Literature Review: Support for caregivers of children on the ketogenic diet for epilepsy and other neurologic disorders.

Epilepsy affects millions of people and when medications are insufficient to maintain seizure control, individuals are diagnosed with refractory epilepsy (RE). Medical ketogenic diet therapy (KDT), a diet high in fat and low in carbohydrates and sufficient in protein, is a well-established treatment for RE. However, compliance is one of the main reasons for discontinuation of KDT and, with pediatric RE patients, the ability of informal caregivers, typically family members, to maintain diet adherence is vital for successful KDT treatment. The central role that informal caregivers play for effective KDT implementation is recognized, however, there is a need to elucidate the rationale and theoretical underpinnings of effective KDT caregiver support programs to inform best practices. Therefore, this systematic literature review aims to identify the existing fundamental understandings of KDT caregiver support to help build a foundation of theory-based knowledge to promote evidenced practice. After screening 137 publications, three studies that discussed potential underlying components of effective caregiver support were included in this review. These articles followed a similar approach as they 1) employed qualitative methods delving into caregiver needs, 2) findings highlighted the importance of support from family, friends, fellow caregivers and their child's medical team, and 3) the inclusion of caregiver support findings were a supplement to the main purpose of the manuscript. Research focused on KDT caregivers is in its infancy. There is a clear need for the systematic examination of support for KDT caregivers to build a foundation for effective support programs and to increase the access to quality support programming to foster KDT implementation, desirable patient outcomes, and caregiver well being. In this article we discuss opportunities to apply self-determination theory to the KDT caregiver support research and practice.

Context-dependent costs and benefits of endosymbiotic interactions in a ciliate-algae system.

Endosymbiosis, an interaction between two species where one lives within the other, has evolved multiple times independently, but the underlying mechanisms remain unclear. Evolutionary theory suggests that for an endosymbiotic interaction to remain stable over time, births of both partners should be higher than their deaths in symbiosis and deaths of both partners should be higher than their births when living independently. However, experimentally measuring this can be difficult and conclusions tend to focus on the host. Using a ciliate-algal system (Paramecium bursaria host and Chlorella endosymbionts), we estimated the benefits and costs of endosymbiosis for both organisms using fitness measurements in different biotic environments to test under which environmental conditions the net effects of the interaction were positive for both partners. We found that the net effects of harbouring endosymbionts were positive for the ciliate hosts as it allowed them to survive in conditions of low-quality bacteria food. The algae benefitted by being endosymbiotic when predators such as the hosts were present, but the net effects were dependent on the total density of hosts, decreasing as hosts densities increased. Overall, we show that including context-dependency of endosymbiosis is essential in understanding how these interactions have evolved.

Central nervous system tumors in children under 5 years of age: a report on treatment burden, survival and long-term outcomes.

PURPOSE: The challenges of treating central nervous system (CNS) tumors in young children are many. These include age-specific tumor characteristics, limited treatment options, and susceptibility of the developing CNS to cytotoxic therapy. The aim of this study was to analyze the long-term survival, health-related, and educational/occupational outcomes of this vulnerable patient population. METHODS: Retrospective study of 128 children diagnosed with a CNS tumor under 5 years of age at a single center in Switzerland between 1990 and 2019. RESULTS: Median age at diagnosis was 1.81 years [IQR, 0.98-3.17]. Median follow-up time of surviving patients was 8.39 years [range, 0.74-23.65]. The main tumor subtypes were pediatric low-grade glioma (36%), pediatric high-grade glioma (11%), ependymoma (16%), medulloblastoma (11%), other embryonal tumors (7%), germ cell tumors (3%), choroid plexus tumors (6%), and others (9%). The 5-year overall survival (OS) was 78.8% (95% CI, 71.8-86.4%) for the whole cohort. Eighty-seven percent of survivors > 5 years had any tumor- or treatment-related sequelae with 61% neurological complications, 30% endocrine sequelae, 17% hearing impairment, and 56% visual impairment at last follow-up. Most patients (72%) attended regular school or worked in a skilled job at last follow-up. CONCLUSION: Young children diagnosed with a CNS tumor experience a range of complications after treatment, many of which are long-lasting and potentially debilitating. Our findings highlight the vulnerabilities of this population, the need for long-term support and strategies for rehabilitation, specifically tailored for young children.

The Cascade Analysis Tool: software to analyze and optimize care cascades.

Introduction: Cascades, which track the progressive stages of engagement on the path towards a successful outcome, are increasingly being employed to quantitatively assess progress towards targets associated with health and development responses. Maximizing the proportion of people with successful outcomes within a budget-constrained context requires identifying and implementing interventions that are not only effective, but also cost-effective. Methods: We developed a software application called the Cascade Analysis Tool that implements advanced analysis and optimization methods for understanding cascades, combined with the flexibility to enable application across a wide range of areas in health and development. The tool allows users to design the cascade, collate and enter data, and then use the built-in analysis methods in order to answer key policy questions, such as: understanding where the biggest drop-offs along the cascade are; visualizing how the cascade varies by population; investigating the impact of introducing a new intervention or scaling up/down existing interventions; and estimating how available funding should be optimally allocated among available interventions in order to achieve a variety of different objectives selectable by the user (such as optimizing cascade outcomes in target years). The Cascade Analysis Tool is available via a user-friendly web-based application, and comes with a user guide, a library of pre-made examples, and training materials. Discussion: Whilst the Cascade Analysis Tool is still in the early stages of existence, it has already shown promise in preliminary applications, and we believe there is potential for it to help make sense of the increasing quantities of data on cascades.

Value of a noise-optimized virtual monoenergetic reconstruction technique in dual-energy CT for planning of transcatheter aortic valve replacement.

OBJECTIVES: To evaluate objective and subjective image quality of a noise-optimized virtual monoenergetic imaging (VMI+) reconstruction technique in dual-energy computed tomography (DECT) angiography prior to transcatheter aortic valve replacement (TAVR). METHODS: Datasets of 47 patients (35 men; 64.1 ± 10.9 years) who underwent DECT angiography of heart and vascular access prior to TAVR were reconstructed with standard linear blending (F_0.5), VMI+, and traditional monoenergetic (VMI) algorithms in 10-keV intervals from 40-100 keV. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of 564 arterial segments were evaluated. Subjective analysis was rated by three blinded observers using a Likert scale. RESULTS: Mean SNR and CNR were highest in 40 keV VMI+ series (SNR, 27.8 ± 13.0; CNR, 26.3 ± 12.7), significantly (all p < 0.001) superior to all VMI series, which showed highest values at 70 keV (SNR, 18.5 ± 7.6; CNR, 16.0 ± 7.4), as well as linearly-blended F_0.5 series (SNR, 16.8 ± 7.3; CNR, 13.6 ± 6.9). Highest subjective image quality scores were observed for 40, 50, and 60 keV VMI+ reconstructions (all p > 0.05), significantly superior to all VMI and standard linearly-blended images (all p < 0.01). CONCLUSIONS: Low-keV VMI+ reconstructions significantly increase CNR and SNR compared to VMI and standard linear-blending image reconstruction and improve subjective image quality in preprocedural DECT angiography in the context of TAVR planning. KEY POINTS: • VMI+ combines increased contrast with reduced image noise. • VMI+ shows substantially less image noise than traditional VMI. • 40-keV reconstructions show highest SNR/CNR of the aortic and iliofemoral access route. • Observers overall prefer 60 keV VMI+ images. • VMI+ DECT imaging helps improve image quality for TAVR planning.

Optimizing Safety, Predictability, and Aesthetics in Direct to Implant Immediate Breast Reconstruction: Evolution of Surgical Technique.

BACKGROUND: Although immediate breast reconstruction with the insertion of a permanent prosthesis rather than a tissue expander (direct to implant [DTI]) has become gradually more preferred and requested by patients, the technique has yet to be fully embraced by most plastic surgeons, presumably due to concerns of patient safety and perceived higher complication and revision rates, despite not being supported by the literature. OBJECTIVES: The authors review the senior author's protocol for patient selection and surgical technique in DTI reconstructions. A simple device is introduced which adds predictability and control in determining the inset suture line for the acellular dermal matrix and thus the position of the inframammary fold and lateral mammary fold, resulting in improved aesthetic outcomes, reduced complications, and reduced reoperation rates. METHODS: A retrospective review of our one surgeon experience with 134 DTI breast reconstructions in 77 patients between 2006 and 2015 is presented. The series is further subdivided into 74 reconstructions in 43 patients in whom their reconstruction was performed before the use of a patented 2-dimensional (2-D) template, and 60 reconstructions in 34 patients in whom the template was used. RESULTS: The overall complication rate requiring reoperation in the first 54 reconstructions was 50% versus 15% in the last 84. Failure of the reconstruction, defined by explantation, occurred in 11 of 74 reconstructions (14.9%) before the use of 2-D templates, and in 5 of 60 reconstructions (8.3%) in which templates were used, representing a 44% reduction. The revision rate specifically for implant malposition dropped from 18.6% before the use of templates to 2.9% after the incorporation of templates. Fifty-three reconstructions in 33 patients (40%) had no complications and no reoperations, correctly described as "one and done." CONCLUSIONS: Direct to implant reconstruction can be technically more demanding and exacting than 2-stage expander/implant reconstructions. A review of this single surgeon series confirms that despite a learning curve with a higher complication rate early in the series, in the setting of proper patient selection DTI immediate reconstruction is both safe and reliable, and can potentially have clinical, psychological, and aesthetic advantages for patients when compared with a 2-stage expander/implant reconstruction, with 40% of patients having 1 operation only. The use of a patented 2-D template has reduced complications and the rate of reoperation.

Noise-optimized advanced image-based virtual monoenergetic imaging for improved visualization of lung cancer: Comparison with traditional virtual monoenergetic imaging.

PURPOSE: To assess the effect of a noise-optimized image-based virtual monoenergetic imaging (VMI+) algorithm in direct comparison with the traditional VMI technique and standard linearly-blended images emulating 120-kVp acquisition (M_0.3) on image quality at dual-energy CT in patients with lung cancer. MATERIALS AND METHODS: Dual-source dual-energy CT examinations of 48 patients with biopsy-proven primary (n=31) or recurrent (n=20) lung cancer were evaluated. Images were reconstructed as M_0.3, and VMI+ and traditional VMI series at 40, 55, and 70keV. Attenuation of tumor, descending aorta, pulmonary trunk, latissimus muscle, and noise were measured. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Five-point scales were used by three observers to subjectively evaluate general image impression, tumor delineation, image sharpness, and image noise. RESULTS: Background noise was consistently lower with VMI+ compared to VMI at all keV levels (all p<0.0001) and M_0.3 (all p≤0.0004). Tumor SNR and CNR peaked in the 40keV VMI+ series, significantly higher compared to all VMI and M_0.3 series (all p<0.0008). Observers preferred the 55keV VMI+ series regarding general image impression and tumor delineation compared to all other series (all p<0.0001). Image sharpness and image noise ratings were highest in the 55keV VMI+ and 70keV VMI and VMI+ reconstructions. CONCLUSIONS: Tumor CNR peaked at 40keV VMI+ while observers preferred 55keV VMI+ series overall other series for dual-energy CT of lung cancer. The noise-optimized VMI+ technique showed significantly lower background noise and higher SNR and CNR compared to the traditional VMI technique at matching keV levels.

Comparative evaluation of non-contrast CAIPIRINHA-VIBE 3T-MRI and multidetector CT for detection of pulmonary nodules: In vivo evaluation of diagnostic accuracy and image quality.

PURPOSE: To evaluate the diagnostic accuracy, subjective image quality, and interobserver agreement of non-contrast Controlled Aliasing In Parallel Imaging Results In Higher Acceleration (CAIPIRINHA) volumetric interpolated breath-hold examination (VIBE) 3T magnetic resonance imaging (MRI) for the detection of pulmonary nodules with intra-individual comparison to computed tomography (CT). MATERIALS AND METHODS: We evaluated 54 patients (27 male, 27 female; mean age, 60.8 ± 11.5 years) who prospectively underwent thoracic 3T-MRI using CAIPIRINHA-VIBE sequences and chest CT. Diagnostic accuracy for the detection of lung nodules on CAIPIRINHA-VIBE MRI by three independent observers were compared to the reference standard CT. Subjective image quality was rated using a 5-point grading scale. Diagnostic accuracy was calculated and interobserver agreement was assessed using intraclass correlation coefficient (ICC). RESULTS: Sensitivity of 3T-MRI for the detection of pulmonary lesions compared to CT was 88.1% (95% confidence interval [CI]: 0.81-0.93) and specifity was 79.1% (95% CI: 0.50-0.95). Sensitivity for lesions <5mm was 77.2% (95% CI: 0.59-0.90) and for lesions from 5 to 10mm was 87.2% (95% CI: 0.76-0.94). Sensitivity for lesions >10mm was 100%. Observer ratings regarding subjective image quality were good to excellent for 3T-MRI (1.54) and CT (1.14) with almost perfect interobserver agreement for 3T-MRI and CT (ICC=0.83, 95% CI: 0.78-0.89; ICC=0.89, 95% CI: 0.85-0.94). CONCLUSIONS: Non-contrast CAIPIRINHA-VIBE 3T-MRI allows for the reliable detection of pulmonary lesions with a diameter >5mm in comparison with chest CT with high diagnostic accuracy, subjective image quality, and interobserver agreement.

Dual-Energy CT in Patients with Suspected Gouty Arthritis: Effects on Treatment Regimen and Clinical Outcome.

RATIONALE AND OBJECTIVES: This investigation aimed to evaluate the impact on treatment regimen and clinical outcome of dual-energy computed tomography (DECT) in patients with suspected gouty arthritis. MATERIALS AND METHODS: We retrospectively analyzed electronic medical records (EMR) of 39 patients (36 male, 3 female; age range, 36-85 years) who underwent DECT of peripheral joints because of suspected gouty arthritis. We assessed the prior medical history, lab results, treatment regimen, and medications before and after DECT, and changes in subjective severity of symptoms as stated by patients in the EMR. The presence of monosodium urate (MSU) crystals in the index joint was verified with DECT. RESULTS: Several patients had a prior diagnosis of gout (n = 9), hyperuricemia (n = 6), rheumatoid arthritis (n = 3), or psoriatic arthritis (n = 3). Elevated uric acid blood levels were detected in 32 patients (82%) before DECT. On DECT, MSU crystals were detected in 23 patients (59%). Of the 36 cases, the current treatment regimen was modified after DECT to gout-specific therapy in 22 cases and other rheumatic diseases were targeted in 14 cases. Several medications were prescribed more frequently based after DECT compared to before DECT imaging, including steroids (n = 20 vs. n = 12, respectively), colchicine (n = 13 vs. n = 4, respectively), and urate-lowering medication (n = 18 vs. n = 11, respectively). A subjective reduction of clinical symptoms during cumulative follow-up was reported by 34 patients (87.2%). CONCLUSIONS: Both positive and negative findings of MSU crystals on DECT have a significant impact on the treatment regimen and clinical outcome of patients with suspected gouty arthritis and facilitate differentiation from other rheumatic diseases.