Nevin Manimala

J Gastrointest Cancer. 2023 Dec 14. doi: 10.1007/s12029-023-00999-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Hepatocellular carcinoma is a lethal disease and there has been a debate regarding the first-line treatment of its advanced and unresectable form. Observational studies have explored atezolizumab plus bevacizumab versus lenvatinib, yielding mixed results. This systematic review and meta-analysis aim to compare efficacy and safety of both treatment arms.

METHODS: A systematic literature review was conducted in accordance with PRISMA guidelines. Randomized control trials, cohort studies, or case-control that included patients above age 60 with unresectable hepatocellular carcinoma confirmed by radiological imaging were included. At least one of the outcomes: overall survival (OS), progression-free survival (PFS), objective response rate (ORR), duration of response, or adverse events was included in the selected studies.

RESULTS: Ten cohorts were included in the analysis with a total of 6493 patients. Nine of the included studies had patients with advanced HCC (BCLC-C) or intermediate HCC (BCLC-B) and 1 study included patients with all three stages (BCLC-A, BCLC-B, and BCLC-C). Of these patients, 2524 patients received atezolizumab plus bevacizumab (A + B) combination while 3969 received lenvatinib. The overall survival was better statistically in the A + B group then the lenvatinib group (MD: – 5.06; 95% CI: – 7.79 to – 2.33; p = 0.0003, I² = 0%). The progression-free survival was significantly improved in A + B arm as well group (MD: – 4.96; 95% CI: – 7.67 to – 2.26; I² = 0%, p = 0. 0003). There was no significant difference in objective response rate, disease control rate, and frequency of adverse events in either of the group.

CONCLUSION: Our study concluded that combination therapy with atezolizumab plus bevacizumab could increase the survival duration without affecting the disease course. Moreover, while the severity of adverse events was greater in the A + B group, their frequency was comparable to the lenvatinib group.

PMID:38095799 | DOI:10.1007/s12029-023-00999-0

Environ Sci Pollut Res Int. 2023 Dec 14. doi: 10.1007/s11356-023-31362-2. Online ahead of print.

ABSTRACT

In this study, a new hybrid bench-scale electrocoagulation-sand filtration (FECF) reactor was developed for purifying nitrate-contaminated samples. Before and after electrochemical treatment, two sand filters were included in this continuous system to facilitate the purification procedure, and the contaminated water flows horizontally through the entire system according to a specific hydraulic gradient within the reactor, resulting in water purification. Significant improvement in treatment performance was observed due to the presence of metal hydroxides in the second filter media that were not fully involved in the electrocoagulation treatment. Energy dispersive X-ray (EDX) analysis was performed to detect metal hydroxide species in the sand media, and the need for filter regeneration was evaluated by monitoring changes in the system flow rate. Moreover, an evaluation of the effects of different factors including operating time, current intensity, initial pH, type of anode and cathode, initial nitrate concentration, hydraulic head level inside the reactor, number of electrodes, and NaCl electrolyte concentration on the performance of nitrate removal was conducted through the Taguchi design. Further, ANOVA analysis verified the accuracy of the predicted model, and the variables were classified based on their relative importance in the FECF process. According to the regression model, 97% of nitrates were removed with Al electrodes as anode and Fe as cathode, 70 min purification time, current intensity of 3 A, 100 mg/l initial nitrate concentration, pH 8, electrolyte concentration of 1 g/l, electrode number of 6, and 1.5 cm head level.

PMID:38095796 | DOI:10.1007/s11356-023-31362-2

Environ Sci Pollut Res Int. 2023 Dec 14. doi: 10.1007/s11356-023-30478-9. Online ahead of print.

ABSTRACT

This research explores the theory that cultural factors shape how people feel about the environment. Both theoretical and empirical approaches are used in our investigation of this problem. In the theoretical part of the study, we provide a model for transferring cultural practices from one generation to the next. To provide empirical evidence for the existence of this cultural factor in environmental views, we analyze survey data from the European Values Research. Using a comparative method, we use differences caused by migration patterns in Europe and America. According to our research, cultural influences on migrants’ ecological beliefs are long-lasting and statistically significant. Variations in migrants’ environmental views may be traced back to societal norms that endure in their home countries. We also demonstrate that ecological views are robust in the face of incentives originating from the external environment, demonstrating that migrants’ choices in the host nation are not much influenced by the environmental circumstances they were exposed to in their home countries. We uncover fascinating variations in the cultural transfer procedure, and our results hold up under various hypotheses. These findings suggest that, in light of the prevalence of ecological problems requiring community action, it is crucial to formulate policies that consider the factors that led to the development of ecological cultures.

PMID:38095793 | DOI:10.1007/s11356-023-30478-9

Curr Pain Headache Rep. 2023 Dec 14. doi: 10.1007/s11916-023-01196-1. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Neuropathic pain (NP) remains a challenge to treat, with 50% of patients experiencing limited efficacy from current treatments. Medicinal cannabis, which contains tetrahydrocannabinol (THC), cannabidiol (CBD) and other minor cannabinoids, is garnering attention as an alternative treatment for NP. This paper reviews the clinical evidence for phytocannabinoid treatment of NP.

RECENT FINDINGS: Seventeen randomised controlled trials (RCT) were identified for inclusion in this review. Of these, ten studies using phytocannabinoid preparations containing THC alone had the most evidence for pain relief. Four studies investigating THC/CBD combinations showed some reductions in pain scores, although not all findings were statistically significant, whereas studies investigating CBD (two studies) or cannabidivarin (one study) showed no analgesic effect over placebo. However, CBD studies were of small sample size when compared to other studies in the review and short duration. Results for treatment of diabetic peripheral neuropathy patients with THC showed better improvements over those for NP induced by chemotherapy and multiple sclerosis, with these trials using vaporised whole plant cannabis. This formulation may have trace amounts of other minor cannabinoids, compared with synthetic cannabinoids such as dronabinol or nabilone that were investigated in other studies. This review provides an overview of RCTs that have investigated phytocannabinoid use for the treatment of NP. There appears to be evidence to necessitate further high quality RCTs into novel formulations of phytocannabinoids for the treatment of NP.

PMID:38095748 | DOI:10.1007/s11916-023-01196-1

Intern Emerg Med. 2023 Dec 14. doi: 10.1007/s11739-023-03490-7. Online ahead of print.

ABSTRACT

To develop and internally validate a multivariable logistic regression model (LRM) for the prediction of the probability of 1-year readmission to the emergency department (ED) in patients with acute alcohol intoxication (AAI). We developed and internally validated the LRM on a previously analyzed retrospective cohort of 3304 patients with AAI admitted to the ED of the Sant’Orsola-Malpighi Hospital (Bologna, Italy). The benchmark LRM employed readmission to the same ED for AAI within 1 year as the binary outcome, age as a continuous predictor, and sex, alcohol use disorder, substance use disorder, at least one previous admission for trauma, mental or behavioral disease, and homelessness as the binary predictors. Optimism correction was performed using the bootstrap on 1000 samples without replacement. The benchmark LRM was gradually simplified to get the most parsimonious LRM with similar optimism-corrected overall fit, discrimination and calibration. The 1-year readmission rate was 15.7% (95% CI 14.4-16.9%). A reduced LRM based on sex, age, at least one previous admission for trauma, mental or behavioral disease, and homelessness, performed nearly as well as the benchmark LRM. The reduced LRM had the following optimism-corrected metrics: scaled Brier score 17.0%, C-statistic 0.799 (95% CI 0.778 to 0.821), calibration in the large 0.000 (95% CI – 0.099 to 0.099), calibration slope 0.985 (95% CI 0.893 to 1.088), and an acceptably accurate calibration plot. An LRM based on sex, age, at least one previous admission for trauma, mental or behavioral disease, and homelessness can be used to estimate the probability of 1-year readmission to ED for AAI. To begin proving its clinical utility, this LRM should be validated in external cohorts.

PMID:38095747 | DOI:10.1007/s11739-023-03490-7

Eur Arch Otorhinolaryngol. 2023 Dec 14. doi: 10.1007/s00405-023-08361-7. Online ahead of print.

ABSTRACT

PURPOSE: Idiopathic sudden sensorineural hearing loss (ISSHL) can cause acute damage not only to the auditory function, but also to the vestibular function in addition to damage to the hearing function. The aim of this study was to perform vestibular assessment using caloric test and video head impulse test in patients with idiopathic sudden sensorineural hearing loss. In addition, to evaluate the relationship of dizziness with vestibular tests and post-treatment responses of vestibular tests.

METHODS: This is an observational, longitudinal and prospective study, including patients diagnosed with idiopathic sudden sensorineural hearing. Patients were divided into two groups according to the presence of vestibular complaints at presentation: Group 1: Patients with vestibular complaints, Group 2: Patients without vestibular complaints. All subjects underwent pure tone audiometry (PTA) testing, cold caloric test and video head impulse test (vHIT) during their admission and on the 10th day, 3rd month, and 1st year of their follow-up outpatient clinic controls. A unilateral weakness (UW) in the caloric test response was quantified according to the Jongkees formula.

RESULTS: A positive and significant relationship was found between the degree of hearing loss according to the ASHA criteria pre-treatment and the level of improvement created according to Siegel criteria at the 10th day, 3rd month, 1st year after treatment (respectively p = 0.001, p = 0.001, p < 0.001). When both short-term and long-term results were evaluated after treatment, a positive improvement in the degree of hearing loss was observed. A statistically significant difference was observed between Groups 1 and 2 when the pre-treatment, at 10 days, 3 months and 1 year after treatment the caloric test UW value was compared (respectively p = 0.020, p = 0.004, p = 0.004, p = 0.004). A statistically significant difference was observed between Groups 1 and 2 when the pre-treatment, at 10 days, 3 months and 1 year after treatment vHIT lateral canal VOR value was compared (respectively p = 0.000, p = 0.001, p = 0.000, p = 0.004). When both short-term and long-term results were evaluated after treatment, a positive improvement was observed in both caloric test results and lateral vHIT VOR values. Pre-treatment, post-treatment 10th day, 3rd month, 1st year vHIT anterior and posterior canal VOR values were found to be VOR˃0.8 in all patients. No difference was observed in anterior and posterior canal VOR values.

CONCLUSION: Vertigo in patients with ISSHL “as objectively confirmed through caloric testing and vHIT” can be considered a sign of severe cochlear damage. Our study demonstrated a significantly increased risk of vestibular affect in patients with ISSHL, especially in the presence of vertigo. Thus, we conclude that the focus in ISSHL should not only be on the cochlea but also on the vestibular system.

PMID:38095708 | DOI:10.1007/s00405-023-08361-7

Equine Vet J. 2023 Dec 14. doi: 10.1111/evj.14034. Online ahead of print.

ABSTRACT

BACKGROUND: Determination of horse breeds predisposed to congenital and juvenile cataracts will enable investigations into potential genetic mechanisms for cataracts in horses.

OBJECTIVE: To investigate horse breed predispositions to congenital and juvenile cataracts in two academic referral populations.

STUDY DESIGN: Retrospective case series.

METHODS: Medical record identification of horses diagnosed with congenital or juvenile cataracts at the Cornell University Equine Hospital (2000-2022) and the University of California-Davis (UCD) Large Animal Clinic (1990-2021). Signalment, examination findings and treatments were recorded. Descriptive statistics were performed, and breed over-representations were determined using Chi-squared or Fisher’s exact tests.

RESULTS: Thirty-one (Cornell) and 70 (UCD) horses with congenital or juvenile cataracts were identified, for a total of 101 affected horses. Seventy-eight horses were affected bilaterally and 23 were affected unilaterally, for a total of 179 affected eyes. Standardbreds were significantly over-represented at both institutions, comprising 32.5% of congenital/juvenile cataract cases and 10% of the equine hospital population at Cornell (p < 0.001) and 4.3% of cataract cases and 1.3% of the equine hospital population at UCD (p = 0.03). Thoroughbreds were under-represented for congenital and juvenile cataracts at both institutions (p = 0.03 Cornell, p = 0.01 UCD).

MAIN LIMITATIONS: Retrospective study, potential for selection bias.

CONCLUSIONS: The over-representation of the Standardbred breed for congenital and juvenile cataracts at two institutions suggests an underlying genetic basis in the breed. Future genetic and genomic studies are warranted to investigate heritable cataracts in Standardbred horses.

PMID:38095155 | DOI:10.1111/evj.14034

Histol Histopathol. 2023 Dec 5:18685. doi: 10.14670/HH-18-685. Online ahead of print.

ABSTRACT

AIM: Studies defining eosinophil densities in the gastrointestinal tract (GIT) are limited. To assess whether eosinophils are pathologically infiltrating the GIT, it is important to evaluate eosinophil densities for specific populations.

METHODS: A retrospective, quantitative, comparative study was conducted to determine the number of eosinophils in the oesophagus, stomach and small bowel of patients in central South Africa and to investigate whether a statistically significant difference occurred between ethnic and gender groups.

RESULTS: In total, 309 histological sections from the oesophagus, gastric corpus, gastric antrum and small intestine were sampled from male and female, African and Caucasian patients. Histology reports and review of the slides confirmed the absence of histological abnormality. The number of eosinophils in the epithelium and lamina propria were manually quantified. The eosinophil values across gender, ethnicity and location were 0-2.0/mm² for the oesophagus, 0-53.0/mm² for the gastric corpus and 7.1-115.3/mm² for the small intestine. Regarding the gastric antrum, African and Caucasian females had eosinophil values of 1.0-35.7/mm² and 0-22.4/mm², respectively. Males had an eosinophil density of 0-31.6/mm² in the gastric antrum. The eosinophil values in the oesophagus, gastric corpus and small bowel were not significantly different between genders and ethnic groups. The only site where ethnicity influenced the number of eosinophils was the gastric antrum, a discrepancy that cannot be explained.

CONCLUSION: To the authors’ knowledge, this is the first report on the eosinophil densities in the oesophagus, stomach and small bowel of adults in South Africa.

PMID:38095145 | DOI:10.14670/HH-18-685

Nucl Med Commun. 2023 Dec 14. doi: 10.1097/MNM.0000000000001797. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the value of 18F-FDG PET/CT tumor metabolic heterogeneity index (HI) and establish and validate a nomogram model for distinguishing head and neck cancer of unknown primary (HNCUP) from lymphoma with head and neck metastatic poorly differentiated cancer.

METHODS: This retrospective analysis was conducted on 1242 patients with cervical metastatic poorly differentiated cancer. 108 patients, who were clinically and pathologically confirmed as HNCUP or lymphoma, were finally enrolled. Two independent sample t-tests and χ2 test were used to compare the clinical and imaging features. Binary logistic regression was used to screen for independent predictive factors.

RESULTS: Among the 108 patients), 65 patients were diagnosed with HNCUP and 43 were lymphoma. Gender (P = 0.001), SUVmax (P < 0.001), SUVmean (P < 0.001), TLG (P = 0.012), and HI (P < 0.001) had statistical significance in distinguishing HNCUP and lymphoma. Female (OR = 4.546, P = 0.003) and patients with HI ≥ 2.37 (OR = 3.461, P = 0.047) were more likely to be diagnosed as lymphoma.

CONCLUSION: For patients with cervical metastatic poorly differentiated cancer, gender and HI were independent predictors of pathological type. For such patients, clinical attention should be paid to avoid misdiagnosing lymphoma as HNCUP, which may delay treatment.

PMID:38095143 | DOI:10.1097/MNM.0000000000001797

Public Health Res (Southampt). 2023 Nov;11(12):1-137. doi: 10.3310/VGTR7431.

ABSTRACT

BACKGROUND: Social skills interventions are commonly recommended to help children and young people with autism spectrum disorder develop social skills, but some struggle to engage in these interventions. LEGO^® (LEGO System A/S, Billund, Denmark) based therapy, a group social skills intervention, aims to be more interesting and engaging.

OBJECTIVE: To evaluate the clinical effectiveness of LEGO^® based therapy on the social and emotional skills of children and young people with autism spectrum disorder in school settings compared with usual support. Secondary objectives included evaluations of cost-effectiveness, acceptability and treatment fidelity.

DESIGN: A cluster randomised controlled trial randomly allocating participating schools to either LEGO^® based therapy and usual support or usual support only.

SETTING: Mainstream schools in the north of England.

PARTICIPANTS: Children and young people (aged 7-15 years) with autism spectrum disorder, their parent/guardian, an associated teacher/teaching assistant and a facilitator teacher/teaching assistant (intervention schools only).

INTERVENTION: Schools randomised to the intervention arm delivered 12 weekly sessions of LEGO^® based therapy, which promotes collaborative play and encourages social problem-solving in groups of three children and young people with a facilitator (trained teacher or teaching assistant). Participants received usual support from school and community services. Participants in the control arm received usual support only. Research assistants and statisticians were blind to treatment allocation.

MAIN OUTCOME MEASURE: The social skills subscale of the Social Skills Improvement System (SSIS), completed by the children and young people’s unblinded teacher pre randomisation and 20 weeks post randomisation. The SSIS social skills subscale measures social skills including social communication, co-operation, empathy, assertion, responsibility and self-control. Participants completed a number of other pre- and post-randomisation measures of emotional health, quality of life, loneliness, problem behaviours, academic competence, service resource utilisation and adverse events.

RESULTS: A total of 250 children and young people from 98 schools were randomised: 127 to the intervention arm and 123 to the control arm. Intention-to-treat analysis of the main outcome measure showed a modest positive difference of 3.74 points (95% confidence interval -0.16 to 7.63 points, standardised effect size 0.18; p = 0.06) in favour of the intervention arm. Statistical significance increased in per-protocol analysis, with a modest positive difference (standardised effect size 0.21; p = 0.036). Cost-effectiveness of the intervention was found in reduced service use costs and a small increase in quality-adjusted life-years. Intervention fidelity and acceptability were positive. No intervention-related adverse events or effects were reported.

CONCLUSIONS: The primary and pre-planned sensitivity analysis of the primary outcome consistently showed a positive clinical difference, with modest standardised effect sizes of between 0.15 and 0.21. There were positive health economics and qualitative findings, corroborated by the difference between arms for the majority of secondary outcomes, which were not statistically significant but favoured the intervention arm. Post hoc additional analysis was exploratory and was not used in drawing this conclusion. Given the small positive change, LEGO^® based therapy for children and young people with autism spectrum disorder in schools should be considered.

LIMITATIONS: The primary outcome measure was completed by an unblinded teacher (rather than by the facilitator).

FUTURE WORK: The study team recommends future research into LEGO^® based therapy, particularly in school environments.

TRIAL REGISTRATION: This trial is registered as ISRCTN64852382.

FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 15/49/32) and is published in full in Public Health Research; Vol. 11, No. 12. See the NIHR Funding and Awards website for further award information.

PMID:38095124 | DOI:10.3310/VGTR7431