Evaluation of Metronomic Therapy as a Low-Cost, Sustainable, Standard-of-Care Option in Desmoid Fibromatosis: Real-World Data From a Tertiary Care Center in India.

PURPOSE: Desmoid fibromatosis (DF) is a locally aggressive tumor with low mortality but significant morbidity. There is a lack of standard of care, and existing therapies are associated with significant barriers including access, cost, and toxicities. This study aimed to explore the efficacy and safety of the metronomic therapy (MT) in DF in a large, homogenous cohort from India. PATIENTS AND METHODS: This study involved histologically confirmed DF cases treated with MT comprising vinblastine (6 mg) and methotrexate (15 mg) both once a week, and tamoxifen (40 mg/m2) in two divided doses once daily between 2002 and 2018. RESULTS: There were 315 patients with a median age of 27 years; the commonest site was extremity (142 of 315; 45.0%). There were 159 (50.1%) male patients. Of the 123 (39.0%) prior treated patients, 119 had surgery. Of 315 patients, 263 (83.5%) received treatment at our institute (MT-151, 77-local treatment, 9-tyrosine kinase inhibitor, and 26 were observed). Among the MT cohort (n = 163, 61.2%), at a median follow-up of 36 (0.5-186) months, the 3-year progression-free and overall survival were 81.1% (95% CI, 74.3 to 88.4) and 99.2% (95% CI, 97.6 to 100), respectively. There were 35% partial responses. Ninety-two patients (56.4%) completed 1-year therapy, which was an independent prognosticator (P < .0001; hazard ratio, 0.177 [95% CI, 0.083 to 0.377]). MT was well tolerated. Predominant grade ≥3 toxicities were febrile neutropenia, 12 (7.4%) without any chemotoxicity-related death. The annual cost of MT was $130 US dollars. CONCLUSION: The novel, low-cost MT qualifies as one of the effective, less toxic, sustainable, standard-of-care options for the treatment of DF with global reach and merits wide recognition.

Nationwide Outcomes After Neoadjuvant Chemotherapy for Locally Advanced Sigmoid Colon Cancer-A Propensity Score-Matched Analysis.

BACKGROUND: The role of neoadjuvant chemotherapy (NAC) in advanced sigmoid colon carcinoma remains to be further characterized. Rationale for NAC includes downstaging on final pathology and optimization of microscopically negative margins (R0 resection). We investigated rates of neoadjuvant chemotherapy use in advanced sigmoid colon cancer at academic cancer centers and assessed factors associated with likelihood of NAC administration. METHODS: The National Cancer Database was queried from 2004 to 2017 for patients with clinical T3 or T4, N0-2, M0 sigmoid colon cancer who underwent surgical resection. Those with neoadjuvant radiation or metastatic disease were excluded. The outcomes of patients who did and did not receive neoadjuvant chemotherapy were evaluated for this retrospective cohort study. RESULTS: There were 23,597 patients of whom 364 (1.5%) received NAC. More patients received NAC at academic (41%, P < .001) and high-volume centers (27%, P < .001). Patients with Medicare/Medicaid (39%) and private insurance (52%) were more likely to receive NAC (P < .001). There was a significantly higher rate of N2 to N1 downstaging in the NAC group. Propensity-score matching demonstrated comprehensive community cancer programs (CCCP) were less likely to provide NAC (OR 0.4; 95% CI 0.23, 0.70, P < .001). There was no difference in survival (P = .20), R0 resection (P = .090), or 30-day readmission rates (P = .30) in the NAC cohort compared to the non-NAC cohort. CONCLUSIONS: Access to centers offering multi-disciplinary care with NAC prior to surgical resection is important. This care was associated with academic and high-volume centers and private or government-sponsored insurance. There was no difference in survival between NAC and non-NAC cohort.

Chitosan-Based Highly Sensitive Viable Humidity Sensor for Human Health Monitoring.

We report a sustainable resistive-type humidity sensor based on chitosan (CS) film deposited on an interdigitated Ti/Au electrode coated SiO2 substrate using a simple drop cast approach for human health monitoring. The sensor revealed remarkably high sensitivity (5.8 MΩ/%RH), fast response/recovery time (21 s/25 s), low hysteresis (∼9.3%), excellent reversibility, wide detecting range (11-95% RH), and high selectivity toward water vapor. The calculated associated uncertainty at different %RH indicates the excellent repeatability and stable performance of the sensor. The developed sensor is tested for different human breath patterns, and it is found that the sensor can clearly distinguish between the variations in rate and depth of respiration patterns during normal, fast, deep, and nasal breathing and can monitor for apnea-like situations. The sensor is also utilized to perform noncontact skin humidity sensing. Overall, the developed CS film humidity sensor provides a viable approach for the detection of respiratory disorders and human health issues, detected by skin moisture, in a noninvasive manner.

Current advances in 2022: A critical review of selected topics by the Association for the Advancement of Blood and Biotherapies (AABB) Clinical Transfusion Medicine Committee.

BACKGROUND: The Association for the Advancement of Blood and Biotherapies Clinical Transfusion Medicine Committee (CTMC) composes a summary of new and important advances in transfusion medicine (TM) on an annual basis. Since 2018, this has been assembled into a manuscript and published in Transfusion. STUDY DESIGN AND METHODS: CTMC members selected original manuscripts relevant to TM that were published electronically and/or in print during calendar year 2022. Papers were selected based on perceived importance and/or originality. References for selected papers were made available to CTMC members to provide feedback. Members were also encouraged to identify papers that may have been omitted initially. They then worked in groups of two to three to write a summary for each new publication within their broader topic. Each topic summary was then reviewed and edited by two separate committee members. The final manuscript was assembled by the first and senior authors. While this review is extensive, it is not a systematic review and some publications considered important by readers may have been excluded. RESULTS: For calendar year 2022, summaries of key publications were assembled for the following broader topics within TM: blood component therapy; infectious diseases, blood donor testing, and collections; patient blood management; immunohematology and genomics; hemostasis; hemoglobinopathies; apheresis and cell therapy; pediatrics; and health care disparities, diversity, equity, and inclusion. DISCUSSION: This Committee Report reviews and summarizes important publications and advances in TM published during calendar year 2022, and maybe a useful educational tool.

Cost minimization analysis of short-duration antiviral prophylaxis for hepatitis C positive donor kidney transplants.

BACKGROUND: Trials describing 4-12 week courses of direct-acting antiviral drugs (DAAs) to treat hepatitis C virus (HCV) transmission from infected donors to uninfected kidney transplant recipients (D+/R-transplants), may be limited in application by costs and delayed access to expensive DAAs. A short prophylactic strategy may be safer and cost-effective. Here, we report a cost minimization analysis using the health system perspective to determine the least expensive DAA regimen, using available published strategies. OBJECTIVES: To conduct cost-minimization analyses (CMAs) from the health system perspective of four DAA regimens to prevent and/or treat HCV transmission from D+/R-kidney transplants. METHODS: CMAs comparing 4 strategies: 1) 7-day prophylaxis with generic sofosbuvir/velpatasvir (SOF/VEL), with 12-week branded glecaprevir/pibrentasvir (G/P) for those with transmission; 2) 8-day branded G/P prophylaxis, with 12-week branded SOF/VEL/voxilaprevir for those with transmission; 3) 4-week perioperative generic SOF/VEL prophylaxis, with 12-week branded G/P for those with transmission; and 4) 8-week branded G/P "transmit-and-treat." We included data from published literature to estimate the probability of viral transmission in patients who received DAA prophylaxis, and assumed a 100% transmission rate for those who received the "transmit-and-treat" approach. RESULTS: In base-case analyses, strategies 1 (expected cost [EC]: $2326) and 2 (expected cost: $2646) were less expensive than strategies 3 (EC: $4859) and 4 (EC: $18,525). Threshold analyses for 7-day SOF/VEL versus 8-day G/P suggested that there were reasonable input levels at which the 8-day strategy may be least costly. The threshold values for the SOF/VEL prophylaxis strategies (7-day vs. 4- week) indicated that the 4-week strategy is unlikely to be less costly under any reasonable value of the input variables. CONCLUSIONS: Short duration DAA prophylaxis using 7 days of SOF/VEL or 8 days of G/P has the potential to yield significant cost savings for D+/R- kidney transplants.

Assessment of lateral resolution of single random phase encoded lensless imaging systems.

In this paper, we have used the angular spectrum propagation method and numerical simulations of a single random phase encoding (SRPE) based lensless imaging system, with the goal of quantifying the spatial resolution of the system and assessing its dependence on the physical parameters of the system. Our compact SRPE imaging system consists of a laser diode that illuminates a sample placed on a microscope glass slide, a diffuser that spatially modulates the optical field transmitting through the input object, and an image sensor that captures the intensity of the modulated field. We have considered two-point source apertures as the input object and analyzed the propagated optical field captured by the image sensor. The captured output intensity patterns acquired at each lateral separation between the input point sources were analyzed using a correlation between the captured output pattern for the overlapping point-sources, and the captured output intensity for the separated point sources. The lateral resolution of the system was calculated by finding the lateral separation values of the point sources for which the correlation falls below a threshold value of 35% which is a value chosen in accordance with the Abbe diffraction limit of an equivalent lens-based system. A direct comparison between the SRPE lensless imaging system and an equivalent lens-based imaging system with similar system parameters shows that despite being lensless, the performance of the SRPE system does not suffer as compared to lens-based imaging systems in terms of lateral resolution. We have also investigated how this resolution is affected as the parameters of the lensless imaging system are varied. The results show that SRPE lensless imaging system shows robustness to object to diffuser-to-sensor distance, pixel size of the image sensor, and the number of pixels of the image sensor. To the best of our knowledge, this is the first work to investigate a lensless imaging system's lateral resolution, robustness to multiple physical parameters of the system, and comparison to lens-based imaging systems.

A Nominal Group Technique Study of Patients Who Identify as Black or African American and Access to Renal Transplantation.

Introduction: Completion of the renal transplant evaluation has been associated with several barriers for patients who identify as Black or African American. This study sought to prioritize barriers to and motivators of completing the renal transplant evaluation. Methods/Approach: Semi-structured interviews and focus groups with a nominal group technique were used to generate priority scores. Transplant professionals (N = 23) were recruited from 9 transplant centers in the Mid-Atlantic, Mid-Western, and Southeastern parts of the United States. Black or African American identifying renal patients (N = 30) diagnosed with end-stage kidney disease were recruited from 1 transplant center in the Mid-Atlantic region. Findings: Priority scores were created to assess the quantitative data of participant rankings of top barriers and motivators. The most significant barriers identified by both patients and transplant professionals comprised financial constraints, insurance issues, difficulty navigating the healthcare system, transportation difficulties, and multiple health problems. Facilitators consisted of family/social support, transplant education, patient navigators, comprehensive insurance, and physician repertoire and investment. A qualitative description of the ranked factors resulted in themes classified as intrapersonal, health, socioeconomic, transplant-specific healthcare, and general healthcare. Conclusion: These findings provided vital information to transplant centers nationwide about assessing the influences of renal transplant evaluation completion. Achieving equity in access to transplantation for Black or African American renal patients requires multilayered approaches.

Seven bypasses simulation set: description and validity assessment of novel models for microneurosurgical training.

OBJECTIVE: Microsurgical training remains indispensable to master cerebrovascular bypass procedures, but simulation models for training that accurately replicate microanastomosis in narrow, deep-operating corridors are lacking. Seven simulation bypass scenarios were developed that included head models in various surgical positions with premade approaches, simulating the restrictions of the surgical corridors and hand positions for microvascular bypass training. This study describes these models and assesses their validity. METHODS: Simulation models were created using 3D printing of the skull with a designed craniotomy. Brain and external soft tissues were cast using a silicone molding technique from the clay-sculptured prototypes. The 7 simulation scenarios included: 1) temporal craniotomy for a superficial temporal artery (STA)-middle cerebral artery (MCA) bypass using the M4 branch of the MCA; 2) pterional craniotomy and transsylvian approach for STA-M2 bypass; 3) bifrontal craniotomy and interhemispheric approach for side-to-side bypass using the A3 branches of the anterior cerebral artery; 4) far lateral craniotomy and transcerebellomedullary approach for a posterior inferior cerebellar artery (PICA)-PICA bypass or 5) PICA reanastomosis; 6) orbitozygomatic craniotomy and transsylvian-subtemporal approach for a posterior cerebral artery bypass; and 7) extended retrosigmoid craniotomy and transcerebellopontine approach for an occipital artery-anterior inferior cerebellar artery bypass. Experienced neurosurgeons evaluated each model by practicing the aforementioned bypasses on the models. Face and content validities were assessed using the bypass participant survey. RESULTS: A workflow for model production was developed, and these models were used during microsurgical courses at 2 neurosurgical institutions. Each model is accompanied by a corresponding prototypical case and surgical video, creating a simulation scenario. Seven experienced cerebrovascular neurosurgeons practiced microvascular anastomoses on each of the models and completed surveys. They reported that actual anastomosis within a specific approach was well replicated by the models, and difficulty was comparable to that for real surgery, which confirms the face validity of the models. All experts stated that practice using these models may improve bypass technique, instrument handling, and surgical technique when applied to patients, confirming the content validity of the models. CONCLUSIONS: The 7 bypasses simulation set includes novel models that effectively simulate surgical scenarios of a bypass within distinct deep anatomical corridors, as well as hand and operator positions. These models use artificial materials, are reusable, and can be implemented for personal training and during microsurgical courses.

Multivariate Data Analysis and Central Composite Design-Oriented Optimization of Solid Carriers for Formulation of Curcumin-Loaded Solid SNEDDS: Dissolution and Bioavailability Assessment.

The study was initiated with two major purposes: investigating the role of isomalt (GIQ9) as a pharmaceutical carrier for solid self-nanoemulsifying drug delivery systems (S-SNEDDSs) and improving the oral bioavailability of lipophilic curcumin (CUN). GIQ9 has never been explored for solidification of liquid lipid-based nanoparticles such as a liquid isotropic mixture of a SNEDDS containing oil, surfactant and co-surfactant. The suitability of GIQ9 as a carrier was assessed by calculating the loading factor, flow and micromeritic properties. The S-SNEDDSs were prepared by surface adsorption technique. The formulation variables were optimized using central composite design (CCD). The optimized S-SNEDDS was evaluated for differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), microscopy, dissolution and pharmacokinetic studies. The S-SNEDDS showed a particle size, zeta potential and PDI of 97 nm, -26.8 mV and 0.354, respectively. The results of DSC, XRD, FTIR and microscopic studies revealed that the isotropic mixture was adsorbed onto the solid carrier. The L-SNEDDS and S-SNEDDS showed no significant difference in drug release, indicating no change upon solidification. The optimized S-SNEDDS showed 5.1-fold and 61.7-fold enhancement in dissolution rate and oral bioavailability as compared to the naïve curcumin. The overall outcomes of the study indicated the suitability of GIQ9 as a solid carrier for SNEDDSs.

Bioanalytical Method Development, Validation and Stability Assessment of Xanthohumol in Rat Plasma.

Xanthohumol (XH) a prenylated chalcone has diverse therapeutic effects against various diseases. In the present study, a bioanalytical method was developed for XH in rat plasma using reverse phase high performance liquid chromatography. The validation of the method was performed as per ICH M10 guidelines using curcumin as an internal standard. The Isocratic elution method was used with a run time of 10 min, wherein the mobile phase ratio 0.1% v/v OPA (A): Methanol (B) was 15:85 v/v at flow rate 0.8 mL/min and injection volume of 20 µL. The chromatograms of XH and curcumin was recorded at a wavelength of 370 nm. The retention time for XH and curcumin was 7.4 and 5.8 min, respectively. The spiked XH from plasma was extracted by the protein precipitation method. The developed method was linear with R2 value of 0.9996 over a concentration range of 50-250 ng/mL along with LLOQ. The results of all the validation parameters are found to be within the accepted limits with %RSD value less than 2 and the percentage recovery was found to be greater than 95%. Based on the %RSD and percentage recovery results it was confirmed that the method was precise and accurate among the study replicates. LOD and LOQ values in plasma samples were found to be 8.49 ng/mL and 25.73 ng/mL, respectively. The stability studies like freeze thaw, short term and long-term stability studies were also performed, %RSD and percentage recovery of the XH from plasma samples were within the acceptable limits. Therefore, the developed bioanalytical method can be used effectively for estimation of XH in plasma samples.

A kNGR Peptide-Tethered Lipid-Polymer Hybrid Nanocarrier-Based Synergistic Approach for Effective Tumor Therapy: Development, Characterization, Ex-Vivo, and In-Vivo Assessment.

The present study aims to design, develop and characterize kNGR (Asn-Gly-Arg) peptide-conjugated lipid-polymer-based nanoparticles for the target-specific delivery of anticancer bioactive(s), i.e., Paclitaxel (PTX). The kNGR-PEG-DSPE conjugate was synthesized and characterized by using spectral analysis. The dual-targeted PLGA-lecithin-PEG core-shell nanoparticles (PLNs-kNGR-NPs) were synthesized using a modified nanoprecipitation process, and their physiological properties were determined. The results support that, compared to other NPs, PLNs-kNGR-NPs are highly cytotoxic, owing to higher apoptosis and intracellular uptake. The significance of rational nanoparticle design for synergistic treatment is shown by the higher tumor volume inhibition percentage rate (59.7%), compared to other designed formulations in Balb/c mice in the HT-1080 tumor-induced model. The overall results indicate that the PLNs-kNGR-NPs-based hybrid lipid-polymer nanoparticles present the highest therapeutic efficacy against solid tumor overexpressing the CD13 receptors.

US payer budget impact of a microarray assay with machine learning to evaluate kidney transplant rejection in for-cause biopsies.

AIM: This study evaluates the economic impact to US commercial payers of MMDx-Kidney used in conjunction with histologic evaluation of for-cause kidney transplant biopsies. MATERIALS AND METHODS: An Excel-based model was developed to assess the cost impact of histology plus MMDx-Kidney versus histology alone for the evaluation of potential rejection in kidney transplant patients who receive a for-cause biopsy. Different model time periods were assessed, ranging from 1 to 5 years post-biopsy. A targeted literature review was used to identify parameter estimates, validated by two external clinicians with expertise in managing kidney transplant rejection. A sensitivity analysis was conducted to evaluate the relative impact of key clinical and cost parameters. In particular, the model identified the magnitude of MMDx-Kidney's impact on graft failure from rejection that would be required for MMDx-Kidney to be cost-neutral. RESULTS: By more accurately characterizing rejection, MMDx-Kidney is estimated to increase antirejection treatment costs by $1,126 per test. Nevertheless, a break-even analysis shows that the costs of MMDx-Kidney and anti-rejection medication, as well as the costs associated with an increase in the number of patients with functioning transplants, may be offset by reductions in costs associated with graft failure (i.e. costs of hospitalizations, dialysis, and repeat transplants) over 5 years, assuming MMDx-Kidney reduces annual graft failure from rejection by at least 5%. For the base case, with a 25% relative reduction in annual rate of graft failures from rejection, MMDx-Kidney increases overall costs incurred in the first year of the model but starts generating savings by the second year of the model. CONCLUSIONS: Compared with histologic evaluation of for-cause kidney transplant biopsies alone, the use of MMDx-Kidney in conjunction with histologic evaluation improves the diagnoses of graft dysfunction and may have the potential to generate overall savings from reductions in rejection-related graft failure.

Manufacturing a chimpanzee adenovirus-vectored SARS-CoV-2 vaccine to meet global needs.

Manufacturing has been the key factor limiting rollout of vaccination during the COVID-19 pandemic, requiring rapid development and large-scale implementation of novel manufacturing technologies. ChAdOx1 nCoV-19 (AZD1222, Vaxzevria) is an efficacious vaccine against SARS-CoV-2, based upon an adenovirus vector. We describe the development of a process for the production of this vaccine and others based upon the same platform, including novel features to facilitate very large-scale production. We discuss the process economics and the "distributed manufacturing" approach we have taken to provide the vaccine at globally-relevant scale and with international security of supply. Together, these approaches have enabled the largest viral vector manufacturing campaign to date, providing a substantial proportion of global COVID-19 vaccine supply at low cost.

Non-Invasive Assessment of Liver Fibrosis and Steatosis in End-Stage Renal Disease Patients Undergoing Renal Transplant Evaluation.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has an increased prevalence in end-stage renal disease (ESRD) due to similar risk factors. The aim of this study was to assess non-invasive testing including transient elastography (TE) for liver stiffness (LS), controlled attenuated parameter (CAP) for steatosis, Fibrosis-4 (FIB-4) score, aspartate aminotransferase (AST) to platelet ratio index (APRI) and NAFLD fibrosis score (NFS), for evaluation of NAFLD along with advanced fibrosis (AF) in patients with ESRD undergoing renal transplant evaluation. METHODS: Data were retrospectively collected within 12 weeks of TE. Primary outcomes were AF, defined by LS ≥ 9 kPa compared to APRI > 1.5, FIB-4 > 2.67, and NFS of 0.675, and ≥ 5% steatosis by CAP ≥ 263 dB/m compared to liver histology when available. RESULTS: A total of 171 patients were evaluated: mean age 56, 65% male, 36% obese, 47% had diabetes, 96% hypertension, and 56% dyslipidemia. Mean LS was 6.5 kPa with 21% having AF. Mean CAP was 232 dB/m, with 25% having steatosis. Those with AF were older with higher NFS. Those with steatosis were obese and had diabetes without higher LS or fibrosis scores. Only NFS was associated with LS ≥ 9 kPa. In those with liver histology, AF was associated with LS ≥ 9 kPa but not with APRI, FIB-4, or NFS. CONCLUSIONS: Despite normal liver enzymes, non-invasive assessment via TE in ESRD patients exhibited high prevalence of AF and steatosis not detected by APRI or FIB-4 scores. This high prevalence was secondary to the common risk factors such as obesity and diabetes, among patients with NAFLD and ESRD.

COVID-19 in Kidney Transplantation: Epidemiology, Management Considerations, and the Impact on Kidney Transplant Practice.

The novel severe acute respiratory syndrome coronavirus 2 was identified in the late 2019 as the cause of coronavirus disease 2019 (COVID-19), an acute respiratory viral illness. Patients with chronic underlying conditions may have an increased risk of morbidity and mortality from COVID-19. Kidney transplant recipients may be at a uniquely increased risk of serious complications from COVID-19 as compared to the general population because of a chronically immunosuppressed state and a high prevalence of comorbidities like diabetes, heart disease, and lung disease. Early data suggest that the mortality of patients on dialysis may be comparable to those with kidney transplants, although more research is needed. This concise review aims to describe the epidemiology of COVID-19 in kidney transplant recipients, manifestations, appropriate management, and clinical outcomes based on the available literature. Current evidence on many of the specific antiviral measures against COVID-19 has not shown a clear-cut benefit in smaller studies and the results of several ongoing larger clinical trials are awaited. In addition, we also highlight the impact of COVID-19 on kidney transplant center practice and volumes; potential living or deceased donors, recipients; and induction immunosuppression and surgical strategies.

Auditory and Visual P300 Responses in Early Cognitive Assessment of Children and Adolescents with Epilepsy.

BACKGROUND: The event-related potential P300 has been suggested to be valuable in the assessment of cognitive dysfunctions. Not a great deal of neurophysiological assessment has been performed at early stages in patients with epilepsy involving visual and auditory P300 measures. AIMS AND OBJECTIVES: This study aimed to assess the cognitive status in patients with epilepsy earlier by visual and auditory P300 and to find their correlation with various risk factors. MATERIALS AND METHODS: P300 was recorded in 60 children with epilepsy in the age-group of 5-18 years and 60 age- and sex-matched controls by a rare-frequent (oddball) paradigm. Mean auditory and visual P300 latencies and amplitudes were compared among patients with epilepsy and controls and among patients with generalized and focal epilepsy by unpaired t-test. Pearson's correlation coefficient test was computed for studying the correlation between risk factors and P300 responses. A value of P < 0.05 was considered statistically significant. RESULTS: Statistically significant delay in P300 latencies and reduction in amplitudes (both visual and auditory) was found in patients with epilepsy as compared to controls and also among patients with generalized and focal epilepsy. In generalized epilepsy, both visual and auditory P300 revealed significant delay, whereas only auditory P300 delay was found in focal form. No significant correlation was obtained with risk factors. No significant difference was found in P300 responses among patients with and without antiepileptic treatment. CONCLUSION: Visual and auditory P300 latencies have an important role in the evaluation of early cognitive dysfunctions in children with epilepsy. P300 potentials are not influenced by antiepileptic treatment, whereas the type of epilepsy alters them.

Do Narrow Networks Affect the Delivery of Outpatient Care in Neurosurgery?: A Statewide Analysis of Marketplace Plans in New Jersey.

BACKGROUND: The aftermath of the Affordable Care Act (ACA) witnessed the rise of narrow networks, which feature fewer providers in exchange for lower premiums. Debate still continues on whether narrow networks provide adequate access to health care, especially in specialty care services such as neurosurgery. The objective of this article was to analyze the 2019 Marketplace plans' impact on delivering outpatient neurosurgical care in New Jersey. METHODS: The 2019 Marketplace Public Use Files were queried for "silver" plans, identifying a total of 11 plans across 3 insurance companies. Online search engines were used to identify the number of in-network neurosurgeons within 20-25 miles of ZIP codes at the center of each county. The primary outcome was the number of neurosurgeon-deficient plans, defined as those having no in-network neurosurgeons within the assigned mile radius. RESULTS: Of all individuals who purchased an insurance plan, 73% (185,797/255,246) opted for a silver plan. Out of 111 active neurosurgeons in New Jersey, 25% (28/111) did not participate in any of the silver plans. Analysis showed 8 plans as neurosurgeon-deficient in Sussex and Warren. Meanwhile, most of the silver plans provided access to >5 neurosurgeons within 20-25 miles of most (17/21) county centers. CONCLUSIONS: In more densely populated states such as New Jersey, the impact of narrow networks on neurosurgical coverage is less apparent. However, frustrations regarding access to care still exist because nearly 25% of neurosurgeons do not participate in the standard ACA insurance product. Furthermore, guidelines that define network adequacy in neurosurgery remain elusive, which calls for more robust parameters to monitor and ensure adequate access to health care.

An analysis of cross-continental scholarship requirements during neurosurgical training and national research productivity.

OBJECTIVE: Engagement in research and scholarship is considered a hallmark of neurosurgical training. However, the participation of neurosurgical trainees in this experience has only recently been analyzed and described in the United States, with little, if any, data available regarding the research environment in neurosurgical training programs across the globe. Here, the authors set out to identify requirements for research involvement and to quantify publication rates in leading neurosurgical journals throughout various nations across the globe. METHODS: The first aim was to identify the research requirements set by relevant program-accrediting and/or board-certifying agencies via query of the literature and published guidelines. For the second part of the study, the authors attempted to determine each country's neurosurgical research productivity by quantifying publications in the various large international neurosurgical journals-World Neurosurgery, Journal of Neurosurgery, and Neurosurgery-via a structured search of PubMed. RESULTS: Data on neurosurgical training requirements addressing research were available for 54 (28.1%) of 192 countries. Specific research requirements were identified for 39 countries, partial requirements for 8, and no requirements for 7. Surprisingly, the authors observed a trend of increased average research productivity with the absence of designated research requirements, although this finding is not unprecedented in the literature. CONCLUSIONS: A variety of countries of various sizes and neurosurgical workforce densities across the globe have instituted research requirements during training and/or prior to board certification in neurosurgery. These requirements range in intensity from 1 publication or presentation to the completion of a thesis or dissertation and occur at various time points throughout training. While these requirements do not correlate directly to national research productivity, they may provide a foundation for developing countries to establish a culture of excellence in research.

Antiretroviral agents in pre-exposure prophylaxis: emerging and advanced trends in HIV prevention.

OBJECTIVES: Antiretroviral agents (ARVs) have been the most promising line of therapy in the management of human immunodeficiency virus (HIV) infections. Some of these ARVs are used in the pre-exposure prophylaxis (PrEP) to suppress the transmission of HIV. Prophylaxis is primarily used in uninfected people, before exposure, to effectively prevent HIV infection. Several studies have shown that ART PrEP prevents HIV acquisition from sexual, blood and mother-to-child transmissions. However, there are also several challenges and limitations to PrEP. This review focuses on the current antiretroviral therapies used in PrEP. KEY FINDINGS: Among ARVs, the most common drugs employed from the class of entry inhibitors are maraviroc (MVC), which is a CCR5 receptor antagonist. Other entry inhibitors like emtricitabine (FTC) and tenofovir (TFV) are also used. Rilpivirine (RPV) and dapivirine (DPV) are the most common drugs employed from the Non-nucleoside reverse transcriptase inhibitor (NNRTIs) class, whereas, tenofovir disoproxil fumarate (TDF) is primarily used in the Nucleoside Reverse Transcriptase Inhibitor (NRTIs) class. Cabotegravir (CAB) is an analog of dolutegravir, and it is an integrase inhibitor. Some of these drugs are also used in combination with other drugs from the same class. SUMMARY: Some of the most common pre-exposure prophylactic strategies employed currently are the use of inhibitors, namely entry inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase and protease inhibitors. In addition, we have also discussed on the adverse effects caused by ART in PrEP, pharmacoeconomics factors and the use of antiretroviral prophylaxis in serodiscordant couples.

Cost-effectiveness of hepatitis C-positive donor kidney transplantation for hepatitis C-negative recipients with concomitant direct-acting antiviral therapy.

Pilot studies suggest that transplanting hepatitis C virus (HCV)-positive donor (D+) kidneys into HCV-negative renal transplant (RT) recipients (R-), then treating HCV with direct-acting antivirals (DAA) is clinically feasible. To determine whether this is a cost-effective approach, a decision tree model was developed to analyze costs and effectiveness over a 5-year time frame between 2 choices: RT using a D+/R- strategy compared to continuing dialysis and waiting for a HCV-negative donor (D-/R-). The strategy of accepting a HCV+ organ then treating HCV was slightly more effective and substantially less expensive and resulted in an expected 4.8 years of life (YOL) with a cost of ≈$138 000 compared to an expected 4.7 YOL with a cost of ≈$329 000 for the D-/R- strategy. The D+/R- strategy remained dominant after sensitivity analyses including the difference in RT death probabilities or acute rejection probabilities between using D+ vs D- kidney; time that D-/R- patients waited for RT; dialysis death probabilities while waitlisted for RT in the D-/R- strategy; DAA therapy expected cure rate; costs of transplant, immunosuppressives, DAA therapy, dialysis, or acute rejection. The D+/R- strategy followed by treatment with DAA is less costly and slightly more effective compared to the D-/R- strategy.