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Nevin Manimala Statistics

Risk Stratification of Acute Invasive Fungal Rhinosinusitis in Patients With Hematologic Pathology

Laryngoscope. 2022 Jun 18. doi: 10.1002/lary.30251. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study is to identify objective perioperative diagnostic factors for acute invasive fungal rhinosinusitis (AIFS) to create a diagnostic scoring system using objective criteria.

METHODS: Retrospective case-control study performed at an academic, tertiary care center. Biopsy-proven cases of AIFS identified from pathology records (2015-2019) were compared to patients the otolaryngology service was consulted to “Rule out AIFS” in the year 2019, only including those with underlying hematologic malignancy. Eighteen patients with AIFS and 20 patients without were included. One and two tailed T-tests were used for p-values. Receiver operating characteristic curves were generated for the significant data, and Youden’s J-statistic was used to create the ideal cutoff values for each. Likelihood ratios were used to give a power for the scoring system.

RESULTS: Compared to patients with non-hematologic malignancy-related AIFS, patients with hematologic malignancy-related AIFS have significantly elevated C-reactive protein (CRP) and blood glucose; while albumin, hematocrit, platelet count, and absolute neutrophil count (ANC) were found to be significantly lower. In addition, Lund-Mackay score asymmetry, extra-sinus spread, aspergillus antigen, and pre-existing diabetes mellitus correlated with disease. A scoring system with three categories: AIFS Unlikely, Indeterminate/AIFS Suspicious, and AIFS Highly Likely was developed.

CONCLUSION: Patients with hematologic malignancy-related AIFS have measurable differences in lab values and standard imaging that could be used in determining the diagnostic probability of AIFS including: CRP, albumin, hematocrit, platelets, ANC, blood glucose, aspergillus antigen, Lund-Mackay score asymmetry, extra-sinus spread, and pre-existing diabetes mellitus. A novel scoring system was proposed that will require prospective validation.

LEVEL OF EVIDENCE: 3 Laryngoscope, 2022.

PMID:35716357 | DOI:10.1002/lary.30251

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Nevin Manimala Statistics

Drug-associated hyperammonaemia: a Bayesian analysis of the WHO Pharmacovigilance Database

Ann Intensive Care. 2022 Jun 18;12(1):55. doi: 10.1186/s13613-022-01026-4.

ABSTRACT

BACKGROUND: Hyperammonaemia is frequent in Intensive Care Unit patients. Some drugs have been described as associated with this condition, but there are no large-scale studies investigating this topic and most descriptions only consist of case-reports.

METHODS: We performed a disproportionality analysis using VigiBase, the World Health Organization Pharmacovigilance Database, using the information component (IC). The IC compares observed and expected values to find associations between drugs and hyperammonaemia using disproportionate Bayesian reporting. An IC0.25 (lower end of the IC 95% credibility interval) > 0 is considered statistically significant. The main demographic and clinical features, confounding factors, and severity of cases have been recorded.

RESULTS: We identified 71 drugs with a disproportionate reporting in 2924 cases of hyperammonaemia. Most of the suspected drugs could be categorised into 4 main therapeutic classes: oncologic drugs, anti-epileptic drugs, immunosuppressants and psychiatric drugs. The drugs most frequently involved were valproic acid, fluorouracil, topiramate, oxaliplatin and asparaginase. In addition to these molecules known to be responsible for hyperammonaemia, our study reported 60 drugs not previously identified as responsible for hyperammonaemia. These include recently marketed molecules including anti-epileptics such as cannabidiol, immunosuppressants such as basiliximab, and anti-angiogenics agents such as tyrosine kinase inhibitors (sunitinib, sorafenib, regorafenib, lenvatinib) and monoclonal antibodies (bevacizumab, ramucirumab). The severity of cases varies depending on the drug class involved and high mortality rates are present when hyperammonaemia occurs in patients receiving immunosuppressant and oncologic drugs.

CONCLUSIONS: This study constitutes the first large-scale study on drug-associated hyperammonaemia. This description may prove useful for clinicians in patients’ care as well as for trial design.

PMID:35716335 | DOI:10.1186/s13613-022-01026-4

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Nevin Manimala Statistics

Do preferences differ based on respondent experience of a health issue and its treatment? A case study using a public health intervention

Eur J Health Econ. 2022 Jun 18. doi: 10.1007/s10198-022-01482-6. Online ahead of print.

ABSTRACT

OBJECTIVES: Preference information is increasingly being elicited to support decision-making. Although discrete choice experiments (DCEs) are commonly used, little is known about how respondents’ relative experience of a health issue, and its treatment, might impact the results of preference studies. The aim of this study was to explore how preferences differ between groups of individuals with varying levels of experience of a health issue and its treatment, using a weight loss maintenance (WLM) programme as a case study.

METHODS: An online DCE survey was provided to four groups, each differing in their level of experience with weight loss and WLM programmes. One group was recruited from a randomised controlled trial of a WLM programme (ISRCTN14657176) and the other three from an online panel. Choice data were analysed using mixed logit models. Relative attribute importance scores and willingness-to-pay (WTP) estimates were estimated to enable comparisons between groups.

RESULTS: Preferences differed between the groups across different attributes. The largest differences related to the outcome (weight re-gain) and cost attributes, resulting in WTP estimates that were statistically significantly different. The most experienced group was willing to pay £0.35 (95% CI: £0.28, £0.42) to avoid a percentage point increase in weight re-gain, compared with £0.12 (95% CI: £0.08, £0.16) for the least experienced group.

CONCLUSION: This study provides evidence in a public health setting to suggest that preferences differ based on respondent experience of the health issue and its treatment. Health preference researchers should therefore carefully consider the appropriate composition of their study samples.

PMID:35716317 | DOI:10.1007/s10198-022-01482-6

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Impact of a diabetes disease management program on guideline-adherent care, hospitalization risk and health care costs: a propensity score matching study using real-world data

Eur J Health Econ. 2022 Jun 18. doi: 10.1007/s10198-022-01486-2. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the impact of a DMP for patients with diabetes mellitus in a Swiss primary care setting.

METHODS: In a prospective observational study, we compared diabetes patients in a DMP (intervention group; N = 538) with diabetes patients receiving usual care (control group; N = 5050) using propensity score matching with entropy balancing. Using a difference-in-difference (DiD) approach, we compared changes in outcomes from baseline (2017) to 1-year (2017/18) and to 2-year follow-up (2017/19). Outcomes included four measures for guideline-adherent diabetes care, hospitalization risk, and health care costs.

RESULTS: We identified a positive impact of the DMP on the share of patients fulfilling all measures for guideline-adherent care [DiD 2017/18: 7.2 percentage-points, p < 0.01; 2017/19: 8.4 percentage-points, p < 0.001]. The hospitalization risk was lower in the intervention group in both years, but only statistically significant in the 1-year follow-up [DiD 2017/18: – 5.7 percentage-points, p < 0.05; 2017/19: – 3.9 percentage points, n.s.]. The increase in health care costs was smaller in the intervention than in the control group [DiD 2017/18: CHF – 852; 2017/19: CHF – 909], but this effect was not statistically significant.

CONCLUSION: The DMP under evaluation seems to exert a positive impact on the quality of diabetes care, reflected in the increase in the measures for guideline-adherent care and in a reduction of the hospitalization risk in the intervention group. It also might reduce health care costs, but only a longer follow-up will show whether the observed effect persists over time.

PMID:35716315 | DOI:10.1007/s10198-022-01486-2

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Nevin Manimala Statistics

Syndrome of inappropriate secretion of antidiuretic hormone as an initial sign of primary central nervous system lymphomas in the hypothalamus

Acta Neurol Belg. 2022 Jun 18. doi: 10.1007/s13760-022-01985-2. Online ahead of print.

ABSTRACT

BACKGROUND: Primary central nervous system lymphoma (PCNSL) rarely originates in the hypothalamus. Hypothalamic PCNSL can present with various symptoms specific to dysfunction of the hypothalamus, including consciousness disturbance, cognitive impairment, hypopituitarism, and diabetes insipidus (DI). However, it remains unclear whether syndrome of inappropriate secretion of antidiuretic hormone (SIADH) can present as an initial sign of hypothalamic PCNSL.

METHODS: Ninety-nine patients with PCNSL were diagnosed between January 2006 and December 2020 at our institutes. The initial symptoms and signs, hypothalamic-pituitary functions, serum sodium (Na) value, Karnofsky Performance Status (KPS) score on admission, and duration from onset to diagnosis were retrospectively investigated from the medical charts.

RESULTS: Eight and 91 patients had hypothalamic PCNSL (hypothalamic group) and PCNSL located in other regions (control group), respectively. Patients’ pathological diagnoses were diffuse large B-cell lymphoma (97 patients) and intravascular lymphoma (two patients). Six patients presented with hyponatremia derived from SIADH or suspected SIADH, and one presented with DI. Statistically significant differences between the hypothalamic and control groups were detected only in the preoperative serum Na values and KPS scores.

CONCLUSION: SIADH can be an initial presentation of hypothalamic PCNSL. Early detection of hypothalamic PCNSL from SIADH may lead to proper management and improved prognosis.

PMID:35716313 | DOI:10.1007/s13760-022-01985-2

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Pre-surgery immune profiles of adult glioma patients

J Neurooncol. 2022 Jun 18. doi: 10.1007/s11060-022-04047-y. Online ahead of print.

ABSTRACT

INTRODUCTION: Although immunosuppression is a known characteristic of glioma, no previous large studies have reported peripheral blood immune cell profiles prior to patient surgery and chemoradiation. This report describes blood immune cell characteristics and associated variables prior to surgery among typical glioma patients seen at a large University practice.

METHODS: We analyzed pre-surgery blood samples from 139 glioma patients diagnosed with a new or recurrent grade II/III glioma (LrGG, n = 64) or new glioblastoma (GBM, n = 75) and 454 control participants without glioma. Relative cell fractions of CD4, CD8, B-cells, Natural Killer cells, monocytes, and neutrophils, were estimated via a validated deconvolution algorithm from blood DNA methylation measures from Illumina EPIC arrays.

RESULTS: Dexamethasone use at time of blood draw varied by glioma type being highest among patients with IDH wild-type (wt) GBM (75%) and lowest for those with oligodendroglioma (14%). Compared to controls, glioma patients showed statistically significant lower cell fractions for all immune cell subsets except for neutrophils which were higher (all p-values < 0.001), in part because of the higher prevalence of dexamethasone use at time of blood draw for IDHwt GBM. Patients who were taking dexamethasone were more likely to have a low CD4 count (< 200, < 500), increased neutrophils, low absolute lymphocyte counts, higher total cell count and higher NLR.

CONCLUSION: We show that pre-surgery blood immune profiles vary by glioma subtype, age, and more critically, by use of dexamethasone. Our results highlight the importance of considering dexamethasone exposures in all studies of immune profiles and of obtaining immune measures prior to use of dexamethasone, if possible.

PMID:35716311 | DOI:10.1007/s11060-022-04047-y

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Urinary polycyclic aromatic hydrocarbon metabolites were associated with hypertension in US adults: data from NHANES 2009-2016

Environ Sci Pollut Res Int. 2022 Jun 18. doi: 10.1007/s11356-022-21391-8. Online ahead of print.

ABSTRACT

Polycyclic aromatic hydrocarbons (PAHs) are widely existing organic pollutants in the environment, and their persistence in the environment makes us have to pay continuous attention to their health effects. However, since the American Heart Association updated its definition of hypertension in 2017, few studies have explored the relationship. This study aimed to investigate the relationship between PAH exposure and hypertension after the updated definition of hypertension and explore whether body mass index (BMI) moderates this relationship. A total of 6332 adult participants from the 2009-2016 National Health and Nutrition Examination Survey (NHANES) were examined. Multiple logistic regression and restricted cubic splines were used to analyze the association between urinary polycyclic aromatic hydrocarbon metabolites and hypertension, and the dose-response relationship. Weighted quantile sum (WQS) regression was applied to blood pressure to reveal multiple exposure effects and the relative weights of each PAH. The prevalence of hypertension in the study population was 48.52%. There was a positive dose-response relationship between high exposure to 1-hydroxynaphthalene, 2&3-hydroxyphenanthrene, and the risk of hypertension. Naphthalene metabolites accounted for the most significant proportion of systolic blood pressure, and phenanthrene metabolites accounted for the most significant proportion of diastolic blood pressure. Obese individuals with high PAH exposure were at greater risk for hypertension than individuals with low PAH exposure and normal BMI. Higher prevalence rate and stronger association of metabolites with outcomes were obtained in the general population of the USA under the new guideline. High levels of exposure to PAHs were positively associated with the risk of hypertension, and these effects were modified by BMI.

PMID:35716300 | DOI:10.1007/s11356-022-21391-8

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Proteomics Reveals Long-Term Alterations in Signaling and Metabolic Pathways Following Both Myocardial Infarction and Chemically Induced Denervation

Neurochem Res. 2022 Jun 18. doi: 10.1007/s11064-022-03636-7. Online ahead of print.

ABSTRACT

Myocardial infraction (MI) is the principal risk factor for the onset of heart failure (HF). Investigations regarding the physiopathology of MI progression to HF have revealed the concerted engagement of other tissues, such as the autonomic nervous system and the medulla oblongata (MO), giving rise to systemic effects, important in the regulation of heart function. Cardiac sympathetic afferent denervation following application of resiniferatoxin (RTX) attenuates cardiac remodelling and restores cardiac function following MI. While the physiological responses are well documented in numerous species, the underlying molecular responses during the initiation and progression from MI to HF remains unclear. We obtained multi-tissue time course proteomics with a murine model of HF induced by MI in conjunction with RTX application. We isolated tissue sections from the left ventricle (LV), MO, cervical spinal cord and cervical vagal nerves at four time points over a 12-week study. Bioinformatic analyses consistently revealed a high statistical enrichment for metabolic pathways in all tissues and treatments, implicating a central role of mitochondria in the tissue-cellular response to both MI and RTX. In fact, the additional functional pathways found to be enriched in these tissues, involving the cytoskeleton, vesicles and signal transduction, could be downstream of responses initiated by mitochondria due to changes in neuronal pulse frequency after a shock such as MI or the modification of such frequency communication from the heart to the brain after RTX application. Development of future experiments, based on our proteomic results, should enable the dissection of more precise mechanisms whereby metabolic changes in neuronal and cardiac tissues can effectively ameliorate the negative physiological effects of MI via RTX application.

PMID:35716295 | DOI:10.1007/s11064-022-03636-7

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Prevalence and factors associated with thirst among postsurgical patients at University of Gondar comprehensive specialized hospital. Institution-based cross-sectional study

J Patient Rep Outcomes. 2022 Jun 18;6(1):69. doi: 10.1186/s41687-022-00476-5.

ABSTRACT

INTRODUCTION: Thirst is a powerfully distressing sensation that occurs most frequently in the immediate postoperative period. Postoperative thirst is prevalent, the moderate-to-severe type is estimated to affect 53.2-69.8% of patients and causes significant patient discomfort.

OBJECTIVE: The objective of this study was to assess the prevalence, and factors associated with postoperative thirst among surgical patients in PACU at the University of Gondar Comprehensive Specialized Hospital from April 20 to June 27, 2021.

METHODS: An institution-based cross-sectional study was conducted at the University of Gondar Comprehensive Specialized Hospital. A total of 424 participants were included in the study. Statistical analysis had performed using SPSS 26.00 version statistical software. Binary logistic regression analysis was performed to identify the association between the prevalence of postoperative thirst and independent variables and only variables with p-value < 0.2 were entered into the multivariable analysis. The strength of the association was presented by odds ratio and 95% Confidence interval. P-value < 0.05 was considered statistically significant.

RESULT: The prevalence of postoperative thirst among postsurgical patients was 59% (95% CI = 54.74-64.13). Inadequate preloading (Adjusted odes ratio (AOR) = 2.137 95% CI 1.260-3.624), prolonged Nil Per Os (NPO) time (AOR = 13.80 95% CI 2.93-65.37), general anesthesia (AOR = 3.90 95% CI 3.56-11.25), and axillary body temperature ≥ 37.5 °C (AOR = 8.07 95% CI 3.63-17.96) were significantly associated with postoperative thirst. Low room temperature (< 20 °C) was protective for the occurrence of postoperative thirst (AOR = 0.162 95% CI 0.37-0.707).

CONCLUSION AND RECOMMENDATIONS: The prevalence of postoperative thirst remains high and need commitment in close monitoring of PACU patients and immediate intervention. We also urge that high-level, ongoing research be conducted in this area, as postoperative thirst is a very common problem with a lot to discover.

PMID:35716262 | DOI:10.1186/s41687-022-00476-5

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Timing of NTRK Gene Fusion Testing and Treatment Modifications Following TRK Fusion Status Among US Oncologists Treating TRK Fusion Cancer

Target Oncol. 2022 Jun 18. doi: 10.1007/s11523-022-00887-w. Online ahead of print.

ABSTRACT

BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers with an estimated prevalence of less than 1% across all solid tumors. Tropomyosin receptor kinase inhibitors (TRKis) block the constitutively activated tyrosine receptor kinase (TRK) fusion protein produced in NTRK gene fusion positive (NTRK+) tumors from downstream signaling. Tropomyosin receptor kinase inhibitors are now first-line (1L) or subsequent treatment options for TRK fusion cancers.

OBJECTIVE: This study assessed timing of NTRK gene fusion testing and treatment modifications among patients with TRK fusion cancers.

PATIENTS AND METHODS: This was a one-time physician questionnaire with a retrospective, multisite patient chart abstraction of oncology practices in the USA. From June to September 2020, medical oncologists from the Oncology Provider Extended Network (OPEN) who treated patients with NTRK+ advanced/metastatic solid tumors abstracted information into electronic case report forms (eCRFs) for adult patients with advanced/metastatic solid tumors and a NTRK+ tumor test result with a known fusion partner. Use of NTRK testing in routine clinical practice among patients with advanced/metastatic solid tumors was assessed. Data included demographic, clinical, and NTRK gene fusion testing characteristics. Responses were summarized using descriptive statistics.

RESULTS: Twenty-eight community-based medical oncologists who had managed or treated 148 patients with advanced/metastatic TRK fusion cancer between 01/01/2016 and 12/31/2019 completed the survey. Lung (27%), thyroid (18%), salivary gland (14%), and colorectal (12%) were the most commonly reported tumor types. A majority (68%) tested NTRK status prior to 1L initiation; testing after disease progression on 1L (36%), 2L (25%), and 3L (21%) was also noted. Most oncologists (96%) reported no difficulty interpreting NTRK reports. Nearly all (96%) indicated using next-generation sequencing (NGS) for determining NTRK status. The majority (57%) indicated that age, tumor type, and performance status did not impact NTRK testing decisions. Less than half (46%) include TRKi therapy following NTRK+ determination. NTRK testing guidelines were commonly reviewed by physicians (89%).

CONCLUSION AND RELEVANCE: Among patients with advanced/metastatic TRK fusion cancer, medical oncologists reported testing for NTRK fusions at diagnosis or prior to 1L. Future research should elucidate why fewer than half of oncologists surveyed (46%) would not use TRKis after NTRK+ status confirmation, assess clinical practices among NTRK+ patients, and characterize treatment patterns and clinical outcomes in real-world settings.

PMID:35716252 | DOI:10.1007/s11523-022-00887-w