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Tolerance limit of external beam radiotherapy combined with low-dose rate brachytherapy in normal rabbit tissue

J Radiat Res. 2023 May 20:rrad036. doi: 10.1093/jrr/rrad036. Online ahead of print.

ABSTRACT

BACKGROUND: Dosage-optimized multimodal radiotherapies that are safe for head and neck cancer patients are desirable. In this study, we investigated tissue tolerance to varying doses of external beam radiotherapy (EBRT) combined with low-dose rate brachytherapy in the neck of a rabbit model.

METHODS: Twenty rabbits were used in the four test groups (five each) with iodine-125 seeds implanted in the neck treated with EBRT in four doses at 50, 40, 30 and 20 Gy each. Twelve rabbits for three control groups (four each). Three months after implantation, all rabbits were euthanized, and target tissues were collected. Analyses included seed implantation assessment, histopathological evaluation, immunohistochemistry staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, electron microscopy and statistics with the SPSS software.

RESULTS: Five rabbits died in the four test groups, and three rabbits died in the three control groups (one per group), which showed no significant difference by survival analysis. The calculated minimum peripheral dose was 17.6 Gy, the maximum dose near the seed was 1812.5 Gy, the D90 was 34.5 Gy and the mean dose was 124.5 Gy. In all groups that received radiation, apoptosis occurred primarily in the esophageal mucosa and corresponded to the dose of radiation; a higher dose caused a greater apoptosis, with significant difference between groups (P < 0.05). Electron microscopy of carotid arteries revealed that endothelial cells were swollen and some were shed from basement membrane, but no other noticeable tissue damages.

CONCLUSIONS: Limited EBRT at maximal dose (50 Gy) combined with the brachytherapy interstitially applied to the neck was tolerated well in the rabbit model.

PMID:37210630 | DOI:10.1093/jrr/rrad036

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Occupational noise exposure and tinnitus: the HUNT Study

Int J Audiol. 2023 May 21:1-8. doi: 10.1080/14992027.2023.2211735. Online ahead of print.

ABSTRACT

OBJECTIVE: We aimed to assess the association between occupational noise exposure and tinnitus. Further, to assess whether the association depends on hearing status.

DESIGN: In this cross-sectional study, tinnitus (>1 h daily) was regressed on job exposure matrix (JEM)-based or self-reported occupational noise exposure, adjusted for confounders.

STUDY SAMPLE: The 14,945 participants (42% men, 20-59 years) attended a population-based study in Norway (HUNT4, 2017-2019).

RESULTS: JEM-based noise exposure, assessed as equivalent continuous sound level normalised to 8-h working days (LEX 8 h), over the working career or as minimum 5 years ≥85 dB) was not associated with tinnitus. Years of exposure ≥80 dB (minimum one) was not associated with tinnitus. Self-reported high noise exposure (>15 h weekly ≥5 years) was associated with tinnitus overall and among persons with elevated hearing thresholds (prevalence ratio (PR) 1.3, 1.0-1.7), however not statistically significantly among persons with normal thresholds (PR 1.1, 0.8-1.5).

CONCLUSIONS: Our large study showed no association between JEM-based noise exposure and tinnitus. This may to some extent reflect successful use of hearing protection. High self-reported noise exposure was associated with tinnitus, but not among normal hearing persons. This supports that noise-induced tinnitus to a large extent depends on audiometric hearing loss.

PMID:37210627 | DOI:10.1080/14992027.2023.2211735

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Efficacy of New Hemostatic Techniques in Nonvariceal Gastrointestinal Bleeding: A Systematic Review and Network Meta-analysis

J Dig Dis. 2023 May 20. doi: 10.1111/1751-2980.13191. Online ahead of print.

ABSTRACT

OBJECTIVE: This systematic review and network meta-analysis aimed to assess the relative efficacy of currently multiple hemostatic modalities in nonvariceal gastrointestinal bleeding (NVGIB).

BACKGROUND: Nonvariceal gastrointestinal bleeding is a frequent medical condition with significant mortality and morbidity. There are currently multiple hemostatic modalities, but their relative efficacy is still unknown.

METHODS: Major databases including PubMed, EMBASE and the Cochrane Library were searched for studies that compared the relative efficacy of different hemostatic techniques for NVGIB (over-the-scope-clip (OTSC), hemostatic powder (HP) and conventional endoscopic treatment (CET)). The 30-day rebleeding rate was the primary outcome. We performed pairwise and network meta-analyses for all treatments. The heterogeneity and transitivity were evaluated.

RESULTS: Twenty-two studies were included. OTSC and HP + CET showed superior efficacy compared with CET (OTSC vs CET: RR, 0.42 [95% CI, 0.28-0.60]; HP + CET vs CET: RR, 0.40 [95% CI, 0.17-0.87]) while their relative efficacy had not detected any statistically significant difference (OTSC vs HP + CET: RR, 0.95 [95% CI, 0.38-2.31]) in the 30-day rebleeding rate. HP + CET was ranked highest in the network ranking estimate. In addition, the sensitivity analysis showed that it was not robust that OTSC was superior to CET in the short-term rebleeding rate and the initial hemostasis rate. None of the other comparisons found a statistically significant difference.

CONCLUSIONS: This systematic review and network meta- analysis showed that OTSC and HP + CET significantly reduced 30-day rebleeding rates compared to CET and had similar efficacy. This article is protected by copyright. All rights reserved.

PMID:37210622 | DOI:10.1111/1751-2980.13191

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Sotalol in neonates for arrythmias: Dosing, safety, and efficacy

J Cardiovasc Electrophysiol. 2023 May 20. doi: 10.1111/jce.15939. Online ahead of print.

ABSTRACT

INTRODUCTION: Various agents may be utilized to manage supraventricular tachycardia (SVT) in neonates and infants. Recently, sotalol has piqued interest given its reported success in managing neonates and infants with SVTs, especially with the intravenous formulation. While the manufacturer recommends using an age-related nomogram in neonates and young infants to guide doses, clinical reports describe various dosing based on weight (mg/kg) or on body surface area (BSA) in mg/m2 . Given the reported variation in clinical practice with regard to dosing in neonates, there is a gap in the literature and translation into clinical practice regarding applicability of the nomogram into clinical practice. The purpose of this study was to describe sotalol doses based on body weight and BSA in neonates for SVT.

METHODS: This is a single center retrospective study evaluating effective sotalol dosing from January 2011 and June 2021 (inclusive). Neonates who received intravenous (IV) or oral (PO) sotalol for SVT were eligible for inclusion. The primary outcome was to describe sotalol doses based on body weight and BSA. Secondary outcomes include comparison of doses to the manufacturer nomogram, description of dose titrations, reported adverse outcomes, and change in therapy. Two-sided Wilcoxon signed-rank tests were used to determine statistically significant differences.

RESULTS: Thirty-one eligible patients were included in this study. The median (range) age and weight were 16.5 (1-28) days and 3.2 (1.8-4.9) kg, respectively. The median initial dose was 7.3 (1.9-10.8) mg/kg or 114.3 (30.9-166.7) mg/m2 /day. Fourteen (45.2%) of patients required a dose increase for SVT control. The median dose required for rhythm control was 8.5 (2-14.8) mg/kg/day or 120.7 (30.9-225) mg/m2 /day. Of note, the median recommended dose per manufacturer nomogram for our patients would have been 51.3 (16.2-73.8) mg/m2 /day, which is significantly lower than both the initial dose (p < .001) and final doses (p < .001) utilized in our study. A total of 7 (22.9%) patients were uncontrolled on sotalol monotherapy using our dosing regimen. Two patients (6.5%) had reports of hypotension and one patient (3.3%) had a report of bradycardia requiring discontinuation of therapy. The average change in baseline QTC following sotalol initiation was 6.8%. Twenty-seven (87.1%), 3 (9.7%), 1 (3.3%) experienced prolongation, no change, or a decrease in QTc, respectively.

CONCLUSIONS: This study demonstrates that a sotalol strategy significantly higher than the manufacture dose recommendations are required for rhythm control in neonates with SVT. There were few adverse events reported with this dosing. Further prospective studies would be advantageous to confirm these findings.

PMID:37210614 | DOI:10.1111/jce.15939

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Compositional and Functional Alterations in Intestinal Microbiota in Patients with Psychosis or Schizophrenia: A Systematic Review and Meta-analysis

Schizophr Bull. 2023 May 20:sbad049. doi: 10.1093/schbul/sbad049. Online ahead of print.

ABSTRACT

BACKGROUND AND HYPOTHESIS: Intestinal microbiota is intrinsically linked to human health. Evidence suggests that the composition and function of the microbiome differs in those with schizophrenia compared with controls. It is not clear how these alterations functionally impact people with schizophrenia. We performed a systematic review and meta-analysis to combine and evaluate data on compositional and functional alterations in microbiota in patients with psychosis or schizophrenia.

STUDY DESIGN: Original studies involving humans and animals were included. The electronic databases PsycINFO, EMBASE, Web of Science, PubMed/MEDLINE, and Cochrane were systematically searched and quantitative analysis performed.

STUDY RESULTS: Sixteen original studies met inclusion criteria (1376 participants: 748 cases and 628 controls). Ten were included in the meta-analysis. Although observed species and Chao 1 show a decrease in diversity in people with schizophrenia compared with controls (SMD = -0.14 and -0.66 respectively), that did not reach statistical significance. We did not find evidence for variations in richness or evenness of microbiota between patients and controls overall. Differences in beta diversity and consistent patterns in microbial taxa were noted across studies. We found increases in Bifidobacterium, Lactobacillus, and Megasphaera in schizophrenia groups. Variations in brain structure, metabolic pathways, and symptom severity may be associated with compositional alterations in the microbiome. The heterogeneous design of studies complicates a similar evaluation of functional readouts.

CONCLUSIONS: The microbiome may play a role in the etiology and symptomatology of schizophrenia. Understanding how the implications of alterations in microbial genes for symptomatic expression and clinical outcomes may contribute to the development of microbiome targeted interventions for psychosis.

PMID:37210594 | DOI:10.1093/schbul/sbad049

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The association between self-treatment and mental health among Swedish physicians

Occup Med (Lond). 2023 May 20:kqad061. doi: 10.1093/occmed/kqad061. Online ahead of print.

ABSTRACT

BACKGROUND: Despite a high prevalence of mental health problems among physicians, the rate of help-seeking behaviour is low. Instead, physicians tend to self-treat. This can have a negative impact on individual physicians and society.

AIMS: The aim was to explore the relationship between self-rated depression, the use of psychotropic medication, and the extent of self-treatment across gender and hierarchical position among Swedish physicians. In addition, the aim was to investigate whether social support can buffer against self-treatment.

METHODS: This study draws on data from the Longitudinal Occupational Health for Health Care in Sweden 2021 study, comprising a representative sample of physicians. Descriptive statistics and logistic regressions were carried out.

RESULTS: The present study showed that approximately 60% of the physicians using narcotic or non-narcotic psychotropic medication were self-prescribing. Male and more senior physicians self-treated to a greater extent. Physicians without depression were self-treating to a greater extent than those with depression. Those who used non-narcotic psychotropic medication intermittently were more likely to self-treat than those who used these medications regularly. The frequency of use was insignificant in relation to self-treatment with narcotic psychotropic medication. No buffering effect from social support at work was found.

CONCLUSIONS: Self-treatment was common among physicians in Sweden, particularly among those who reported mild or no symptoms of depression. This may have negative long-term effects on an individual level and for Swedish health care at large.

PMID:37210591 | DOI:10.1093/occmed/kqad061

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Poorer Survival after Out-of-Hospital Cardiac Arrest among Cancer Patients – A Population-Based Register Study

Eur Heart J Acute Cardiovasc Care. 2023 May 20:zuad053. doi: 10.1093/ehjacc/zuad053. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The association between cancer and survival after out-of-hospital cardiac arrest (OHCA) has not been thoroughly investigated. We aimed to address this knowledge gap using national, population-based registries.

METHODS: For this study, 30,163 OHCA patients (≥18 years) were included from the Swedish Register of Cardiopulmonary Resuscitation. Via linkage to the National Patient Registry, 2,894 patients (10%) with cancer diagnosed within 5 years prior to OHCA were identified. Differences in 30-day survival between cancer patients and controls (defined as OHCA patients without previous cancer diagnosis) were assessed related to cancer stage (locoregional vs metastasized cancer) and cancer site (i.e. lung cancer, breast cancer etc.) using logistic regression adjusted for prognostic factors. Long-term survival is presented as a Kaplan-Meier curve.

RESULTS: For locoregional cancer no statistically significant difference in return of spontaneous circulation (ROSC) was seen compared to controls, metastasized disease was associated with poorer chance of ROSC. Cancer was associated with lower 30-day survival for all cancers (Adjusted odds ratio, OR, 0.57, CI 0.49-0.66), locoregional cancer (Adjusted OR 0.68, CI 0.57-0.82) and metastasized cancer (Adjusted OR 0.24, CI 0.14-0.40) compared to controls. Lower 30-day survival compared to controls was seen for lung cancer, gynaecological and haematological cancers.

CONCLUSION: Cancer is associated with poorer 30-day survival after OHCA. This study suggests that cancer site and disease stage are more relevant factors than cancer in general with regard to its effect on survival after OHCA.

PMID:37210580 | DOI:10.1093/ehjacc/zuad053

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Statistical analysis plans for two randomised controlled trials of the Narrative Experiences Online (NEON) Intervention: impact of receiving recorded mental health recovery narratives on quality of life in people experiencing psychosis (NEON) and people experiencing non-psychosis mental health problems (NEON-O)

Trials. 2023 May 20;24(1):343. doi: 10.1186/s13063-023-07246-8.

ABSTRACT

BACKGROUND: Mental health recovery narratives are a first-hand account of an individual’s recovery from mental health distress, access to narratives can aid recovery. The NEON Intervention is a web-application providing access to a managed collection of narratives. We present the statistical analysis plan for assessing the effectiveness of the NEON Intervention in improving quality of life at 1-year post-randomisation. We pay particular focus on the statistical challenges encountered due to the online nature of this trial.

METHODS AND DESIGN: The NEON Intervention is assessed in two trial populations, one for people with experience of psychosis in the last 5 years, and mental health distress in the last six months (NEON Trial) and one for people with experience of non-psychosis mental health problems (NEON-O Trial). Both NEON trials are two-arm randomised controlled superiority trials comparing the effectiveness of the NEON Intervention with usual care. The target sample size is 684 randomised participants for NEON and 994 for NEON-O. Participants were randomised centrally in a 1:1 ratio.

RESULTS: The primary outcome is the mean score of subjective items on the Manchester Short Assessment of Quality-of-Life questionnaire (MANSA) at 52 weeks. Secondary outcomes are scores from the Herth Hope Index, Mental Health Confidence Scale, Meaning of Life questionnaire, CORE-10 questionnaire and Euroqol 5-Dimension 5-Level (EQ-5D-5L).

CONCLUSION: This manuscript is the statistical analysis plan (SAP) for the NEON trials. Any post hoc analysis, such as those requested by journal reviewers will be clearly labelled as such in the final trial reporting. Trial registration Both trials were prospectively registered. NEON Trial: ISRCTN11152837, registered on 13 August 2018. NEON-O Trial: ISRCTN63197153, registered on 9 January 2020.

PMID:37210551 | DOI:10.1186/s13063-023-07246-8

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Lack of impact of ipragliflozin on endothelial function in patients with type 2 diabetes: sub-analysis of the PROTECT study

Cardiovasc Diabetol. 2023 May 20;22(1):119. doi: 10.1186/s12933-023-01856-x.

ABSTRACT

BACKGROUND: We assessed the impact of 24 months of treatment with ipragliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on endothelial function in patients with type 2 diabetes as a sub-analysis of the PROTECT study.

METHODS: In the PROTECT study, patients were randomized to receive either standard antihyperglycemic treatment (control group, n = 241 ) or add-on ipragliflozin treatment (ipragliflozin group, n = 241) in a 1:1 ratio. Among the 482 patients in the PROTECT study, flow-mediated vasodilation (FMD) was assessed in 32 patients in the control group and 26 patients in the ipragliflozin group before and after 24 months of treatment.

RESULTS: HbA1c levels significantly decreased after 24 months of treatment compared to the baseline value in the ipragliflozin group, but not in the control group. However, there was no significant difference between the changes in HbA1c levels in the two groups (7.4 ± 0.8% vs. 7.0 ± 0.9% in the ipragliflozin group and 7.4 ± 0.7% vs. 7.3 ± 0.7% in the control group; P = 0.08). There was no significant difference between FMD values at baseline and after 24 months in both groups (5.2 ± 2.6% vs. 5.2 ± 2.6%, P = 0.98 in the ipragliflozin group; 5.4 ± 2.9% vs. 5.0 ± 3.2%, P = 0.34 in the control group). There was no significant difference in the estimated percentage change in FMD between the two groups (P = 0.77).

CONCLUSIONS: Over a 24-month period, the addition of ipragliflozin to standard therapy in patients with type 2 diabetes did not change endothelial function assessed by FMD in the brachial artery.

TRIAL REGISTRATION: Registration Number for Clinical Trial: jRCT1071220089 ( https://jrct.niph.go.jp/en-latest-detail/jRCT1071220089 ).

PMID:37210524 | DOI:10.1186/s12933-023-01856-x

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The impact of PTSD on risk of cardiometabolic diseases: a national patient cohort study in Norway

BMC Psychiatry. 2023 May 20;23(1):349. doi: 10.1186/s12888-023-04866-x.

ABSTRACT

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with cardiometabolic diseases, concurrent anxiety, alcohol use disorder and depression. The relationship between PTSD and cardiometabolic diseases are still unclear, and less is known about the effects of socioeconomic status, comorbid anxiety, comorbid alcohol use disorder and comorbid depression. The study, therefore, aims to examine the risk of developing cardiometabolic diseases including type 2 diabetes mellitus over time in PTSD patients, and to what extent socioeconomic status, comorbid anxiety, comorbid alcohol use disorder and comorbid depression attenuate associations between PTSD and risk of developing cardiometabolic diseases.

METHOD: A retrospective, register-based cohort study with 6-years follow-up of adult (> 18 years) PTSD patients (N = 7 852) compared with the general population (N = 4 041 366), was performed. Data were acquired from the Norwegian Patient Registry and Statistic Norway. Cox proportional regression models were applied to estimate hazard ratios (HRs) (99% confidence intervals) of cardiometabolic diseases among PTSD patients.

RESULTS: Significantly (p < 0.001) higher age and gender adjusted HRs were disclosed for all cardiometabolic diseases among PTSD patients compared to the population without PTSD, with a variation in HR from 3.5 (99% CI 3.1-3.9) for hypertensive diseases to HR = 6.5 (5.7-7.5) for obesity. When adjusted for socioeconomic status and comorbid mental disorders, reductions were observed, especially for comorbid depression, for which the adjustment resulted in HR reduction of about 48.6% for hypertensive diseases and 67.7% for obesity.

CONCLUSIONS: PTSD was associated with increased risk of developing cardiometabolic diseases, though attenuated by socioeconomic status and comorbid mental disorders. Health care professionals should be attentive towards the burden and increased risk that low socioeconomic status and comorbid mental disorders may represent for PTSD patients’ cardiometabolic health.

PMID:37210523 | DOI:10.1186/s12888-023-04866-x