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.

Association of BCG Vaccination in Childhood With Subsequent Cancer Diagnoses: A 60-Year Follow-up of a Clinical Trial.

Importance: The BCG vaccine is currently the only approved tuberculosis vaccine and is widely administered worldwide, usually during infancy. Previous studies found increased rates of lymphoma and leukemia in BCG-vaccinated populations. Objective: To determine whether BCG vaccination was associated with cancer rates in a secondary analysis of a BCG vaccine trial. Design, Setting, and Participants: Retrospective review (60-year follow-up) of a clinical trial in which participants were assigned to the vaccine group by systematic stratification by school district, age, and sex, then randomized by alternation. The original study was conducted at 9 sites in 5 US states between December 1935 and December 1998. Participants were 2963 American Indian and Alaska Native schoolchildren younger than 20 years with no evidence of previous tuberculosis infection. Statistical analysis was conducted between August 2018 and July 2019. Interventions: Single intradermal injection of either BCG vaccine or saline placebo. Main Outcomes and Measures: The primary outcome was diagnosis of cancer after BCG vaccination. Data on participant interval health and risk factors, including smoking, tuberculosis infection, isoniazid use, and other basic demographic information, were also collected. Results: A total of 2963 participants, including 1540 in the BCG vaccine group and 1423 in the placebo group, remained after exclusions. Vaccination occurred at a median (interquartile range) age of 8 (5-11) years; 805 participants (52%) in the BCG group and 710 (50%) in the placebo group were female. At the time of follow-up, 97 participants (7%) in the placebo group and 106 participants (7%) in the BCG vaccine group could not be located; total mortality was 633 participants (44%) in the placebo group and 632 participants (41%) in the BCG group. The overall rate of cancer diagnosis was not significantly different in BCG vaccine vs placebo recipients (hazard ratio, 0.82; 95% CI, 0.66-1.02), including for lymphoma and leukemia. The rate of lung cancer was significantly lower in BCG vs placebo recipients (18.2 vs 45.4 cases per 100 000 person-years; hazard ratio, 0.38; 95% CI, 0.20-0.74; P = .005), controlling for sex, region, alcohol overuse, smoking, and tuberculosis. Conclusions and Relevance: Childhood BCG vaccination was associated with a lower risk of lung cancer development in American Indian and Alaska Native populations. This finding has potentially important health implications given the high mortality rate associated with lung cancer and the availability of low-cost BCG vaccines.

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.

Goblet cell response after photorefractive keratectomy and laser in situ keratomileusis.

PURPOSE: To determine whether patients without dry eye preoperatively have an altered conjunctival goblet cell density and mucin secretion postoperatively and to explore what factors affect changes in goblet cell density and mucin secretion. SETTING: The former Walter Reed Army Medical Center, Washington, DC, USA. DESIGN: Prospective nonrandomized clinical study. METHODS: Impression cytology was used to determine conjunctival goblet cell density before and 1 week, 1 month, and 3 months after photorefractive keratectomy (PRK) or laser in situ keratomileusis (LASIK). The McMonnies questionnaire, Schirmer test, tear breakup time, corneal sensitivity, rose bengal staining, and computerized videokeratoscopy were also performed to assess tear-film and ocular-surface health. RESULTS: The ratio of goblet cell to total cells changed postoperatively from baseline in both groups (P < .001). The most significant change was a median 29% decrease 1 month postoperatively. However, there were no significant differences between groups over time (P = .772). The ratio of filled goblet cell to total goblet cell did not change significantly over the same time period (P = .128), and there were no significant differences between the PRK group and the LASIK group over time (P = .282). CONCLUSIONS: Patients without apparent dry eye had an altered conjunctival goblet cell population after PRK or LASIK. The conjunctival goblet cell population tended to decrease in the early postoperative period after either surgery and was most affected by preoperative goblet cell density. The changes in the tear film and ocular surface did not seem to affect goblet cell mucin secretion after either procedure. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Systemic inflammatory response and neuromuscular involvement in amyotrophic lateral sclerosis.

OBJECTIVE: To evaluate the combined blood expression of neuromuscular and inflammatory biomarkers as predictors of disease progression and prognosis in amyotrophic lateral sclerosis (ALS). METHODS: Logistic regression adjusted for markers of the systemic inflammatory state and principal component analysis were carried out on plasma levels of creatine kinase (CK), ferritin, and 11 cytokines measured in 95 patients with ALS and 88 healthy controls. Levels of circulating biomarkers were used to study survival by Cox regression analysis and correlated with disease progression and neurofilament light chain (NfL) levels available from a previous study. Cytokines expression was also tested in blood samples longitudinally collected for up to 4 years from 59 patients with ALS. RESULTS: Significantly higher levels of CK, ferritin, tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß, IL-2, IL-8, IL-12p70, IL-4, IL-5, IL-10, and IL-13 and lower levels of interferon (IFN)-γ were found in plasma samples from patients with ALS compared to controls. IL-6, TNF-α, and IFN-γ were the most highly regulated markers when all explanatory variables were jointly analyzed. High ferritin and IL-2 levels were predictors of poor survival. IL-5 levels were positively correlated with CK, as was TNF-α with NfL. IL-6 was strongly associated with CRP levels and was the only marker showing increasing expression towards end-stage disease in the longitudinal analysis. CONCLUSIONS: Neuromuscular pathology in ALS involves the systemic regulation of inflammatory markers mostly active on T-cell immune responses. Disease stratification based on the prognostic value of circulating inflammatory markers could improve clinical trials design in ALS.

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.

Swallowed glucocorticoid therapy for eosinophilic esophagitis in children does not suppress adrenal function.

OBJECTIVE: The purpose of this study was to examine the effect of chronic swallowed glucocorticoids on adrenal function during the treatment of eosinophilic esophagitis (EoE) in children. METHODS: Serum cortisol levels were obtained in children with EoE pre- and post-treatment with swallowed glucocorticoids. Exclusion criteria included those on any additional steroid therapy. Once diagnosed with EoE by esophageal biopsy, subjects were treated based on current standard of care with either swallowed fluticasone or budesonide. At the time of follow-up, esophagogastroduodenoscopy and blood sampling was repeated. Both pre- and post-treatment serum cortisol samples were collected fasting, between 07:00 and 10:00, and determined using a competitive binding method assay. The distribution of differences in cortisol levels between the pre- and post-treatment samples satisfied the assumption for normality and were subsequently analyzed using the paired t-test. RESULTS: Pre- and post-treatment serum cortisol levels were examined in 14 children who met clinical and histological diagnostic criteria for EoE. Mean age was 10.1 years (range 2-17 years) with 71% male and 29% female subjects. Swallowed glucocorticoid treatment included fluticasone in 79% and budesonide in 21% of subjects. Mean dosage of fluticasone was 704 µg daily (range 220-880 µg daily) and budesonide 0.8 mg daily (range 0.5-1 mg daily), along with a mean treatment length of 17 weeks (range 8-43 weeks). No significant difference in serum cortisol was found following treatment with swallowed fluticasone or budesonide (mean change 1.9 µg/dL, p=0.75, SD of the change=21.2). CONCLUSIONS: Swallowed glucocorticoid therapy does not appear to significantly affect the adrenal axis in children, and therefore, may represent a safe therapy for EoE.

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.

Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study.

BACKGROUND: Amyotrophic lateral sclerosis shares characteristics with some cancers, such as onset being more common in later life, progression usually being rapid, the disease affecting a particular cell type, and showing complex inheritance. We used a model originally applied to cancer epidemiology to investigate the hypothesis that amyotrophic lateral sclerosis is a multistep process. METHODS: We generated incidence data by age and sex from amyotrophic lateral sclerosis population registers in Ireland (registration dates 1995-2012), the Netherlands (2006-12), Italy (1995-2004), Scotland (1989-98), and England (2002-09), and calculated age and sex-adjusted incidences for each register. We regressed the log of age-specific incidence against the log of age with least squares regression. We did the analyses within each register, and also did a combined analysis, adjusting for register. FINDINGS: We identified 6274 cases of amyotrophic lateral sclerosis from a catchment population of about 34 million people. We noted a linear relationship between log incidence and log age in all five registers: England r(2)=0·95, Ireland r(2)=0·99, Italy r(2)=0·95, the Netherlands r(2)=0·99, and Scotland r(2)=0·97; overall r(2)=0·99. All five registers gave similar estimates of the linear slope ranging from 4·5 to 5·1, with overlapping confidence intervals. The combination of all five registers gave an overall slope of 4·8 (95% CI 4·5-5·0), with similar estimates for men (4·6, 4·3-4·9) and women (5·0, 4·5-5·5). INTERPRETATION: A linear relationship between the log incidence and log age of onset of amyotrophic lateral sclerosis is consistent with a multistage model of disease. The slope estimate suggests that amyotrophic lateral sclerosis is a six-step process. Identification of these steps could lead to preventive and therapeutic avenues. FUNDING: UK Medical Research Council; UK Economic and Social Research Council; Ireland Health Research Board; The Netherlands Organisation for Health Research and Development (ZonMw); the Ministry of Health and Ministry of Education, University, and Research in Italy; the Motor Neurone Disease Association of England, Wales, and Northern Ireland; and the European Commission (Seventh Framework Programme).

An extended chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids phenotype.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described central nervous system inflammatory condition. In this case report we describe a patient initially with features consistent with this syndrome, who represented with seizures (not previously reported in this syndrome) and corresponding prominent cortical involvement on imaging (also not previously noted). Owing to diagnostic uncertainty, cerebral biopsy was performed revealing histology consistent with CLIPPERS, excluding other differentials. Following a further brainstem relapse, this patient was treated with high-dose steroids, subsequently switched to a tapering oral regime and now, azathioprine, a steroid-sparing agent. She remains well on this.

Voice outcomes after total thyroidectomy, partial thyroidectomy, or non-neck surgery using a prospective multifactorial assessment.

BACKGROUND: Voice alteration remains a significant complication of thyroid surgery. We present a comparison of voice outcomes between total thyroidectomy (TT), partial thyroidectomy (PT), and non-neck (NN) surgery using a multifactorial voice-outcomes classification tool. STUDY DESIGN: Patients with normal voice (n = 112) were enrolled between July 2004 and March 2009. The patients underwent TT (n = 54), PT (n = 35), or NN (n = 23) surgery under general endotracheal anesthesia as part of a prospective observational study involving serial multimodality voice evaluation preoperatively, and at 2 weeks, 3 months, and 6 months postoperatively. Patients with adverse voice outcomes were grouped into the negative voice outcomes (NegVO) category, including patients with objective (abnormality on videolaryngostroboscopy and substantial voice dysfunction) and subjective (normal videolaryngostroboscopy but with notable voice impairment) NegVO. Voice outcomes were compared among study groups. RESULTS: Negative voice outcomes occurred in 46% (95% CI, 34-59%) and 14% (95% CI, 6-30%) of TT and PT groups, respectively. No NegVOs were observed after NN surgery. Early NegVOs were more common in the TT group than in the NN or PT groups (p < 0.001). Most voice disturbances resolved by 6 months (TT 84%; PT 92%) with no difference in NegVO among all groups (p = 0.23). Black race and significant changes in certain voice outcomes measures at the 2-week follow-up visit were identified as predictors of late (3 to 6 months) NegVO. CONCLUSIONS: This comprehensive voice outcomes study revealed that the extent of thyroidectomy impacts voice outcomes in the early postoperative period, and identified risk factors for late NegVO in post-thyroidectomy patients who should be considered for early voice rehabilitation referral.

Impact of degree of extrathyroidal extension of disease on papillary thyroid cancer outcome.

BACKGROUND: The clinical importance of extrathyroidal extension (ETE) on outcome of papillary thyroid cancer (PTC), particularly with respect to disease extending to the surgical margin is not well established. This study assessed the importance of surgical margin and extrathyroidal invasion relative to local control of disease and oncologic outcome. METHODS: A retrospective analysis of a prospective institutional endocrine database was conducted on 276 patients with PTC treated between 1955 and 2004 to determine the impact of margin-negative resection (n=199, 72%), disease up to within 1 mm of surgical margin (n=19, 7%), microscopic (n=39, 14%), and gross (n=19, 7%) ETE. Data were compared with Fisher's exact test or analysis of variance (ANOVA). RESULTS: Median follow-up was 3.1-6.8 years per study group (disease-free survival, range 1-37 years). The proportion of those with age >45 years, prior radiation exposure, distant metastasis at presentation, and those undergoing total thyroidectomy was not significantly different between groups. Tumor size and multifocality correlated with extent of local disease, which in turn was significantly associated with regional nodal disease at time of primary operation as well as prevalence of persistence of disease after multimodality therapy. Extent of local disease correlated significantly with subsequent clinical recurrence after a disease-free period (p=0.006); however, recurrence rates were not significantly different between negative and close (≤1 mm) margin resection. CONCLUSION: Oncological outcome correlates with the extent of extrathyroidal invasion. Outcome is worse in patients with gross extrathyroidal disease extension than in those with microscopic local invasion apparent on histopathological assessment. However, the risk of clinical recurrence appears similar between patients undergoing margin-negative and "close margin" resection.

A clinicopathologic study of vaginal intraepithelial neoplasia.

OBJECTIVE: To evaluate the natural history of vaginal intraepithelial neoplasia (VAIN) and to identify risk factors for invasive vaginal carcinoma. METHODS: The records of all women with VAIN diagnosed at military treatment facilities over a 10-year period with minimum follow-up of 12 months were reviewed. Patient demographics and clinical information related to the diagnosis and treatment of VAIN were recorded. RESULTS: One hundred twenty-seven women with VAIN met inclusion criteria. The mean age was 47.4 years, and median surveillance was 34 months (range 12-169 months). Seventy-five patients had low-grade vaginal dysplasia as their initial diagnosis, and 15 (20%) of these patients underwent treatment. Fifty-two patients had high-grade vaginal dysplasia, of which 38 (73%) underwent treatment. Overall, 113 patients (89%) demonstrated normalization of disease, 11 patients (9%) demonstrated persistence of disease, and three patients (2%) experienced recurrence of disease. No patients experienced development of invasive vaginal carcinoma. However, median time to normalization was 6 months longer in patients with low-grade dysplasia compared with those with high-grade dysplasia (15.9 months compared with 10.0 months; hazard ratio 1.5; 95% confidence interval 1.004-2.1; P=.045). Patients with high-grade dysplasia had more biopsies performed during their surveillance than patients with low-grade dysplasia (3.3 compared with 2.5; P=.045). CONCLUSION: Overall, 89% of patients demonstrated normalization of VAIN, and none had progression to invasive cancer. Normalization, persistence, and recurrence rates did not significantly differ by grade of dysplasia or treatment status. Based on our findings regarding the time to normalization, annual surveillance with combined cytology and colposcopy is likely adequate. Because 11% of patients with VAIN either will experience recurrence or will have persistent disease, lifetime surveillance is recommended. LEVEL OF EVIDENCE: : III.

The management of osteoarthritis in movement disorders: a case discussion.

BACKGROUND: A 37-year-old female with a hyperkinetic movement disorder due to chorea-acanthocytosis developed severe painful degenerative arthritis of her left knee as a consequence of repetitive involuntary flexion and extension dystonic and ballistic movements. CASE REPORT: Despite profound limitation in her mobility a total knee replacement was successfully undertaken. DISCUSSION: The case emphasizes that patients with progressive neurodegenerative disorders may derive relief or resolution of pain by joint replacement even if mobility does not improve following surgery. A multidisciplinary approach to care is essential.

The effect of secular trends and specialist neurocritical care on mortality for patients with intracerebral haemorrhage, myasthenia gravis and Guillain-Barré syndrome admitted to critical care : an analysis of the Intensive Care National Audit & Research Centre (ICNARC) national United Kingdom database.

PURPOSE: To analyse mortality for spontaneous intracerebral haemorrhage (ICH), myasthenia gravis (MG) and Guillain-Barré syndrome (GBS) from 1996 to 2009 in UK intensive care units (ICUs). METHODS: We used the Intensive Care National Audit & Research Centre (ICNARC) database. We identified specialised neurosciences critical care units (NCCUs) (n = 16), general ICUs with full neurological support (n = 48) and general ICUs with limited neurological support (n = 138) and undertook descriptive analyses for each condition. Poisson regression was used to identify trends in admission rates, median regression to identify trends in lengths of stay (LOS), and logistic regression (Wald test) to analyse interaction between unit type and time period; odds ratios were calculated for hospital mortality associated with unit types. RESULTS: For ICH (n = 10,313 cases), overall ICU mortality was 42.4 %, and acute hospital mortality 62.1 %. In NCCU, LOS was longer, but mortality lower, and over time, mortality from ICH decreased faster. For MG (n = 1,064 cases) and GBS (n = 1,906 cases), overall mortality was relatively high (MG: 8.7 % ICU mortality and 22 % acute hospital mortality; GBS: 7.7 and 16.7 %, respectively); overall mortality did not decrease over time. CONCLUSIONS: This first large-scale analysis of outcomes in acute neurological disease in the UK demonstrates real-life mortality higher than published series. NCCU care is associated with increased survival in conditions requiring highly specialised intensive care techniques, but high-quality step-down care is pivotal in others. Strategies that truly improve outcomes must integrate emergency department management, ICU admission criteria, NCCU treatment, high-quality step-down care and neurorehabilitation.

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.

Utility of the voice handicap index as an indicator of postthyroidectomy voice dysfunction.

OBJECTIVES/HYPOTHESES: The Voice Handicap Index (VHI) is a simple, reliable, self-administered questionnaire that has been used to identify negative voice outcomes after thyroidectomy. This study provides an updated report of a multiyear study examining the predictive ability of the VHI to classify normal versus negative voice outcomes (VOs). STUDY DESIGN: Prospective observational, longitudinal study of the patient reported impact of voice changes after thyroidectomy using the VHI. Since the preliminary report, the sample size doubled and methods for classifying voice outcomes (VOs) were refined. METHODS: Ninety-one adults provided voice assessment data preoperatively (baseline) and at approximately 2 weeks postthyroidectomy. VO was defined according to endoscopic laryngeal examination, acoustic, auditory perceptual, and patient report parameters. The VHI was tested for its sensitivity and specificity for identifying VO. RESULTS: Twenty-two participants (24.2%) qualified as having adverse VOs during the early postoperative period. A change from baseline in VHI of 13-16 points had a diagnostic accuracy of 86% sensitivity and 88% specificity for classifying early VO and had 70% and 95% positive and negative predictive values, respectively. The Functional and Physical subscales of the VHI had higher predictive value than the Emotional subscale. Adjunctive analyses of a two-subscale version of the VHI and of the 10 items that comprises the VHI-10 also revealed high predictive value for differentiating groups by VO. CONCLUSIONS: Balanced sensitivity and specificity are achieved at a change in the total VHI score of 13-16. These results are generally consistent with several other studies examining voice problems over time. The VHI, as well as its alternate versions, appear to be useful and should be incorporated into the diagnostic process for identifying patients with voice problems after thyroidectomy.

Racial disparities in voice outcomes after thyroid and parathyroid surgery.

BACKGROUND: There is evidence that the outcomes of head and neck surgery may differ across racial and ethnic groups. Vocal changes related to the operation are an anticipated risk of thyroidectomy and parathyroidectomy. Race-specific voice outcomes after thyroid and parathyroid operations have not been reported. Therefore, our aim was to examine the potential disparity in voice outcomes between white and black patients after thyroid or parathyroid operations. PATIENTS AND METHODS: Eighty-seven patients (59 white and 28 black) were included in a prospective observational trial. Subjects were evaluated before operation, and 2 weeks, 3 months, and 6 months postoperatively using a comprehensive battery of functional voice assessments of voice characteristics. The association of race with voice outcomes over time was evaluated with generalized linear models. RESULTS: Aside from volume of pathologic specimen (black, 117.5 cm3 vs. white, 43.2 cm3; P = .004), presence of multinodular goiter (black, 32.1% vs. white, 6.8%; P = .004) or Hashimoto's thyroiditis (black, 3.6% vs. white, 28.8%; P = .009), there were no differences between racial groups. Blacks were more likely than whites to have negative voice outcomes (odds ratio, 2.6; 95% confidence interval, 1.1-6.2; P = .034] throughout the postoperative period, especially at 6 months (black, 25% vs. white, 4%; P = .018). This finding was related principally to divergent scores on the voice-related quality-of-life scale, the voice handicap index. CONCLUSION: We observed greater rates of self-reported, negative voice outcomes among blacks than whites after thyroid or parathyroid operations. The precise mechanism for this disparity has not been described. The observed racial disparity in self-perceived voice impairment in this study merits further investigation.