Sex Differences in Inflammation-Related Biomarkers Detected with OCT in Patients with Diabetic Macular Edema.

Purpose: To investigate sex-based differences in inflammation-related biomarkers on spectral-domain OCT. Design: Cross-sectional study. Participants: Patients with diabetic macular edema (DME) between February 1, 2019, and March 31, 2023, without intravitreal anti-VEGF injection within the previous 6 months. Methods: We reviewed each patient's medical record for age, biological sex, race and ethnicity, most recent glycated hemoglobin A1c (HbA1c) level, visual acuity (VA), and central macular thickness (CMT). OCT biomarkers that have been found in literature to be associated with inflammation, including disorganization of retinal inner layers (DRIL), retinal hyperreflective retinal foci (HRFs), hyperreflective choroidal foci (HCFs), subfoveal neuroretinal detachment (SND), and perturbation in retinal nerve fiber layer thickness, ganglion cell layer thickness, and inner nuclear layer (INL) thickness were evaluated by graders masked to the clinical characteristics of the patients. We performed multivariable regression analyses with the OCT biomarkers as the outcome variables and sex, age, HbA1c, and CMT as independent variables. Main Outcome Measures: OCT inflammation-related biomarkers, as listed above. Results: Female patients were, on average, 2 years older than male patients (P = 0.041). There were no significant differences in race and ethnicity, HbA1c, VA, or CMT between male and female patients. After controlling for age, HbA1c, and CMT, we found male sex to be associated with more HRF (incidence rate ratio [IRR] = 1.19; 95% confidence interval [CI] = 1.10-1.29), more HCF (odds ratio = 2.01; 95% CI = 1.12-3.64), and thicker INL (7 µm thicker in males; 95% CI = 2-12). Sex was not a significant predictor for either DRIL or SND in the multivariable regression models. Patients with higher HbA1c were more likely to have more HRF (IRR = 1.02 per 1 point increase; 95% CI = 1.00-1.04) after controlling for other factors. Conclusions: Male sex was correlated with more inflammation-related biomarkers on OCT including more HRF, more HCF, and thicker INL, after accounting for age, glycemic control, and amount of DME. Further studies are needed to evaluate the potential implications of these sex-based differences for individualized treatment. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Low-cost and convenient screening of disease using analysis of physical measurements and recordings.

In recent years, there has been substantial work in low-cost medical diagnostics based on the physical manifestations of disease. This is due to advancements in data analysis techniques and classification algorithms and the increased availability of computing power through smart devices. Smartphones and their ability to interface with simple sensors such as inertial measurement units (IMUs), microphones, piezoelectric sensors, etc., or with convenient attachments such as lenses have revolutionized the ability collect medically relevant data easily. Even if the data has relatively low resolution or signal to noise ratio, newer algorithms have made it possible to identify disease with this data. Many low-cost diagnostic tools have been created in medical fields spanning from neurology to dermatology to obstetrics. These tools are particularly useful in low-resource areas where access to expensive diagnostic equipment may not be possible. The ultimate goal would be the creation of a "diagnostic toolkit" consisting of a smartphone and a set of sensors and attachments that can be used to screen for a wide set of diseases in a community healthcare setting. However, there are a few concerns that still need to be overcome in low-cost diagnostics: lack of incentives to bring these devices to market, algorithmic bias, "black box" nature of the algorithms, and data storage/transfer concerns.

Radiofrequency ablation for the treatment of uterine fibroids: A systematic review and meta-analysis by the AAGL Practice Committee.

OBJECTIVE: To systematically review clinical and patient-reported outcomes after radiofrequency ablation (RFA) for the treatment of uterine fibroids. DATA SOURCES: We searched Medline, EMBASE, Cochrane Registry of Controlled Trials (CENTRAL) on September 8, 2023, and requested additional data from industry sources. We included published, peer-reviewed studies of patient-centered outcomes of RFA when used for symptomatic fibroids. Abstracts and potentially relevant full-text articles were screened and data were extracted regarding study characteristics, arms, outcomes, and results, together with risk of bias assessment. METHODS OF STUDY SELECTION: We included 30 studies published in 49 articles (3 randomized controlled trials, 1 nonrandomized comparative study, and 26 single-group studies, as well as 4 publications from the TRUST Study) with variable risks of bias. TABULATION, INTEGRATION, AND RESULTS: The study populations were demographically diverse and clinically heterogeneous. Across studies, RFA treatment was associated with fibroid volume reduction of 46.0% (95% confidence interval [CI] 52.1, 40.0; 11 studies) at 3 months and 65.4% (95% CI 74.7, 56.1; 10 studies) at 12 months. All studies reported a decrease in proportion of patients experiencing abnormal, heavy, or prolonged menstrual bleeding, with the most substantial improvement within the first 3 months. Meta-analyses of health-related quality of life (HRQOL) scores demonstrated significant improvements in scores from baseline for Uterine Fibroid Symptoms and Quality of Life [UFS-QOL] (53.4, 95% CI 48.2, 58.5; 19 studies), EuroQol 5 Dimension [EQ-5D] (71.6, 95% CI 65.0, 78.1; 4 studies), and Symptom Severity Score [SSS] (52.2, 95% CI 46.4, 58.1; 17 studies), with a peak at 6 months on the UFS-QOL scale (88.0, 95% CI 83.0, 92.9; 11 studies), a peak at 24 months on the EuroQol-5D scale (88.3, 95% CI 86.0, 90.6; 2 studies), and a trough at 12 months for SSS (12.8, 95% CI 7.0, 18.6; 11 studies). Studies mostly demonstrated return to work and normal activities within 2 weeks. Reported unplanned hospitalizations were infrequent, and durations of hospital stay were generally short. Post-procedure complications were inconsistently reported, but assessed overall to be infrequent. Long-term need for medical and surgical re-intervention varied. Post-RFA hysterectomy rates ranged from 2/205 (1.0%) to 15/62 (24.1%) with variable follow-up periods ranging from 45 days to 74 months. Most studies did not include patients who desired to maintain fertility; thus, reproductive data are insufficient for interpretation. CONCLUSION: There is a paucity of comparative studies, and the small number of RCTs are limited by lack of blinding. Few studies had the long-term follow-up time required to draw definitive conclusions regarding the durability of symptom relief. However, despite these limitations, there is overall agreement on several important clinical measures following RFA, such as decreased fibroid volume, improved uterine bleeding and improved quality of life. Future high quality randomized controlled trials with standardized outcomes measures are required to better characterize the use of RFA among fibroid patients.

Relationships of B12 and Homocysteine with Outcomes in the SURE-PD, SURE-PD3, and STEADY-PDIII Trials.

Background: DATATOP was a study of early Parkinson's disease (PD) conducted in the 1980 s, before mandatory folic acid fortification in the United States. Our analysis of its baseline serum samples revealed a geometric mean vitamin B12 of 369 pg/mL and homocysteine (tHcy) of 9.5µmol/l. We also found that low B12 predicted greater worsening of ambulatory capacity (AC) and elevated tHcy (>15µmol/L) predicted greater declines in cognitive function. Objective: We sought to measure B12 and tHcy in contemporary trial participants with early PD who had not started dopaminergic treatment and to determine whether these analytes were associated with clinical progression. Methods: We measured B12 and tHcy from baseline and end-of-study blood samples from three recent clinical trials. Results: Baseline geometric mean B12 levels for these studies ranged from 484- 618 pg/ml and for tHcy ranged from 7.4- 10µmol/L. Use of B12-containing supplements ranged from 41- 61%, and those taking supplements had higher B12 and lower tHcy. Those who began levodopa, but were not taking B12-supplements, had greater end-of-study tHcy. There was no association of baseline tHcy > 15µmol/L with annualized change in Montreal Cognitive Assessment and no association of baseline B12 tertiles with change in AC. Conclusions: In these longitudinal trials, B12 levels were higher than for DATATOP, due in large part to increased B12-supplement intake, while tHcy levels were similar. Initiation of levodopa was associated with increases of tHcy in those not taking a B12-containing supplement. These smaller studies did not replicate prior findings of low B12 and elevated tHcy with features of progression, possibly due to higher baseline B12.

Blood Pressure and Cardiovascular Risk in Women With Breast Cancer: The Pathways Heart Study.

Background: Hypertension is an important contributor to cardiovascular disease (CVD) in breast cancer (BC) survivors; however, research on blood pressure (BP) and CVD outcomes in BC survivors is limited. Objectives: The purpose of this study was to better characterize the association between BP and CVD in a large, longitudinal cohort of BC patients. Methods: Women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California were matched 1:5 to women without BC. Patient data were obtained from electronic health records. Multivariable Cox regression and penalized spline models were used to explore the linear and nonlinear relationship of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on CVD outcomes. Results: BC cases (n = 12,713) and controls (n = 55,886) had median follow-up of 9.6 years (IQR: 5.0-11.9 years). Women with BC had a mean age of 60.6 years; 64.8% were non-Hispanic White. For ischemic heart disease (IHD), every 10 mmHg increase in SBP and DBP was associated with 1.23 (95% CI: 1.14-1.33) and 1.10 (95% CI: 0.98-1.24) risk, respectively, in women with BC. For stroke, every 10 mmHg increase in SBP and DBP was associated with a 1.45 (95% CI: 1.34-1.58) and 1.91 (95% CI: 1.68-2.18) risk, respectively. A U-shaped relationship was observed between heart failure/cardiomyopathy and BP. The associations between BP and risk of IHD, stroke, and any primary CVD were not statistically different comparing women with BC to controls, but risks varied by BC status for heart failure/cardiomyopathy (P for interaction = 0.01). Conclusions: Women with and without BC showed similar risks for IHD, stroke, and any primary CVD suggesting similar BP targets should be pursued regardless of BC survivorship status.

SSN2: The next generation of spatial stream network modeling in R.

The SSN2 R package provides tools for spatial statistical modeling, parameter estimation, and prediction on stream (river) networks. SSN2 is the successor to the SSN R package (Ver Hoef, Peterson, Clifford, & Shah, 2014), which was archived alongside broader changes in the R-spatial ecosystem (Nowosad, 2023) that included 1) the retirement of rgdal (Bivand, Keitt, & Rowlingson, 2021), rgeos (Bivand & Rundel, 2020), and maptools (Bivand & Lewin-Koh, 2021) and 2) the lack of active development of sp (Bivand, Pebesma, & Gómez-Rubio, 2013). SSN2 maintains compatibility with the input data file structures used by the SSN R package but leverages modern R-spatial tools like sf (Pebesma, 2018). SSN2 also provides many useful features that were not available in the SSN R package, including new modeling and helper functions, enhanced fitting algorithms, and simplified syntax consistent with other R generic functions.

Intergrader Agreement in Grading Optical Coherence Tomography Morphologic Features in Eyes With Intermediate Nonexudative Age-Related Macular Degeneration.

Purpose: To determine the reliability of a nine-point summary scale for grading intermediate age-related macular degeneration (AMD) image morphologic features based on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Methods: Two trained graders independently divided spectral domain-optical coherence tomography (SD-OCT) scans into nine subfields and then graded each subfield for the presence of intraretinal hyperreflective foci (HRF), reticular pseudodrusen (RPD), and incomplete or complete retinal pigment epithelium and outer retinal atrophy (iRORA or cRORA). Grading results were assessed by summing the subfield grades into a nine-point summary score and also by using an eye-level binary grade for presence of the finding in any subfield. Gwet's first-order agreement coefficient (AC1) was calculated to assess intergrader agreement. Results: Images of 79 eyes from 52 patients were evaluated. Intergrader agreement was higher when the OCT grades were summarized with a nine-point summary score (Gwet's AC1 0.92, 0.89, 0.99, and 0.99 for HRF, RPD, iRORA, and cRORA, respectively) compared with the eye-level binary grade (Gwet's AC1 0.75, 0.76, 0.97, and 0.96 for HRF, RPD, iRORA, and cRORA, respectively), with significant differences detected for HRF and RPD. Conclusions: The use of a nine-point summary score showed higher reliability in grading when compared to the binary subfield- and eye-level data, and thus may offer more precise estimation of AMD disease staging. Translational Relevance: These findings suggest that a nine-point summary score could be a useful means of disease staging by using findings on OCT in clinical studies of AMD.

Retisert implantation without incisional sclerotomy in patients with uveitis and extensive pars plana fibrosis.

Purpose: To describe an alternate surgical technique for fluocinolone acetonide (Retisert) implantation in patients with extensive pars plana and pars plicata fibrosis secondary to chronic non-infectious uveitis. Methods: This retrospective, interventional case series included five eyes of four patients who had poorly controlled chronic non-infectious uveitis. Retisert was implanted successfully using a novel approach. The device was introduced into the posterior segment through the anterior chamber and posterior capsulotomy, forgoing the need for full-thickness scleral incision and minimizing the risk of retinal detachment and associated complications. Results: Five eyes underwent passage of Retisert implant through the anterior segment via a limbal incision and a posterior capsulotomy. Retisert was successfully implanted in all patients in the posterior chamber. No intraoperative or postoperative complications were encountered. Up until the last follow-up, all eyes demonstrated the stability of the implant. Visual acuity improved in four out of five eyes. Conclusions: Retisert can be implanted via the anterior chamber in patients with extensive fibrosis in the pars plana and pars plicata regions. This approach may minimize the risk of retinal traction and damage to the implant when compared to the traditional full-thickness sclerotomy method in these high-risk cases.

High Variability in Standardized Outcome Thresholds of Clinically Important Changes in Shoulder Instability Surgery: A Systematic Review.

PURPOSE: The purpose of this study was to examine reported MCID and PASS values for PROMs following shoulder instability surgery and assess variability in published values depending on the surgery performed. Secondarily, our aims were to describe the methods used to derive MCID and PASS values in the published literature, including anchor-based, distribution-based, or other approaches, and to assess the frequency of MCID and PASS usage in studies on shoulder instability surgery. METHODS: A systematic review of MCID and PASS values following Bankart, Latarjet, and Remplissage procedures was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The Embase, Pubmed, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were queried from 1985 to 2023. Inclusion criteria included studies written in English, and studies reporting utilization MCID or PASS for patient reported outcome measures (PROMS) following Latarjet, Bankart, Remplissage approaches for shoulder instability surgery. Extracted data included study population characteristics, intervention characteristics, and outcomes of interest. Continuous data were described using median and range. Categorical variables, including PROMs reported and MCID/PASS methods, were described using percentages. As MCID is a patient-level metric and not a group-level metric, the authors validated that all included studies reported proportions (%) of subjects that met or exceeded the MCID. RESULTS: A total of 174 records were screened, and 8 studies were included in this review. MCID was the most widely utilized outcome threshold which was reported in all 8 studies, with only 2 studies reporting both the MCID and the PASS. The most widely studied PROMs were the American Shoulder and Elbow Surgeons (ASES) (range 5.65-9.6 for distribution MCID, 8.5 anchor MCID, 86 anchor PASS); Single Assessment Numeric Evaluation (SANE) (range 11.4-12.4 distribution MCID, 82.5-87.5 anchor PASS); visual analog scale (VAS) (range 1.1-1.7 distribution MCID, 1.5-2.5 PASS); Western Ontario Shoulder Instability Index (WOSI) (range 60.7-254.9 distribution MCID, 126.43 anchor MCID, 571-619.5 anchor PASS); and Rowe scores (range 5.6-8.4 distribution MCID, 9.7 anchor MCID). Notably, no studies reported on substantial clinical benefit (SCB) or maximal outcome improvement (MOI). CONCLUSION: Despite the wide array of available PROMs for assessing shoulder instability surgery outcomes, the availability of clinically significant outcome thresholds such as MCID and PASS remains relatively limited. While MCID has been the most frequently reported metric, there is considerable inter-study variability observed in their values. CLINICAL RELEVANCE: Knowing the outcome thresholds such as MCID and PASS of the PROMs frequently used to evaluate the results of glenohumeral stabilization surgery is fundamental, since they allow us to know what is a clinically significant improvement for the patient.

Single-shot interscalene block with liposomal bupivacaine vs. non-liposomal bupivacaine in shoulder arthroplasty.

BACKGROUND: Regional anesthesia is a valuable component of multimodal pain control in total shoulder arthroplasty (TSA), and multiple interscalene block anesthetic options exist, including nonliposomal interscalene bupivacaine (NLIB) and liposomal interscalene bupivacaine (LIB). The purpose of this study was to compare pain control and opioid consumption within 48 hours postoperation in those undergoing TSA with either LIB or NLIB. METHODS: This was a retrospective cohort study at a single academic medical center including consecutive patients undergoing inpatient (>23-hour hospitalization) primary anatomic or reverse TSA from 2016 to 2020 who received either LIB or an NLIB for perioperative pain control. Perioperative patient outcomes were collected including pain levels and opioid usage, as well as 30- and 90-day emergency department (ED) visits or readmissions. The primary outcome was postoperative pain and opioid use. RESULTS: Overall, 489 patients were included in this study (316 LIB and 173 NLIB). Pain scores at 3, 6, 12, and 48 hours postoperatively were not statistically significantly different (P > .05 for all). However, the LIB group had improved pain scores at 24 and 36 hours postoperation (P < .05 all). There was no difference in the incidence of severe postoperative pain, defined as a 9 or 10 numeric rating scale-11 score, between the 2 anesthesia groups after adjusting for preoperative pain and baseline opioid use (odds ratio 1.25, 95% confidence interval 0.57-2.74; P = .57). Overall, 99 of 316 patients receiving LIB (31.3%) did not require any postoperative opioids compared with 38 of 173 receiving NLIB (22.0%); however, this difference was not statistically significant after adjusting for prior opioid use and preoperative pain (P = .33). No statistically significant differences in postoperative total morphine equivalents or mean daily morphine equivalents consumed between the groups were found during their hospital stays (P > .05 for both). Finally, no significant differences were found in 30- and 90-day ED visits or readmission rates (all P > .05). CONCLUSION: LIB and NLIB demonstrated differences in patient-reported pain scores at 24 and 36 hours postoperation, although these did not reach clinical significance. There were no statistically significant differences in opioid consumption during the hospital stay, including opioid use, total morphine equivalents, and daily mean morphine equivalents consumed during the hospital stay. Additionally, no differences were observed in 30- and 90-day ED visits or readmission rates.

Evidence for direct CO2 -mediated alterations in cerebral oxidative metabolism in humans.

AIM: How the cerebral metabolic rates of oxygen and glucose utilization (CMRO2 and CMRGlc, respectively) are affected by alterations in arterial PCO2 (PaCO2) is equivocal and therefore was the primary question of this study. METHODS: This retrospective analysis involved pooled data from four separate studies, involving 41 healthy adults (35 males/6 females). Participants completed stepwise steady-state alterations in PaCO2 ranging between 30 and 60 mmHg. The CMRO2 and CMRGlc were assessed via the Fick approach (CBF × arterial-internal jugular venous difference of oxygen or glucose content, respectively) utilizing duplex ultrasound of the internal carotid artery and vertebral artery to calculate cerebral blood flow (CBF). RESULTS: The CMRO2 was altered by 0.5 mL × min-1 (95% CI: -0.6 to -0.3) per mmHg change in PaCO2 (p < 0.001) which corresponded to a 9.8% (95% CI: -13.2 to -6.5) change in CMRO2 with a 9 mmHg change in PaCO2 (inclusive of hypo- and hypercapnia). The CMRGlc was reduced by 7.7% (95% CI: -15.4 to -0.08, p = 0.045; i.e., reduction in net glucose uptake) and the oxidative glucose index (ratio of oxygen to glucose uptake) was reduced by 5.6% (95% CI: -11.2 to 0.06, p = 0.049) with a + 9 mmHg increase in PaCO2. CONCLUSION: Collectively, the CMRO2 is altered by approximately 1% per mmHg change in PaCO2. Further, glucose is incompletely oxidized during hypercapnia, indicating reductions in CMRO2 are either met by compensatory increases in nonoxidative glucose metabolism or explained by a reduction in total energy production.

Creative Arts Therapies in Rehabilitation.

Appreciation for the utility of creative arts therapy in rehabilitation is on the rise. The limitations of conventional approaches to address posttraumatic stress disorder and co-occurring traumatic brain injury is spurring the development and increased use of creative arts therapies, especially in US military health care systems. However, emerging applications of creative arts therapies in rehabilitation extend well beyond posttraumatic stress disorder/traumatic brain injury and military populations to span the continuum of care, from the intensive care unit, postoperative recovery unit, acute inpatient medical and surgical wards, outpatient clinics, and home health, as well as in traditional long-term care and psychiatric settings. Critical steps to more fully integrating creative arts therapies in rehabilitation include the following: (1) incorporation of education about creative arts therapies into the curricula across rehabilitation disciplines; (2) alteration of national and state policies to promote greater inclusion of creative arts therapies as reimbursable treatments for a wide array of clinical diagnoses and conditions; and (3) significant expansion of creative arts therapies' evidence base. This can be achieved by increasing funding levels to encourage rigorously designed and controlled studies to determine the efficacy, populations, diagnoses and conditions, cofactors, and the mechanisms of action of creative arts therapies. The time has come for a concentrated effort from the community of rehabilitation professional associations, advocacy organizations, and practitioners to promote the advancement and inclusion of creative arts therapies into appropriate clinical settings to optimize outcomes for patients.

ASPEN survey of parenteral nutrition access issues: How the system fails the patient.

BACKGROUND: Product shortages and a lack of qualified providers to manage care may impact the safety and efficacy of parenteral nutrition (PN). This survey assessed the frequency and extent to which limitations to PN-related access affects patients. METHODS: Outpatient/patients receiving home PN were surveyed. Questions were developed to characterize the population and determine the extent and severity of PN access issues with components, devices, healthcare professionals, and transfers of care. Reimbursement issues surveyed included insurance coverage, contribution of healthcare costs to annual income, and the extent to which adjunctive therapy was reimbursed. Burdens surveyed included impact on disease symptoms and medical outcomes as well as the types and frequency of medical or system errors experienced, adverse events, or resultant nutrition problems. RESULTS: Respondents (N = 170) were well educated, rented or owned their own home, and were either employed or retired. All age populations were represented. Patients made frequent contact with care providers. Most were able to manage PN costs but feared losing insurance or changes to insurance. Patients used additional prescribed therapies that are poorly covered by insurance. Patients reported symptoms or exacerbation of disease, development or worsening of malnutrition, and episodes of nutrient deficiency. Patients noted errors occur, especially during periods of transitions of care, when they also often encounter clinicians with little understanding of PN. These are high-acuity patients who have difficulty finding providers for their care. CONCLUSION: This patient survey provides evidence that access issues can result in the "failure of the PN system" to assure care is consistently safe and effective.

X-ray Imaging Versus Anatomical Dissection for Identification of the Fabella.

INTRODUCTION: Reported prevalence rates of the fabella sesamoid bone vary widely, particularly between studies based on either X-ray imaging or anatomical dissection approaches. The purpose of this study was to directly compare these two methodologies in their detection of fabellae and investigate whether variability in the density of fabellae could explain any discrepancies. METHODS: Fifty cadaveric knee segments were examined for the presence of a fabella by both X-ray imaging and anatomical dissection. The relative density of each excised fabella specimen was then quantified using a separate set of radiographs.  Results: Fabellae were detected in 40% of the sample knees via a manual dissection approach but in just 12% of those same specimens using X-ray imaging. Relative density measurements confirmed that fabellae identifiable only via dissection were significantly less dense than fabellae visible in whole knee radiographs but denser than the surrounding tissue. CONCLUSION: Radiology cannot reliably detect cartilaginous or incompletely ossified fabellae, which were found in 28% of the study population. Clinicians should consider the potential occurrence of a fabella when diagnosing posterolateral knee pain, even if it may not be visible via X-ray.

Parenteral nutrition compatibility and stability: Practical considerations.

Parenteral nutrition (PN) is a complex preparation that contains multiple component products with the associated risk for incompatibilities and diminished stabilities when combined together as an admixture. Significant patient harm can result from prescribing, preparing, and administering PN without confirming compatibility and stability. Incompatibility or instability is rarely obvious to the unaided eye, so safe PN admixture relies on incorporating physicochemical properties of the included components into compatibility and stability decisions. Practices include applying active ingredient concentration limits to reduce risk for incompatibilities and instabilities. The purpose of the current article is to distill the wide-ranging information on PN compatibility and stability into a feasible blueprint that individual healthcare organizations can then use to design and implement practical initiatives. Compatibility and stability considerations can be incorporated into the routine tasks of PN prescribing, order reviewing, preparing, and administering. The focus of this review is on identifying potential physicochemical interactions that can be addressed at each step in the PN use process. Organizations should incorporate compatibility and stability considerations into the routine procedures and practices of all clinicians involved with PN therapy. Those clinicians in healthcare organizations and caregivers in the home should then be in a position to safely provide the appropriate PN admixtures in terms of compatibility and stability.

Comparative Efficacy of Neoadjuvant Nivolumab Plus Chemotherapy versus Conventional Comparator Treatments in Resectable Non-Small-Cell Lung Cancer: A Systematic Literature Review and Network Meta-Analysis.

BACKGROUND: This study aimed to estimate the relative efficacy of neoadjuvant nivolumab in combination with chemotherapy (neoNIVO + CT) compared to relevant treatments amongst resectable non-metastatic non-small-cell lung cancer (rNSCLC) patients. METHODS: Treatment comparisons were based on a network meta-analysis (NMA) using randomized clinical trial data identified via systematic literature review (SLR). The outcomes of interest were event-free survival (EFS) and pathological complete response (pCR). NeoNIVO + CT was compared to neoadjuvant chemotherapy (neoCT), neoadjuvant chemoradiotherapy (neoCRT), adjuvant chemotherapy (adjCT), and surgery alone (S). Due to the potential for effect modification by stage, all-stage and stage-specific networks were considered. Fixed-effect (FE) and random-effects Bayesian NMA models were run (EFS = hazard ratios [HR]; pCR = odds ratios [OR]; 95% credible intervals [CrI]). RESULTS: Sixty-one RCTs were identified (base case = 9 RCTs [n = 1978 patients]). In the all-stages FE model, neoNIVO + CT had statistically significant EFS improvements relative to neoCT (HR = 0.68 [95% CrI: 0.49, 0.94]), S (0.59 [0.42, 0.82]), adjCT (0.66 [0.45, 0.96]), but not relative to neoCRT (HR = 0.77 [0.52, 1.16]). NeoNIVO + CT (5 RCTs) had statistically significant higher odds of pCR relative to neoCT (OR = 12.53 [5.60, 33.82]) and neoCRT (7.15 [2.31, 24.34]). Stage-specific model findings were consistent. CONCLUSIONS: This NMA signals improved EFS and/or pCR of neoNIVO + CT relative to comparators among patients with rNSCLC.

Child Access Prevention Laws and Pediatric Firearm Injury: A Rapid Review.

Introduction: US child firearm fatality rates have risen since 2013. Child Access Prevention (CAP) laws aimed at reducing minors' access to firearms have existed since the 1980s. However, specific requirements for safe storage of firearms, standards of negligence, and penalties for offenders vary significantly by state, yielding a heterogeneous body of CAP legislation. A few studies have investigated the relative impacts of these laws on child firearm injury rates, with sometimes conflicting results. Here, we present a rapid review of the existing literature on CAP laws and their apparent impact on firearm-related injuries among US children, to assess whether CAP laws are an effective tool for reducing child firearm injuries. Methods: We conducted a rapid review of published reports that evaluated the impact of CAP laws on pediatric firearm injuries and/or deaths in the United States. We extracted target population data and outcomes of each study. The data are presented narratively. Results: A total of 14 articles met criteria for evaluation. Taken together, these studies showed that implementation of CAP legislation was associated with reduced pediatric firearm injuries and fatalities. Moreover, longitudinal or time-series studies that examined changes in pediatric firearm injuries pre/post-CAP legislation yielded the most consistent and robust findings. Conclusion: CAP laws were found to be associated with reduced pediatric firearm injuries and deaths, with the magnitude of effect being proportional to CAP law stringency.

Pathophysiology and Management of Chest Wall Pain after Surgical and Non-Surgical Local Therapies for Lung Cancer.

Chest wall pain syndromes can emerge following local therapies for lung cancer and can adversely affect patients' quality-of-life. This can occur after lung surgery, radiation therapy, or percutaneous image-guided thermal ablation. This review describes the multifactorial pathophysiology of chest wall pain syndromes that develop following surgical and non-surgical local therapies for lung cancer and summarizes evidence-based management strategies for inflammatory, neuropathic, myofascial, and osseous pain. It discusses a step-wise approach to treating chest wall pain that begins with non-opioid oral analgesics and includes additional pharmacologic treatments as clinically indicated, such as anticonvulsants, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, and various topical treatments. For myofascial pain, physical medicine techniques, such as acupuncture, trigger point injections, deep tissue massage, and intercostal myofascial release can also offer pain relief. For severe or refractory cases, opioid analgesics, intercostal nerve blocks, or intercostal nerve ablations may be indicated. Fortunately, palliation of treatment-related chest wall pain syndromes can be managed by most clinical providers, regardless of the type of local therapy utilized for a patient's lung cancer treatment. In cases where a patient's pain fails to respond to initial medical management, clinicians can consider referring to a pain specialist who can tailor a more specific pharmacologic approach or perform a procedural intervention to relieve pain.

Defining pseudoparalysis and pseudoparesis: a consensus study.

BACKGROUND: The purpose of this study was to establish consensus statements via a modified Delphi process on the definition of shoulder pseudoparalysis and pseudoparesis. METHODS: A consensus process on the definition of a diagnosis of pseudoparalysis utilizing a modified Delphi technique was conducted, and 26 shoulder/sports surgeons from 11 countries, selected based on their level of expertise in the field, participated in these consensus statements. Consensus was defined as achieving 80%-89% agreement, whereas strong consensus was defined as 90%-99% agreement, and unanimous consensus was indicated by 100% agreement with a proposed statement. RESULTS: Three statements regarding the diagnosis of pseudoparalysis reached strong (>89%) consensus: passive range of motion should be unaffected, the passive range of abduction should not be considered, and diagnosis should be excluded if lidocaine injection produces a substantial improvement in range of motion. Additionally, consensus (>79%) was reached that the active range of external rotation should not be considered for diagnosis, pain as a cause of restricted motion must be excluded, and that distinctions between restricted active flexion and external rotation should be made by range of motion rather than tear characteristics. No consensus could be reached on statements regarding the size, number of tendons or chronicity of cuff tears. Nor was there agreement on the active range of flexion permitted or on the difference between pseudoparalysis and pseudoparesis. CONCLUSION: A modified Delphi process was utilized to establish consensus on the definition of shoulder pseudoparalysis and pseudoparesis. Unfortunately, almost half of the statements did not reach consensus, and agreement could not be reached across all domains for a unifying definition for the diagnosis of pseudoparalysis in the setting of rotator cuff tears. Furthermore, it was not agreed how or whether pseudoparalysis should be differentiated from pseudoparesis. Based on the lack of a consensus for these terms, studies should report explicitly how these terms are defined when they are used.