Costs of pediatric liver transplantation among commercially insured and Medicaid-insured patients with cholestasis in the US.

Children with rare cholestatic liver diseases, such as Alagille syndrome, progressive familial intrahepatic cholestasis, and biliary atresia typically require liver transplantation (LT). The objective of this analysis was to assess the economic burden of LT on these patients. Health care resource utilization and costs associated with pediatric LT were retrospectively assessed using insurance claims data from the US IBM MarketScan Commercial and Medicaid databases collected between October 2015 and December 2019. Inclusion criteria were as follows: ≥1 procedure code for LT, <18 years old at transplant, and ≥6 months of insurance eligibility at baseline. A cholestatic liver disease population who received LT was selected in the absence of specific diagnosis codes by excluding other severe liver conditions (ie, acute liver failure, malignancy) and by excluding severely decompensated individuals requiring ICU admission before LT. Annualized rates were reported. Over a mean study duration of 1.8 years, 53 commercially insured and 100 Medicaid-insured children received LT, with mean (SD) ages at baseline of 6.9 (6.0) and 5.7 (5.4) years, respectively. During this period, commercially insured and Medicaid-insured patients had annualized means of 65.3 and 52.8 medical visits, respectively. Most were outpatient visits, although the burden of inpatient visits was also high, with mean inpatient stays (inclusive of LT stay) of 37.2 and 31.6 days per year, respectively. Commercially insured and Medicaid-insured patients averaged US$512,124 and $211,863 in medical costs and $26,998 and $15,704 in pharmacy costs, respectively. These costs remained substantial throughout the first year after transplant. Overall, pediatric LT resulted in substantial health care resource utilization and cost burden in both commercially- and Medicaid-insured patients. Novel targeted medications that negate the need for pediatric LT could decrease the associated morbidity and costs.

Health Care Resource Utilization by Patients with Alagille Syndrome.

OBJECTIVE: To assess and characterize health care resource utilization (HRU) in children with the rare, genetic, multisystem disorder, Alagille syndrome. STUDY DESIGN: This retrospective analysis reviewed commercially insured and Medicaid-insured claims from October 1, 2015 to December 31, 2019 to assess HRU in patients with Alagille syndrome. As there is no specific International Classification ofDiseases-10 code for Alagille syndrome, patients were identified using the following algorithm: ≥1 claim with diagnosis code Q44.7 (other congenital malformations of the liver); <18 years of age, with no history of biliary atresia (International Classification ofDiseases-10 code: Q44.2); and ≥6 months of insurance eligibility prior to diagnosis. HRU was summarized per patient per year over all available claims postdiagnosis. RESULTS: A total of 171 commercially insured and 215 Medicaid-insured patients with Alagille syndrome were available for analysis. Annually, commercially insured and Medicaid-insured patients averaged 31 medical visits (range, 1.5-237) and 48 medical visits (range, 0.7-690), respectively. The most common visits were outpatient with the majority encompassing lab/imaging and primary care visits (commercially insured: 21 [range, 0.0-183]; Medicaid-insured: 26 [range, 0.0-609]). Inpatient visits were the highest driver of costs in both the commercial and Medicaid populations. CONCLUSIONS: Patients with Alagille syndrome have a substantial HRU burden driven largely by numerous outpatient visits and costly inpatient stays. Given the complexity and variability of Alagille syndrome presentation, patients may benefit from multidisciplinary and subspecialized care.

Maralixibat Treatment Response in Alagille Syndrome is Associated with Improved Health-Related Quality of Life.

OBJECTIVE: The objective of this study was to assess the impact of treatment response to the ileal bile acid transporter inhibitor maralixibat on health-related quality of life (HRQoL) in children with Alagille syndrome. STUDY DESIGN: This analysis used data from the ICONIC trial, a phase 2 study with a 4-week double-blind, placebo-controlled, randomized drug withdrawal period in children with Alagille syndrome with moderate-to-severe pruritus. Clinically meaningful treatment response to maralixibat was defined a priori as a ≥1-point reduction in the Itch-Reported Outcome (Observer) score, from baseline to week 48. HRQoL was assessed using the Pediatric Quality of Life Inventory Generic Core, Family Impact, and Multidimensional Fatigue scale scores, which were collected via the caregiver. The minimal clinically important difference for HRQoL ranged from 4 to 5 points, depending on the scale. RESULTS: Twenty of the 27 patients (74%) included in this analysis achieved an Itch-Reported Outcome (Observer) treatment response at week 48. The mean (SD) change in Multidimensional Fatigue score was +25.8 (23.0) for responders vs -3.1 (19.8) for nonresponders (P = .03). Smaller and non-statistically significant mean changes were observed for the Pediatric Quality of Life Inventory Generic Core and Family Impact scores. Controlling for baseline Family Impact score, responders' Family Impact scores increased an average of 16.9 points over 48 weeks compared with non-responders (P = .05). Smaller and non-statistically significant point estimates were observed for the Pediatric Quality of Life Inventory Generic Core and Multidimensional Fatigue scores. CONCLUSION: The significant improvements in pruritus seen with maralixibat at week 48 of the ICONIC study are clinically meaningful and are associated with improved HRQoL. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02160782.

Two emerging phenotypes of atypical inclusion body myositis: illustrative cases.

OBJECTIVES: Sporadic inclusion body myositis (IBM) is the most common acquired myopathy in those aged above 50. It is classically heralded by weakness in the long finger flexors and quadriceps. The aim of this article is to describe five atypical cases of IBM, outlining two potential emerging clinical subsets of the disease. METHODS: We reviewed relevant clinical documentation and pertinent investigations for five patients with IBM. RESULTS: The first phenotype we describe is young-onset IBM in two patients who had symptoms since their early thirties. The literature supports that IBM can rarely present in this age range or younger. We describe a second phenotype in three middle-aged women who developed early bilateral facial weakness at presentation in tandem with dysphagia and bulbar impairment followed by respiratory failure requiring non-invasive ventilation (NIV). Within this group, two patients were noted to have macroglossia, another possible rare feature of IBM. CONCLUSIONS: Despite the classical phenotype described within the literature IBM can present in a heterogenous fashion. It is important to recognise IBM in younger patients and investigate for specific associations. The described pattern of facial diplegia, severe dysphagia, bulbar dysfunction and respiratory failure in female IBM patients requires further characterisation. Patients with this clinical pattern may require more complex and supportive management. Macroglossia is a potentially under recognised feature of IBM. The presence of macroglossia in IBM warrants further study, as its presence may lead to unnecessary investigations and delay diagnosis.

Shell Shock: The Response of UK Neurology.

The neurological and psychological manifestations of trauma, confinement, and terror became apparent throughout Europe as soldiers were evacuated from the trenches of the Western Front. The response in the UK evolved as a result of the experience of medical staff embedded with the troops in base hospitals and the philosophy of those treating returned soldiers in specialist establishment. There were widely disparate approaches to the management encompassing simple supportive care, a psychanalytic approach and radical electric shock therapy. The latter was partially driven by the Queen Square experience in the UK but was also concurrently widely pursued throughout Europe. With experience, care was increasingly undertaken close to the front lines using a philosophy of immediacy and expectation of recovery. Post-war analysis was startlingly unsympathetic, yet the experiences and management of shell shock have guided psychiatric and medical understanding of functional illness and post-traumatic stress over the subsequent century. In this historical review, we have sought to present features of the UK response to the neurological manifestations of trauma, the way in which these changed as the war proceeded and the political and medical response in the aftermath of war.

The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings.

Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

Risk of Meningitis in Infants Aged 29 to 90 Days with Urinary Tract Infection: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the risk of bacterial meningitis in infants aged 29-90 days with evidence of urinary tract infection (UTI). METHODS: PubMed (MEDLINE), Embase, and the Cochrane Library were systematically searched for studies reporting rates of meningitis in infants aged 29-90 days with abnormal urinalysis or urine culture. Observational studies in infants with evidence of UTI who underwent lumbar puncture (LP) reporting age-specific event rates of bacterial meningitis and sterile cerebrospinal fluid pleocytosis were included. Prevalence estimates for bacterial meningitis in infants with UTI were pooled in a random effects meta-analysis. RESULTS: Three prospective and 17 retrospective cohort studies were included in the meta-analysis. The pooled prevalence of concomitant bacterial meningitis in infants with UTI was 0.25% (95% CI, 0.09%-0.70%). Rates of sterile pleocytosis ranged from 0% to 29%. Variation in study methods precluded calculation of a pooled estimate for sterile pleocytosis. In most studies, the decision to perform a LP was up to the provider, introducing selection bias into the prevalence estimate. CONCLUSIONS: The risk of bacterial meningitis in infants aged 29-90 days with evidence of UTI is low. A selective approach to LP in infants identified as low risk for meningitis by other clinical criteria may be indicated.

A Cell Line-based Immunohistochemical p53 Expression Pattern Control Panel.

TP53 gene mutations are known to manifest in distinct p53 immunohistochemical staining patterns; overexpression, wild-type, and null. These stratified staining patterns are routinely utilized in subtyping ovarian cancer subtypes. Three ovarian cancer cell lines were used in the construction of an immunohistochemical p53 expression pattern control panel that highlight respective TP53 mutation status. The cell line control panel sections demonstrated consistent clean and easily interpretable p53 immunohistochemical staining. Procured resection, biopsy, and cytologic specimens were submitted along with either standard control tissue or a p53 cell line control panel to pathologists of varying experience for interrater reliability analysis. Individual interrater reliability was near-perfect and was improved with the p53 cell line control panel when compared with the tissue control. The cell line control panel demonstrated decreased misinterpretation of null expression pattern as wild-type. Next-generation sequencing analysis was performed on the cell lines and select cases, in which there was discordance in p53 expression pattern interpretation. Next-generation sequencing analysis demonstrated low-frequency variant mutations in some cases in which there was reviewer discordance. This study suggests the addition of a p53 cell line expression pattern control panel could potentially increase p53 interpretation accuracy for ovarian cancer subtypes. We developed a cell line-based p53 control panel that has the potential to increase individual interrater reliability for p53 immunohistochemical expression pattern determination, support immunohistochemical optimization, and direct submission of difficult to interpret p53 staining cases to next-generation sequencing.

Respiratory failure because of neuromuscular disease.

PURPOSE OF REVIEW: Understanding the mechanisms and abnormalities of respiratory function in neuromuscular disease is critical to supporting the patient and maintaining ventilation in the face of acute or chronic progressive impairment. RECENT FINDINGS: Retrospective clinical studies reviewing the care of patients with Guillain-Barré syndrome and myasthenia have shown a disturbingly high mortality following step-down from intensive care. This implies high dependency and rehabilitation management is failing despite evidence that delayed improvement can occur with long-term care. A variety of mechanisms of phrenic nerve impairment have been recognized with newer investigation techniques, including EMG and ultrasound. Specific treatment for progressive neuromuscular and muscle disease has been increasingly possible particularly for the treatment of myasthenia, metabolic myopathies, and Duchenne muscular dystrophy. For those conditions without specific treatment, it has been increasingly possible to support ventilation in the domiciliary setting with newer techniques of noninvasive ventilation and better airway clearance. There remained several areas of vigorous debates, including the role for tracheostomy care and the place of respiratory muscle training and phrenic nerve/diaphragm pacing. SUMMARY: Recent studies and systematic reviews have defined criteria for anticipating, recognizing, and managing ventilatory failure because of acute neuromuscular disease. The care of patients requiring long-term noninvasive ventilatory support for chronic disorders has also evolved. This has resulted in significantly improved survival for patients requiring domiciliary ventilatory support.

A Randomized Controlled Comparison of Esophageal Clearance Times of Oral Budesonide Preparations.

BACKGROUND: Topical steroids prepared as oral viscous slurries have become common in the treatment of eosinophilic esophagitis. Esophageal mucosal contact time correlates with clinical and histologic improvement. AIM: To compare the mucosal contact time of alternative oral viscous budesonide (OVB) slurries with the conventional sucralose OVB. METHODS: A blinded randomized crossover trial investigating esophageal clearance of three OVB slurry preparations was done on healthy adults. Honey and xanthan gum OVB slurries were compared with standard sucralose OVB in 24 randomly assigned subjects. Each subject ingested the sucralose OVB and either the honey or xanthan gum OVB slurries. The esophageal clearance of each slurry was evaluated as an area under the curve (AUC) using 1 millicurie of technetium-99m-sulfur colloid (Tc99) co-administered in each OVB preparation using nuclear scintigraphy. A standardized taste survey was also administered. RESULTS: Xanthan gum had greater mucosal contact time compared to sucralose as measured by a higher AUC at 3 min (P = 0.002), while honey showed no significant difference in esophageal clearance relative to sucralose. Taste scores were significantly higher in the honey group, while scores for xanthan gum were no different from standard sucralose. CONCLUSION: OVB slurries utilizing xanthan gum may be a superior alternative to a sucralose-based slurry due to its increased mucosal contact time and similar taste tolerance. Honey may be a suitable alternative as well, due to its similar contact time and favorable taste.

Multimodal Assessment of Body Pain in Orofacial Pain Patients.

OBJECTIVE: . Patients with complaints of orofacial pain (OFP) often have other body pain, yet many do not report these to their providers. Uncontrolled pain at any location may impact the successful management of an OFP complaint. The objective of this study was to determine the number of pain regions throughout the body, and the underreporting of pain, in patients who presented to a tertiary military OFP clinic. DESIGN: A retrospective chart review was conducted on 423 consecutive new patients. Patients were given three assessment opportunities to report their pain on a whole-body pain map: 1) prior to evaluation (Pt1), 2) following an explanatory statement by their provider on the relationship between pain and prognosis (Pt2), and 3) during directed pain inquiry of specific body regions (Pro). The pain map was divided into nine anatomical regions that were assessed for the presence of pain after Pt1, Pt2, and Pro. RESULTS: Initially, 60.5% of patients did not report all pain locations (Pt1). Following the explanatory statement (Pt2), 30.5% still did not report all pain. Following the completion of all assessment methods, the most commonly reported number of pain regions was five (17.0%), and 91.5% of patients reported multiple pain regions. CONCLUSIONS: Most patients had multiple pain complaints outside the chief complaint, yet the majority did not report these until multiple forms of assessment were utilized. These data encourage the use of a pain map, a verbal pain explanation, and directed pain questioning to more accurately capture pain location and facilitate multidisciplinary care.

Plasma neurofilament heavy chain levels and disease progression in amyotrophic lateral sclerosis: insights from a longitudinal study.

OBJECTIVE: To investigate the role of longitudinal plasma neurofilament heavy chain protein (NfH) levels as an indicator of clinical progression and survival in amyotrophic lateral sclerosis (ALS). METHODS: A cross-sectional study involving 136 clinically heterogeneous patients with ALS and 104 healthy and neurological controls was extended to include a prospective analysis of 74 of these ALS cases, with samplings at approximately 3-month intervals in a follow-up period of up to 3 years. We analysed the correlation between longitudinal NfH-phosphoform levels and disease progression. Temporal patterns of NfH changes were evaluated using multilevel linear regression. RESULTS: Baseline plasma NfH levels were higher than controls only in patients with ALS with short disease duration to baseline sampling. Compared with controls, fast-progressing patients with ALS, particularly those with a short diagnostic latency and disease duration, had higher plasma NfH levels at an early stage and lower levels closer to end-stage disease. Lower NfH levels between visits were associated with rapid functional deterioration. We also detected antibodies against NfH, NfH aggregates and NfH cleavage products. CONCLUSIONS: Disease progression in ALS involves defined trajectories of plasma NfH levels, reflecting speed of neurological decline and survival. Intervisit plasma NfH changes are also indicative of disease progression. This study confirms that longitudinal measurements of NfH plasma levels are more informative than cross-sectional studies, where the time of sampling may represent a bias in the interpretation of the results. Autoantibodies against NfH aggregates and NfH cleavage products may explain the variable expression of plasma NfH with disease progression. TRAIL REGISTRATION NUMBER: NIHRID6160.

Lymph Node Micrometastases in Early-Stage Cervical Cancer are Not Predictive of Survival.

Although patients with early-stage cervical cancer have in general a favorable prognosis, 10% to 40% patients still recur depending on pathologic risk factors. The objective of this study was to evaluate if the presence of lymph node micrometastasis (LNmM) had an impact on patient's survival. We performed a multi-institutional retrospective review on patients with early-stage cervical cancer, with histologically negative lymph nodes, treated with radical hysterectomy and pelvic lymphadenectomy for the study period 1994 to 2004. Tissue blocks of lymph nodes from the patient's original surgery were recut and then evaluated for the presence of micrometastases. One hundred twenty-nine patients were identified who met inclusion criteria. LNmM were found in 26 patients (20%). In an average follow-up time of 70 mo, there were 11 recurrences (8.5%). Of the 11 recurrences, 2 (18%) patients had LNmM. Patients with LNmM were more likely to have received adjuvant radiation and chemotherapy. In stratified log-rank analysis, LNmM were not associated with any other high-risk clinical or pathologic variables. Survival data analysis did not demonstrate an association between the presence of LNmM and recurrence or overall survival. The presence of LNmM was not associated with an unfavorable prognosis nor was it associated with other high-risk clinical or pathologic variables predicting recurrence. Further study is warranted to understand the role of micrometastases in cervical cancer.

Risk factors for urinary retention after laparoscopic inguinal hernia repairs.

BACKGROUND: Postoperative urinary retention (POUR) is a common entity following surgery, particularly after laparoscopic inguinal hernia repair. Here the intent is to investigate the incidence of POUR in all comers at a single institution following laparoscopic inguinal hernia repair. METHODS: A retrospective chart review of all patients who underwent laparoscopic hernia repair at our institution from January 2010 through December 2013 was performed. POUR was defined as the inability to spontaneously urinate following surgery, requiring straight catheterization or placement of a Foley catheter. Perioperative data including narcotic use, operative time, type of mesh, and intraoperative fluid use were also recorded for each patient. RESULTS: A total of 346 patients underwent laparoscopic inguinal hernia repair in the specified time period, 340 patients were included in this study. The incidence of POUR after laparoscopic inguinal hernia repair at our institution was 8.2 % (n = 28) with the most common presentation of POUR being failure to void (n = 23). Postoperative narcotic use of 6.5 mg or greater of morphine or morphine equivalent was associated with higher risk of POUR via ROC analysis (OR 2.5, 95 % CI 1.2-5.6, p = 0.025). In univariate analysis, age greater than 50 years was also a risk factor for developing POUR (OR 2.8, 95 % CI 1.2-6.4, p = 0.02). Factors not found to be significant included intraoperative IV fluids, history of BPH, unilateral versus bilateral repair, and preoperative void time in relation to surgery start. CONCLUSIONS: Minimizing postoperative narcotic medications may reduce the risk of developing POUR after laparoscopic inguinal hernia repairs. If possible surgeons should consider non-steroidal anti-inflammatory drugs, acetaminophen, or regional anesthetic blocks to minimize postoperative narcotic requirements.

Fatigued on Venus, sleepy on Mars-gender and racial differences in symptoms of sleep apnea.

OBJECTIVE: Clinical guidelines for the care of obstructive sleep apnea (OSA) recommend evaluation of daytime sleepiness but do not specify evaluation of fatigue. We studied how subjects with and without OSA experience fatigue and sleepiness, examining the role of gender and race. DESIGN, SETTING, PATIENTS: Consecutive subjects entering our heart health registry completed validated questionnaires including Berlin Questionnaire for OSA, Fatigue Scale, and Epworth Sleepiness Scale. Data analysis was performed only with Whites and Blacks as there were too few subjects of other races for comparison. RESULTS: Of 384 consecutive subjects, including 218 women (57 %), there were 230 Whites (60 %) and 154 Blacks (40 %), with average age of 55.9 ± 12.8 years. Berlin Questionnaires identified 221 subjects (58 %) as having high likelihood for OSA. Fatigue was much more common in women (75 %) than in men (46 %) with OSA (p < 0.001), while frequency of fatigue was similar in women (30 %) and men (29 %) without OSA (p = 0.86). In multivariate analysis, men with OSA were sleepier than women; Black men with OSA had higher Epworth scores (mean ± SD, 12.8 ± 5.2) compared to White men (10.6 ± 5.3), White women (10.0 ± 4.5), and Black women (10.5 ± 5.2), p = 0.05. These gender differences were not related to the effects of age, body mass index, perceived stress, sleep duration, or thyroid function. CONCLUSIONS: Women report fatigue more commonly with OSA than men. Men experience sleepiness more commonly with OSA than women. The findings suggest that evaluation of sleep disorders must include an assessment of fatigue in addition to sleepiness to capture the experience of women.

Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurodegenerative disorders that share significant clinical, pathological and genetic overlap and are considered to represent different ends of a common disease spectrum. Mutations in Profilin1 have recently been described as a rare cause of familial ALS. The PFN1 E117G missense variant has been described in familial and sporadic cases, and also found in controls, casting doubt on its pathogenicity. Interpretation of such variants represents a significant clinical-genetics challenge. OBJECTIVE AND RESULTS: Here, we combine a screen of a new cohort of 383 ALS patients with multiple-sequence datasets to refine estimates of the ALS and FTD risk associated with PFN1 E117G. Together, our cohorts add up to 5118 ALS and FTD cases and 13 089 controls. We estimate a frequency of E117G of 0.11% in controls and 0.25% in cases. Estimated odds after population stratification is 2.44 (95% CI 1.048 to ∞, Mantel-Haenszel test p=0.036). CONCLUSIONS: Our results show an association between E117G and ALS, with a moderate effect size.

Serum free ropivacaine concentrations among patients receiving continuous peripheral nerve block catheters: is it safe for long-term infusions?

BACKGROUND: Ropivacaine is a long-acting local anesthetic used for continuous peripheral nerve catheter infusions. Catheters may remain in situ for prolonged time periods. In the present study, patients were enrolled to receive continuous peripheral nerve catheters with measurement of free serum ropivacaine concentrations. METHODS: Peripheral nerve catheters were placed for postoperative pain management in trauma patients and infused with ropivacaine 0.2% or bolused with 0.5%. Blood samples were obtained from each subject on days 0 (preinfusion), 3, 5, 7, 10, and every third day until catheter removal. Serum free ropivacaine concentrations were measured via high-performance liquid chromatography and were compared using the Wilcoxon signed rank test. RESULTS: One hundred thirty-three blood samples were analyzed in 35 patients; all serum free ropivacaine concentrations after infusion initiation (99 samples from 35 subjects) were below 0.34 mg/L (previously determined toxic threshold). The highest concentration achieved in a blood sample was 0.19 mg/L; all other values were <0.09 mg/L. The total amount of drug received during the study ranged from 1146 to 22,320 mg (median of 3722 mg). Catheters remained in situ for a median of 7 days (range: 3-23). From day 0 to 3 (preinfusion), 77% of the study participants had an increase in the serum free-fraction ropivacaine concentrations. The median concentration on day 3 was 0.025 mg/L (95% upper confidence limit for mean: 0.05, range: <0.01-0.19); P < 0.001 compared with preinfusion levels). From day 3 to 5, 68% of the participants had a decrease in the serum free ropivacaine concentrations (median level 0.016 mg/L [95% upper confidence limit for mean: 0.021] P = 0.007 for day 5 compared with day 3). CONCLUSIONS: In this study, free serum ropivacaine concentrations remained well below toxic values despite large amounts of drug administration in combat-wounded patients. The administration of continuous ropivacaine infusions over prolonged time periods, coupled with multiple drug boluses, did not produce toxic or near-toxic serum concentrations.

Technical effects of adding 1 % lidocaine to technetium sulfur colloid for sentinel lymphatic mapping in early breast cancer: analysis of data from a double-blind randomized controlled trial.

BACKGROUND: A practice standard in sentinel lymph node (SLN) mapping in breast cancer is intradermal injection of technetium-99m sulfur colloid (Tc-99m), resulting in significant patient discomfort and pain. A previous randomized controlled trial showed that adding lidocaine to Tc-99m significantly reduced radioisotope injection-related pain. We tested whether 1 % lidocaine admixed with Tc-99m affects feasibility of SLN mapping. METHODS: Between January 2006 and April 2009, 140 patients with early breast cancer were randomly assigned (1:1:1:1) to receive standard topical 4 % lidocaine cream and intradermal Tc-99m (control) or to one of three other study groups: topical placebo cream and injection of Tc-99m containing sodium bicarbonate (NaHCO3), 1 % lidocaine, or both. All SLN data were collected prospectively. RESULTS: Study groups were comparable for clinicopathological parameters. As previously reported, the addition of 1 % lidocaine to the radioisotope solution significantly improved patient comfort. Overall SLN identification rate in the trial was 93 %. Technical aspects of SLN biopsy were similar for all groups, including time from injection to operation, first SLN (SLN 1) gamma probe counts, ex vivo counts for SLN 1 and SLN 2, and axillary bed counts. SLN identification rates were comparable statistically: control (96 %), lidocaine (90 %), sodium bicarbonate (97 %), and sodium bicarbonate-lidocaine (90 %). The control group had a significantly higher SLN 2/SLN 1 ex vivo count ratio, and the number of SLNs detected was significantly reduced in the lidocaine versus no-lidocaine groups (p < 0.05). CONCLUSIONS: Addition of 1 % lidocaine to standard radioisotope solution for SLN mapping in breast cancer is associated with fewer SLNs detected, but it does not appear to compromise SLN identification.