=1262; RR 0.90, 95% CI [0.63-1.29], I2=0).

CONCLUSION: Few studies address interventions in people with a BMI≥40kg/m2 and most studies did not demonstrate a benefit. Either staples or suture are recommended for subcuticular closure, but available data do not support prophylactic NPWT after cesarean delivery for people with a BMI ≥40kg/m2.

PMID:38494155 | DOI:10.1016/j.ajogmf.2024.101354