Evaluation of a New Method for CyberKnife Treatment for Central Lung and Mediastinal Tumors by Tracheobronchial Tracking.

BACKGROUND: CyberKnife treatment for central lung tumors and mediastinal tumors can be difficult to perform with marker less. PURPOSE: We aimed to evaluate a novel tracheobronchial-based method (ie, tracheobronchial tracking) for the purpose of minimally invasive CyberKnife treatment for central lung and mediastinal tumors. METHODS: Five verification plans were created using an in-house phantom. Each plan included five irradiation sessions. The reference plan irradiated and tracked the simulated tumor (using the target tracking volume, TTV). Trachea plans tracked the simulated tracheo-bronchus and irradiated the simulated tumor and included two types of subplans: correlated plans in which the displacement of the simulated tracheobronchial and the simulated tumor were correlated, and non-correlated plans in which these factors were not correlated. Moreover, 15 mm and 25 mm TTVs were evaluated for each plan. The sin waveform and the patient's respiratory waveform were prepared as the respiratory model. Evaluations were performed by calculating the dose difference between the radiophotoluminescent glass dosimeter (RPLD)-generated mean dose values (generated by the treatment planning system, TPS) and the actual absorbed RPLD dose. Statistical analyses were performed to evaluate findings for each plan. Correlation and prediction errors were calculated for each axis of each plan using log files to evaluate tracking accuracy. RESULTS: Dose differences were statistically significant only in comparisons with the non-correlated plan. When evaluated using the sin waveform, the mean values for correlation and prediction errors in each axis and for all plans were less than 0.6 mm and 0.1 mm, respectively. In the same manner, they were less than 1.1 mm and 0.2 mm when evaluated using the patient's respiratory waveform. CONCLUSION: Our newly-developed tracheobronchial tracking method would be useful in facilitating minimally invasive CyberKnife treatment in certain cases of central lung and mediastinal tumors.

Measurement of Skin Thickness Using Ultrasonography to Test the Usefulness of Elastic Compression Stockings for Leg Edema in Pregnant Women.

Background: One of the most common treatments for leg edema during pregnancy is the use of compression stockings. The purpose of this study was to evaluate the objective effectiveness in pregnant women, by measuring the changes of skin thickness using ultrasonography. Methods: Pregnant women were diagnosed with leg edema using the pitting edema method at 36 weeks of gestation. Twenty-four pregnant women (48 legs) with leg edema spent time without wearing elastic stockings at 36−37 weeks of gestation. Then, they wore elastic stockings for one week at 37−38 weeks of gestation. We measured the grade of edema (from 0 to 3) and the skin thickness of the lower leg by portable ultrasonography at 36, 37, and 38 weeks of gestation (a before-and-after study). Results: In 24 pregnant women, thigh edema was not detected in any of the 48 legs before or after the use of elastic stockings. All 48 legs in 24 pregnant women had physiological lower leg edema, but not thigh edema. The average grade of pitting edema in each lower leg significantly decreased after using the stockings (36 weeks, 1.77 ± 0.85; 37 weeks, 1.79 ± 0.77; 38 weeks, 1.04 ± 0.74, p < 0.0001). In addition, the skin thickness of the lower legs was significantly decreased after the use of elastic stockings (36 weeks, 7.47 ± 2.45 mm; 37 weeks, 7.93 ± 2.83 mm; 38 weeks, 7.15 ± 2.35 mm, p < 0.0001). Conclusions: The wearing of elastic compression stockings on the lower legs is objectively effective for improving leg edema in pregnant women.

Cost-effectiveness of insertable cardiac monitors for diagnosis of atrial fibrillation in cryptogenic stroke in Australia.

INTRODUCTION: Detection of atrial fibrillation (AF) is required to initiate oral anticoagulation (OAC) after cryptogenic stroke (CS). However, paroxysmal AF can be difficult to diagnose with short term cardiac monitoring. Taking an Australian payer perspective, we evaluated whether long-term continuous monitoring for 3 years with an insertable cardiac monitor (ICM) is cost-effective for preventing recurrent stroke in patients with CS. METHODS: A lifetime Markov model was developed to simulate the follow-up of patients, comparing long-term continuous monitoring with an ICM to monitoring by conventional care. We used a linked evidence approach to estimate the rates of recurrent stroke when AF detection leads to initiation of OAC, as detected using ICM during the lifetime of the device or as detected using usual care. All diagnostic and patient management costs were modeled. Other model inputs were determined by literature review. Probabilistic sensitivity analysis (PSA) was undertaken to explore the effect of parameter uncertainty according to CHADS2 score and OAC treatment effect. RESULTS: In the base-case analysis, the model predicted an incremental cost-effectiveness ratio (ICER) of A$29 570 per quality-adjusted life year (QALY). Among CHADS2 subgroups analyses, the ICER ranged from A$26 342/QALY (CHADS2 = 6) to A$42 967/QALY (CHADS2 = 2). PSA suggested that the probabilities of ICM strategy being cost-effective were 53.4% and 78.7%, at thresholds of $30 000 (highly cost-effective) and $50 000 per QALY (cost-effective), respectively. CONCLUSIONS: Long-term continuous monitoring with an ICM is a cost-effective intervention to prevent recurrent stroke in patients following CS in the Australian context.

Assessment of grip-motion characteristics in carpal tunnel syndrome patients using a novel finger grip dynamometer system.

BACKGROUND: Grip strength measurement is widely used in daily medical practice, and it has been reported that the grip strength decreases in patients with carpal tunnel syndrome (CTS). However, conventional grip dynamometers evaluate only the maximum power of total grip strength and cannot measure the time course of grip motion. In this report, we aimed to determine the grip characteristics of CTS patients by measuring the time course of each finger's grip motion and to analyze the relationship between finger grip strength and subjective symptoms using this new grip system. METHODS: The grip strength of each finger was measured using the new grip system that has four pressure sensors on the grip parts of each finger of the Smedley grip dynamometer. We analyzed the time course of grip motion and relationship between finger grip strength and subjective symptoms in 104 volunteer and 51 CTS hands. The Japanese Society for Surgery of the Hand version of the Carpal Tunnel Syndrome Instrument (CTSI-JSSH) and the Disability of Arm, Shoulder, and Hand questionnaire (DASH) were used as subjective evaluation scores. RESULTS: In the CTS group, the grip time with the index, middle, and ring fingers was longer, and the time at which strength was lost after reaching the maximum was earlier. Patients with severe subjective symptoms tended to not use the index and middle fingers during grip motion. CONCLUSIONS: This new system that measures each finger's grip strength at one time and record the time course of grip motion could quantify a patient's symptoms easily and objectively, which may contribute to the evaluation of hand function.

Cost-Effectiveness of IncobotulinumtoxinA in the Treatment of Sialorrhea in Patients with Various Neurological Conditions.

INTRODUCTION: Sialorrhea is a common and debilitating symptom associated with neurological conditions, which can result in considerable physical and psychosocial complications. In Australia, management options are limited and further impeded by the lack of approved treatments. Whilst there is emerging evidence for the efficacy and tolerability of botulinum toxin (BoNT) for the treatment of sialorrhea in patients with neurological conditions, the cost-effectiveness of the treatment is yet to be established. OBJECTIVES: To evaluate the cost-effectiveness of incobotulinumtoxinA for the treatment of chronic troublesome sialorrhea caused by various neurological conditions from the Australian healthcare perspective. METHODS: A Markov state transition model was developed to perform a cost-utility analysis comparing incobotulinumtoxinA with standard of care (SoC). The model consisted of a hypothetical cohort of patients transiting between three severity-based health states, defined according to the Drooling Severity and Frequency Scale (DSFS), in 16-weekly cycles over 5 years. All clinical and utility inputs were sourced from a single placebo-controlled randomised clinical trial. Only direct healthcare costs were considered, and potential indirect costs such as carer's time and lost productivity were ignored. The primary outcome measure was the incremental cost per quality-adjusted life-year (QALY). Univariate and probabilistic sensitivity analyses were conducted. RESULTS: The model demonstrated that proportionally more patients spent time in less severe sialorrhea health states in the incobotulinumtoxinA arm. For example, over the 5-year period, patients receiving incobotulinumtoxinA were estimated to spend 1.6 years with minimal or no sialorrhea, while no patients achieved this level of improvement under SoC. IncobotulinumtoxinA was shown to have an incremental cost per QALY gained of A$23,445 when compared with SoC. CONCLUSIONS: The quality of life (QoL) of patients with sialorrhea caused by neurological conditions was considerably compromised. IncobotulinumtoxinA was shown to successfully alleviate sialorrhea and it was demonstrated to be a cost-effective intervention when compared with SoC alone.

Presence of a family history and excessive pressure on the first toe pad during walking in female subjects with pincer nails.

Pincer nails (PN) are defined as a transverse overcurvature of the nail plate. Although there have been advancements in therapeutic approaches, the precise underlying mechanisms for the development of PN are still not fully understood. Currently, PN are assumed to develop due to lack of upward mechanical force on the toes. We developed a novel wireless device to observe detailed gait motion. We analyzed trends of gait motion in healthy individuals without PN, healthy individuals with PN without a family history of PN, and healthy individuals with PN and a family history of PN. We found that a family history of PN is an independent risk factor for PN, irrespective of gait motion. Moreover, healthy individuals with PN but without a family history of PN exhibit strong and concentrated pressure on the first toe pad during walking. In sum, a family history of PN and excess upward mechanical forces on the first toe pad during walking may be risk factors for the development of PN.

Multiple Skin Abscesses Caused by Rhizopus sp. Infection after Candida albicans Infection in an Immunocompromised Patient.

A 66-year-old woman with diabetes who was treated with prednisolone (15 mg/day) for autoimmune hepatitis developed multiple erythematous nodules with retention of purulent fluid on her lower right limb. Candida albicans was cultured from the nodules. She was started on oral fluconazole, and the lesions subsided. However, multiple dark-red abscesses and indurations newly appeared on the left crus. Histopathological examination showed numerous branched hyphae, and tissue culture yielded a Rhizopus microsporus-related fungus. She was treated with liposomal amphotericin B combined with drainage and debridement. However, she died because of poor control of the infection and hepatic disorder.

Cost Effectiveness of Long-Term Incobotulinumtoxin-A Treatment in the Management of Post-stroke Spasticity of the Upper Limb from the Australian Payer Perspective.

BACKGROUND: In Australia, the reimbursement of botulinum neurotoxin-A (BoNT-A) on the Pharmaceutical Benefits Scheme for the treatment of moderate to severe spasticity of the upper limb following a stroke (PSS-UL) is restricted to four treatment cycles per upper limb per lifetime. This analysis examined the cost effectiveness of extending the treatment beyond four treatments among patients with an adequate response to previous treatment cycles. METHODS: A Markov state transition model was developed to perform a cost-utility analysis of extending the use of incobotulinumtoxin-A beyond the current restriction of four treatment cycles among patients who have shown a successful response in previous treatment cycles ('known responders'). The Markov model followed patients in 12-weekly cycles for 5 years, estimating the proportion of patients with or without response over this period in each of the modelled treatment arms. Post hoc analysis of an open-label extension phase study informed the Markov model. The perspective of the analysis was the Australian healthcare system, meaning only direct healthcare costs were included. Utility values by response status were derived from EQ-5D data from a published double-blind, placebo-controlled study. The primary outcome measure was the incremental cost per quality-adjusted life-year (QALY). Univariate and probabilistic sensitivity analyses were conducted. RESULTS: The open-label extension study data demonstrated the probability of treatment response after four injections was greater among 'known responders' than those without prior response. The incremental cost per QALY gained of continued use of incobotulinumtoxin-A beyond the current restriction of four treatments was A$59,911. CONCLUSION: Limiting BoNT-A treatment to four cycles per patient per lifetime is likely to be suboptimal in many patients with PSS-UL. Treatment response beyond four cycles is highest among known responders, and allowing such patients to continue treatment beyond four cycles appears cost effective.

Cost-effectiveness of mechanical thrombectomy for acute ischemic stroke: an Australian payer perspective.

AIMS: The goal of this study was to assess the cost-effectiveness of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) from an Australian payer perspective. METHODS: This study used a Markov model that employed a life-time time horizon, modeling patients from symptom onset of stroke until end of life. Clinical efficacy and safety data were taken from an individual patient level data (IPD) meta-analysis of clinical studies. The treatment effect of MT compared to usual care was measured by changes in modified Rankin Score (mRS). Post-treatment mRS scores were used to determine short- and long-term stroke care costs. Treatment costs were modeled, with health state utility values determined by literature review. All analyses were conducted using Microsoft Excel. RESULTS: In comparison to usual care, MT is associated with higher costs ($10,666 per patient) and additional quality-adjusted life years (QALYs) (0.8281 per patient), resulting in an incremental cost per QALY of $12,880. Sensitivity analyses demonstrated the reliability of the base case results across a range of assumptions. The higher cost associated with MT is, to an extent, offset by the cost savings resulting from lower stroke care costs due to improved patient outcomes. The life-time cost savings in terms of stroke care costs are estimated to be more than $8,000 per patient for patients who had received MT in combination with usual care. LIMITATIONS: Stroke care costs based on patient disability/functional level were not available and were derived. As a consequence, long-term care costs for patients with poorer outcomes may be under-estimated. Patient outcomes at 90 days were extrapolated to a lifetime horizon, but this approach was supported by long-term evidence on stroke survival. CONCLUSIONS: Mechanical thrombectomy is a cost-effective treatment option for AIS, with clinical benefits translating to short- and long-term cost benefits. This analysis supports rapid update of stroke care pathways to incorporate this therapy as a treatment option.

A Case of Fingernail Onychomycosis due to Aspergillus flavus.

A 56-year-old woman on insulin therapy for diabetes visited our clinic due to whitish discoloration on the right index finger. Despite topical application of 1% lanoconazole solution, the lesion grew, causing paronychia. Direct microscopy revealed non-dermatophyte molds. Based on the morphological features and genetic analysis of the isolate, the pathogen was identified as Aspergillus flavus. The patient was diagnosed with proximal subungual onychomycosis due to A. flavus. Following itraconazole pulse therapy, she was cured in 6 months. To our knowledge, this is the first reported case of fingernail onychomycosis due to A. flavus in Japan.

Cost-consequence analysis of daily continuous remote monitoring of implantable cardiac defibrillator and resynchronization devices in the UK.

AIMS: The need for ongoing and lifelong follow-up (FU) of patients with cardiac implantable electric devices (CIED) requires significant resources. Remote CIED management has been established as a safe alternative to conventional periodical in-office FU (CFU). An economic model compares the long-term cost and consequences of using daily Home Monitoring® (HM) instead of CFU. METHODS AND RESULTS: A cost-consequence evaluation comparing HM vs. CFU was performed using a Markov cohort model and data relating to events and costs identified via a systematic review of the literature. The model is conservative, without assuming a reduction of cardiovascular events by HM such as decompensated heart failure or mortality, or considering cost savings such as for transportation. Also cost savings due to an improved timing of elective device replacement, and fewer FU visits needed in patients near device replacement are not considered. Over 10 years, HM is predicted to be cost neutral at about GBP 11 500 per patient in either treatment arm, with all costs for the initial investment into HM and fees for ongoing remote monitoring included. Fewer inappropriate shocks (-51%) reduce the need for replacing devices for battery exhaustion (-7%); the number of FU visits is predicted to be halved by HM. CONCLUSION: From a UK National Health Service perspective, HM is cost neutral over 10 years. This is mainly accomplished by reducing the number of battery charges and inappropriate shocks, resulting in fewer device replacements, and by reducing the number of in-clinic FU visits.

Cutaneous hyalohyphomycosis by Scedosporium apiospermum in an immunocompromised patient.

Scedosporium apiospermum is a ubiquitous filamentous fungus that may infect immunocompetent patients after trauma and may cause severe and often fatal infections in immunocompromised hosts. Here, we present the case of a 28-year-old female with S. apiospermum infection on the left forearm that had developed while she was on long-term immunosuppressant therapy. Analysis of a skin biopsy specimen showed a mixed cell granuloma with hyaline septate hyphae. Culture of the abscess revealed S. apiospermum which was identified as S. apiospermum sensu stricto by sequencing of the internal transcribed spacer-1 region of ribosomal DNA genes. Resection of the eruption and oral itraconazole (100 mg day(-1)) therapy for 4 months was effective in curing the infection.

Mass spectrometric analysis of microtubule co-sedimented proteins from rat brain.

Microtubules (MTs) play crucial roles in a variety of cell functions, such as mitosis, vesicle transport and cell motility. MTs also compose specialized structures, such as centrosomes, spindles and cilia. However, molecular mechanisms of these MT-based functions and structures are not fully understood. Here, we analyzed MT co-sedimented proteins from rat brain by tandem mass spectrometry (MS) upon ion exchange column chromatography. We identified a total of 391 proteins. These proteins were grouped into 12 categories: 57 MT cytoskeletal proteins, including MT-associated proteins (MAPs) and motor proteins; 66 other cytoskeletal proteins; 4 centrosomal proteins; 10 chaperons; 5 Golgi proteins; 7 mitochondrial proteins; 62 nucleic acid-binding proteins; 14 nuclear proteins; 13 ribosomal proteins; 28 vesicle transport proteins; 83 proteins with diverse function and/or localization; and 42 uncharacterized proteins. Of these uncharacterized proteins, six proteins were expressed in cultured cells, resulting in the identification of three novel components of centrosomes and cilia. Our present method is not specific for MAPs, but is useful for identifying low abundant novel MAPs and components of MT-based structures. Our analysis provides an extensive list of potential candidates for future study of the molecular mechanisms of MT-based functions and structures.

Identification and characterization of the novel centrosomal protein centlein.

Centrosomes function as the major microtubule (MT)-organizing center. They are composed of a pair of centrioles which are surrounded by the pericentriolar material. Here, we describe the molecular characterization of a novel protein, named centlein (centrosomal protein). Centlein was a protein of 721 amino acids with a calculated molecular weight of 82,717 and possessed coiled-coil domains. Western blot analysis indicated that centlein was ubiquitously expressed. Endogenous centlein as well as enhanced green fluorescent protein-fused centlein was localized at centrosomes in interphase and mitosis. When centrosomes were isolated from cells treated with nocodazole, an MT-disrupting agent, centlein and the centrosomal protein, gamma-tubulin, were enriched in the same fractions. These data indicate that centlein is a widespread centrosomal protein and that its association with centrosomes is independent of MTs. Centlein appeared to be enriched in the mother centriole in G1 phase, suggesting possible involvement of centlein in mother-centriole-related functions, such as duplication of centrioles and generation of primary cilia.