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Price transparency is an increasingly popular solution for high healthcare expenditures in the United States, but little is known about its potential to facilitate patient price shopping. Our objective was to analyze interhospital and interpayer price variability in spine surgery and spine imaging using newly public payer-specific negotiated charges (PNCs). We selected a subset of billing codes for spine surgery and spine imaging at 12 hospitals within a Saint Louis metropolitan area healthcare system. We then compared PNCs for these procedures and tested for significant differences in interhospital and interinsurer IQR using the Mann-Whitney U Test. We found significantly greater IQRs of PNCs as a factor of the insurance plan than as a factor of the hospital for cervical spinal fusions (interinsurer IQR $8256; interhospital IQR $533; P.0001), noncervical spinal fusions (interinsurer IQR $28 423; interhospital IQR $5512; P.001), computed tomographies of the lower spine (interinsurer IQR $595; interhospital IQR $113; P.0001), and MRIs lower spinal canal (interinsurer IQR $1010; interhospital IQR $158; P.0001). There was no significant difference between the interinsurer IQR and the interhospital IQR for lower spine x-rays (interinsurer IQR $107; interhospital IQR $67; P = .0543). Despite some between-hospital heterogeneity, we show significantly higher price variability between insurers than between hospitals. Our single system analysis limits our ability to generalize, but our results suggest that savings depend more on hospital and provider negotiations than patient price shopping, given the difficulty of switching insurers.

BACKGROUND Early diagnosis of HIV infection improves patient outcomes and reduces transmission. Adolescents make up one-fifth of new HIV diagnoses in the United States. We sought to quantify the number of missed opportunity encounters (MOEs) before HIV diagnosis for adolescents at a pediatric hospital (PediHosp) and a proximate adult hospital which employs universal HIV screening in its emergency department (ED) (CountyHosp). METHODS An observational study at 2 academic tertiary care hospitals in the United States that included all adolescents 13-20 years old with a new diagnosis of behaviorally-acquired HIV infection from 2006 to 2017. MOE were defined as any encounter at PediHosp or CountyHosp after the latter of the individual's 13th birthday or the date 3 months after the individual's most recent negative HIV screen, and before the encounter of HIV diagnosis. Comparisons were made by site of diagnosis and location of MOE. RESULTS Two-hundred five subjects met inclusion criteria: 68% male, 76% Black and 81% men who have sex with men. There were 264 MOE, the proportion of adolescent ED encounters that were MOE at the PediHosp ED was 8.3 MOE per 10,000 encounters and the proportion at the CountyHosp ED was 1.2 (relative risk = 6.7; 95% CI: 4.1-11.0; P < 0.001). CONCLUSIONS MOE for HIV diagnosis in adolescents occur frequently and are greater in number at a PediHosp as compared with a similar adult setting with universal screening. Universal HIV screening protocols at PediHosp may identify HIV-positive adolescents earlier.

Leukemia-predisposing conditions, such as GATA2 haploinsufficiency, are known for their high penetrance and expressivity profiles. These disorders pose a difficult diagnostic challenge to even the most experienced clinician when they first present. We describe the case of a 17-year-old male presenting with features of nontuberculous mycobacterial infection, pulmonary fibrinoid granulomatous vasculitis, and myelodysplasia in the setting of a pathogenic GATA2 frameshift mutation confirmed by next-generation sequencing. The broad differential for GATA2 haploinsufficiency requires prompt recognition of key clinical features and laboratory abnormalities towards directing diagnosis and guiding appropriate and perhaps life-saving therapy.

We present a preterm infant who developed a fever and mild respiratory disease on the second day of life. Infant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nasopharyngeal testing was positive at 24 and 48 hours of life. Placenta histopathology revealed SARS-CoV-2 infection by electron microscopy and immunohistochemistry. Further understanding of the risk factors that lead to in utero transmission of SARS-CoV-2 infection is needed.

Endoplasmic reticulum (ER) stress and disrupted proteostasis contribute to the pathogenesis of a variety of glomerular and tubular diseases. Thus, it is imperative to develop noninvasive biomarkers for detecting ER stress in podocytes or tubular cells in the incipient stage of disease, when a kidney biopsy is not yet clinically indicated. Mesencephalic astrocyte–derived neurotrophic factor (MANF) localizes to the ER lumen and is secreted in response to ER stress in several cell types. Here, using mouse models of human nephrotic syndrome caused by mutant laminin β2 protein–induced podocyte ER stress and AKI triggered by tunicamycin– or ischemia-reperfusion–induced tubular ER stress, we examined MANF as a potential urine biomarker for detecting ER stress in podocytes or renal tubular cells. ER stress upregulated MANF expression in podocytes and tubular cells. Notably, urinary MANF excretion concurrent with podocyte or tubular cell ER stress preceded clinical or histologic manifestations of the corresponding disease. Thus, MANF can potentially serve as a urine diagnostic or prognostic biomarker in ER stress–related kidney diseases to help stratify disease risk, predict disease progression, monitor treatment response, and identify subgroups of patients who can be treated with ER stress modulators in a highly targeted manner.

Background— PCSK9 loss-of-function (LOF) variants allow for the examination of the effects of lifetime reduced low-density lipoprotein cholesterol (LDL-C) on cardiovascular events. We examined the association of PCSK9 LOF variants with LDL-C and incident coronary heart disease and stroke through a meta-analysis of data from 8 observational cohorts and 1 randomized trial of statin therapy. Methods and Results— These 9 studies together included 17 459 blacks with 403 (2.3%) having at least 1 Y142X or C679X variant and 31 306 whites with 955 (3.1%) having at least 1 R46L variant. Unadjusted odds ratios for associations between PCSK9 LOF variants and incident coronary heart disease (851 events in blacks and 2662 events in whites) and stroke (523 events in blacks and 1660 events in whites) were calculated using pooled Mantel–Haenszel estimates with continuity correction factors. Pooling results across studies using fixed-effects inverse-variance-weighted models, PCSK9 LOF variants were associated with 35 mg/dL (95% confidence interval [CI], 32–39) lower LDL-C in blacks and 13 mg/dL (95% CI, 11–16) lower LDL-C in whites. PCSK9 LOF variants were associated with a pooled odds ratio for coronary heart disease of 0.51 (95% CI, 0.28–0.92) in blacks and 0.82 (95% CI, 0.63–1.06) in whites. PCSK9 LOF variants were not associated with incident stroke (odds ratio, 0.84; 95% CI, 0.48–1.47 in blacks and odds ratio, 1.06; 95% CI, 0.80–1.41 in whites). Conclusions— PCSK9 LOF variants were associated with lower LDL-C and coronary heart disease incidence. PCSK9 LOF variants were not associated with stroke risk.

Men and boys who present with bleeding associated with low factor VIII levels and normal von Willebrand studies are assumed to have hemophilia A until proven otherwise. However, routinely available coagulation assays cannot easily distinguish mild hemophilia A from the 2N variant of von Willebrand disease. We present a case that highlights the difficulties of recognizing this diagnosis, the role of genetic testing, and the identification of a 2N variant that has not been previously described.

Introduction: Sulfonylureas are a commonly-used class of diabetes medication that can prolong the QT-interval, which is a leading cause of drug withdrawals from the market given the possible risk of life-threatening arrhythmias. Previously, we conducted a meta-analysis of genome-wide association studies of sulfonylurea-genetic interactions on QT interval among 9 European-ancestry (EA) cohorts using cross-sectional data, with null results. To improve our power to identify novel drug-gene interactions, we have included repeated measures of medication use and QT interval and expanded our study to include several additional cohorts, including African-American (AA) and Hispanic-ancestry (HA) cohorts with a high prevalence of sulfonylurea use. To identify potentially differential effects on cardiac depolarization and repolarization, we have also added two phenotypes - the JT and QRS intervals, which together comprise the QT interval. Hypothesis: The use of repeated measures and expansion of our meta-analysis to include diverse ancestry populations will allow us to identify novel pharmacogenomic interactions for sulfonylureas on the ECG phenotypes QT, JT, and QRS. Methods: Cohorts with unrelated individuals used generalized estimating equations to estimate interactions; cohorts with related individuals used mixed effect models clustered on family. For each ECG phenotype (QT, JT, QRS), we conducted ancestry-specific (EA, AA, HA) inverse variance weighted meta-analyses using standard errors based on the t-distribution to correct for small sample inflation in the test statistic. Ancestry-specific summary estimates were combined using MANTRA, an analytic method that accounts for differences in local linkage disequilibrium between ethnic groups. Results: Our study included 65,997 participants from 21 cohorts, including 4,020 (6%) sulfonylurea users, a substantial increase from the 26,986 participants and 846 sulfonylureas users in the previous meta-analysis. Preliminary ancestry-specific meta-analyses have identified genome-wide significant associations (P < 5х10–8) for each ECG phenotype, and analyses with MANTRA are in progress. Conclusions: In the setting of the largest collection of pharmacogenomic studies to date, we used repeated measurements and leveraged diverse ancestry populations to identify new pharmacogenomic loci for ECG traits associated with cardiovascular risk.

Background— The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans. Methods and Results— We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and ≈2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (λ range: 0.9–1.1), although not after genomic control correction was applied to the overall meta-analysis (λ: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1 , and TBX5 to African American populations at the genome-wide significance level ( P −8 ), we also identified a novel locus: ITGA9 , located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR ( P −8 ). Conclusions— This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent.

Background— Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval. Methods and Results— First, individual estimates of African and European ancestry were inferred from genome-wide single-nucleotide polymorphism (SNP) data in 7 population-based cohorts of African Americans (n=12 097) and regressed on measured QT interval from ECGs. Second, imputation was performed for 2.8 million SNPs, and a genome-wide association study of QT interval was performed in 10 cohorts (n=13 105). There was no evidence of association between genetic ancestry and QT interval ( P =0.94). Genome-wide significant associations ( P –8 ) were identified with SNPs at 2 loci, upstream of the genes NOS1AP (rs12143842, P =2×10 –15 ) and ATP1B1 (rs1320976, P =2×10 –10 ). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low probability values ( P –5 ) were observed for SNPs at several other loci previously identified in genome-wide association studies in individuals of European ancestry, including KCNQ1 , KCNH2 , LITAF , and PLN . Conclusions— We observed no difference in duration of cardiac repolarization with global genetic indices of African American ancestry. In addition, our genome-wide association study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include individuals of African ancestry.

OBJECTIVES: Two surges in influenza-like illness (ILI) visits to Children's Medical Center Emergency Departments, Dallas and Legacy, occurred in late spring (wave 1) and late summer 2009 (wave 2). This study describes respiratory viruses identified during the first weeks of waves 1 and 2 of the 2009 influenza A(H1N1) pandemic (pH1N1) and compares patients infected with pH1N1 with those infected with other respiratory viruses during wave 1. METHODS: From April 27 to May 7 and August 23 to September 7, 2009, nasopharyngeal swab specimens from all patients with temperature 38.2°C or higher plus 2 or more symptoms of ILI were tested by rapid antigen, direct fluorescent antibody, or multiplex polymerase chain reaction assays. Patients with pH1N1 during wave 1 were classified as cases and 3 age- and sex-matched controls were randomly selected from patients with 1 respiratory virus other than pH1N1. Odds ratios (ORs) and associated 95% confidence intervals (95% CIs) of characteristics associated with patients with pH1N1 were estimated using conditional logistic regression models. RESULTS: During wave 1, single viruses identified in 1023 symptomatic children were confirmed pH1N1 (55, 5.4%), rhinovirus (505, 49.4%), parainfluenza 3 (199, 19.5%), and human metapneumovirus (169, 16.5%). By multivariable analysis, duration of fever (OR, 1.49; 95% CI, 1.02-2.20) and myalgia at presentation (OR, 3.09; 95% CI, 1.09-8.76) were independent predictors associated with pH1N1. During wave 2, 114 (59.7%) of single viruses were pH1N1. CONCLUSIONS: During the epidemic of ILI in Spring 2009, other respiratory viruses were identified more frequently than pH1N1 influenza in children with ILIs. Clinical presentation was similar for all respiratory viruses. Molecular diagnostic testing can define the prevalent viruses during community outbreaks and provide guidance to physicians making treatment decisions in emergency departments.

The G allele of the FOXO3 SNP rs2802292 has a strong, consistently replicated protective association with longevity. We investigated the effect of FOXO3 genotype on coronary heart disease (CHD) mortality - a major cause of mortality worldwide. We genotyped DNA collected in 1991-93, at Exam 4 of the Honolulu Heart Program (HHP), from 3,584 American males of Japanese ancestry aged 71-93 years. Study participants were followed for up to 9 years for CHD mortality and for up to 11 years in a replication cohort - the Health Aging and Body Composition (Health ABC) study. Health ABC is a prospective observational study of 3,075 well functioning, community-dwelling, male and female, white and black Americans, aged 70-79 years at baseline. Cox proportional hazards models demonstrated that Americans of Japanese, white and black ethnicity who were G allele carriers had a combined risk reduction of 31% for CHD mortality (HR = 0.69; 95% CI, 0.58-0.82; P =0.00002). Reduction in risk of death from CHD was 38% in Japanese, 24% in whites and 29% in blacks. This finding remained virtually unchanged when included in a multivariable model of common CHD risk factors. We subsequently assessed the contribution of FOXO3 genotype, relative to other common risk factors, to CHD mortality in these populations by estimating population attributable risk (PAR). In the Americans of Japanese ancestry, PAR for the TT (non-protective) genotype was high, at 24%, equivalent to hypertension (24%), and greater than diabetes (21%), hypercholesterolemia (12%) and ever smoking (6%). PAR for FOXO3 genotype was lower at 9% and 3% in white and black Americans, respectively, principally due to lower prevalence of the TT (risk) genotype. We subsequently measured C-reactive protein (CRP) in a population subsample, and found lower blood CRP levels in G allele carriers ( P G allele of the FOXO3 SNP rs2802292 has a major protective effect on CHD mortality, possibly related to lower blood levels of inflammation. The findings support further research on potential mechanisms and point to FoxO3 as a potential target therapeutic target.

UNLABELLED Tangential radiotherapy for left-sided breast cancer may be cardiotoxic. Shaping the field with a heart block reduces cardiac exposure but may under-dose the breast and/or chest wall. We compared the incidence and location of local recurrences in patients irradiated with and without a heart block. METHODS AND MATERIALS Between 1994 and 1998, 180 patients irradiated to the left breast and/or chest wall were retrospectively reviewed. The local recurrence rates in patients treated with and without a heart block were compared using a 2-tailed Fisher exact test. An in-depth dosimetric analysis was performed in 23 patients to assess the percentage of breast tissue under-dosed by inclusion of the heart block. RESULTS Overall, the local recurrence rates in patients with or without a heart block were similar. In postlumpectomy patients with inferiorly located tumors, the rates of local recurrence with and without a heart block were 2 of 6 patients versus 0 of 19 patients, respectively. In the dosimetric analysis, the average percentage of breast tissue under-dosed by the inclusion of a heart block was 2.8% (range, 0%-11%). DISCUSSION A heart block is a reasonable method to limit cardiac dose but should be used cautiously following a lumpectomy in patients with inferiorly located tumors. Additional study with larger numbers of patients is warranted.

Clinical vignette-based surveys have been used for more than 30 years to measure variation in physicians' approaches to the diagnosis and treatment of patients with similar health problems. Vignettes offer advantages over medical record reviews, analysis of claims data, and standardized patients. A vignette-based survey can be completed more quickly than a record review or standardized patient program. Research has shown that vignette-based surveys produce better measures of quality of care than medical record reviews when used to measure differential diagnosis, selection of tests, and treatment decisions. Although standardized patients are preferred when measuring communication and physical examination skills, vignettes are more cost-effective than standardized patients when assessing clinical physicians' decision making. Vignettes offer better opportunities to isolate physicians' decision making and to control case-mix variation than do analyses of claims data sets. Clinical vignette-based surveys are simple and economical tools that can be used to characterize physicians' practice variation.

High-dose therapy with stem-cell transplantation is a potentially curative therapy for younger patients with relapsed aggressive non-Hodgkin's lymphoma (NHL) and is also under investigation in relapsed indolent NHL. There are, however, risks associated with this treatment strategy. Autologous stem-cell transplantation (ASCT) continues to be associated with a high risk of relapse, while graft-versus-host disease is a major limiting factor with allogeneic stem-cell transplantation. The presence of minimal residual disease (MRD) in the harvested, re-infused stem cells, or remaining in the patient following chemotherapy, is associated with relapse after ASCT. As a result, monitoring and eradicating MRD has become a major focus of many studies in NHL. Rearrangement and overexpression of the bcl-1 and bcl-2 genes are the hallmarks of mantle-cell and follicular lymphoma, respectively, and evidence suggests that they are promising surrogate markers of MRD. Polymerase chain reaction analysis is a sensitive methodology used to monitor the status of occult lymphoma cells bearing these genetic aberrations, and results from trials of ASCT have shown that clearance of bcl-1/JH- and bcl-2/JH-positive cells following treatment is associated with a significant improvement in outcome. Rituximab, the anti-CD20 monoclonal antibody, is increasingly used for in vivo purging and can effectively eradicate bcl-1/JH- and bcl-2-positive cells. If the encouraging preliminary results with rituximab are maintained with a longer follow-up, this agent could play a pivotal role in improving outcome after stem-cell transplantation in NHL.

Objective: To determine whether long-term results of one of three different management protocols for severe tibial pilon fractures offer advantages over the other two. Design: In a retrospective study, patients were examined clinically and radiologically after internal fixation of severe tibial plafond fractures (i.e., 92 percent Type C fractures according to the AO-ASIF classification). Setting: Department of Traumatology, Hanover Medical School. Level I trauma center. Patients: Fifty-one of seventy-seven patients treated between 1982 and 1992 were examined clinically and radiologically at an average of sixty-eight months (range 13 to 130 months) after injury. Interventions: The patients were treated in three different ways: primary internal fixation with a plate following the AO-ASIF principles (n = 15), which was reserved for patients with closed fractures without severe soft tissue trauma; one-stage minimally invasive osteosynthesis for reconstruction of the articular surface with long-term transarticular external fixation of the ankle for at least four weeks (n = 28); and a two-stage procedure entailing primary reduction and reconstruction of the articular surface with minimally invasive osteosynthesis and short-term transarticular external fixation of the ankle joint followed by secondary medial stabilization with a plate using a technique requiring only limited skin incisions (a reduced invasive technique) (n = 8). Main Outcome Measurements: Objective evaluation criteria were infection rate, amount of posttraumatic arthritis, range of ankle movement, and number of arthrodeses. Subjective criteria were pain, swelling, and restriction of work or leisure activities. Results: Because only closed fractures were treated by primary internal fixation with a plate, there was a statistically significant difference (p < 0.005) in the distribution of open fractures between the three treatment groups. Fracture classification in these groups were not significantly different. All but four fractures were classified as Type C lesions according to the AO-ASIF system. The soft tissue was closed in 63 percent (n = 32) and open in 37 percent (n = 19). No significant relationship could be found between the soft tissue damage and degree of arthritis or between the type of surgical treatment and extent of posttraumatic arthritis. However, none of the patients who required secondary arthrodesis (23 percent of all cases) were in the group who had undergone two-step surgery (p < 0.05). The range of ankle movement was much greater in the two-step group than in the others: these patients also had less pain, more frequently continued working in their previous profession, and had fewer limitations in their leisure activities. These differences did not reach statistical significance. The incidence of wound infection did not differ significantly among the three groups. Conclusions: On the basis of our results, we now prefer a two-step procedure for the treatment of severe tibial piton fractures with extensive soft tissue damage. In the first stage, primary reduction and internal fixation of the articular surface is performed using stab incisions, screws, and K-wires. Temporary external fixation is applied across the ankle joint. After recovery of the soft tissues, the second stage entails internal fixation with a medial plate using a reduced invasive technique.

To determine physician and patient compliance rates for diabetes testing in patients with previous gestational diabetes.Questionnaires regarding follow-up testing and personal health history were sent to 66 patients with previous gestational diabetes who did not have diabetes when they participated in a follow-up study conducted 5 years earlier. A 2-hour glucose tolerance test (GTT) was offered to those whose last test was done more than 1 year previously.All 66 individuals returned the questionnaire and 20 (30.3%) reported having received a yearly 2-hour GTT. Of the remaining 46, 19 had been tested at least once in the previous 5 years, but 27 had not been tested. Of the patients who had been tested at least once in the 5-year period, their physicians initiated testing 61.5% of the time and the patients initiated the remainder. There were no significant differences between physician specialty and rate or appropriateness of the testing. Of 39 individuals who had been tested at least once in the 5-year period, eight had diabetes and four were glucose intolerant. Of 12 individuals who had not been tested in the past year and agreed to be tested in 1995, four had diabetes and two had glucose intolerance.Although physicians and their gestational diabetic patients knew the risks of diabetes development, compliance with follow-up testing was poor and the risk of developing diabetes high.

The liver has been judged relatively resistant to ischemia, but prolonged inflow occlusion at normothermic conditions can produce evidence of reversible or irreversible hepatocellular damage. Cytoprotective agents have been used both experimentally and clinically to afford extended viability of hepatocytes under reduced perfusion. One agent, prostaglandin E1, has been described clinically as effective in sustaining liver function under ischemic conditions. We have sought to verify this observation in an experimental model using prolonged normothermic inflow occlusion. Twenty miniature pigs were anesthetized and subjected to subtotal normothermic hepatic inflow occlusion (portal vein, hepatic artery, choledochal vessels) to allow for sufficient splanchnic decompression. Half of the animals received pretreatment with prostaglandin E1 (alprostadil) 500 micrograms intravenously. Inflow occlusion was maintained for 2 hours followed by reperfusion and killing 24 hours later. As a measure of functional preservation, the tissue adenine nucleotides adenosine monophosphate, diphosphate, and triphosphate (AMP, ADP, ATP) were measured in ischemic liver by freeze-clamping and high-performance liquid chromatography during occlusion and after reperfusion. Cytosolic enzyme determinations (aspartate transaminase, alanine transaminase, lactate dehydrogenase) were also made before occlusion and after reperfusion. As a possible indicator of cellular injury, blood ionized Ca++ was measured before inflow occlusion and after reperfusion. Although no difference was found in levels of AMP and ADP between prostaglandin E1 and control animals, ATP levels rose significantly higher during recovery in prostaglandin E1 animals at 60 minutes and 24 hours after reperfusion (13.97 +/- 1.29 and 13.60 +/- 0.91 mumoles/gm dry weight prostaglandin E1 vs. 9.25 +/- 0.97 and 9.80 +/- 0.85 mumoles/gm dry weight co control, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Study Design. Ten subjects (seven with neurogenic claudication and three control subjects) underwent examination of lower limb muscle blood flow before and after exercise using positron emission tomography. Objectives. To investigate the hypothesis that lower limb muscle ischemia was the origin of symptoms in neurogenic claudication. Background. Patients with neurogenic claudication secondary to spinal stenosis experience lower limb discomfort after exercise similar to that of ischemic claudication. However, they do not have clinical evidence of peripheral vascular disease. The authors postulated that the lower limb discomfort in patients with neurogenic claudication may arise from muscle ischemia due to inadequate dilatation of arterioles in response to exercise, this itself arising secondary to sympathetic dysfunction due to spinal stenosis. Method. Using O 15 -labeled water and positron emission tomography measured thigh and leg muscle blood flow response to exercise bilaterally in seven patients with unilateral neurogenic claudication and three constrol subjects were measured. Results. The average values obtained for mid-thigh and mid-calf muscle perfusion at rest were 2.57 ml/min/100 g tissue (2.23-3.90) and 2.39 ml/ml/100 g tissue (2.03-3.46), respectively. The average values obtained from mid-thigh and mid-calf perfusion after exercise were 4.41 ml/min/100 g tissue (2.8-6.0) and 4.87 ml/min/100 g (2.2-11.7). We found no difference in muscle perfusion between symptomatic and asymptomatic limbs in this group of patients. Conclusions. These studies suggest that muscle ischemia is not the origin is not the origin of symptoms in most patients with neurogenic claudication

Pretreatment with topical nonsteroidal anti-inflammatory drugs is common practice to maintain maximal pupil dilation for cataract surgery. Most surgeons also inject a cholinergic agent intracamerally for miosis after intraocular lens insertion. We evaluated the effects of topical suprofen and flurbiprofen on the miosis induced by anterior chamber irrigation with either acetylcholine or carbachol. One eye of 30 pigmented rabbits was dilated with cyclopentolate HCl and phenylephrine HC1. Three groups, each composed of ten eyes, received flurbiprofen, suprofen, or a control. In each group, five eyes received acetylcholine by anterior chamber irrigation and five received carbachol. Pupil diameters were measured with calipers before and five minutes after irrigation by an observer unaware of the treatment regimen. Irides irrigated with carbachol constricted less than those irrigated with acetylcholine (P = .016). In anterior chambers irrigated with carbachol, suprofen was associated with less miosis than either tears (P = .005) or flurbiprofen (P = .0091; however, if the infusion was performed with acetylcholine, no differences between the three groups were noted (P = .44).

Background : Indications for heart failure (HF) device therapy are well-established. Cardiac resynchronization therapy (CRT) and internal cardiovertor defibrillator (ICD) use, alone or in combination, reduce morbidity and mortality. However, the frequency of device implantation in situations with limited survival is unknown. This study assessed, in an unselected population, what proportion of patients had a < 1 year survival and whether such survival was affected by age or gender after HF device therapy. Methods : All patients admitted from 2000 –2006 to a referral center for de novo HF device therapy were identified using ICD-9 codes: 0050 (CRT), 0051 (CRT & ICD), and 3794 (ICD). Mortality rates were estimated using Kaplan Meier product limit estimation and between group comparisons for gender and age were made using logistic regression. Results : From 2000 to 2006, 1,735 patients received CRT, ICD, or CRT & ICD. Of these, 1,331 (77%) were men and averaged 66.7 years of age while the women averaged 64.7 years (p = 0.347). One-year survival for all patients was 91%. One-year mortality by age and gender (see Table ), demonstrates that the proportion deriving a less than one year survival benefit after device implantation increases with age, but is not affected by gender. Conclusions : One-year survival after HF device implantation is high, suggestive of appropriate patient selection. However, advanced age increases the likelihood of deriving a shorter term benefit of device therapy, suggesting that careful patient selection is particularly important in older adults to avoid the futile use of expensive technologies. While no apparent gender differences were found related to survival, the overwhelming majority of devices were implanted in men, suggesting gender bias, gender-based co-morbidities affecting care, or gender-based differences in care preferences. Table

OBJECTIVE: Increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin levels were noted incidentally after a laparoscopic cholecystectomy. The percentage in which such elevation occurs and its clinical significance in the absence of bile duct injury were investigated. SUMMARY BACKGROUND DATA: Bile duct injury is the most feared complication of laparoscopic cholecystectomy. Some laboratory tests may be indicative of this complication, such as increases in liver enzyme (AST, ALT, and alkaline phosphatase [ALP]) and bilirubin. These parameters have not been investigated in patients who had laparoscopic cholecystectomy and in whom no damage to the bile duct was noted. METHODS: Sixty-seven patients with normal results of preoperative liver function test were entered into the study. Blood was collected 24 hours after laparoscopic cholecystectomy, and AST, ALT, ALP, and bilirubin levels were measured. RESULTS: A mean 1.8-fold increase in AST occurred in 73% of patients; 82% showed a 2.2-fold increase in ALT. A statistically nonsignificant increase was noted in 53% of patients (ALP remained within normal limits), and in 14% of patients bilirubin levels were increased (they were primarily of the unconjugated type). CONCLUSIONS: In many patients a significant increase in AST and ALT levels occurred after laparoscopic cholecystectomy, but they returned to normal values within 72 hours. The cause of this is unclear, and these elevations appear to have no clinical significance.

Physical and psychological decline is common in the post-treatment breast cancer population, yet the efficacy of concurrent interventions to meet both physical- psychosocial needs in this population has not been extensively examined. PURPOSE: This study explores the effects of a combined exercise and psychosocial intervention model on selected physiological-psychological parameters in post-treated breast cancer. METHODS: Forty-one breast cancer survivors were randomly assigned to one of four groups for an 8-week intervention: exercise only [EX, n=13] (aerobic and resistance training), psychosocial therapy only [PS, n=11] (biofeedback), combined EX and PS [EX+PS, n=11], or to control conditions [CO, n=6]. Mean delta score (post-intervention - baseline) were calculated for each of the following: body weight, % body fat (skin folds), predicted VO2max (Modified Bruce Protocol), overall dynamic muscular endurance [OME] (RMCRI protocol), static balance (Single leg stance test), dynamic balance (360° turn and 4-square step test), fatigue (Revised Piper Scale), and quality of life (FACT-B). A one-way ANOVA was used to analyze the preliminary results of this on-going randomized trial. RESULTS: Overall, there were significant differences in the delta scores for predicted VO2max, OME, and dynamic balance among the 4 groups (p

In a new analysis of a case-control study based on the French KIDSEP cohort, Mikaeloff et al.1 conclude that there is no overall association of hepatitis B vaccine (HB) with acute onset demyelinating disease but that there is a long-term increase in the risk of multiple sclerosis (MS) in children compliant with national vaccination schedules and immunized against HB with the Engerix B® vaccine. Unfortunately, these results were leaked to the lay press before their publication in Neurology ®, fueling new rumors about the risk of HB vaccination. We would like to stress major interpretational issues that preclude any reliable conclusion from being drawn about a possible link in this study between the Engerix R® vaccine and the risk of MS in children. A very large number of analyses were undertaken. A total of 50 results appear in the article, and the list of “sensitivity” analyses suggests that many more were done. The probability of detecting several significant associations through pure chance was therefore very high. Concluding that there is a difference between Engerix B® and other vaccines because the odds …