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Nevin Manimala Statistics

Impact of intraventricular hemorrhage symmetry on endoscopic third ventriculostomy with choroid plexus cauterization for posthemorrhagic hydrocephalus: an institutional experience of 50 cases

J Neurosurg Pediatr. 2022 Dec 30:1-7. doi: 10.3171/2022.12.PEDS22492. Online ahead of print.

ABSTRACT

OBJECTIVE: The success rate of endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) in the management of posthemorrhagic hydrocephalus (PHH) following intraventricular hemorrhage (IVH) in infants is not well defined. Furthermore, parameters of IVH at initial presentation have not been tested for predictive associations of ETV/CPC success in this setting. The authors sought to summarize their institutional outcomes to identify possible predictors of ETV/CPC success within this niche.

METHODS: A retrospective review was conducted of all ETV/CPC procedures performed at the authors’ institution for PHH between 2011 and 2021. Patients were screened against a set of selection criteria including follow-up time of at least 6 months. Associations with ETV/CPC failure were evaluated using regression and Kaplan-Meier analyses.

RESULTS: A total of 50 patients satisfied all criteria. There were 32 (64%) male and 18 (36%) female patients with a mean gestational birth age of 26 weeks. The presenting IVH was symmetric in 30 (60%) and asymmetric in 20 (40%) patients, and the maximum IVH grade was IV in 30 (60%) patients overall. Six months after the procedure, ETV/CPC success was seen in 18 (36%) patients and failure in 32 (64%) patients. The median overall follow-up was 42 months, at which point ETV/CPC success was observed in 11 (22%) patients and ETV/CPC failure in 39 (78%) patients. Regression analyses indicated that radiological IVH symmetry was a statistically significant predictor of ETV/CPC failure at 6 months (OR 3.46, p = 0.04) and overall (OR 5.33, p = 0.03). Overall rates of failure were 89% versus 62% (p = 0.02) when comparing symmetric versus asymmetric IVH patients, and time to failure occurred at median times of 1.4 versus 6.5 months (p = 0.03) after the initial procedure. Higher maximum IVH grade and younger age at initial ETV/CPC only trended toward increased failure rates. When the etiology component of the ETV Success Score was adjusted such that symmetric IVH was scored 0, the area under the curve for failure at 6 months increased from 0.58 to 0.69.

CONCLUSIONS: Overall, approximately 1 in 5 infants with PHH can expect to not require further intervention following ETV/CPC. The authors demonstrate that IVH symmetry is statistically predictive of ETV/CPC failure in this setting independent of all other parameters, where PHH infants with symmetric IVH are more likely to experience failure, and sooner, than PHH infants with asymmetric IVH. When discussing possible success rates of ETV/CPC for PHH, IVH symmetry should be considered.

PMID:36585872 | DOI:10.3171/2022.12.PEDS22492

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Nevin Manimala Statistics

Implementation of a spine triage program and its effect on outpatient radiology utilization

J Neurosurg Spine. 2022 Dec 30:1-9. doi: 10.3171/2022.11.SPINE22827. Online ahead of print.

ABSTRACT

OBJECTIVE: Clinical care pathways designed to triage spinal disorders have been shown to reduce wait times and improve patient satisfaction. The goal of this study was to perform an analysis of outpatient radiology costs before and after the implementation of a spine care triage pathway.

METHODS: All imaging orders and surgical procedures were captured in a prospective spine registry for patients referred to the department of neurosurgery within a single academic center between July 1, 2017, and November 3, 2020. A spine triage algorithm was developed and implemented January 1, 2018. Healthcare utilization was recorded for 1 year after the first appointment in the department of neurosurgery. Imaging costs were estimated using publicly available data from the Centers for Medicare and Medicaid Services. Statistical analysis consisted of an independent sample t-test or randomization test for continuous variables and a chi-square test for categorical variables.

RESULTS: A total of 3854 patients were included in this study. The mean age was 60 years (50.8% female) and 89.8% had undergone advanced imaging before being referred to the department of neurosurgery. In total, 12.6% of patients were referred with a specific surgical diagnosis (i.e., spinal stenosis, lumbar spondylolisthesis, etc.). During the pretriage phase 1810 patients were enrolled, and there were 2044 patients enrolled after the triage algorithm was implemented. Advanced imaging (CT or MRI) was ordered more frequently by providers before the triage program was initiated, with imaging ordered in 34% (617/1810) of patients pretriage versus 14.8% (302/2044) after the triage pathway was implemented (p < 0.001). The authors calculated a significant reduction in cost associated with reduced radiology utilization. Before triage, the cost of radiology utilization was $85,475/1000 patients compared with $40,107/1000 patients afterward (p < 0.001). The triage program did not change the utilization of surgery (14.6% before, 13.6% after).

CONCLUSIONS: Among patients treated after a spinal triage program was implemented in a single neurosurgery department, there was a substantial reduction in the use of advanced imaging and a 50% reduction in cost associated with outpatient radiology utilization. The triage program did not change the rate of spine surgery being performed.

PMID:36585871 | DOI:10.3171/2022.11.SPINE22827

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Nevin Manimala Statistics

Tumor sound, auditory cues, and tissue pathology in glioma surgery: a proof-of-concept study

J Neurosurg. 2022 Dec 30:1-9. doi: 10.3171/2022.11.JNS222114. Online ahead of print.

ABSTRACT

OBJECTIVE: Visual, tactile, and auditory cues are used during surgery to differentiate tissue type. Auditory cues in glioma surgery have not been studied previously. The objectives of this study were 1) to evaluate the feasibility of recording sound generated by the suction device during glioma surgery in matched tissue samples, and 2) to characterize the acoustic variation that occurs in different tissue samples.

METHODS: This was a prospective observational proof-of-concept study. Recordings were attempted in 20 patients in order meet the accrual target of 10 patients with matched sound and tissue data. For each patient, three 30- to 60-second recordings were made at these sites: normal white matter, infiltrative margin, and tumor. Tissue samples at each site were then reviewed by experienced neuropathologists, and agreement with surgical identification was estimated with the kappa statistic. Acoustic parameters were characterized for each sample.

RESULTS: Data from 20 patients were analyzed. Patient-related or technical issues resulted in missing data for 10 patients, but the final 10 patients had both audio and tissue data for analysis. Among all tissue samples, fair agreement was observed between surgeon identification and actual pathology (κ = 0.24, standard error 0.096, p = 0.006). Acoustic data suggested that 1) the acoustic stimulus is broadband, 2) acoustic features are somewhat consistent within cases, 3) high-entropy values indicate irregularity of sound over time, and 4) bimodal pitch distributions could differentially reflect cues of interest.

CONCLUSIONS: This study supports the feasibility of collecting intraoperative data on acoustic features during glioma surgery, and it provides an example of how an analysis could be performed to compare different types of tissues.

PMID:36585869 | DOI:10.3171/2022.11.JNS222114

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Sex differences in patient journeys to diagnosis, referral, and surgical treatment of trigeminal neuralgia: implications for equitable care

J Neurosurg. 2022 Dec 30:1-9. doi: 10.3171/2022.11.JNS221191. Online ahead of print.

ABSTRACT

OBJECTIVE: Trigeminal neuralgia (TN) is an orofacial pain disorder that is more prevalent in females than males. Although an increasing number of studies point to sex differences in chronic pain, how sex impacts TN patients’ journeys to care has not been previously addressed. This study sought to investigate sex differences in patients’ journeys to diagnosis, referral, and treatment of TN within a large national context.

METHODS: Patients with classic TN (n = 100; 50 females and 50 males) were randomly selected through chart reviews at the largest surgical treatment center for TN in Canada for a cross-sectional study. Statistical tests, including Welch’s t-test, the chi-square test, Pearson’s correlations, and analyses of covariance, were conducted with Python.

RESULTS: Key discrepancies between sexes in access to care were identified. Females had a significantly longer referral time interval (average 53.2 months vs 20.4 months, median 27.5 months vs 11.0 months, p = 0.018) and total time interval (average 121.1 months vs 67.8 months, median 78.0 months vs 45.2 months, p = 0.018) than males, despite reporting higher pain intensity at referral. Although medically intolerant patients had a significantly shorter referral time interval than medically tolerant patients (average 13.0 months vs 41.0 months, median 6.0 months vs 17.0 months, p < 0.001), medically tolerant females had a significantly longer referral time interval than medically tolerant males (average 59.9 months vs 21.7 months, median 30.0 months vs 12.0 months, p = 0.017). No statistically significant differences were detected between the sexes for diagnostic time interval (average 63.3 months vs 43.0 months, median 24.0 months vs 24.0 months, p = 0.263) or treatment time interval (average 4.6 months vs 4.7 months, median 4.0 months vs 3.0 months, p = 0.986).

CONCLUSIONS: Critical sex differences in patients’ journeys to TN surgical treatment were identified, with females enduring considerably longer referral timelines and expressing significantly greater pain intensity than males at referral. Taken together, our findings suggest the presence of unconscious bias and discrimination against females and highlight the need for expediting TN treatment referral for female TN patients.

PMID:36585864 | DOI:10.3171/2022.11.JNS221191

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Altered profile of plasma phospholipids in woman with recurrent pregnancy loss and recurrent implantation failure treated with lipid emulsion therapy

Am J Reprod Immunol. 2022 Dec 31. doi: 10.1111/aji.13673. Online ahead of print.

ABSTRACT

BACKGROUND: Recurrent Pregnancy Loss (RPL) and Recurrent Implantation Failure (RIF) are highly heterogeneous condition and many of the mechanisms involved still require elucidation. The aim was to analyze the lipidomic profile in plasma of women with RPL and RIF before and after receiving the Lipid Emulsion Therapy (LET) containing 10% fish oil (SMOFlipid® 20%).

METHODS: This study included twenty-six women with RPL or RIF from immunological or inflammatory causes, with elevated natural killer cell levels and divided into a Pregnancy Loss or a Live Birth group according to the outcome. The women received intravenous LET and sample collecting was done before the first, third and fifth dose of LET in the pregnant women. Ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF MS) and multivariate statistical methods were performed to evaluate the profile of phospholipids present in the women’s plasma.

RESULTS: An increase of phosphatidylcholines (PC) 40:8 and 36:5 levels with predominance of n6 polyunsaturated fatty acids (PUFA) was observed in plasma lipids of the Pregnancy Loss Group compared to Live Birth Group. We also observed an increase in the relative abundance of n3 PUFA-PC species (42:10 and 36:6) and LysoPC 15:0 with the long term use of LET.

CONCLUSION: The greater availability of n3 PUFA in plasma of the pregnant women stemming from LET use can be considered advantageous regarding the alteration of the phospholipid profile and its postulated anti-inflammatory and immunomodulatory role. This article is protected by copyright. All rights reserved.

PMID:36585861 | DOI:10.1111/aji.13673

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Nevin Manimala Statistics

Development and validation of an electronic health records-based opioid use disorder algorithm by expert clinical adjudication among patients with prescribed opioids

Pharmacoepidemiol Drug Saf. 2022 Dec 31. doi: 10.1002/pds.5591. Online ahead of print.

ABSTRACT

BACKGROUND: In the US, over 200 lives are lost from opioid overdoses each day. Accurate and prompt diagnosis of opioid use disorders (OUD) may help prevent overdose deaths. However, International Classification of Disease (ICD) codes for OUD are known to underestimate prevalence, and their specificity and sensitivity are unknown. We developed and validated algorithms to identify OUD in electronic health records (EHR) and examined the validity of OUD ICD codes.

METHODS: Through four iterations, we developed EHR-based OUD identification algorithms among patients who were prescribed opioids from 2014-2017. The algorithms and OUD ICD codes were validated against 169 independent “gold standard” EHR chart reviews conducted by an expert adjudication panel across four healthcare systems. After using 2014-2020 EHR for validating iteration 1, the experts were advised to use 2014-2017 EHR thereafter.

RESULTS: Of the 169 EHR charts, 81 (48%) were reviewed by more than one expert and exhibited 85% expert agreement. The experts identified 54 OUD cases. The experts endorsed all 11 OUD criteria from the Diagnostic and Statistical Manual of Mental Disorders-5, including craving (72%), tolerance (65%), withdrawal (56%), and recurrent use in physically hazardous conditions (50%). The OUD ICD codes had 10% sensitivity and 99% specificity, underscoring large underestimation. In comparison our algorithm identified OUD with 23% sensitivity and 98% specificity.

CONCLUSIONS AND RELEVANCE: This is the first study to estimate the validity of OUD ICD codes and develop validated EHR-based OUD identification algorithms. This work will inform future research on early intervention and prevention of OUD.

PMID:36585827 | DOI:10.1002/pds.5591

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Is anticholinergic and sedative drug burden associated with postdischarge institutionalization in community-dwelling older patients acutely admitted to hospital? A Norwegian registry-based study

Pharmacoepidemiol Drug Saf. 2022 Dec 30. doi: 10.1002/pds.5590. Online ahead of print.

ABSTRACT

PURPOSE: Investigate the association between anticholinergic (AC) and sedative (SED) drug burden before hospitalization and post-discharge institutionalization (PDI) in community-dwelling older patients acutely admitted to hospital.

METHODS: A cross-sectional study using data from the Norwegian Patient Registry and the Norwegian Prescription Database. We studied acutely hospitalized community-dwelling patients ≥70 years during 2013 (N=86,509). Patients acutely admitted to geriatric wards underwent subgroup analyses (n=1,715). We calculated drug burden by the Drug Burden Index (DBI), use of AC/SED drugs, and the number of AC/SED drugs. Piecewise linearity of DBI vs PDI and a knot point (DBI=2.45) was identified. Statistical analyses included an adjusted multivariable logistic regression model.

RESULTS: In the total population, 45.4% were exposed to at least one AC/SED drug, compared to 52.5% in the geriatric subgroup. AC/SED drugs were significantly associated with PDI. The DBI with Odds Ratios (ORs) of 1.11 (95% CI 1.07-1.15) for DBI<2.45 and 1.08 (95% CI 1.04-1.13) for DBI≥2.45. The number of AC/SED drugs with OR of 1.07 (95% CI 1.05-1.09). The AC component of DBI with OR 1.23 and the number of AC drugs with OR 1.13. In the subgroup, ORs were closer to 1 for AC drugs.

CONCLUSIONS: The use of AC/SED drugs was highly prevalent in older patients before acute hospital admissions, and significantly associated with PDI. The number, or just using AC/SED drugs, gave similar associations with PDI compared to applying the DBI. Using AC drugs showed higher sensitivity, indicating that to reduce the risk of PDI, a clinical approach could be to reduce the number of AC drugs.

PMID:36585814 | DOI:10.1002/pds.5590

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Design and characterization of lipid nanocarriers for oral delivery of immunotherapeutic peptides

J Biomed Mater Res A. 2022 Dec 30. doi: 10.1002/jbm.a.37477. Online ahead of print.

ABSTRACT

The use of therapeutic proteins and peptides is of great interest for the treatment of many diseases, and advances in nanotechnology offer a path toward their stable delivery via preferred routes of administration. In this study, we sought to design and formulate a nanostructured lipid carrier (NLC) containing a nominal antigen (insulin peptide) for oral delivery. We utilized the design of experiments (DOE) statistical method to determine the dependencies of formulation variables on physicochemical particle characteristics including particle size, polydispersity (PDI), melting point, and latent heat of melting. The particles were determined to be non-toxic in vitro, readily taken up by primary immune cells, and found to accumulate in regional lymph nodes following oral administration. We believe that this platform technology could be broadly useful for the treatment of autoimmune diseases by supporting the development of oral delivery-based antigen specific immunotherapies.

PMID:36585800 | DOI:10.1002/jbm.a.37477

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Health-related quality of life and productivity costs in breast cancer patients treated with tamoxifen in the Netherlands

Biomed Pharmacother. 2022 Dec 28;158:114158. doi: 10.1016/j.biopha.2022.114158. Online ahead of print.

ABSTRACT

The aim of this study was to describe health-related quality of life (HRQoL) and productivity in Dutch breast cancer patients treated with tamoxifen in an adjuvant setting. Patients who started treatment with a standard dose of tamoxifen and who gave written informed consent, were eligible for participation in this trial. A total of 145 patients were asked to complete a survey at 3 months (T1) and 6 months (T2) after initiation of tamoxifen. HRQoL was measured by the EQ-5D-5L and the FACT-B questionnaire, and productivity by using the iMTA Productivity Costs Questionnaire. At 3 months 137 (95%) and at 6 months 133 (92%) patients responded to the surveys. EQ-5D-5 L utility values for T1 and T2 were 0.81 ± 0.17 and 0.81 ± 0.18, respectively. FACT-B scores for T1 and T2 were 109 ± 17.9 and 108 ± 20.0, respectively. No differences in both EQ-5D-5 L utility and FACT-B scores were found between T1 and T2 (p > 0.05). Age and employment status were statistically significantly associated with FACT-B scores (p = 0.04 and p = 0.03, respectively), indicating that younger and unemployed respondents had lower FACT-B scores. Importantly, both short-term and long-term productivity improved during the first six months of tamoxifen treatment (p < 0.05). Here, short-term productivity losses (consisting of absenteeism, presenteeism and unpaid work) for T1 and T2 were estimated at € 855,- and € 396,-, respectively. Long-term productivity losses (consisting of absenteeism) for T1 and T2 were estimated at € 2876,- and € 1104,-, respectively. In conclusion, this study presents HRQoL scores using different instruments and detailed loss of productivity estimates for breast cancer patients treated with adjuvant endocrine therapy. The results presented here can be used to inform input parameters in health economic evaluations of interventions for patients with breast cancer in the Netherlands and other Western countries and ultimately support decision making.

PMID:36584427 | DOI:10.1016/j.biopha.2022.114158

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Octanol/Air Partition Coefficient─A General-Purpose Fragment Model to Predict Log Koa from Molecular Structure

Environ Sci Technol. 2022 Dec 30. doi: 10.1021/acs.est.2c06170. Online ahead of print.

ABSTRACT

The octanol/air partition coefficient Koa is important for assessing the bioconcentration of airborne xenobiotics in foliage and in air-breathing organisms. Moreover, Koa informs about compound partitioning to aerosols and indoor dust, and complements the octanol/water partition coefficient Kow and the air/water partition coefficient Kaw for multimedia fate modeling. Experimental log Koa at 25 °C has been collected from literature for 2161 compounds with molecular weights from 16 to 959 Da. The curated data set covers 18.2 log units (from -1.0 to 17.2). A newly developed fragment model for predicting log Koa from molecular structure outperforms COSMOtherm, EPI-Suite KOAWIN, OPERA, and linear solvation energy relationships (LSERs) regarding the root-mean-squared error (rms) and the maximum negative and positive errors (mne and mpe) (rms: 0.57 vs 0.86 vs 1.09 vs 1.19 vs 1.05-1.53, mne: -2.55 vs -3.95 vs -7.51 vs -7.54 vs (-5.63) – (-7.34), mpe: 2.91 vs 5.97 vs 7.54 vs 4.24 vs 6.89-10.2 log units). The prediction capability, statistical robustness, and sound mechanistic basis are demonstrated through initial separation into a training and prediction set (80:20%), mutual leave-50%-out validation, and target value scrambling in terms of temporarily wrong compound-Koa allocations. The new general-purpose model is implemented in a fully automatized form in the ChemProp software available to the public. Regarding Koa indirectly determined through Kow and Kaw, a new approach is developed to convert from wet to dry octanol, enabling higher consistency in experimental (and thus also predicted) Koa.

PMID:36584390 | DOI:10.1021/acs.est.2c06170