Category: Nevin Manimala

Worldviews Evid Based Nurs. 2022 May 24. doi: 10.1111/wvn.12589. Online ahead of print.

ABSTRACT

BACKGROUND: Quality cancer care necessitates opportunities for patient participation, supposedly recognizing the individual’s preferences and experiences for being involved in their health and healthcare issues. Previous research shows that surgical cancer patients wish to be more involved, requiring professionals to be sensitive of patients’ needs.

AIMS: To explore preference-based patient participation in surgical cancer care.

METHODS: A cross-sectional study was conducted. The Patient Preferences for Patient Participation tool (4Ps) was used, which includes 12 attributes of preferences for and experiences of patient participation. Data were analyzed with descriptive and comparative statistical methods.

RESULTS: The results are based on a total of 101 questionnaires. Having reciprocal communication and being listened to by healthcare staff were commonly deemed crucial for patient participation. While 60% of the patients suggested that taking part in planning was crucial for their participation, they had experienced this only to some extent. Learning to manage symptoms and phrasing personal goals were items most often representing insufficient conditions for preference-based patient participation.

LINKING EVIDENCE TO ACTION: To support person-centered surgical care, further efforts to suffice preference-based participation are needed, including opportunities for patients to share their experiences and engage in the planning of healthcare activities.

PMID:35607906 | DOI:10.1111/wvn.12589

J Endourol. 2022 May 24. doi: 10.1089/end.2022.0103. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the oncological outcomes and recurrence patterns of clinically node-negative patients with renal pelvic and/or upper or middle ureteral tumors after a template-based retroperitoneal lymph node dissection (RPLND) in conjunction with retroperitoneal laparoscopic radical nephroureterectomy (LRNU).

METHODS: A total of 283 patients who received LRNU with and without RPLND at three Japanese institutions were enrolled. The template of RPLND included the renal hilar and paraaortic lymph nodes (LNs) (left side) and renal hilar, paracaval, retrocaval, and intra-aortocaval LNs (right side). The LNs and kidneys were removed en bloc. The primary endpoint was set as recurrence-free survival. All RPLND cases were matched one-to-one with no RPLND cases using a propensity score matching approach, and 47 matched pairs were included in analyses.

RESULTS: Compared to the control group, significant differences were not observed in the RPLND group in terms of operation time, blood loss, postoperative complication rate, and pathological findings. The estimated five-year recurrence-free survival was significantly higher in the RPLND group (86.8%) compared to the group without RPLND (64.2%) (p = 0.014). The estimated five-year cancer-specific survival showed a similar tendency; however, it did not reach a statistically significant difference (87.5% vs 71.3%, respectively; p = 0.168). As for the first recurrence site, the RPLND group showed a lower incidence of distant recurrence, while a significant difference was not observed in the rate of regional LN recurrence.

CONCLUSION: This study suggests that a template-based RPLND in conjunction with retroperitoneal LRNU efficiently improves the recurrence-free survival by reducing distant recurrences.

PMID:35607848 | DOI:10.1089/end.2022.0103

Neurol Neurochir Pol. 2022 May 24. doi: 10.5603/PJNNS.a2022.0036. Online ahead of print.

ABSTRACT

AIM OF THE STUDY: The purpose of our study was the evaluation of the effect of 2,000 mg levetiracetam monotherapy over a 3-month period on nocturnal sleep in patients with epilepsy.

CLINICAL RATIONALE: Levetiracetam (LEV) is a novel antiepileptic drug with a unique anticonvulsive mechanism of action. It has been commonly reported to cause sleep disruption and daytime sleepiness in epilepsy patients. Its advantages (its broad antiepileptic spectrum, optimal pharmacokinetics, good safety and tolerability) have led to its frequent use in clinical practice, although little is yet known about LEV’s effect on nocturnal sleep architecture.

MATERIAL AND METHODS: The effect of LEV on nocturnal sleep was assessed through a full-night lab polysomnography (PSG), followed by a four-nap multiple sleep latency test. Both procedures were performed at baseline and after three months of LEV treatment. The dynamics of seven main PSG variables was evaluated prior to, and three months after, LEV therapy.

RESULTS: Twenty five patients with newly diagnosed or untreated epilepsy completed the study. We found no statistically significant difference at baseline and after LEV therapy in the following sleep parameters: total sleep time, sleep onset, wake after sleep onset, N1 stage and rapid eye movement (REM) sleep (minutes and percentages), and latency of all sleep stages including REM sleep. However, we found a statistically significant increase in the number of awakenings and arousals, an increase in N2 and a decrease in N3 stages (minutes and percentages) after therapy. We also observed an increase in N1 stage and a trend toward a reduction in REM sleep (in both minutes and percentages), but they did not reach statistical significance.

CONCLUSIONS: Levetiracetam 2,000 mg/day does not affect sleep continuity and may be considered a sleep-friendly antiepileptic drug.

PMID:35607879 | DOI:10.5603/PJNNS.a2022.0036

Stat Med. 2022 May 24. doi: 10.1002/sim.9446. Online ahead of print.

ABSTRACT

Are weak associations between a treatment and a binary outcome always sensitive to small unmeasured biases in observational studies? This possibility is often discussed in epidemiology. The familiar Mantel-Haenszel test for a 2×2×S$$ 2times 2times S $$ contingency table exaggerates sensitivity to unmeasured biases when the population odds ratios vary among the S$$ S $$ strata. A statistic built from several components, here from the S$$ S $$ strata, is said to have demonstrated insensitivity to bias if it uses only those components that provide indications of insensitivity to bias. Briefly, such a statistic is a d$$ d $$ -statistic. There are 2S–1$$ {2}^S-1 $$ candidate statistics with S$$ S $$ strata, and a d$$ d $$ -statistic considers them all. To have level α$$ alpha $$ , a test based on a d$$ d $$ -statistic must pay a price for its double use of the data, but as the sample size increases, that price becomes small, while the gain may be large. The price is paid by conditioning on the limited information used to identify components that are insensitive to a bias of specified magnitude, basing the test result on the information that remains after conditioning. In large samples, the d$$ d $$ -statistic achieves the largest possible design sensitivity, so it does not exaggerate sensitivity to unmeasured bias. A simulation verifies that the large sample result has traction in samples of practical size. A study of sunlight as a cause of cataract is used to illustrate issues and methods. Several extensions of the method are discussed. An R package dstat2x2xk implements the method.

PMID:35607846 | DOI:10.1002/sim.9446

Pilot Feasibility Stud. 2022 May 23;8(1):108. doi: 10.1186/s40814-022-01058-4.

ABSTRACT

BACKGROUND: Dietary interventions have been previously explored in children with ADHD. Elimination diets and supplementation can produce beneficial behaviour changes, but little is known about the mechanisms mediating change. We propose that these interventions may work, in part, by causing changes in the gut microbiota. A microbiome-targeted dietary intervention was developed, and its feasibility assessed.

METHODS: A non-randomised feasibility study was conducted on nine non-medicated children with ADHD, aged 8-13 years (mean 10.39 years), using a prospective one-group pre-test/post-test design. Participants were recruited from ADHD support groups in London and took part in the 6-week microbiome-targeted dietary intervention, which was specifically designed to impact the composition of gut bacteria. Children were assessed pre- and post-intervention on measures of ADHD symptomatology, cognition, sleep, gut function and stool-sample microbiome analysis. The primary aim was to assess the study completion rate, with secondary aims assessing adherence, adverse events (aiming for no severe and minimal), acceptability and suitability of outcome measures.

RESULTS: Recruitment proved to be challenging and despite targeting 230 participants directly through support groups, and many more through social media, nine families (of the planned 10) signed up for the trial. The completion rate for the study was excellent at 100%. Exploration of secondary aims revealed that (1) adherence to each aspect of the dietary protocol was very good; (2) two mild adverse events were reported; (3) parents rated the treatment as having good acceptability; (4) data collection and outcome measures were broadly feasible for use in an RCT with a few suggestions recommended; (5) descriptive data for outcome measures is presented and suggests that further exploration of gut microbiota, ADHD symptoms and sleep would be helpful in future research.

CONCLUSIONS: This study provides preliminary evidence for the feasibility of a microbiome-targeted dietary intervention in children with ADHD. Recruitment was challenging, but the diet itself was well-tolerated and adherence was very good. Families wishing to trial this diet may find it an acceptable intervention. However, recruitment, even for this small pilot study, was challenging. Because of the difficulty experienced recruiting participants, future randomised controlled trials may wish to adopt a simpler dietary approach which requires less parental time and engagement, in order to recruit the number of participants required to make meaningful statistical interpretations of efficacy.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03737877 . Registered 13 November 2018-retrospectively registered, within 2 days of the first participant being recruited.

PMID:35606889 | DOI:10.1186/s40814-022-01058-4

BMC Res Notes. 2022 May 23;15(1):189. doi: 10.1186/s13104-022-06074-4.

ABSTRACT

OBJECTIVE: The present study aimed to investigate the effects of nano-curcumin supplementation on adipokines levels and clinical signs in obese and overweight patients with migraine.

RESULTS: Forty-four patients with episodic migraine participated in this clinical trial and were divided into two groups nano-curcumin (80 mg/day) and the control group over 2-month period. At the baseline and the end of the research, the serum levels of MCP-1, Resistin, and Visfatin were measured using the ELISA method. In addition, the headache attack frequencies, severity, and duration of pain were recorded. The results of the present study showed that nano-curcumin can significantly reduce MCP-1 serum levels in the nano-curcumin supplemented group (P = 0.015, size effect = 13.4%). In the case of resistin and visfatin, nano-curcumin supplementation exerted no statistically significant changes in serum levels (P > 0.05). Nano-curcumin also significantly reduced the attack frequencies, severity, and duration of headaches (P < 0.05). These findings indicate that targeting curcumin can be a promising approach to migraine management. However, further comprehensive human trials are needed to confirm these findings.

TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20160626028637N2 on the date 2020-07-10.

PMID:35606882 | DOI:10.1186/s13104-022-06074-4

Genome Med. 2022 May 24;14(1):55. doi: 10.1186/s13073-022-01058-2.

ABSTRACT

BACKGROUND: Genome-wide association studies of asthma have revealed robust associations with variation across the human leukocyte antigen (HLA) complex with independent associations in the HLA class I and class II regions for both childhood-onset asthma (COA) and adult-onset asthma (AOA). However, the specific variants and genes contributing to risk are unknown.

METHODS: We used Bayesian approaches to perform genetic fine-mapping for COA and AOA (n=9432 and 21,556, respectively; n=318,167 shared controls) in White British individuals from the UK Biobank and to perform expression quantitative trait locus (eQTL) fine-mapping in immune (lymphoblastoid cell lines, n=398; peripheral blood mononuclear cells, n=132) and airway (nasal epithelial cells, n=188) cells from ethnically diverse individuals. We also examined putatively causal protein coding variation from protein crystal structures and conducted replication studies in independent multi-ethnic cohorts from the UK Biobank (COA n=1686; AOA n=3666; controls n=56,063).

RESULTS: Genetic fine-mapping revealed both shared and distinct causal variation between COA and AOA in the class I region but only distinct causal variation in the class II region. Both gene expression levels and amino acid variation contributed to risk. Our results from eQTL fine-mapping and amino acid visualization suggested that the HLA-DQA1*03:01 allele and variation associated with expression of the nonclassical HLA-DQA2 and HLA-DQB2 genes accounted entirely for the most significant association with AOA in GWAS. Our studies also suggested a potentially prominent role for HLA-C protein coding variation in the class I region in COA. We replicated putatively causal variant associations in a multi-ethnic cohort.

CONCLUSIONS: We highlight roles for both gene expression and protein coding variation in asthma risk and identified putatively causal variation and genes in the HLA region. A convergence of genomic, transcriptional, and protein coding evidence implicates the HLA-DQA2 and HLA-DQB2 genes and HLA-DQA1*03:01 allele in AOA.

PMID:35606880 | DOI:10.1186/s13073-022-01058-2

Hum Resour Health. 2022 May 23;20(1):46. doi: 10.1186/s12960-022-00743-y.

ABSTRACT

BACKGROUND: Given the demands for public health and infectious disease management skills during COVID-19, a shortage of the public health workforce, particularly with skills and competencies in epidemiology and biostatistics, has emerged at the Centers for Disease Controls (CDCs) in China. This study aims to investigate the employment preferences of doctoral students majoring in epidemiology and biostatistics, to inform policy-makers and future employers to address recruitment and retention requirements at CDCs across China.

METHODS: A convenience sampling approach for recruitment, and an online discrete choice experiment (DCE) survey instrument to elicit future employee profiles, and self-report of their employment and aspirational preferences during October 20 and November 12, 2020. Attributes included monthly income, employment location, housing benefits, children’s education opportunities, working environment, career promotion speed and bianzhi (formally established post).

RESULTS: A total of 106 doctoral epidemiology and biostatistics students from 28 universities completed the online survey. Monthly income, employment location and bianzhi was of highest concern in the seven attributes measured, though all attributes were statistically significant and presented in the expected direction, demonstrating preference heterogeneity. Work environment was of least concern. For the subgroup analysis, employment located in a first-tier city was more likely to lead to a higher utility value for PhD students who were women, married, from an urban area and had a high annual family income. Unsurprisingly, when compared to single students, married students were willing to forgo more for good educational opportunities for their children. The simulation results suggest that, given our base case, increasing only monthly income from 10,000 ($ 1449.1) to 25,000 CNY ($ 3622.7) the probability of choosing the job in the third-tier city would increase from 18.1 to 53.8% (i.e., the location choice is changed).

CONCLUSION: Monthly income and employment location were the preferred attributes across the cohort, with other attributes then clearly ranked and delineated. A wider use of DCEs could inform both recruitment and retention of a public health workforce, especially for CDCs in third-tier cities where resource constraints preclude all the strategies discussed here.

PMID:35606873 | DOI:10.1186/s12960-022-00743-y

J Otolaryngol Head Neck Surg. 2022 May 23;51(1):22. doi: 10.1186/s40463-022-00580-y.

ABSTRACT

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease that may require biological therapy. Omalizumab is an anti-IgE biologic that was recently approved by the FDA and Health Canada for use in severe CRS with nasal polyps (CRSwNP) recalcitrant to intranasal corticosteroids. Dosing is based on weight and pre-treatment serum IgE, with elevated levels of the latter being an indication for biologic treatment according to EPOS and EUFOREA guidelines. The goal of this study was to identify variables that predict IgE-high type 2 inflammation and serve as indicators for biologic treatment in CRS.

METHODS: Patients ≥ 19 yo diagnosed with CRS undergoing functional endoscopic sinus surgery were included retrospectively. Demographics, past medical history, preoperative blood work, Lund-Mackay (LM), Lund Kennedy (LK), and SNOT-22 scores were extracted. Descriptive statistics and binary logistic regression analyses were conducted. Model superiority was based on Nagelkerke R2 scores and receiver operating characteristic curves.

RESULTS: Sixty-five patients, average age 49.96 ± 13.59 years, were included. Sixty-one binary logistic regression models for elevated serum IgE were created. Among the top 3 models, the best model had sensitivity, specificity, positive predictive value and negative predictive values of 82.1, 69.2, 80.0, and 72.0. All performance measures except sensitivity exceeded the Canadian Biologics Guideline model. Serum eosinophils ≥ 300 cell/uL, CRSwNP and LM ≥ 17 increased the odds of elevated IgE.

CONCLUSIONS: IgE-high type-2 inflammation can be predicted by a model that includes eosinophil ≥ 300 cell/uL, CRSwNP, LM ≥ 17, asthma diagnosis and SNOT-22 ≥ 40. Patients meeting these parameters have a high pretest probability for elevated IgE and would benefit from IgE serology to determine qualification for omalizumab. This could reduce unwarranted IgE serology in patients with CRSwNP but also target a patient population for further workup that will lead to optimization of resource allocation and improve healthcare equity in rural and remote areas within Canada.

PMID:35606866 | DOI:10.1186/s40463-022-00580-y

Breast Cancer Res. 2022 May 23;24(1):35. doi: 10.1186/s13058-022-01528-w.

ABSTRACT

BACKGROUND: CCR5 is a motility chemokine receptor implicated in tumor progression, whose activation and subsequent endocytosis may identify highly aggressive breast cancer cell subtypes likely to spread into the circulatory system.

METHODS: The MDA-MB-231 cell line was used to model and visualize CCR5 activation by stimulation with RANTES, in an effort to quantify CCR5 endocytosis from the cell surface to the perinuclear space. CCR5 expression was then examined in tumor-associated cells (TACs), consisting of circulating tumor cells and circulating stromal cells, isolated from the peripheral blood of 54 metastatic breast cancer (mBC) patients to evaluate these CCR5 pooling patterns as they relate to progression and survival over 2 years.

RESULTS: In MB231 experiments, it was observed that CCR5 formed ~ 1 micron clusters identified as “CCR5 pools” on the surface of the cell, which in the presence of RANTES were endocytosed and translocated to the cell cytoplasm. When TACs from patients were analyzed, CCR5 pools were observed on the cell surface and translocating to the nuclear area, with CCR5 also having a positive statistical correlation between increased numbers of TACs and increased CCR5 pools on the cells. Further, it was determined that patients with very high numbers of CCR5 (> 10 CCR5 pools), specifically in the circulating stromal cells, were associated with worse progression-free survival (hazard ratio = 4.5, p = 0.002) and worse overall survival (hazard ratio = 3.7, p = 0.014).

CONCLUSIONS: Using a liquid biopsy approach, we evaluated two populations of tumor-associated cells emanating from primary tumors, with data suggesting that upregulation of the motility chemokine CCR5 in TACs provides clinically relevant opportunities for treating and tracking drug targetable receptors in mBC.

PMID:35606863 | DOI:10.1186/s13058-022-01528-w