Nevin Manimala

Eur Arch Otorhinolaryngol. 2022 Dec 31. doi: 10.1007/s00405-022-07797-7. Online ahead of print.

ABSTRACT

BACKGROUND: The optimal treatments for adult benign laryngotracheal stenosis presently remains controversial. The majority of the disadvantages of endoscopic interventions with high recurrence rate and open surgical therapy accompanied by sophisticated techniques, complication and mortality, highlights the dilemma of option for treatments.

PURPOSE: To compare endoscopic treatments with open surgical interventions in adult patients with benign laryngotracheal stenosis, analyze their clinical outcomes, recurrence, complication and mortality.

METHODS: In the meta-analysis, the databases including PubMed, Embase, Ovid and Web of Science were searched for studies reporting adult benign laryngotracheal stenosis, and clinical outcomes were compared. The duplicate publications, reviews, comments or letters, conference abstracts, case reports were excluded. The random effect model was used for calculating the pooled effect estimates.

RESULTS: Eight studies (1627 cases) referring to six retrospective and two prospective researches were ultimately included in the meta-analysis. The decreased risk estimates of recurrence rate in patients receiving open surgical interventions were detected, comparing with endoscopic interventions (P < 0.05). Subgroup analysis revealed that decreased risk estimates of restenosis rate were also observed in patients receiving open surgical interventions compared with endoscopic interventions (P < 0.05), based on prospective studies, Europe and America, < 2-year follow-up, laryngeal stenosis, stenotic length without inter-group difference or stenotic grade II alone. However, there were no statistically significant difference of recurrence rate between the two interventions (P > 0.05) based on retrospective studies, South Asia and Africa, ≥ 2-year follow-up, involving tracheal lesion, stenotic length with inter-group difference, or stenotic grades of I-IV. No notable difference in the incidence of complication or mortality were identified.

CONCLUSIONS: Open surgical interventions were more suitable for most laryngotracheal stenosis without contraindications. Endoscopic interventions are increasingly being used to treat simple laryngotracheal stenosis, as well as complex airway stenosis in carefully selected cases. Multi-center prospective randomized controlled trials should be conducted to search for the standard treatments for laryngotracheal stenosis.

PMID:36585989 | DOI:10.1007/s00405-022-07797-7

Eur J Pain. 2022 Dec 31. doi: 10.1002/ejp.2074. Online ahead of print.

ABSTRACT

BACKGROUND: A recent randomized controlled trial (N=140) was indicative of large and sustained average improvements of internet-based exposure for fibromyalgia, as compared to a waitlist. However, little is known about who benefits the most from this treatment.

OBJECTIVES: To test for potential moderating effects of age, educational attainment, the duration of fibromyalgia, baseline overall fibromyalgia severity, pain intensity, fibromyalgia-related avoidance behavior, and symptom preoccupation on the waitlist-controlled effect of 10-weeks of internet-based exposure for fibromyalgia.

METHODS: Secondary analysis of a randomized controlled trial (ClinicalTrials.gov NCT02638636). We used linear mixed effects models to determine whether the waitlist-controlled effect of exposure therapy on overall fibromyalgia severity (Fibromyalgia Impact Questionnaire) differed as a function of the potential moderators.

RESULTS: Only pain intensity (0-10) was found to be a significant moderator, where a higher baseline pain intensity predicted a more limited waitlist-controlled effect of internet-based exposure (B=3.48, 95% CI: 0.84 – 6.13). Standardized point estimates of effects were small for the sociodemographic variables, and in the moderate range for some clinical variables that did not reach statistical significance such as behavioral avoidance and time with the fibromyalgia diagnosis.

CONCLUSIONS: Results suggest that internet-based exposure treatment was more useful for participants with lower baseline levels of pain, and less so for participants with higher baseline levels of pain. The treatment had relatively similar effects across the other tested moderators.

PMID:36585933 | DOI:10.1002/ejp.2074

Biometrics. 2022 Dec 31. doi: 10.1111/biom.13818. Online ahead of print.

ABSTRACT

In recent years, the field of precision medicine has seen many advancements. Significant focus has been placed on creating algorithms to estimate individualized treatment rules (ITRs), which map from patient covariates to the space of available treatments with the goal of maximizing patient outcome. Direct Learning (D-Learning) is a recent one-step method which estimates the ITR by directly modeling the treatment-covariate interaction. However, when the variance of the outcome is heterogeneous with respect to treatment and covariates, D-Learning does not leverage this structure. Stabilized Direct Learning (SD-Learning), proposed in this paper, utilizes potential heteroscedasticity in the error term through a residual reweighting which models the residual variance via flexible machine learning algorithms such as XGBoost and random forests. We also develop an internal cross-validation scheme which determines the best residual model amongst competing models. SD-Learning improves the efficiency of D-Learning estimates in binary and multi-arm treatment scenarios. The method is simple to implement and an easy way to improve existing algorithms within the D-Learning family, including original D-Learning, Angle-based D-Learning (AD-Learning), and Robust D-Learning (RD-Learning). We provide theoretical properties and justification of the optimality of SD-Learning. Head-to-head performance comparisons with D-Learning methods are provided through simulations, which demonstrate improvement in terms of average prediction error (APE), misclassification rate, and empirical value, along with a data analysis of an AIDS randomized clinical trial. This article is protected by copyright. All rights reserved.

PMID:36585916 | DOI:10.1111/biom.13818

Ann Neurol. 2022 Dec 31. doi: 10.1002/ana.26593. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore longitudinal changes in synaptic density after ischemic stroke in vivo with synaptic vesicle protein 2A (SV2A) PET.

METHODS: We recruited patients with an ischemic stroke to undergo ¹¹ C-UCB-J PET/MR within the first month and 6 months after stroke. We investigated longitudinal changes of partial volume corrected ¹¹ C-UCB-J SUVR (standardized uptake value ratio; relative to centrum semiovale) within the ischemic lesion, peri-ischemic area and unaffected ipsilesional and contralesional grey matter. We also explored crossed cerebellar diaschisis at 6 months. Additionally, we defined brain regions potentially influencing upper limb motor recovery after stroke and studied ¹¹ C-UCB-J SUVR evolution in comparison to baseline.

RESULTS: In 13 patients (age = 67±15 years) we observed decreasing ¹¹ C-UCB-J SUVR in the ischemic lesion (ΔSUVR = -1.0, p=0.001) and peri-ischemic area (ΔSUVR = -0.31, p=0.02) at 6 months after stroke compared to baseline. Crossed cerebellar diaschisis as measured with ¹¹ C-UCB-J SUVR was present in 11/13 (85%) patients at 6 months. ¹¹ C-UCB-J SUVR did not augment in ipsilesional or contralesional brain regions associated with motor recovery. On the contrary, there was an overall trend of declining ¹¹ C-UCB-J SUVR in these brain regions, reaching statistical significance only in the non-lesioned part of the ipsilesional supplementary motor area (ΔSUVR = -0.83, p=0.046).

INTERPRETATION: At 6 months after stroke, synaptic density further declined in the ischemic lesion and peri-ischemic area compared to baseline. Brain regions previously demonstrated to be associated with motor recovery after stroke did not show increases in synaptic density. This article is protected by copyright. All rights reserved.

PMID:36585914 | DOI:10.1002/ana.26593

J Clin Endocrinol Metab. 2022 Dec 31:dgac758. doi: 10.1210/clinem/dgac758. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: Hyperinsulinemia and adiposity are associated with one another, but the directionality of this relation is debated. Here, we tested the direction of the causal effects of fasting insulin (FI) levels, body fat accumulation/distribution using two-sample bidirectional Mendelian randomization (MR).

METHODS: We included summary statistics from large-scale genome-wide association studies for body mass index (BMI, n=806,834), waist-to-hip ratio adjusted for BMI (WHRadjBMI, n=694,649), abdominal subcutaneous, visceral, and gluteofemoral adipose tissue (n=38,965), FI levels (n=98,210), pancreatic islets gene expression (n=420) and hypothalamus gene expression (n=155). We used inverse variance-weighted and robust MR methods that relied on statistically and biologically driven genetic instruments.

RESULTS: Both BMI and WHRadjBMI were positively associated with FI. Results were consistent across all robust MR methods and when variants mapped to the hypothalamus (presumably associated with food behaviour) were included. In multivariable MR analyses, when waist circumference and BMI were mutually adjusted, the direct effect of waist circumference on FI was 2.43 times larger than the effect of BMI on FI. FI was not associated with adiposity. By contrast, using genetic instruments mapped to gene expression in pancreatic islets (presumably more specific to insulin secretion), insulin was positively associated with BMI and abdominal subcutaneous and gluteofemoral adipose tissue, but not with visceral adipose tissue.

CONCLUSIONS/INTERPRETATION: Although these results will need to be supported by experimental investigations, results of this MR study suggest that abdominal adiposity may be a key determinant of circulating insulin levels. Alternatively, insulin secretion may promote peripheral adipose tissue accumulation.

PMID:36585897 | DOI:10.1210/clinem/dgac758

J Am Geriatr Soc. 2022 Dec 31. doi: 10.1111/jgs.18166. Online ahead of print.

ABSTRACT

BACKGROUND: Primary care is essential for persons with Alzheimer’s disease and related dementias (ADRD). Prior research suggests that the propensity to provide high-quality, continuous primary care varies by provider setting, but the settings used by Medicare-Medicaid dual-eligibles with ADRD have not been described at the population level.

METHODS: Using 2012-2018 Medicare data, we identified dual-eligibles with ADRD. For each person-year, we identified primary care visits occurring in six settings. We calculated descriptive statistics for beneficiaries with a majority of visits in each setting, and conducted a k-means cluster analysis to determine utilization patterns, using the standardized count of primary care visits in each setting.

RESULTS: Each year from 2012 to 2018, at least 45.6% of dual-eligibles with ADRD received a majority of their primary care in nursing facilities, while at least 25.2% did so in physician offices. Over time, the share relying on nursing facilities for primary care decreased by 5.2 percentage points, offset by growth in Federally Qualified Health Centers (FQHCs) and miscellaneous settings (2.3 percentage points each). Dual-eligibles relying on nursing facilities had more annual primary care visits (16.1) than those relying on other settings (range: 6.8-10.7 visits). Interpersonal care continuity was also higher in nursing facilities (97.0%) and physician offices (87.9%) than in FQHCs (54.2%), rural health clinics (RHCs, 46.6%), or hospital-based clinics (56.8%). Among dual-eligibles without care continuity, 82.7% were assigned to a cluster with few primary care visits.

CONCLUSIONS: A trend toward care in different settings likely reflects improved access to patient-centered primary care. Low rates of interpersonal care continuity in FQHCs, RHCs, and physician offices may warrant concern, unless providers in these settings function as a care team. Nonetheless, every healthcare system encounter presents an opportunity to designate a primary care provider for dual-eligibles with ADRD who use little or no primary care.

PMID:36585893 | DOI:10.1111/jgs.18166

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

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

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

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