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The diagnosis and management of the patient in coma demands rigorous clinical assessment that encompasses a meticulous approach to history-taking and systemic and neurological examination. Following immediate resuscitation and acute management, the level of consciousness must be assessed and evidence of meningism, brainstem or lateralizing neurological signs sought. The prognosis depends on the underlying cause and the appropriateness of acute management. The diagnosis of brain death depends on establishing the aetiology of irreversible brain damage, excluding reversible causes and establishing the absence of any brainstem reflexes.

Background and purpose Factors influencing the outcome after the critical care unit (CCU) for patients with status epilepticus (SE) are poorly understood. Survival for these patients was examined to establish (i) whether the risk of mortality has changed over time and (ii) whether admission to different unit types affects mortality risk over and above other risk factors. Methods The Intensive Care National Audit and Research Centre database and the Case Mix Programme database (January 2001 to December 2016) were analysed. Units were defined as neuro-CCU (NCCU), general CCU with 24-h neurological support (GCCU-N) or general CCU with limited neurological support (GCCU-L). Results There were 35 595 CCU cases of SE with a 3-fold increase over time (4739 in 2001-2004 to 14 166 in 2013-2016). More recent admissions were older and were more often unsedated on admission. Mortality declined for all units although this was more marked for NCCUs (8.1% in 2001-2004 to 4.4% in 2013-2016 compared to 5.1% and 4.1% for GCCU-L). Acute hospital mortality was two to three times higher than CCU mortality although this has also declined with time. GCCU-L appeared to have lower mortality than NCCUs (odds ratio 0.84, 95% confidence interval 0.72, 0.98) but after post hoc adjustment for case mix there were no differences. Older age and markers of seriousness of morbidity were all associated with increased mortality risk. Conclusions The number of patients admitted to a CCU for SE is rising but critical care and acute hospital mortality is decreasing. Patients treated in an NCCU have higher mortality but this is explicable by more severe underlying disease.

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.

Recent reviews of both spinal cord infarction and spinal dural arteriovenous malformations have highlighted the importance of vascular disease as a cause of acute or chronic myelopathy.1–3 Spinal cord stroke is generally encountered following aortic surgery, aortic dissection or after periods of prolonged hypotension associated with advanced vascular disease. Fibrocartilage embolism is a rare but important cause of spinal cord infarction, particularly in young people where the consequences can be devastating. Retrograde embolisation of fragments of the nucleus pulposus from the vertebral vasculature to the radiculomedullary arteries is provoked by physical exertion, trauma and Valsalva manoeuvre, and may account for 5% of spinal cord infarction.4 Spinal cord infarction generally affects the anterior spinal territory and causes a sudden flaccid paralysis associated with areflexia, loss of sensation to pain and temperature, and autonomic deficits (atonic bowel/bladder, paralytic ileus and loss of sphincter tone). There is often acute back pain at the onset, usually at the level of the lesion.5 Dorsal column function is generally well preserved although there is considerable variability. Other acute presentations of cord infarction include respiratory failure, posterior spinal artery territory infarction causing loss of proprioception, complete transverse cord infarction with loss of all motor, sensory and autonomic modalities below the lesion, Brown-Sequard syndrome and central cord involvement. Following spinal surgery, urgent spinal imaging is essential to exclude compressive epidural haematoma. New spinal cord infarction diagnostic criteria emphasise three major components: first, the rapid development of severe deficits within 12 hours; second, MR imaging excluding compression; and third, cerebrospinal fluid (CSF) showing no inflammatory changes. The MR imaging is normal in about a third of patients, but characteristic abnormalities may include T2 hyperintensity ‘owl eyes’, pencil-like …

Objective:To examine whether blast exposure alone and blast-associated concussion result in similar neurologic and mental health symptoms.Methods:A 14-item questionnaire was administered to male US Marines on their return from deployment in Iraq and/or Afghanistan.Results:A total of 2,612 Marines (median age 22 years) completed the survey. Of those, 2,320 (88.9%) reported exposure to ≥1 blast during their current and/or prior deployments. In addition, 1,022 (39.1%) reported ≥1 concussion during the current deployment, and 731 (28.0%) had experienced at least 1 prior lifetime concussion. Marines were more likely to have sustained a concussion during the current deployment if they had a history of 1 (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2–2.0) or ≥1 (OR 2.3, 95% CI 1.7–3.0) prior concussion. The most common symptoms were trouble sleeping (38.4%), irritability (37.9%), tinnitus (33.8%), and headaches (33.3%). Compared to those experiencing blast exposure without injury, Marines either experiencing a concussion during the current deployment or being moved or injured by a blast had an increased risk of postinjury symptoms.Conclusions:There appears to be a continuum of increasing total symptoms from no exposure to blast exposure plus both current deployment concussion and past concussion. Concussion had a greater influence than blast exposure alone on the presence of postdeployment symptoms. A high blast injury score can be used to triage those exposed to explosive blasts for evaluation.

To compare the circumference measurement (CM) body composition method and 8-point segmental bioelectrical impedance analysis (DSM-BIA) to dual energy X-ray absorptiometry (DEXA) in military members.The objective was to compare three body composition methods. Our hypothesis was the CM is as accurate as DSM-BIA and DEXA in assessing body fat percentage (%BF).Cross sectional, observational study.Healthy active duty military males and nonpregnant females. Seventy-six participants (mean age 35.0 ± 9.7 years, mean body mass index 28.9 ± 4.7 kg/mAgreement between DEXA and the other two methods was examined using an intraclass correlation coefficient (ICC) using the two-way random method with absolute agreement. Repeated measures analysis of covariance was used to examine the effect of gender and waist circumference on differences in %BF.The agreement of DSM-BIA with DEXA for females was ICC = 0.93 (95% confidence interval [CI]: 0.87-0.96) and for males, ICC = 0.89 (95% CI: 0.78-0.94). For the agreement of CM with DEXA, the ICC for females was 0.83 (95% CI: 0.71-0.91) and for males the ICC = 0.72 (95% CI: 0.49-0.85). For females with smaller waists (81.3 cm), the DSM-BIA underestimated the DEXA measurement by a mean of 1.6% (95% CI: 0.5-2.6%). For males with larger waists (≥95.3 cm), the DSM-BIA overestimated the DEXA measurement by a mean of 2.6% (95% CI: 0.9-4.3%). For females with larger waists (≥81.3 cm), the CM overestimated the DEXA %BF by an average of 2.4% (95% CI: 0.7-4.1%).There was good agreement between the three methods assessed in this study. Both waist circumference and gender had an effect on the accuracy of the DSM-BIA and CM measurements.

We report a retrospective review of 110 patients with acute Guillain-Barré syndrome (GBS) admitted to a specialised intensive care unit (ICU) in a tertiary referral centre over a 25 year period, the start of which coincided with the widespread introduction of plasma exchange (PE) and intravenous immunoglobulin (IVIG). The results were analysed by comparing 52 patients admitted in the first decade (1991-2000; Group 1) with 58 patients admitted between 2001-2014 (Group 2). Patients in both groups were comparable with respect to age and sex, and had a similar incidence and range of ICU complications. They received a comparable range of immunomodulatory treatments including IVIG and PE. However, the delay from presentation to referral to the tertiary ICU was longer in patients in Group 2. They also required mechanical ventilation for a longer duration, and had longer ICU and hospital stays. In Group 2, there was a higher incidence of axonal neuropathy (51%, compared to 24% in Group 1). Despite the longer delay to referral, the prevalence of axonal neuropathy and the duration of ventilation, overall mortality showed a downward trend (Group 1: 13.5%; Group 2: 5.2%). There was no late mortality in either group after step-down to neuro-rehabilitation or following discharge home or to the referring hospital. The rehabilitation outcomes were similar. This data show a shift in the pattern of referral to a tertiary referral ICU between the first and second decades following the wider availability of IVIG and PE for the treatment of GBS. The possible causes and implications of these findings are discussed.

Importance Individuals with sickle cell disease (SCD) have reduced life expectancy; however, there are limited data available on lifetime income in patients with SCD. Objective To estimate life expectancy, quality-adjusted life expectancy, and income differences between a US cohort of patients with SCD and an age-, sex-, and race/ethnicity-matched cohort without SCD. Design, Setting, and Participants Cohort simulation modeling was used to (1) build a prevalent SCD cohort and a matched non-SCD cohort, (2) identify utility weights for quality-adjusted life expectancy, (3) calculate average expected annual personal income, and (4) model life expectancy, quality-adjusted life expectancy, and lifetime incomes for SCD and matched non-SCD cohorts. Data sources included the Centers for Disease Control and Prevention, National Newborn Screening Information System, and published literature. The target population was individuals with SCD, the time horizon was lifetime, and the perspective was societal. Model data were collected from November 29, 2017, to March 21, 2018, and the analysis was performed from April 28 to December 3, 2018. Main Outcomes and Measures Life expectancy, quality-adjusted life expectancy, and projected lifetime income. Results The estimated prevalent population for the SCD cohort was 87 328 (95% uncertainty interval, 79 344-101 398); 998 were male and 952 were female. Projected life expectancy for the SCD cohort was 54 years vs 76 years for the matched non-SCD cohort; quality-adjusted life expectancy was 33 years vs 67 years, respectively. Projected lifetime income was $1 227 000 for an individual with SCD and $1 922 000 for a matched individual without SCD, reflecting a lost income of $695 000 owing to the 22-year difference in life expectancy. One study limitation is that the higher estimates of life expectancy yielded conservative estimates of lost life-years and income. The analysis only considered the value of lost personal income owing to premature mortality and did not consider direct medical costs or other societal costs associated with excess morbidity (eg, lost workdays for disability, time spent in the hospital). The model was most sensitive to changes in income levels and mortality rates. Conclusions and Relevance In this simulated cohort modeling study, SCD had societal consequences beyond medical costs in terms of reduced life expectancy, quality-adjusted life expectancy, and lifetime earnings. These results underscore the need for disease-modifying therapies to improve the underlying morbidity and mortality associated with SCD.

Intracerebral haemorrhage (ICH) accounts for 8–13% of all strokes and results from a variety of disorders. ICH is more likely to result in death or major disability than ischaemic stroke or subarachnoid haemorrhage. Rapid imaging allows early diagnosis and characterization of the localization and severity of the haemorrhage. Patients with acute ICH should be managed in an intensive care unit. Treatment entails general supportive care, control of blood pressure (BP) and intracranial pressure (ICP), prevention of haematoma expansion and, where indicated, neurosurgical intervention. The 30-day mortality from intracerebral haemorrhage (ICH) ranges from 35–52%. Among survivors, the prognosis for functional recovery depends upon the location of haemorrhage, size of the haematoma, level of consciousness, patient age, and overall medical health and condition. Rupture of arterial aneurysms is the major cause of subarachnoid haemorrhage (SAH). Aneurysm rupture releases blood directly into the cerebrospinal fluid (CSF) which spreads quickly within the CSF, rapidly increasing intracranial pressure. Death or deep coma ensues if the bleeding continues. The bleeding usually lasts only a few seconds but rebleeding is common and associated with a high mortality. Surgical clipping and endovascular coiling are effective in preventing rebleeding and generally should be performed early. Clinically significant vasospasm complicates 20–30% of aneurysmal SAH and is associated with delayed cerebral ischaemia and worse neurologic outcome.

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.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.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.

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. To compare the mucosal contact time of alternative oral viscous budesonide (OVB) slurries with the conventional sucralose OVB. 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. 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. 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.

IntroductionRhabdomyolysis is often encountered in austere environments where the diagnosis can be challenging due to the expense or unavailability of creatine phosphokinase (CPK) testing. CPK concentration ≥5,000 U/L has previously been found to be a sensitive marker for progression to renal failure. This study sought to propose a model utilizing an alternate biomarker to allow for the diagnosis and monitoring of clinically significant rhabdomyolysis in the absence of CPK.Materials and MethodsWe performed a retrospective chart review of 77 patients admitted to a tertiary medical center with a primary diagnosis of rhabdomyolysis. A linear regression model with aspartate aminotransferase (AST) as the independent variable was developed and used to predict CPK ≥5,000 U/L on admission and CPK values on subsequent hospital days. The study was approved and monitored by the Institutional Review Board at Walter Reed National Military Medical Center.ResultsLn(AST) explained over 80% of the variance in ln(CPK) (adjusted R2 = 0.802). The diagnostic accuracy to predict CPK ≥5,000 U/L was high (AUC 0.959; 95% CI: 0.921–0.997, P < 0.001). A cut point of AST ≥110 U/L in our study population had a 97.1% sensitivity and an 85.7% specificity for the detection of a CPK value ≥5,000 U/L. The agreement between actual CPK and predicted CPK for subsequent days of hospitalization was fair with an intraclass correlation coefficient of 0.52 (95% CI: 0.38–0.63). The developed model based on day 1 data tended to overpredict CPK values on subsequent hospital days.ConclusionsWe propose a threshold concentration of AST that has an excellent sensitivity for detecting CPK concentration ≥5,000 U/L on day of admission in a patient population with a diagnosis of rhabdomyolysis. A formula with a fair ability to predict CPK levels based on AST concentrations on subsequent hospital days was also developed.

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.

Aim: The purpose of this randomized, single-blind trial was to evaluate the efficacy of battlefield acupuncture in reducing postoperative pain and opioid consumption after adult tonsillectomy. Methods: Adult participants undergoing a tonsillectomy were randomized to either receive auricular ‘battlefield’ acupuncture or not. Groups were compared using the Wilcox rank sum test, Fisher's exact test and a generalized estimating equations model for post-discharge pain scores. Results: Statistically significant difference was not noted for morphine equivalent opioid use, nor was there any difference noted in the pain scores between the control group and treatment group. Conclusion: Acupuncture is cheap, safe and effective in many settings. Peri-operative battlefield auricular acupuncture did not reduce postoperative pain or opioid consumption in this study.

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.

To compare visual performance, marksmanship performance, and threshold target identification following wavefront-guided (WFG) versus wavefront-optimized (WFO) photorefractive keratectomy (PRK).In this prospective, randomized clinical trial, active duty U.S. military Soldiers, age 21 or over, electing to undergo PRK were randomized to undergo WFG (n = 27) or WFO (n = 27) PRK for myopia or myopic astigmatism. Binocular visual performance was assessed preoperatively and 1, 3, and 6 months postoperatively: Super Vision Test high contrast, Super Vision Test contrast sensitivity (CS), and 25% contrast acuity with night vision goggle filter. CS function was generated testing at five spatial frequencies. Marksmanship performance in low light conditions was evaluated in a firing tunnel. Target detection and identification performance was tested for probability of identification of varying target sets and probability of detection of humans in cluttered environments.Visual performance, CS function, marksmanship, and threshold target identification demonstrated no statistically significant differences over time between the two treatments. Exploratory regression analysis of firing range tasks at 6 months showed no significant differences or correlations between procedures. Regression analysis of vehicle and handheld probability of identification showed a significant association with pretreatment performance.Both WFG and WFO PRK results translate to excellent and comparable visual and military performance.

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.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.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 (p0.001). 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.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.

Determine the incidence, severity, and associated risk factors for the development of low bone mineral density (BMD) after combat-related lower extremity amputation.Retrospective case-control comparison.Tertiary care military treatment facility.One hundred fifty-six lower extremity amputees, representing 182 amputations (121 unilateral, 35 bilateral).All patients underwent dual energy x-ray absorptiometry scanning during the treatment period.The Z score was the main outcome measure. We identified all patients with low BMD (Z-1.0) and conducted multivariate analysis to identify significant risk factors for low BMD development.The observed rate of low BMD was 42%. The average Z score was -0.6 ± 1.1 among unilateral amputations and -1.2 ± 1.0 among bilateral amputations (P = 0.005). Risk factors for the development of low BMD were prolonged time to first ambulation [odds ratio (OR) = 1.39; 95% confidence interval (CI): 1.003-1.93; P = 0.048], prolonged time to dual energy x-ray absorptiometry (OR = 1.10; 95% CI: 1.02-1.18; P = 0.009), and more proximal amputation level (OR = 7.27; 95% CI: 3.21-16.49; P0.001). Among unilateral amputees, we detected a significant difference in the BMD of the intact and amputated limbs (-1.0; 95% CI: -1.1 to -0.8; P0.001).Proximal amputation level and delayed ambulation demonstrated a significant relationship with low BMD after traumatic and trauma-related amputation. We conclude that transfemoral amputees are at greater risk of BMD loss and that disuse atrophy is a primary factor in the development of low BMD. Prevention should focus on early and aggressive weight bearing rehabilitation and assessing levels and appropriately supplementing calcium and vitamin D.

Admission to the intensive care unit (ICU) is frequently required for the safe management of patients with anti-NMDA receptor encephalitis (NMDARE). Here, we present 22 patients (18 female, median age 28, range 17–59) with seropositive NMDARE, admitted to our neurological ICU between 2006- 18. Most commonly, patients were admitted following intubation and sedation for seizures/status epilepticus (7), depressed GCS (5), or agitation (2). Two were not intubated but admitted for monitoring, and four were admitted for plasma exchange (PLEX) only. Most were transferred to our centre for diagnostic work-up and specialist management. ICU-specific interventions included supervision of ventilation and respiratory weaning, and management of seizures. Autonomic dysfunction was frequent, including two patients with asystolic episodes on valsalva manoeuvres. Disease- specific treatments included IVIg, PLEX, steroids, rituximab and bortezomib. A teratoma was found in 9 women, including in two women who were also found to have another malignancy requiring treatment during admission. Length of ICU stay was frequently prolonged (median 66 days, range 4–457) with complex rehabilitation requirements on discharge. However, given sufficient recovery time, many returned to independence, and only three died. These data show the importance of good ICU care with specialised neurological input, to optimise outcomes in NMDARE.

An immobile or fasciculating tongue is an unusual finding in isolation. Its presence generally indicates a problem with the hypoglossal nerve which controls all the intrinsic and extrinsic muscles of the tongue except the palatoglossus and has five segments; the medullary, cisternal, skull base, carotid space and sublingual. This case series discusses five patients who initially presented with isolated hypoglossal nerve palsies. In each patient the lesion localised to a different segment of the nerve with clear imaging confirmation to support their respective causes. The cases (in anatomical order) include hypoglossal nerve damage as a complication of over-shunting in a patient with idiopathic intracranial hypertension, hypoglossal chronic inflammatory demyelinating polyneuropathy, hypoglossal canal fracture, glomus tumour and tongue malignancy. These cases highlight the broad range of differential diagnoses that should come to mind when assessing a patient with poor tongue movement, wasting and or fasciculation. A structured, anatomical approach to lesions of the hypoglossal nerve is fundamental to accurate diagnosis.

Key Points Question What is the association of BCG vaccination during childhood with subsequent cancer development? Findings In this 60-year follow-up of a clinical trial of the BCG vaccine that included 2963 participants vaccinated at a median age of 8 years, those who received the BCG vaccine had a subsequent lung cancer rate of 18.2 cases per 100 000 person-years. Participants who received the placebo had a lung cancer rate of 45.4 cases per 100 000 person-years. Meaning The findings suggest that receiving BCG vaccination during early childhood is associated with reduced risk of subsequent lung cancer development., This 60-year follow-up of a clinical trial investigates the association between BCG vaccination during childhood and diagnosis with cancer in adulthood., 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.

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.

ObjectivesThe case records at Queen Square afford a unique opportunity to understand the evolution of neurological diagnosis between 1870 and 1920. This period witnessed a shift from the descriptive and observational to a sophisticated and detailed understanding of discrete disease patterns.ResultsBy 1870, the introduction of microscopic pathological analysis of the nervous system had led to the recognition of disease processes including tumour, haemorrhage, infarction, meningitis and sclerosis. However, the most frequent diagnoses remained symptomatic (epilepsy, movement and functional disorders, visual loss and paralysis). Syphilis, paralysis agitans, and poliomyelitis were amongst the few specific diagnoses. The final decade of the 19th century saw the description of disease patterns, particularly in France, Germany and the US. These included disseminated and amyotrophic lateral sclerosis, myasthenia gravis and latterly eponymous disorders and signs attributed to Dejerine, Duchenne, Sanger Brown, Huntington, Marie, Romberg, Wernicke, Babinski and Charcot as well as Bright, Jackson, Gowers and Wilson in the UK.ConclusionsThe case record diagnoses, as well as the writings of Gowers and others, show how rapidly neurological thought evolved over 50 years. Queen Square was able to systematise neurological disease but was also remarkably responsive in understanding, accepting and adopting the neurological advances made across Europe.

ObjectivesThe neurological response to psychological trauma during the Great War changed between the initial engagements, the final offensive and the later reflections of the Southborough enquiry.DesignAt Queen Square, neurasthenia was a recorded diagnosis from 1890 and, for the next 30 years, between 4%–8% of all admissions were so described. The term ‘shell shock’ was first used in 1914 but the diagnosis burgeoned until, by 1918, it amounted to 25% of all admissions.SubjectsEarly in the war, affected soldiers were rapidly evacuated to the UK, but attitudes changed after the Somme, because of the need to expedite return to the frontline. The use of ‘Electrical Therapy’ at Queen Square was an example of this imperative (Linden 2013).ResultsReview of the case records suggests that ‘Shell Shock’ became an increasingly pejorative term as the condition was seen as a ‘contagious psychological response of the weak.’ The records show it was largely restricted to the lower ranks whilst officers were generally considered to have neurasthenia requiring a more gentle psychotherapeutic approach, occasionally involving transfer to specialist facilities.ConclusionsUltimately, at Queen Square, the diagnosis and management of acute traumatic neurosis was driven by the needs of war but also by popular prejudice.

ObjectivesTo assess the clinical usefulness of HVT over the first 2 years.DesignCohort observational.Subjects60 patients (49 F) with epilepsies or non-epileptic paroxysmal clinical events.Methods48–72 hour continuous video EEG at patients’ own environment.ResultsHVT answered the primary clinical question in 45/60 patients (75%), and provided additional clinical information in 5 patients [2 with unsuspected coexistent psychogenic non-epileptic seizures (PNES) and 3 with unsuspected sleep disorders (SD)]. Of the 12 patients with Idiopathic Generalized Epilepsy, absences had been overestimated in 6 and underestimated in 4, while absence status was recorded in 1 of the 2 patients in whom it had been suspected. Valproate was possible to drastically reduce or stop in 3/6 women. Focal seizures were recorded in 19 of 28 patients with focal epilepsies, PNES were the habitual seizures in further 2 patients, while syndrome classification changed in one. In all 4 patients referred for differentiation between SD and epilepsy, HVT confirmed parasomnias in 2, daytime naps in 1 and idiopathic hypersomnia in 1. The diagnosis of PNES was confirmed in 8 of 13 suspected patients. HVT was unhelpful in the 3 patients referred for not witnessed, poorly understood episodes of loss of consciousness. Three patients switched off the video and 2 failed to change battery on day 2.ConclusionsHVT is a useful diagnostic test provided that diagnostic hypothesis and clinical question are appropriate.

To evaluate the natural history of vaginal intraepithelial neoplasia (VAIN) and to identify risk factors for invasive vaginal carcinoma.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.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).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.: III.

Neuromyelitis Optica (NMO) and Myasthenia Gravis (MG) are rare antibody mediated disorders of the central nervous system (CNS) and neuromuscular junction (NMJ) respectively. Both diseases are predominantly mediated by IgG1 antibodies that activate complement. There have been increasing reports of patients who develop both disorders. Given the rarity of both diseases it would seem that these occurrences are not purely coincidental. There is heterogeneity between the cases described in the literature but common trends are observed in patients who develop both disorders. Most patients described are female. Typically the MG precedes the NMO and the majority of patients have undergone thymectomy. Generally, the symptoms of MG are mild but the NMO tends to follow a more aggressive clinical course. The pathogenesis of NMO in combination with MG is unknown, but thymectomy has been implicated in a subset of patients. We present the case of a female patient who developed NMO on a background of sero-positive MG and discuss the relevant literature.

To analyse mortality for spontaneous intracerebral haemorrhage (ICH), myasthenia gravis (MG) and Guillain–Barre syndrome (GBS) from 1996 to 2009 in UK intensive care units (ICUs). 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. 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. 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.

Summary 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.

Thymectomy is a frequently used treatment for myasthenia gravis (MG) and is virtually always indicated in MG patients who have a thymoma. However, the evidence for thymectomy in non-thymomatous MG remains less certain-no randomised controlled trials have been published to date, although one is currently underway. We reviewed the management and clinical outcome of patients with MG who underwent thymectomy over a 12 year period. Eighty-nine patients who underwent transsternal thymectomy were identified. A thymoma was identified on histology in 24 %, whereas 48, 9 and 19 % had hyperplastic, atrophic and normal thymic histology, respectively. One patient developed post operative myasthenic crisis but generally the procedure was well tolerated. Outcome was favourable for the majority of patients, with 34 % achieving complete stable remission (CSR) and an additional 33 % achieving pharmacological remission. Moreover, steroid requirements fell progressively during follow-up. Patients with a hyperplastic gland had a significantly greater chance of achieving CSR compared to other histological subtypes and the incidence of CSR increased with a longer duration of follow-up. Thymectomy for MG is generally safe and well tolerated and is associated with a sustained improvement of symptoms in the majority of patients.

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. 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. 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

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 cm 3 vs white, 43.2 cm 3 ; 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.

Excessive daytime sleepiness is common,1 yet opportunities to learn about sleep medicine in medical school are rare; a survey in 1998 indicated that undergraduate courses devoted a median of five minutes to sleep and its disorders.2 In this review we provide an update on the biology, diagnosis, and management of narcolepsy—an important, yet often misdiagnosed, cause of sleepiness that has seen exciting recent advances. We also briefly outline the other principal causes of daytime sleepiness and aim to equip the general reader with a practical approach to the assessment of patients who complain of excessive daytime sleepiness. This paper is based on a literature search conducted to produce evidence based guidelines on the diagnosis and management of narcolepsy in adults and children.3 We searched Medline, Embase, the Cochrane Collaboration, and two specialist sleep literature resources for abstracts with the key word “narcolepsy.” We read the full text of relevant papers and hand searched these for other relevant material. A multidisciplinary working party prepared the guidelines, and a group of 10 independent experts later reviewed them. These guidelines can be downloaded from the news section of http://www.sleeping.org.uk/ (accessed July 2004). Narcolepsy is a chronic neurological disorder affecting sleep regulation and causing excessive sleepiness and, in most cases, cataplexy (brief attacks of weakness on emotional arousal).3 4 The excessive sleepiness of narcolepsy comprises both a background feeling of sleepiness present much of the time and a strong, sometime irresistible, urge to sleep recurring at intervals through the day. This desire is heightened by conducive, monotonous circumstances, but naps at inappropriate times—such as during meals—are characteristic. The naps of narcolepsy usually last from minutes to an hour and occur a few times each day. Cataplexy refers to partial or generalised, almost invariably bilateral, loss of skeletal muscle tone and …

We aimed to assess whether rural residence is associated with amyotrophic lateral sclerosis in the south-east of England using a population based register. Previous studies in different populations have produced contradictory findings. Residence defined by London borough or non-metropolitan district at time of diagnosis was recorded for each incident case in the South-East England ALS Register between 1995 and 2005. Each of the 26 boroughs or districts of the catchment area of the register was classified according to population density. Age- and sex-adjusted incidence of ALS was calculated for each region and the relationship with population density tested by linear regression, thereby controlling for the underlying population structure. We found that population density in region of residence at diagnosis explained 25% of the variance in ALS rates (r = 0.5, p < 0.01). Thus, in this cohort in the south-east of England, people with ALS were more likely to be resident in areas of high population density at diagnosis.

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.The former Walter Reed Army Medical Center, Washington, DC, USA.Prospective nonrandomized clinical study.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.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).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.None of the authors has a financial or proprietary interest in any material or method mentioned.

Introduction: Slow channel congenital myasthenic syndrome is a dominant disorder characterized by prolonged acetylcholine receptor ion-channel activation. Methods: Molecular genetic techniques, electrophysiology, and binding studies in human embryonic kidney (HEK) 293 cells determined mutant function and expression levels. Patient response to treatment was measured by quantitative myasthenic gravis and Medical Research Council grade strength scores. Results: We report an unusual case due to heteroallelic mutations in CHRNE. The slow channel mutation, p.eS278del, is accompanied by a severe low-expression mutation, p.eR217L, on the second allele. Expression studies and cosegregation of p.eS278del with the disorder in the patient's offspring demonstrate robust expression of the p.eS278del mutation. The patient showed modest benefits from standard treatment with fluoxetine, but there was dramatic improvement when salbutamol was combined with fluoxetine. Conclusions: This case suggests that salbutamol, which is beneficial in some other congenital myasthenic syndromes, might also be considered in addition to fluoxetine in slow channel syndrome. Muscle Nerve, 2013

Background Pseudofolliculitis barbae (PFB) significantly impacts the military population, especially deployed personnel. Objective This study was designed to determine whether the addition of topical eflornithine to hair laser treatment would improve efficacy in treating PFB. Methods This was a randomized, double-blinded, placebo-controlled, paired (right and left neck) comparison study examining a combination of eflornithine and hair laser versus placebo and hair laser for the treatment of PFB. In all, 27 male patients with clinical PFB were treated with a long-pulsed neodymium:yttrium-aluminum-garnet laser with an energy fluence of 25 to 30 J/cm 2 , a pulse duration of 20 to 30 milliseconds, and a 10-mm spot size to the entire bearded neck region. The laser treatment was performed every 4 weeks for a total of 16 weeks. Between laser treatments, patients applied eflornithine and placebo creams twice daily to opposite sides of the bearded neck region. The number of hairs and inflammatory papules were counted bilaterally at each visit. Results The eflornithine side had a statistically significant decrease in the number of hairs and inflammatory papules compared with the placebo side. At 16 weeks, the eflornithine side had a median hair reduction of 99.5% from baseline (range 48.5%-100.0%), whereas the placebo side had an 85.0% median hair reduction from baseline (range 50.5%-94.5%), P less than .001. Limitations Patients were not followed up beyond 16 weeks. Conclusion The addition of topical eflornithine to hair laser treatment decreased hairs and inflammatory papules faster when compared with hair laser therapy alone in the treatment of PFB.

Background. Disparity between patient report and physician perception of pain from radiotracer injection for sentinel node biopsy is thought to center on the severity of the intervention, ethnic composition of population queried, and socioeconomic factors. Objective. The objectives of this study were, first, to explore agreement between physicians' and their breast cancer patients' pain assessment during subareolar radionucleotide injection; and second, to evaluate potential ethnic differences in ratings. Methods. A trial was conducted, from January 2006 to April 2009, where 140 breast cancer patients were randomly assigned to standard topical lidocaine-4% cream and 99mTc-sulfur colloid injection, or to one of three other groups: placebo cream and 99mTc-sulfur colloid injection containing NaHCO3, 1% lidocaine, or NaHCO3 + 1% lidocaine. Providers and patients completed numeric pain scales (0–10) immediately after injection. Results. Patients and providers rated pain similarly over the entire cohort (median, 3 vs 2, P = 0.15). Patients rated pain statistically significantly higher than physicians in the standard (6 vs 5, P = 0.045) and placebo + NaHCO3 (5 vs 4, P = 0.032) groups. No significant difference in scores existed between all African Americans and their physicians (3 vs 4, P = 0.27). Conclusion. Patient–physician pain assessment congruence over the less painful injections and their statistically similar scores with the more painful methods suggests the importance of utilizing the least painful method possible. Providers tended to underestimate patients with the highest pain ratings—those in the greatest analgesic need. Lack of statistical difference between African American and physician scores may reflect the equal-access-to-care over the entire patient cohort, supporting the conclusion that socioeconomic factors may lie at the heart of previously reported discrepancies.

Background Voice changes after thyroidectomy are common but not always related to recurrent laryngeal nerve (RLN) injury. We evaluated if RLN neuromonitoring correlated with non-RLN injury-related changes in voice after thyroidectomy. Methods Prospective multi-dimensional voice assessment was conducted on patients undergoing thyroidectomy before, 1–4 weeks, and 6 months postoperatively. Voice outcome (VO) was determined as normal (NormVO) or negative (NegVO) based upon combinations of patient-reported symptoms, videolaryngoscopy, a composite of acoustic measurements, and clinician-perceived voice quality. Groups with and without neuromonitoring were compared for early and durable differences in VO. Results Ninety-one patients underwent thyroidectomy; 39 with RLN neuromonitoring and 52 without. The two study groups were similar with regard to baseline characteristics including voice assessment. There was no difference in NegVO between neuromonitored and non-monitored patients at 1–4 weeks (n = 89; 32% vs. 27%; P = 0.81) and 6 months (n = 71, 14% vs. 7%; P = 0.42) after thyroidectomy. Neuromonitoring was associated with a 48-min increase in median operative time, but this finding was not statistically significant in a multivariate model. Conclusion In this study, recurrent laryngeal neuromonitoring did not appear to influence non-RLN injury related VO as measured by a comprehensive multidimensional voice assessment. J. Surg. Oncol. 2012; 105:4–9. © 2011 Wiley Periodicals, Inc.

Object There are no published long-term data for patients with penetrating head injury treated with bilateral supratentorial craniectomy, or supra- and infratentorial craniectomy. The authors report their experience with 33 patients treated with bilateral or bicompartmental craniectomy from the ongoing conflicts in Iraq and Afghanistan. Methods An exploratory analysis of Glasgow Outcome Scale (GOS) scores at 6 months in 33 patients was performed. Follow-up lasting a median of more than 2 years was performed in 30 (91%) of these patients. The association of GOS score with categorical variables was explored using the Wilcoxon rank-sum test or Kruskal-Wallis analysis of variance. The Spearman correlation coefficient was used for ordinal/continuous data. To provide a clinically meaningful format to present GOS scores with categorical variables, patients with GOS scores of 1–3 were categorized as having a poor outcome and those with scores of 4 and 5 as having a good outcome. This analysis does not include the patients who died in theater or in Germany who underwent bilateral decompressive craniectomy because those figures have not been released due to security concerns. Results All patients were men with a median age of 24 years (range 19–46 years) and a median initial Glasgow Coma Scale (GCS) score of 5 (range 3–14). At 6 months, 9 characteristics were statistically significant: focus of the initial injury, systemic infection, initial GCS score, initial GCS score excluding patients with a GCS score of 3, GCS score on arrival to the US, GCS score on dismissal from the medical center, Injury Severity Score, and patients with cerebrovascular injury. Six factors were significant at long-term follow-up: focus of initial injury, systemic infection, initial GCS score excluding patients with a GCS score of 3, GCS score on arrival to the US, and GCS score on dismissal from the medical center. At long-term follow-up, 7 (23%) of 30 patients had died, 5 (17%) of 30 had a GOS score of 2 or 3, and 18 (60%) of 30 had a GOS score of 4 or 5. Conclusions In this selected group of patients who underwent bilateral or bicompartmental craniectomy, 60% are independent at long-term follow-up. Patients with bifrontal injury fared best. Systemic infection and cerebrovascular injury corresponded with a worse outcome.

Thiazolidinediones (TZDs) are insulin-sensitizing agents that are associated with peripheral edema and have been reported to be associated with diabetic macular edema (DME). We hypothesized that TZDs produce subclinical increases in retinal thickness that may be detected by optical coherence tomography (OCT) but are not seen on routine dilated funduscopic examination.We used OCT to screen for subclinical DME in a cross-sectional study of patients with type 2 diabetes; 29 patients were taking TZDs and 58 were not taking TZDs. We analyzed data using multiple linear regression analysis to investigate associations of retinal thickness with clinical characteristics.There was no significant difference between the central subfield retinal thickness in the non-TZD group (206.4 ± 28.0 microns; n = 59) and TZD group (204.1 ± 26.1 microns; n = 29) (p = .72) nor were there significant differences in any other retinal subfield. There was no significant correlation of retinal thickness with laboratory results studies--peripheral edema, gender, age, duration of diabetes, individual, or combinations of medications. Retinal thickness differences between regions displayed normal anatomical variation. However, ethnic differences were found in which African-Americans had thinner retinas in all regions than Caucasians regardless of whether or not they used TZDs.These data suggest that TZDs do not cause subclinical DME in a demographically diverse patient population with diabetes. The established normal ranges for macular thickness may require adjustment based on ethnicity.

Purpose To compare the efficacy of oral gabapentin versus placebo for the control of severe pain after photorefractive keratectomy (PRK). Setting Center for Refractive Surgery, Walter Reed Army Medical Center, Washington, DC, USA. Design Randomized masked clinical trial. Methods This single-center clinical trial comprised active-duty United States Army soldiers aged 21 years or older having bilateral PRK for myopia with or without astigmatism. Patients received gabapentin 300 mg or placebo 3 times daily for 7 days beginning 2 days before and continuing for 4 days after surgery. Current and maximum pain levels were assessed using the Visual Analog Pain scale 2 hours after surgery and then daily on days 1 through 4. Repeated-measures analysis of variance (ANOVA) was used to compare the current and maximum pain scores over time between the gabapentin group and the placebo group. The Fisher exact test was used to determine whether there was a difference in severe pain (>7/10) between the 2 groups. Results Forty-two patients received gabapentin and 41 patients, placebo. The repeated-measures ANOVA showed no significant difference between the 2 groups in current pain ( P =.84) or in maximum pain over time ( P =.35). Oxycodone–acetaminophen use in the gabapentin group was significantly higher than in the placebo group 1 day postoperatively ( P =.034). Conclusion When added to a standardized postoperative pain regimen, gabapentin use led to no additional improvement in PRK pain control compared with a placebo at the dose and the time intervals tested. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Introduction Sickle cell disease (SCD) is a lifelong and costly chronic disease characterized by hemolytic anemia, pain crisis, and multi-end organ damage. Published estimates of SCD prevalence in the United States (US) range from approximately 85,000 to 100,000 people, most of whom are African American or Hispanic American. Individuals with SCD on average live two to three decades less than the general US population (Piel et al 2017). They also have markedly impaired patient-reported health-related quality-of-life (HRQOL) due in part to fatigue, pain, and impaired physical functioning, which leads to a significant reduction in work productivity. However, there are limited data available on the societal costs of SCD, such as lost lifetime earnings, which may lead to an underestimate of the true impact of this disease in a vulnerable population. Objectives We developed a simulation model to estimate the differences in life expectancy measured in years, quality-adjusted life-years (QALY) and income lost due to reduced life expectancy. Results were compared between a population of patients born with SCD in the US and a sex- and race-matched US population born without SCD and to the general US population. Methods To build the model, we (1) generated a Poisson regression from published birth and mortality estimates for SCD supplemented with data from the Centers for Disease Control (CDC) Multiple Cause of Death database to create age-specific life tables for a population of individuals with SCD (SCD population); (2) used published life tables from the CDC to develop age-specific death rates for a population without SCD (non-SCD population); (3) incorporated published utility weights for SCD adolescents and adults, and for the US general population to estimate the impact of the disease on HRQOL; (4) used US Bureau of Labor Statistics Supplemental Survey of Annual Personal Income data to calculate the expected annual personal income based on age, race, and gender; (5) built a cohort simulation model using R (version 3.4.2) to estimate the life expectancy, QALYs, and lost income for the SCD population compared to the non-SCD population, and the US general population. All analyses used Monte Carlo sampling to characterize uncertainty. Results We estimated that there would be 1,950 newborns with SCD born in the US annually. The projected life expectancy at birth is 54 years for the SCD population compared with 76 years for the age- and race-matched non-SCD population and 79 years for the general US population. Moreover, the quality-adjusted life expectancy of the SCD population (33 years) is less than half that of the matched non-SCD population (67 years) and general US population (69 years). Projected lifetime income for an individual in the SCD population is approximately $1.2 million compared with $1.9 million for an individual in the matched non-SCD population and $2.0 million in the general US population (Figure). Therefore, our model estimates that each individual with SCD loses over $700,000 in lifetime income due to early mortality associated with SCD. Conclusions A contemporary simulated cohort of individuals born with SCD is projected to live 22 years less than a matched population of individuals without SCD. Moreover, when adjusted for diminished HRQOL, our model suggests that patients living with SCD lose over three decades in life expectancy compared to a matched non-SCD population. Given the 22-year difference in life expectancy results in approximately $700,000 in lost lifetime income for each person born with SCD, a contemporary SCD birth cohort of 1,950 individuals would lose over $1.4 billion in lifetime income due to premature mortality. These losses are a conservative estimate since they do not include any direct medical costs or other societal costs such as lost educational potential, lost workdays due to caregivers caring for their affected children, or patient time spent in the hospital or visiting the emergency department; nor do they account for additional challenges in finding and maintaining active employment that have been previously described as substantial among individuals with SCD. In conclusion, SCD has devastating societal consequences beyond the resources required to provide medical care for patients underscoring the urgent need to develop disease-modifying therapies that can improve the underlying morbidity and mortality of individuals living with SCD. Disclosures Agodoa: Global Blood Therapeutics: Employment. Lubeck:Global Blood Therapeutics: Research Funding. Danese:Global Blood Therapeutics: Consultancy, Research Funding. Pappu:Global Blood Therapeutics: Employment. Howard:Global Blood Therapeutics: Employment. Gleeson:Global Blood Therapeutics: Consultancy, Research Funding. Halperin:Global Blood Therapeutics: Consultancy, Research Funding. Lanzkron:PCORI: Research Funding; NHLBI: Research Funding; GBT: Research Funding; selexys: Research Funding; Ironwood: Research Funding; Pfizer: Research Funding; Prolong: Research Funding; HRSA: Research Funding.

This article reviews the role of EEG in the diagnosis and management of patients with epilepsies. We review the morphologic and behavioral characteristics of the interictal and ictal EEG markers of the different types of epilepsy that should guide recording strategies to augment its diagnostic yield, and we attempt to delineate those particular features that may be relevant to the main epilepsy syndromes. Particular emphasis is placed on the activation methods, including hyperventilation, sleep deprivation and sleep, and specific triggers, as well as how these may differ between idiopathic and cryptogenic/symptomatic generalized and focal epilepsies, commenting on possible diagnostic pitfalls and areas of uncertainty. We also consider the indications for long-term recordings (video--telemetry and ambulatory) and emphasize the diagnostic value of polygraphic recordings.

Background Evaluation of peritoneal metastases by computed tomography (CT) scans is challenging and has been reported to be inaccurate. Methods A multi-institutional prospective observational registry study of patients with peritoneal carcinomatosis from colorectal cancer was conducted and a subset analysis was performed to examine peritoneal cancer index (PCI) based on CT and intraoperative exploration. Results Fifty-two patients (mean age 52.6 ± 12.4 years) from 16 institutions were included in this study. Inaccuracies of CT-based assessment of lesion sizes were observed in the RUQ (P = 0.004), LLQ (P