Improved outcomes with early immunosuppression in patients with immune-checkpoint inhibitor induced myasthenia gravis, myocarditis and myositis: a case series.

PURPOSE: Myasthenia gravis (MG) is a rare but life-threatening complication of immune-checkpoint inhibitor (ICI) therapy and often co-presents with myositis and myocarditis. Previous case series of ICI-related MG have reported high mortality rates. We present a series of ten patients from a tertiary oncology centre outlining outcomes of an early multi-modal immunosuppression strategy. METHODS: We reviewed The Christie Hospital database of immunotherapy-related toxicity from 2017 to 2020. Symptom severity was assessed using the Myasthenia Gravis Foundation of America (MGFA) classification. RESULTS: Ten patients with ICI-related MG were identified. All patients presented following 1 (n = 4) or 2 (n = 6) cycles of ICI. Symptom progression was rapid with a median of 3 days from onset of symptoms to admission. Concomitant myositis and myocarditis were observed in nine patients. AChR or MuSK autoantibodies were positive in six patients. All patients received urgent treatment with intravenous methylprednisolone (IVMP) and eight received intravenous immunoglobulin (IVIG). A single patient died from myasthenia-related symptoms; the remaining 9 patients were successfully discharged. CONCLUSION: In our cohort, we demonstrate good outcomes associated with early intensive immunosuppressive treatment with IVIG and IVMP. An agreed national treatment protocol or clinical discussion forum would be beneficial.

High power zinc iodine redox flow battery with iron-functionalized carbon electrodes.

The zinc iodine (ZI) redox flow battery (RFB) has emerged as a promising candidate for grid-scale electrical energy storage owing to its high energy density, low cost and environmental friendliness. In this work, ZI RFBs were made with electrodes comprising carbon nanotubes (CNT) with redox-active iron particles, yielding higher discharge voltages, power densities, and 90% lower charge transfer resistances compared to cells with inert carbon electrodes. Analysis of the polarization curves reveals that cells with iron-containing electrodes have lower mass transfer resistances and 100% increase in power density (44 mW cm-2 to 90 mW cm-2) at 110 mA cm-2 relative to cells with inert carbon electrodes.

Biostimulation of jarosite and iron oxide-bearing mine waste enhances subsequent metal recovery.

Novel resource recovery technologies are required for metals-bearing hazardous wastes in order to achieve circular economy outcomes and industrial symbiosis. Iron oxide and co-occurring hydroxysulphate-bearing wastes are globally abundant and often contain other elements of value. This work addresses the biostimulation of indigenous microbial communities within an iron oxide/ hydroxysulphate-bearing waste and its effect on the subsequent recoverability of metals by hydrochloric, sulphuric, citric acids, and EDTA. Laboratory-scale flow-through column reactors were used to examine the effect of using glycerol (10% w/w) to stimulate the in situ microbial community in an iron oxide/ hydroxysulphate-bearing mine waste. The effects on the evolution of leachate chemistry, changes in microbiological community, and subsequent hydrometallurgical extractability of metals were studied. Results demonstrated increased leachability and selectivity of Pb, Cu, and Zn relative to iron after biostimulation with a total of 0.027 kg of glycerol per kg of waste. Biostimulation, which can be readily applied in situ, potentially opens new routes to metal recovery from globally abundant waste streams that contain jarosite and iron oxides.

Structural Model of a Porphyromonas gingivalis type IX Secretion System Shuttle Complex.

Porphyromonas gingivalis is a gram-negative oral anaerobic pathogen and is one of the key causative agents of periodontitis. P. gingivalis utilises a range of virulence factors, including the cysteine protease RgpB, to drive pathogenesis and these are exported and attached to the cell surface via the type IX secretion system (T9SS). All cargo proteins possess a conserved C-terminal signal domain (CTD) which is recognised by the T9SS, and the outer membrane ß-barrel protein PorV (PG0027/LptO) can interact with cargo proteins as they are exported to the bacterial surface. Using a combination of solution nuclear magnetic resonance (NMR) spectroscopy, biochemical analyses, machine-learning-based modelling and molecular dynamics (MD) simulations, we present a structural model of a PorV:RgpB-CTD complex from P. gingivalis. This is the first structural insight into CTD recognition by the T9SS and shows how the conserved motifs in the CTD are the primary sites that mediate binding. In PorV, interactions with extracellular surface loops are important for binding the CTD, and together these appear to cradle and lock RgpB-CTD in place. This work provides insight into cargo recognition by PorV but may also have important implications for understanding other aspects of type-IX dependent secretion.

Measuring quality effects in equilibrium.

Unlike demand studies in other industries, models of provider demand in health care often must omit a price, or any other factor that equilibrates the market such as a waiting time. Estimates of the consumer response to quality may consequently be attenuated, if the limited capacity of individual physicians prevents some consumers from obtaining higher quality. We propose a tractable method to address this problem by adding a congestion effect to standard discrete-choice models. We show analytically how this can improve forecasts of the consumer response to quality. We then apply this method to the market for heart surgery, and find that the attenuation bias in estimated quality effects can be important empirically.

Development of a Metric to Detect and Decrease Low-Value Prescribing in Older Adults.

Importance: Metrics that detect low-value care in common forms of health care data, such as administrative claims or electronic health records, primarily focus on tests and procedures but not on medications, representing a major gap in the ability to systematically measure low-value prescribing. Objective: To develop a scalable and broadly applicable metric that contains a set of quality indicators (EVOLV-Rx) for use in health care data to detect and reduce low-value prescribing among older adults and that is informed by diverse stakeholders' perspectives. Design, Setting, and Participants: This qualitative study used an online modified-Delphi method to convene an expert panel of 15 physicians and pharmacists. This panel, comprising clinicians, health system leaders, and researchers, was tasked with rating and discussing candidate low-value prescribing practices that were derived from medication safety criteria; peer-reviewed literature; and qualitative studies of patient, caregiver, and physician perspectives. The RAND ExpertLens online platform was used to conduct the activities of the panel. The panelists were engaged for 3 rounds between January 1 and March 31, 2021. Main Outcomes and Measures: Panelists used a 9-point Likert scale to rate and then discuss the scientific validity and clinical usefulness of the criteria to detect low-value prescribing practices. Candidate low-value prescribing practices were rated as follows: 1 to 3, indicating low validity or usefulness; 3.5 to 6, uncertain validity or usefulness; and 6.5 to 9, high validity or usefulness. Agreement among panelists and the degree of scientific validity and clinical usefulness were assessed using the RAND/UCLA (University of California, Los Angeles) Appropriateness Method. Results: Of the 527 low-value prescribing recommendations identified, 27 discrete candidate low-value prescribing practices were considered for inclusion in EVOLV-Rx. After round 1, 18 candidate practices were rated by the panel as having high scientific validity and clinical usefulness (scores of ≥6.5). After round 2 panel deliberations, the criteria to detect 19 candidate practices were revised. After round 3, 18 candidate practices met the inclusion criteria, receiving final median scores of 6.5 or higher for both scientific validity and clinical usefulness. Of those practices that were not included in the final version of EVOLV-Rx, 3 received high scientific validity (scores ≥6.5) but uncertain clinical usefulness (scores <6.5) ratings, whereas 6 received uncertain scientific validity rating (scores <6.5). Conclusions and Relevance: This study culminated in the development of EVOLV-Rx and involved a panel of experts who identified the 18 most salient low-value prescribing practices in the care of older adults. Applying EVOLV-Rx may enhance the detection of low-value prescribing practices, reduce polypharmacy, and enable older adults to receive high-value care across the full spectrum of health services.

Pneumothorax management: current state of practice in the UK.

BACKGROUND AND OBJECTIVE: Spontaneous pneumothorax is a common pathology but optimal initial treatment regime is not well defined. Treatment options including conservative management, needle aspiration (NA) or insertion of a small-bore chest drain. Recent large randomised controlled trials may change the treatment paradigm: comparing conservative and ambulatory management to standard care, but current guidelines need to be updated. The aim of this study was to assess the current "state of play" in the management of pneumothorax in the UK. METHODS: Physicians and respiratory healthcare staff were invited to complete an online survey on the initial and subsequent management of pneumothorax. RESULTS: This study is the first survey of pneumothorax practice across the UK, which highlights variation in practice: 50% would manage a large primary pneumothorax with minimal symptoms conservatively, compared to only 3% if there were significant symptoms; 64% use suction if the pneumothorax had not resolved after > 2 days, 15% always clamp the chest drain prior to removal; whereas 30% never do. NICE guidance recommends the use of digital suction but this has not translated into widespread usage: only 23% use digital suction to check for resolution of air leak). CONCLUSION: Whilst there has always been allowance for individual clinician preference in guidelines, there needs to be consensus on the optimum management strategy. The challenge the new guidelines face is to design a simple and pragmatic approach, using this new evidence base.

Impact of Procedural Sedation on the Clinical Outcome of Microelectrode Recording Guided Deep Brain Stimulation in Patients with Parkinson's Disease.

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) has become a routine treatment of advanced Parkinson's disease (PD). DBS surgery is commonly performed under local anesthesia (LA) to obtain reliable microelectrode recordings. However, procedural sedation and/or analgesia (PSA) is often desirable to improve patient comfort. The impact of PSA in addition to LA on outcome is largely unknown. Therefore, we performed an observational study to assess the effect of PSA compared to LA alone during STN DBS surgery on outcome in PD patients. METHODS: Seventy PD patients (22 under LA, 48 under LA + PSA) scheduled for STN DBS implantation were included. Dexmedetomidine, clonidine or remifentanil were used for PSA. The primary outcome was the change in Movement Disorders Society Unified Parkinson's Disease Rating Score III (MDS-UPDRS III) and levodopa equivalent daily dosage (LEDD) between baseline, one month before surgery, and twelve months postoperatively. Secondary outcome measures were motor function during activities of daily living (MDS-UPDRS II), cognitive alterations and surgical adverse events. Postoperative assessment was conducted in "on" stimulation and "on" medication conditions. RESULTS: At twelve months follow-up, UPDRS III and UPDRS II scores in "on" medication conditions were similar between the LA and PSA groups. The two groups showed a similar LEDD reduction and an equivalent decline in executive function measured by the Stroop Color-Word Test, Trail Making Test-B, and verbal fluency. The incidence of perioperative and postoperative adverse events was similar between groups. CONCLUSION: This study demonstrates that PSA during STN DBS implantation surgery in PD patients was not associated with differences in motor and non-motor outcome after twelve months compared with LA only.

Prescriber perspectives on low-value prescribing: A qualitative study.

BACKGROUND: Health systems are increasingly implementing interventions to reduce older patients' use of low-value medications. However, prescribers' perspectives on medication value and the acceptability of interventions to reduce low-value prescribing are poorly understood. OBJECTIVE: To identify the characteristics that affect the value of a medication and those factors influencing low-value prescribing from the perspective of primary care physicians. DESIGN: Qualitative study using semi-structured interviews. SETTING: Academic and community primary care practices within University of Pittsburgh Medical Center health system. PARTICIPANTS: Sixteen primary care physicians. MEASUREMENTS: We elicited 16 prescribers' perspectives on definitions and examples of low-value prescribing in older adults, the factors that incentivize them to engage in such prescribing, and the characteristics of interventions that would make them less likely to engage in low-value prescribing. RESULTS: We identified three key themes. First, prescribers viewed low-value prescribing among older adults as common, characterized both by features of the medications themselves and of the particular patients to whom they were prescribed. Second, prescribers described the causes of low-value prescribing as multifactorial, with factors related to patients, prescribers, and the health system as a whole, making low-value prescribing a default practice pattern. Third, interventions addressing low-value prescribing must minimize the cognitive load and time pressures that make low-value prescribing common. Interventions increasing time pressure or cognitive load, such as increased documentation, were considered less acceptable. CONCLUSIONS: Our findings demonstrate that low-value prescribing is a well-recognized phenomenon, and that interventions to reduce low-value prescribing must consider physicians' perspectives and address the specific patient, prescriber and health system factors that make low-value prescribing a default practice.

Economic analysis of screening for subclinical rejection in kidney transplantation using protocol biopsies and noninvasive biomarkers.

Subclinical rejection (SCR) screening in kidney transplantation (KT) using protocol biopsies and noninvasive biomarkers has not been evaluated from an economic perspective. We assessed cost-effectiveness from the health sector perspective of SCR screening in the first year after KT using a Markov model that compared no screening with screening using protocol biopsy or biomarker at 3 months, 12 months, 3 and 12 months, or 3, 6, and 12 months. We used 12% subclinical cellular rejection and 3% subclinical antibody-mediated rejection (SC-ABMR) for the base-case cohort. Results favored 1-time screening at peak SCR incidence rather than repeated screening. Screening 2 or 3 times was favored only with age <35 years and with high SC-ABMR incidence. Compared to biomarkers, protocol biopsy yielded more quality-adjusted life years (QALYs) at lower cost. A 12-month biopsy cost $13 318/QALY for the base-case cohort. Screening for cellular rejection in the absence of SC-ABMR was less cost effective with 12-month biopsy costing $46 370/QALY. Screening was less cost effective in patients >60 years. Using biomarker twice or thrice was cost effective only if biomarker cost was <$700. In conclusion, in KT, screening for SCR more than once during the first year is not economically reasonable. Screening with protocol biopsy was favored over biomarkers.

English version of the self-administered Fabry Pain Questionnaire for adult patients.

BACKGROUND: Pain is an early symptom of Fabry disease (FD) and is characterized by a unique phenotype with mainly episodic acral and triggerable burning pain. Recently, we designed and validated the first pain questionnaire for adult FD patients in an interview and a self-administered version in German: the Würzburg Fabry Pain Questionnaire (FPQ). We now report the validation of the English version of the self-administered FPQ (enFPQ). METHODS: After two forward-backward translations of the FPQ by native German and native English speakers, the enFPQ was applied at The Mark Holland Metabolic Unit, Manchester, UK for validation. Consecutive patients with genetically ascertained FD and current or previous FD pain underwent a face-to-face interview using the enFPQ. Two weeks later, patients filled in the self-administered enFPQ at home. The agreement between entries collected by supervised administration and self-administration of the enFPQ was assessed via Gwet's AC1-statistics (AC1) for nominal-scaled scores and intraclass correlation coefficient (ICC) for interval-scaled elements. RESULTS: Eighty-three FD patients underwent the face-to-face interview and 54 patients sent back a completed self-administered version of the enFPQ 2 weeks later. We found high agreement with a mean AC1-statistics of 0.725 for 55 items, and very high agreement with a mean ICC of 0.811 for 9 items. CONCLUSIONS: We provide the validated English version of the FPQ for self-administration in adult FD patients. The enFPQ collects detailed information on the individual FD pain phenotype and thus builds a solid basis for better pain classification and treatment in patients with FD.

Manometry performed at indwelling pleural catheter insertion to predict unexpandable lung.

BACKGROUND: The finding of unexpandable lung (UL) at an early timepoint is of increasing importance in guiding treatment decisions in patients with malignant pleural effusion (MPE). Pleural manometry is the most common technique to delineate UL, however it has never been measured via an indwelling pleural catheter (IPC). To further the evidence base we analysed all patients in the IPC-PLUS study who had manometry performed during IPC insertion for the ability to predict substantial UL using manometry. METHODS: All patients enrolled in IPC-PLUS who had manometry performed at IPC insertion and radiographic assessment of UL at day 10 were included. Elastance curves were visually inspected for each patient. Initial pleural pressure, closing pleural pressure, and terminal elastance were analysed for their differences and predictive ability in those with substantial UL, defined as ≥25% entrapment on chest radiography. RESULTS: A total of 89 patients had manometry performed at IPC insertion with subsequent radiographic assessment of UL and interpretable elastance curves. Those with substantial UL had a significantly lower median closing pleural pressure (-15.00 vs. 0.00 cmH2O, P=0.012) and higher terminal elastance (12.03 vs. 8.59 cmH2O/L, P=0.021) compared to a combined group with no or partial UL. However, the predictive ability of these factors to discriminate substantial UL was poor, with areas under the receiver operating characteristic curves of 0.695 and 0.680 for closing pleural pressure and elastance respectively. CONCLUSIONS: Our results suggest that manometry is not useful in accurately predicting substantial UL when used via an IPC at the time of insertion.

Influence of Anesthesia and Clinical Variables on the Firing Rate, Coefficient of Variation and Multi-Unit Activity of the Subthalamic Nucleus in Patients with Parkinson's Disease.

BACKGROUND: Microelectrode recordings (MER) are used to optimize lead placement during subthalamic nucleus deep brain stimulation (STN-DBS). To obtain reliable MER, surgery is usually performed while patients are awake. Procedural sedation and analgesia (PSA) is often desirable to improve patient comfort, anxiolysis and pain relief. The effect of these agents on MER are largely unknown. The objective of this study was to determine the effects of commonly used PSA agents, dexmedetomidine, clonidine and remifentanil and patient characteristics on MER during DBS surgery. METHODS: Data from 78 patients with Parkinson's disease (PD) who underwent STN-DBS surgery were retrospectively reviewed. The procedures were performed under local anesthesia or under PSA with dexmedetomidine, clonidine or remifentanil. In total, 4082 sites with multi-unit activity (MUA) and 588 with single units were acquired. Single unit firing rates and coefficient of variation (CV), and MUA total power were compared between patient groups. RESULTS: We observed a significant reduction in MUA, an increase of the CV and a trend for reduced firing rate by dexmedetomidine. The effect of dexmedetomidine was dose-dependent for all measures. Remifentanil had no effect on the firing rate but was associated with a significant increase in CV and a decrease in MUA. Clonidine showed no significant effect on firing rate, CV or MUA. In addition to anesthetic effects, MUA and CV were also influenced by patient-dependent variables. CONCLUSION: Our results showed that PSA influenced neuronal properties in the STN and the dexmedetomidine (DEX) effect was dose-dependent. In addition, patient-dependent characteristics also influenced MER.

Novel MT-ND Gene Variants Causing Adult-Onset Mitochondrial Disease and Isolated Complex I Deficiency.

Mitochondrial complex I deficiency is associated with a diverse range of clinical phenotypes and can arise due to either mitochondrial DNA (mtDNA) or nuclear gene defects. We investigated two adult patients who exhibited non-syndromic neurological features and evidence of isolated mitochondrial complex I deficiency in skeletal muscle biopsies. The first presented with indolent myopathy, progressive since age 17, while the second developed deafness around age 20 and other relapsing-remitting neurological symptoms since. A novel, likely de novo, frameshift variant in MT-ND6 (m.14512_14513del) and a novel maternally-inherited transversion mutation in MT-ND1 were identified, respectively. Skewed tissue segregation of mutant heteroplasmy level was observed; the mutant heteroplasmy levels of both variants were greater than 70% in muscle homogenate, however, in blood the MT-ND6 variant was undetectable while the mutant heteroplasmy level of the MT-ND1 variant was low (12%). Assessment of complex I assembly by Blue-Native PAGE demonstrated a decrease in fully assembled complex I in the muscle of both cases. SDS-PAGE and immunoblotting showed decreased levels of mtDNA-encoded ND1 and several nuclear encoded complex I subunits in both cases, consistent with functional pathogenic consequences of the identified variants. Pathogenicity of the m.14512_14513del was further corroborated by single-fiber segregation studies.

Clinical, morphological and genetic characterization of Brody disease: an international study of 40 patients.

Brody disease is an autosomal recessive myopathy characterized by exercise-induced muscle stiffness due to mutations in the ATP2A1 gene. Almost 50 years after the initial case presentation, only 18 patients have been reported and many questions regarding the clinical phenotype and results of ancillary investigations remain unanswered, likely leading to incomplete recognition and consequently under-diagnosis. Additionally, little is known about the natural history of the disorder, genotype-phenotype correlations, and the effects of symptomatic treatment. We studied the largest cohort of Brody disease patients to date (n = 40), consisting of 22 new patients (19 novel mutations) and all 18 previously published patients. This observational study shows that the main feature of Brody disease is an exercise-induced muscle stiffness of the limbs, and often of the eyelids. Onset begins in childhood and there was no or only mild progression of symptoms over time. Four patients had episodes resembling malignant hyperthermia. The key finding at physical examination was delayed relaxation after repetitive contractions. Additionally, no atrophy was seen, muscle strength was generally preserved, and some patients had a remarkable athletic build. Symptomatic treatment was mostly ineffective or produced unacceptable side effects. EMG showed silent contractures in approximately half of the patients and no myotonia. Creatine kinase was normal or mildly elevated, and muscle biopsy showed mild myopathic changes with selective type II atrophy. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) activity was reduced and western blot analysis showed decreased or absent SERCA1 protein. Based on this cohort, we conclude that Brody disease should be considered in cases of exercise-induced muscle stiffness. When physical examination shows delayed relaxation, and there are no myotonic discharges at electromyography, we recommend direct sequencing of the ATP2A1 gene or next generation sequencing with a myopathy panel. Aside from clinical features, SERCA activity measurement and SERCA1 western blot can assist in proving the pathogenicity of novel ATP2A1 mutations. Finally, patients with Brody disease may be at risk for malignant hyperthermia-like episodes, and therefore appropriate perioperative measures are recommended. This study will help improve understanding and recognition of Brody disease as a distinct myopathy in the broader field of calcium-related myopathies.

Combining Gamma With Alpha and Beta Power Modulation for Enhanced Cortical Mapping in Patients With Focal Epilepsy.

About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping (ESM) is the gold standard for the identification of "eloquent" areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects. Broadband gamma activity (55-200 Hz) recorded with extraoperative electrocorticography (ECoG) during cognitive tasks may be an alternative to ESM but until now has not proven of definitive clinical value. Considering their role in cognition, the alpha (8-12 Hz) and beta (15-25 Hz) bands could further improve the identification of eloquent cortex. We compared gamma, alpha and beta activity, and their combinations for the identification of eloquent cortical areas defined by ESM. Ten patients with intractable focal epilepsy (age: 35.9 ± 9.1 years, range: 22-48, 8 females, 9 right handed) participated in a delayed-match-to-sample task, where syllable sounds were compared to visually presented letters. We used a generalized linear model (GLM) approach to find the optimal weighting of each band for predicting ESM-defined categories and estimated the diagnostic ability by calculating the area under the receiver operating characteristic (ROC) curve. Gamma activity increased more in eloquent than in non-eloquent areas, whereas alpha and beta power decreased more in eloquent areas. Diagnostic ability of each band was close to 0.7 for all bands but depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient's degree of attention to the stimulus. We show that diagnostic ability can be increased by 3-5% by combining gamma and alpha and by 7.5-11% when gamma and beta were combined. We then show how ECoG power modulation from cognitive testing can be used to map the probability of eloquence in individual patients and how this probability map can be used in clinical settings to optimize ESM planning. We conclude that the combination of gamma and beta power modulation during cognitive testing can contribute to the identification of eloquent areas prior to ESM in patients with refractory focal epilepsy.

Effect of Thoracoscopic Talc Poudrage vs Talc Slurry via Chest Tube on Pleurodesis Failure Rate Among Patients With Malignant Pleural Effusions: A Randomized Clinical Trial.

Importance: Malignant pleural effusion (MPE) is challenging to manage. Talc pleurodesis is a common and effective treatment. There are no reliable data, however, regarding the optimal method for talc delivery, leading to differences in practice and recommendations. Objective: To test the hypothesis that administration of talc poudrage during thoracoscopy with local anesthesia is more effective than talc slurry delivered via chest tube in successfully inducing pleurodesis. Design, Setting, and Participants: Open-label, randomized clinical trial conducted at 17 UK hospitals. A total of 330 participants were enrolled from August 2012 to April 2018 and followed up until October 2018. Patients were eligible if they were older than 18 years, had a confirmed diagnosis of MPE, and could undergo thoracoscopy with local anesthesia. Patients were excluded if they required a thoracoscopy for diagnostic purposes or had evidence of nonexpandable lung. Interventions: Patients randomized to the talc poudrage group (n = 166) received 4 g of talc poudrage during thoracoscopy while under moderate sedation, while patients randomized to the control group (n = 164) underwent bedside chest tube insertion with local anesthesia followed by administration of 4 g of sterile talc slurry. Main Outcomes and Measures: The primary outcome was pleurodesis failure up to 90 days after randomization. Secondary outcomes included pleurodesis failure at 30 and 180 days; time to pleurodesis failure; number of nights spent in the hospital over 90 days; patient-reported thoracic pain and dyspnea at 7, 30, 90, and 180 days; health-related quality of life at 30, 90, and 180 days; all-cause mortality; and percentage of opacification on chest radiograph at drain removal and at 30, 90, and 180 days. Results: Among 330 patients who were randomized (mean age, 68 years; 181 [55%] women), 320 (97%) were included in the primary outcome analysis. At 90 days, the pleurodesis failure rate was 36 of 161 patients (22%) in the talc poudrage group and 38 of 159 (24%) in the talc slurry group (adjusted odds ratio, 0.91 [95% CI, 0.54-1.55]; P = .74; difference, -1.8% [95% CI, -10.7% to 7.2%]). No statistically significant differences were noted in any of the 24 prespecified secondary outcomes. Conclusions and Relevance: Among patients with malignant pleural effusion, thoracoscopic talc poudrage, compared with talc slurry delivered via chest tube, resulted in no significant difference in the rate of pleurodesis failure at 90 days. However, the study may have been underpowered to detect small but potentially important differences. Trial Registration: ISRCTN Identifier: ISRCTN47845793.

Effect of Anesthesia on Microelectrode Recordings during Deep Brain Stimulation Surgery in Tourette Syndrome Patients.

BACKGROUND: Deep brain stimulation (DBS) is an accepted treatment for patients with medication-resistant Tourette syndrome (TS). Sedation is commonly required during electrode implantation to attenuate anxiety, pain, and severe tics. Anesthetic agents potentially impair the quality of microelectrode recordings (MER). Little is known about the effect of these anesthetics on MER in patients with TS. We describe our experience with different sedative regimens on MER and tic severity in patients with TS. METHODS: The clinical records of all TS patients who underwent DBS surgery between 2010 and 2018 were reviewed. Demographic data, stimulation targets, anesthetic agents, perioperative complications, and MER from each hemisphere were collected and analyzed. Single-unit activity was identified by filtering spiking activity from broadband MER data and principal component analysis with K-means clustering. Vocal and motor tics which caused artifacts in the MER data were manually selected using visual and auditory inspection. RESULTS: Six patients underwent bilateral DBS electrode implantation. In all patients, the target was the anterior internal globus pallidus. Patient comfort and hemodynamic and respiratory stability were maintained with conscious sedation with one or more of the following anesthetic drugs: propofol, midazolam, remifentanil, clonidine, and dexmedetomidine. Good quality MER and clinical testing were obtained in 9 hemispheres of 6 patients. In 3 patients, MER quality was poor on one side. CONCLUSION: Cautiously applied sedative drugs can provide patient comfort, hemodynamic and respiratory stability, and suppress severe tics, with minimal interference with MER.

Molecular Testing Versus Diagnostic Lobectomy in Bethesda III/IV Thyroid Nodules: A Cost-Effectiveness Analysis.

Background: Molecular tests (MT) using gene expression and/or mutational analysis have been developed to reduce the need for diagnostic surgery for indeterminate (Bethesda III/IV) thyroid nodules. Prior cost-effectiveness studies have shown mixed results but none has included the recent and more comprehensive versions of the two commonly utilized MT. The aim of this study is to compare the cost-effectiveness of diagnostic lobectomy (DL), the Afirma Gene Sequencing Classifier (GSC), and ThyroSeq version 3 (TSv3). Methods: A decision tree from the payer perspective was created using a base case of a 40-year-old euthyroid woman with a solitary 2 cm Bethesda III or IV thyroid nodule. In this model, all patients in the DL arm had lobectomy, which was also performed for patients with positive MT, while those with negative MT underwent 20 years of surveillance. The outcome was a correct diagnosis, defined as malignant histology after DL or 20 years of nodule stability after negative MT. Costs were obtained from the Centers for Medicare & Medicaid Services (CMS) data and existing literature, and probabilities were obtained from the literature. Sensitivity analysis was performed for costs, pretest probability of malignancy, and performance parameters. Results: The cost per correct diagnosis was $14,277 for TSv3, $17,873 for GSC, and $38,408 for DL. TSv3 was preferred over both GSC and DL. One-way sensitivity analysis between TSv3 and GSC demonstrated that the results were robust to variations in cost, cancer prevalence, and length of surveillance. In the two-way sensitivity analysis, TSv3 was preferred over GSC at all considered test costs, and in probabilistic sensitivity analysis, TSv3 was the preferred management strategy in 68.5% of cases. Conclusions: In hypothetical modeling to determine whether surgery versus MT is optimal for indeterminate (Bethesda III/IV) nodules, either of the major MT was considerably more cost-effective than DL, although TSv3 was more likely to be cost-effective than GSC. Use of either MT adjunct should be strongly considered in the absence of other indications for thyroidectomy.

Prolonged Zika Virus RNA Detection in Semen of Immunosuppressed Patient.

Zika virus RNA has been detected in semen samples collected <370 days after symptom onset. We report unusual persistence of Zika virus RNA in semen, confirmed by sequencing at 515 days after symptom onset and detectable for >900 days, in a patient with immunosuppression.