Tag: nevin manimala

Eur J Gastroenterol Hepatol. 2023 Jul 31. doi: 10.1097/MEG.0000000000002616. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Celiac disease is a risk factor for osteopenia and osteoporosis. Our aim was to evaluate the possible correlation between villous atrophy extension and dual-energy X-ray absorptiometry (DXA)-derived parameters of bone status.

METHODS: We have retrospectively analyzed data of 47 celiac patients (36 women, 52 ± 14 years of age) who underwent video capsule endoscopy and DXA scans within 1 year of interval from 2006 to 2019. Quantitative, qualitative and geometric DXA parameters were collected only from the most recent DXA measurements.

RESULTS: . Patients were divided into three categories; the first included those with no lesions at video capsule endoscopy (23 patients), the second those with typical lesions (mucosal atrophy, mosaicism and scalloping) in less than one-third of the small bowel (SB) (16 patients) and the third those with typical lesions in more than one-third of the SB (7 patients). In the third group, bone mineral density seemed to be lower in both the lumbar spine and the hip (P = 0.026 and P = 0.011, respectively). The deterioration of bone structure in patients with severe and extended SB atrophy was statistically significant (P = 0.032). Furthermore, bone density, structure and geometry did not correlate with the duration of the gluten-free diet. Notably, autoimmune comorbidities did not affect DXA results.

CONCLUSION: Neither endoscopic nor histological atrophy itself can explain the deterioration of bone mineralization and structure, whereas atrophy extension appeared to be responsible for bone impairment.

PMID:37577844 | DOI:10.1097/MEG.0000000000002616

Int Nurs Rev. 2023 Aug 14. doi: 10.1111/inr.12874. Online ahead of print.

ABSTRACT

AIM: This study investigated anxiety, depression, and stress and their influencing factors among nurses during the COVID-19 pandemic and after the flood in Henan Province, China. It aimed to provide the theoretical foundation for the management of relevant hospital departments, improvement of nursing quality, implementation of antiepidemic work, and other relevant studies.

BACKGROUND: In December 2019, COVID-19 was reported in Wuhan, China and became a global pandemic. In July 2021, unprecedented flooding occurred in Henan Province, China. Under the dual pressure of COVID-19 and the flood, nurses’ mental health problems deteriorated.

METHODS: In August 2021, 1229 nurses from various departments of the First Affiliated Hospital of Xinxiang Medical University in Xinxiang City, Henan Province,China were invited to participate in a questionnaire survey using a general condition questionnaire and the Chinese version of the Depression-Anxiety-Stress Scale. Descriptive statistics were used to analyze the status of nurses’ anxiety, depression, and stress. Analysis of variance, t-test, and multiple linear regression models were used to analyze the factors influencing anxiety, depression, and stress among nurses.

RESULTS: Of the participants, 36.1%, 10.1%, and 15.5% had moderate to high levels of anxiety, stress, and depression, respectively. Moreover, 42 (3.4%) participants experienced high to severe levels of stress, anxiety, and depression. The scores showed significant differences based on gender, harmonious family relationships, department position, work intensity, sleep quality, physical exercise, participation in leisure activities, health status, involvement in emotion management-related training, and attending self-care-related training (all P < 0.05). Gender, work intensity, harmonious family relationships, health condition, sleep quality, and participation in leisure activities influenced stress, anxiety, and depression scores. Department position influenced anxiety and stress scores, and average monthly earnings influenced anxiety scores.

CONCLUSION: All the nurses experienced various levels of stress, anxiety, and depression. Related departments should pay special attention to male nurses and nurses with high work intensity, unharmonious family relationships, poor health, and sleep quality, and who engage in fewer leisure activities.

IMPLICATIONS FOR NURSING AND HEALTH POLICY: It is recommended that departments allocate human resources and arrange schedules reasonably, encourage nurses to participate in more recreational activities, and implement emotion management and self-care-related training to relieve emotional distress, and ultimately maintain nurses’ mental health.

PMID:37577826 | DOI:10.1111/inr.12874

Diabet Med. 2023 Aug 14:e15199. doi: 10.1111/dme.15199. Online ahead of print.

ABSTRACT

AIMS: This study aimed to devise and validate a clinical scoring system for risk prediction of bladder cancer to guide urgent cystoscopy evaluation among diabetes patients.

METHODS: Diabetes patients who received cystoscopy from a large database in a Chinese population (2009-2018). We recruited a derivation cohort based on random sampling from 70% of all individuals. We used the adjusted odds ratios (aORs) for independent risk factors to devise a risk score, ranging from 0 to 5: 0-2 ‘average risk’ (AR) and 3-5 ‘high risk’ (HR).

RESULTS: A total of 5,905 diabetes patients, among which 123 patients with BCa were included. The prevalence rate in the derivation (n=4,174) and validation cohorts (n=1,731) was 2.2 and 1.8%. Using the scoring system constructed, 79.6% and 20.4% in the derivation cohort were classified as AR and HR. The prevalence rate in the AR and HR groups was 1.57% and 4.58%. The risk score consisted of age (18-70: 0; >70: 2), male (1), ever/ex-smoker (1), duration of diabetes (≥ 10 years: 1). Individuals in the HR group had 3.26-fold (95% CI=1.65 to 6.44, p=0.025) increased prevalence of bladder than the AR group. The concordance (c-) statistics was 0.72, implying a good discriminatory capability of the risk score to stratify high risk individuals who should consider earlier cystoscopy.

CONCLUSIONS: The risk prediction algorithm may inform urgency of cystoscopy appointments, thus allowing a more efficient use of resources and contributing to early detection of BCa among patients planned to be referred.

PMID:37577820 | DOI:10.1111/dme.15199

Eur J Gastroenterol Hepatol. 2023 Aug 14. doi: 10.1097/MEG.0000000000002627. Online ahead of print.

ABSTRACT

OBJECTIVES: Pegylated interferon α-2b (PegIFNα-2b) therapy can help inactive hepatitis B surface antigen (HBsAg) carriers (IHCs) achieve clinical cure. To explore and compare the efficacy, safety, and relevant influential factors of PegIFNα-2b monotherapy and PegIFNα-2b-based immunotherapy for IHCs.

METHODS: This exploratory, prospective, single-center, randomized controlled trial enrolled 40 IHCs who were randomized into group A (PegIFNα-2b treatment for 68 weeks) and group B (two cycles of PegIFNα-2b treatment with a lead-in period of GM-CSF and vaccine treatment before each cycle). The primary endpoint was 68-week HBsAg loss rate.

RESULTS: At week 68, the HBsAg loss rates were 45.45% [full analysis set (FAS)] and 46.67% [per-protocol set (PPS)]. There was no statistically significant difference in HBsAg loss rate between groups A and B (P > 0.05). Univariate analysis revealed that age ≤40 years old, baseline HBsAg <200 IU/ml, and 24-week HBsAg decline ≥2 log10 IU/ml were significantly associated with HBsAg loss in FAS population (P < 0.05). Multivariate analysis showed that only 24-week HBsAg decline ≥2 log10 IU/ml was the independent influencing factor in both FAS and PPS populations (P < 0.05). The adverse events were common and mild, and the therapies were well-tolerated.

CONCLUSION: Treatment of IHCs with PegIFNα-2b-based therapy could result in a high HBsAg loss rate. The HBsAg loss rate of combined immunotherapy was similar to that of PegIFNα-2b monotherapy, and the safety was good.

CLINICALTRIALSGOV ID: NCT05451420.

PMID:37577817 | DOI:10.1097/MEG.0000000000002627

J Enzyme Inhib Med Chem. 2023 Dec;38(1):2245168. doi: 10.1080/14756366.2023.2245168.

ABSTRACT

The formal mechanism of linear mixed and non-competitive enzyme inhibition implies the binding of inhibitors to both the active site of the free enzyme in competition with the substrate, and to an allosteric site on the enzyme-substrate complex. However, it is evident from a review of the scientific literature that the two-site mechanism is frequently mistaken as the actual underlying mechanism of mixed inhibition. In this study, we conducted a comprehensive assessment of the mechanistic relevance of this type of inhibition using a statistical approach. By combining a statistical analysis of the inhibition cases documented in the BRENDA database with a theoretical investigation of inhibition models, we conclude that mixed inhibitors exclusively bind to the active site of enzymes. Hence ruling out any implication of allosteric sites and depriving the two-site model of any mechanistic relevance.

PMID:37577806 | DOI:10.1080/14756366.2023.2245168

Eur J Gastroenterol Hepatol. 2023 Jul 31. doi: 10.1097/MEG.0000000000002623. Online ahead of print.

ABSTRACT

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, allergic disease of the esophagus. Current treatment options are limited. One experimental therapy is antibodies against interleukin-5 (IL-5). However, it is unknown why some patients respond to anti-IL-5 treatment whereas others do not. We sought to delineate predictors of histologic response to anti-IL-5 therapy in pediatric EoE.

METHODS: This post hoc analysis of a multicenter, double-blind clinical trial (ClinicalTrial.gov identifier: NCT00358449) evaluated mepolizumab for the treatment of EoE in pediatric patients. Predictors were assessed for their association with a histologic response at week 12 of treatment. A histologic response was defined as either <15 eosinophils per hpf or a reduction in peak eosinophil counts by ≥50%. Predictors on univariate analysis with P < 0.10 were included in multivariate logistic regression models. Statistical significance for multivariate comparisons was set at P < 0.05.

RESULTS: Patients with a higher BMI were more likely to attain histologic response at week 12, defined as <15 eosinophils per hpf [aOR, 1.31; 95% confidence interval (CI), 1.07-1.60; P = 0.008]. Higher BMI (aOR, 1.70; 95% CI, 1.06-2.74; P = 0.029) and signs of exudate plaques on endoscopy (aOR, 18.30; 95% CI, 2.11-158.53; P = 0.008) were significant predictors of histologic response at week 12 where a histologic response was defined as a reduction in peak eosinophil counts by ≥50.

CONCLUSION: Higher BMI and signs of exudative plaques on endoscopy may be predictors of histologic response in pediatric EoE patients treated with antibodies against IL-5. Further studies are needed to validate our findings.

PMID:37577798 | DOI:10.1097/MEG.0000000000002623

Int J Drug Policy. 2023 Aug 11;120:104154. doi: 10.1016/j.drugpo.2023.104154. Online ahead of print.

ABSTRACT

BACKGROUND: Xylazine, a sedative analgesic drug approved as an animal tranquilizer but not for human use, has become an adulterant in the illicit opioid marketplace in North America. Recently declared an emerging health threat in the U.S., the prevalence of xylazine in overdose deaths increased 5.5-fold between 2019 and 2021. More information is needed about the impact of xylazine on opioid users and harm reduction service providers.

METHODS: The impact of xylazine adulteration was triangulated through examination of (1) opioid overdose fatalities in Connecticut between 2017 and 2021 reported by the Office of the Chief Medical Examiner data, (2) a convenience survey of people in Connecticut who use drugs (PWUD) regarding their knowledge of and attitude about the local illicit drug supply, and (3) semi-structured interviews of harm reduction service providers in Connecticut and Philadelphia in response to prompts on the impacts of and responses to xylazine adulteration.

RESULTS: The presence of fentanyl or its analogues in fatal opioid overdoses was a statistically significant predictor of xylazine presence [OR = 25.0, 95%CI (10.7,81.1)] as was being Hispanic [OR = 1.36, 95%CI (1.03,1.77)]. A survey of people who used drugs revealed that 43% (n = 286) were concerned that the drug supply was always unpredictable. Three-quarters of respondents were aware of xylazine and two-thirds would use a xylazine test strip if one was available. Respondents who identified as White, Hispanic were most likely to be aware of xylazine, to have used a fentanyl test strip, and to be interested in a xylazine test strip. Respondents who injected drugs were 3.6-fold more likely than those who did not inject to endorse an interest in a xylazine test strip. Harm reduction service providers were cognizant of a range of problems surrounding the use and injection of xylazine. Although they reported implementing practices to better respond to xylazine harms, they recognized the absence of solutions to many of the problems encountered.

CONCLUSION: The prevalence of xylazine has expanded, especially in combination with fentanyl. Harm reduction education efforts with fidelity to best practices have emerged, but the harms persist and community prevention needs are largely unmet.

PMID:37574646 | DOI:10.1016/j.drugpo.2023.104154

Stat Med. 2023 Aug 13. doi: 10.1002/sim.9869. Online ahead of print.

ABSTRACT

Current status data arise when each subject under study is examined only once at an observation time, and one only knows the failure status of the event of interest at the observation time rather than the exact failure time. Moreover, the obtained failure status is frequently subject to misclassification due to imperfect tests, yielding misclassified current status data. This article conducts regression analysis of such data with the semiparametric probit model, which serves as an important alternative to existing semiparametric models and has recently received considerable attention in failure time data analysis. We consider the nonparametric maximum likelihood estimation and develop an expectation-maximization (EM) algorithm by incorporating the generalized pool-adjacent-violators (PAV) algorithm to maximize the intractable likelihood function. The resulting estimators of regression parameters are shown to be consistent, asymptotically normal, and semiparametrically efficient. Furthermore, the numerical results in simulation studies indicate that the proposed method performs satisfactorily in finite samples and outperforms the naive method that ignores misclassification. We then apply the proposed method to a real dataset on chlamydia infection.

PMID:37574218 | DOI:10.1002/sim.9869

Clin Cancer Res. 2023 Aug 14:OF1-OF15. doi: 10.1158/1078-0432.CCR-23-0370. Online ahead of print.

ABSTRACT

PURPOSE: The TNT trial (NCT00532727) showed no evidence of carboplatin superiority over docetaxel in metastatic triple-negative breast cancer (mTNBC), but carboplatin benefit was observed in the germline BRCA1/2 mutation subgroup. Broader response-predictive biomarkers are needed. We explored the predictive ability of DNA damage response (DDR) and immune markers.

PATIENTS AND METHODS: Tumor-infiltrating lymphocytes were evaluated for 222 of 376 patients. Primary tumors (PT) from 186 TNT participants (13 matched recurrences) were profiled using total RNA sequencing. Four transcriptional DDR-related and 25 immune-related signatures were evaluated. We assessed their association with objective response rate (ORR) and progression-free survival (PFS). Conditional inference forest clustering was applied to integrate multimodal data. The biology of subgroups was characterized by 693 gene expression modules and other markers.

RESULTS: Transcriptional DDR-related biomarkers were not predictive of ORR to either treatment overall. Changes from PT to recurrence were demonstrated; in chemotherapy-naïve patients, transcriptional DDR markers separated carboplatin responders from nonresponders (P values = 0.017; 0.046). High immune infiltration was associated with docetaxel ORR (interaction P values < 0.05). Six subgroups were identified; the immune-enriched cluster had preferential docetaxel response [62.5% (D) vs. 29.4% (C); P = 0.016]. The immune-depleted cluster had preferential carboplatin response [8.0% (D) vs. 40.0% (C); P = 0.011]. DDR-related subgroups were too small to assess ORR.

CONCLUSIONS: High immune features predict docetaxel response, and high DDR signature scores predict carboplatin response in treatment-naïve mTNBC. Integrating multimodal DDR and immune-related markers identifies subgroups with differential treatment sensitivity. Treatment options for patients with immune-low and DDR-proficient tumors remains an outstanding need. Caution is needed using PT-derived transcriptional signatures to direct treatment in mTNBC, particularly DDR-related markers following prior chemotherapy.

PMID:37574209 | DOI:10.1158/1078-0432.CCR-23-0370

Altern Ther Health Med. 2023 Sep;29(6):12-24.

ABSTRACT

CONTEXT: Turmeric is a well-known herb that has been used in many traditional medicinal systems since ancient times. Turmeric roots contain hydrophobic polyphenols called curcuminoids, which have proven anti-inflammatory and antioxidant effects and are shown to be beneficial for the management of musculoskeletal health. Various products containing curcumin or turmeric extract are commercially available.

OBJECTIVE: This systematic review and meta-analysis of randomized clinical trials (RCTs) is intended to evaluate the effective dose, safety, and efficacy of commercial turmeric extract and curcumin supplements in musculoskeletal health.

DESIGN: The research team performed a systematic literature search of PubMed, Google Scholar, and Cochrane Library databases and conducted a meta-analysis according to PRISMA guidelines.

SETTING: Authors from India and USA contributed to this systematic review and meta-analysis.

RESULTS: The research team analyzed 21 prospective, randomized clinical studies, of which seven studies were focused on skeletal muscle health and fourteen on joint health. Statistical heterogeneity was established based on the results of heterogeneity analysis of a Chi-square (χ2) value for Cochran’s Q statistic of 29.3765 for musculoskeletal and 3666.80 for joint health studies (P < .0001 for both analyses). Therefore, the random effects model was used. The χ2 value of the random effects model was 216.5545 for skeletal muscle health studies and 1400.65 for joint health studies, which was statistically significant with P < .0001 for both analyses.

CONCLUSIONS: Turmeric extract and curcumin supplements can be effective adjuvants for the management of musculoskeletal health, with a low incidence of AEs. The water-dispersible turmeric extract, WDTE60N, at a dose of 250 mg per day, was found to be more effective than other curcumin products. However, the studies included in the analysis were conducted using diverse doses and treatment durations. Further evaluation using comparisons in future clinical trials can establish the appropriate effective dose of curcumin supplements for the overall maintenance of musculoskeletal health.

PMID:37574203