Use of local anesthesia for inguinal hernia repair has decreased over time in the VA system.

PURPOSE: In 2003, randomized trials demonstrated potentially improved outcomes when local instead of general anesthesia is used for inguinal hernia repair. Our study aimed to evaluate how the use of local anesthesia for this procedure changed over time following the publication of the trials' level 1 evidence. METHODS: We used the 1998-2018 Veterans Affairs Surgical Quality Improvement Program database to identify adults who underwent open, unilateral inguinal hernia repair under local or general anesthesia. Our primary outcome was the percentage of cases performed under local anesthesia. We used a time-series design to examine the trend and rate of change of the use of local anesthesia. RESULTS: We included 97,437 veterans, of which 22,333 (22.9%) had hernia surgery under local anesthesia. The median age of veterans receiving local anesthesia remained stable at 64-67 years over time. The use of local anesthesia decreased steadily, from 38.2% at the beginning year to 15.1% in the final year (P < 0.0001). The publication of results from randomized trials (in 2003) did not appear to increase the overall use or change the rate of decline in the use of local anesthesia. Overall, we found that the use of local anesthesia decreased by about 1.5% per year. CONCLUSION: The utilization of local anesthesia for inguinal hernia repair in the VA has steadily declined over the last 20 + years, despite data showing equivalence or superiority to general anesthesia. Future studies should explore barriers to the use of local anesthesia for hernia repair.

The association of congenital heart disease with necrotizing enterocolitis in preterm infants: a birth cohort study.

OBJECTIVE: To test the hypothesis that congenital heart disease (CHD) in preterm infants with severe CHD (cyanotic or left-sided obstructive lesions, or congestive heart failure) is independently associated with necrotizing enterocolitis (NEC, stage II or greater). STUDY DESIGN: Single-institution retrospective birth cohort of preterm infants with gestational age 23(0/7) to 34(6/7) weeks delivered between 1 January 2002 and 31 December 2011, excluding infants who received comfort care. Patients were classified into severe CHD, mild CHD and control groups. RESULTS: Among 4678 infants, 170 (3.6%) had CHD and 118 (2.5%) developed NEC. The risk for NEC increased with severe CHD (adjusted relative risk (RR)=3.72; 95% confidence interval (CI)=1.37 to 10.10) but not with mild CHD (RR=0.65; CI=0.27 to 1.55). CONCLUSION: In this cohort, severe but not mild CHD was independently associated with increased risk for NEC. This finding, if confirmed by other studies, may help identify patients at risk for NEC.

Denture cream: an unusual source of excess zinc, leading to hypocupremia and neurologic disease.

BACKGROUND: Chronic, excess zinc intake can result in copper deficiency and profound neurologic disease. However, when hyperzincemia is identified, the source often remains elusive. We identified four patients, one previously reported, with various neurologic abnormalities in the setting of hypocupremia and hyperzincemia. Each of these patients wore dentures and used very large amounts of denture cream chronically. OBJECTIVE: To determine zinc concentration in the denture creams used by the patients as a possible source of excess zinc ingestion. METHODS: Detailed clinical and laboratory data for each patient were compiled. Tubes of denture adhesives were analyzed for zinc content using dynamic reaction cell-inductively coupled plasma-mass spectrometry. Patients received copper supplementation. Copper and zinc levels were obtained post-treatment at varying intervals. RESULTS: Zinc concentrations ranging from about 17,000 to 34,000 mug/g were identified in Fixodent and Poli-Grip denture creams. Serum zinc levels improved in three patients following cessation of denture cream use. Copper supplementation resulted in mild neurologic improvement in two patients who stopped using denture cream. No alternative source of excess zinc ingestion or explanation for hypocupremia was identified. CONCLUSION: Denture cream contains zinc, and chronic excessive use may result in hypocupremia and serious neurologic disease.

Lack of prognostic significance of intratumoral angiogenesis in nonmetastatic osteosarcoma.

BACKGROUND: A need exists to stratify patients with nonmetastatic osteosarcoma into risk subcategories to administer risk-adapted therapy. Intratumoral angiogenesis determined at diagnosis may have a prognostic significance in this malignancy. PATIENTS AND METHODS: The authors performed a retrospective immunohistochemical study on archival pathologic material from patients with nonmetastatic osteosarcoma, excluding patients with purely chondroblastic tumors associated with hypovascularity of the cartilaginous stroma. Representative sections from the diagnostic biopsies were stained with a murine monoclonal antibody directed against CD34, an endothelial cell marker. Two pathologists unaware of the patients' long-term outcome counted microvessels in 10 microscopic fields from the most active areas of neovascularization. RESULTS: Between March 1988 and December 1996, 15 girls and 14 boys (median age 12.6 y, range 4.3-18.3) were identified. Seven patients had died of metastatic disease at a median of 3.4 years (range 0.8-7.4) after diagnosis; 22 were alive with no evidence of disease at a median follow-up of 6.8 years (range 2.7-11.4). There was no significant difference in the number of microvessels per field (pathologist 1, median 19 vs. 18.5; pathologist 2, median 15 vs. 10) between survivors or patients who died of metastatic disease. The correlation between the measurements of the two pathologists was excellent (correlation coefficient 0.87). CONCLUSIONS: Intratumoral neovascularization determined at diagnosis does not correlate with long-term outcome in patients with nonmetastatic osteosarcoma. A prospective study is necessary to confirm these results.

Minor furocoumarins of Murraya koenigii.

Xanthotoxin, isobyakangelicol, phellopterin, gosferol, neobyakangelicol, byakangelicol, byakangelicin and isogosferol are reported as minor furocoumarins of Murraya koenigii seeds.

Protease inhibitor-based therapy is associated with decreased HIV-related health care costs in men treated at a Veterans Administration hospital.

BACKGROUND: Protease inhibitor (PI) therapy for HIV infection is associated with decreased rates of opportunistic infections and death. Statistical models predict that decreased complications will be associated with decreased hospitalization costs. A recent report suggested that the decrease in the HIV hospitalization costs were offset by increases in demand for outpatient services. We performed a study of hospital use and HIV-associated health care costs in our center to determine the following: whether PI therapy is associated with decreased inpatient use; whether PI therapy is associated with decreased outpatient use and costs; whether decreased HIV health care costs are associated with increased use of nucleoside analogues. METHODS: The Dallas Veteran Affairs Medical Center provides comprehensive inpatient and outpatient HIV care and thus can evaluate the relation between inpatient and outpatient costs. The mean monthly number of hospital days, Infectious Diseases clinic visits, emergency department visits, other outpatient clinic visits, inpatient costs, outpatient costs, and PI costs were determined from January 1, 1995 through July 31, 1997. This time period was then divided into three intervals. Comparisons of PI use and HIV-related health care costs were during the three intervals was performed using analysis of variance (ANOVA). Significant differences between the baseline characteristics were further analyzed through multiple linear regression. RESULTS: A decrease in hospital days, and all outpatient visits including emergency visits, and HIV clinic visits was determined. No difference was found in the rate of use of other outpatient services. The per patient costs of HIV care decreased from a monthly average of $1905 U.S. in the first interval to $1122 U.S. in the last interval (p < .01). Linear regression demonstrated an inverse relation between PI use and total HIV costs (B=-0.67, p=.00, adjusted R2=0.52) but no relation between nucleoside use, stage of disease or financial class. CONCLUSIONS: PI therapy is associated with decreased hospital days and use of outpatient services. Total patient costs decreased, but a concomitant rise in outpatient costs took place. This increase was primarily a result of increased costs of acquiring PI. Increases in the number of nucleoside agents prescribed were not associated with decreased costs.

Beneficial effect of intravenous dexamethasone in children with mild to moderately severe acute chest syndrome complicating sickle cell disease.

Acute chest syndrome (ACS) in patients with sickle cell disease (SCD) has historically been managed with oxygen, antibiotics, and blood transfusions. Recently high-dose corticosteroid therapy was shown to reduce the duration of hospitalization in children with SCD and vaso-occlusive crisis. Therefore, we chose to assess the use of glucocorticoids in ACS. We conducted a randomized, double-blind placebo-controlled trial to evaluate the efficacy and toxicity of intravenous dexamethasone (0.3 mg/kg every 12 hours x 4 doses) in children with SCD hospitalized with mild to moderately severe ACS. Forty-three evaluable episodes of ACS occurred in 38 children (median age, 6.7 years). Twenty-two patients received dexamethasone and 21 patients received placebo. There were no statistically significant differences in demographic, clinical, or laboratory characteristics between the two groups. Mean hospital stay was shorter in the dexamethasone-treated group (47 hours v 80 hours; P = .005). Dexamethasone therapy prevented clinical deterioration and reduced the need for blood transfusions (P < .001 and = .013, respectively). Mean duration of oxygen and analgesic therapy, number of opioid doses, and the duration of fever was also significantly reduced in the dexamethasone-treated patients. Of seven patients readmitted within 72 hours after discharge (six after dexamethasone; P = .095), only one had respiratory complications (P = 1.00). No side effects clearly related to dexamethasone were observed. In a stepwise multiple linear regression analysis, gender and previous episodes of ACS were the only variables that appeared to predict response to dexamethasone, as measured by lengh of hospital stay. Intravenous dexamethasone has a beneficial effect in children with SCD hospitalized with mild to moderately severe acute chest syndrome. Further study of this therapeutic modality is indicated.

Magnetic resonance imaging of muscle in amyotrophic lateral sclerosis.

OBJECTIVE: To characterize leg muscle abnormalities in patients with ALS using MRI, and to correlate MRI with standard neurologic measures of motor neuron dysfunction. METHODS: Eleven ALS patients were studied twice (once at baseline and again after 4 months) and compared with eight normal control subjects. MRI data of the lower extremities were compared with tibialis anterior compound muscle action potential amplitude (CMAPa) and foot dorsiflexion maximal voluntary isometric contraction (MVIC). RESULTS: Muscle MRI was abnormal by visual inspection in six of 11 patients. The mean muscle T1 time and muscle volume were not different in patients compared with normal control subjects (p > 0.1). However, the mean T2 times were increased in the patients compared with normal control subjects (p = 0.009). T1 times did not correlate with CMAPa or MVIC. Muscle volume correlated with MVIC (r = 0.73 to 0.78, p < 0.02) but not with CMAPa (p > 0.05). There was a strong negative correlation (r < -0.8, p < or = 0.01) between muscle T2 time and MVIC and CMAPa. Also, the change in T2 relaxation time correlated with the change in CMAPa as the disease progressed (r = -0.63, p = 0.037). CONCLUSION: Of the MRI characteristics studied, T2 relaxation time was the best indicator of motor neuron dysfunction and may have a role in objective evaluation of motor neuron dysfunction.

Proposed cutoff values to define bladder outlet obstruction in women.

OBJECTIVES: There is no accepted urodynamic definition of outlet obstruction in women. Currently, the diagnosis is made on the basis of history and radiographic and endoscopic findings. The goal of this study is to design a pressure-flow nomogram (PdetQmax/Qmax) and define cut-off values for obstruction. METHODS: Two groups were studied prospectively in an open study: 124 control and 35 clinically obstructed patients. All had a complete history, physical examination, normal neurologic evaluation, cystoscopy, voiding cystography, and urodynamics-with-pressure-flow study. Pressure-flow plot and receiver operator characteristic curves (ROCs) were constructed to determine optimal cut-off values to predict obstruction for peak flow rate (Qmax) and detrusor pressure at maximal flow (PdetQmax). RESULTS: The etiology of obstruction was previous anti-incontinence surgery (n = 13), large cystocele (n = 11), urethral stricture (n = 6), and other (n = 5). On the basis of ROC curves, using cut-off values of Qmax of 15 mL/s or less and 12 mL/s or less, sensitivity was 85.7% and 71.4%, and specificity 78.2% and 90.3%, respectively. Using cut-off values of PdetQmax of more than 25 and more than 30 cm H2O, sensitivity was 74.3% and 71.4%, and specificity 79.8% and 88.7%, respectively. Using a combined cut-off value of Qmax of 1 5 mL/s or less and PdetQmax of more than 20 cm H2O, sensitivity was 74.3% and specificity was 91.1%. CONCLUSIONS: Based on this prospective, controlled study, preliminary cut-off values were obtained for refining the definition of outlet obstruction in women.

Expertise partnering--occupational health services and EAPs. Successful program.

1. Positive partnering is another way of working together to develop a business plan providing quality assured, cost effective health care programs. 2. In a professional atmosphere of trust and mutual respect, creative programs develop naturally. 3. Professional interdisciplinary partnering can lead to more cost effective, quality assured health care delivery.

Pediatric phase I drug tolerance: a review and comparison of recent adult and pediatric phase I trials.

PURPOSE: We evaluated the ratio of pediatric to adult maximum tolerated doses (MTDs) from 70 Phase I studies conducted between 1975 and 1995. The aim of this study was to determine whether previously observed differences in drug tolerance between adult and pediatric Phase I patients have persisted over the 20-year period of this analysis. PATIENTS AND METHODS: Phase I trials of pediatric and adult patients with solid tumors as the predominant diagnosis and sharing similar dosing regimens were evaluated. For consistent comparison between Phase I studies, the MTD was defined as the drug dose one level below that yielding dose-limiting toxicity in >30% of patients. The ratio of pediatric to adult MTDs was calculated and plotted chronologically by year of pediatric study closure. Statistical evaluation of MTD ratios included regression and correlation analysis. The extent of therapy before Phase I study entry was also examined. RESULTS: Ninety-three Phase I studies were reviewed. Twenty-one drugs (70 studies) met our criteria for paired review of MTDs and analysis of the variation of ratio with time. The pediatric to adult MTD ratios ranged from 0.4 to 2.8, with a median of 1.2. Regression analysis of the ratio of MTD versus date of pediatric study closure supports a linear relationship of decreasing ratio with time (p<0.01). Analysis of the regression line predicts MTD ratios of 2.02 and 0.76 for 1974 and 1995, respectively. Of patients included in this analysis, 37.1% and 68.6% of adult and pediatric patients, respectively, were considered to have been heavily pretreated before study entry. A significant (p<0.001) downward trend with time was observed in the proportion of adult patients entering Phase I studies who had received both radiation and chemotherapy. CONCLUSIONS: The results of this review continue to show an equal or greater drug tolerance in the pediatric population when compared with adult patients for most drugs studied during Phase I trials. However, there appears to be significant trend of decreasing differences in drug tolerance between pediatric and adult Phase I patients with time, as defined by the descent of the MTD ratio toward values <1.0. Mechanisms to explain greater drug tolerance in children and the observation of decreasing maximum tolerated dose ratios with time are discussed. Limited data suggest that changes in degree of therapy before Phase I study entry may be influencing the MTD ratio.

Recent advances in the treatment of cystinosis.

Cysteamine bitartrate capsules (Cystagon) have been approved by the US Food and Drug Administration for use in patients with nephropathic cystinosis. Plasma cysteamine concentrations were virtually identical at various times following ingestion of either cysteamine hydrochloride or Cystagon capsules in 24 normal control subjects. A transfer study was done with eight cystinosis patients who had been receiving either cysteamine hydrochloride or phosphocysteamine for many years. The plasma cysteamine concentration was significantly higher 2h after Cystagon and the leukocyte cystine content was significantly lower at all times after Cystagon compared to older forms of the drug. These differences are probably the result of greater patient compliance in taking the capsules compared to the older, liquid forms of the drug. A new method for following the course of renal glomerular deterioration in diseases such as cystinosis has been published recently. This method was used to re-analyse data on the efficacy of cysteamine treatment and to re-analyse new data on treating cystinosis patients with either of two doses of cysteamine (1.30 g/m2 per day and 1.95 g/m2 per day). This new method agrees well with other methods and shows that both doses of drug are equally effective in maintaining glomerular function.

Detection and localization of autofluorescent substances in thymus tissue of sheep.

An oxygenated sterol was detected by chemical analysis of sheep thymus lipid extracts. It was characterized as 7 beta-hydroxycholesterol, which is well known for its biological activity. Using fluorescence microscopy, attempts were made to correlate this substance to particular histological structures of the thymus tissue. Microscopy revealed an intense yellow-green primary fluorescence distributed throughout the entire thymic parenchyma, which was predominant in the cortico-medullary junction, the vicinity of the Hassall's bodies and the subcapsular space. This indicated an accumulation of the fluorogenic substance in special tissue structures of sheep thymus. This result can be assumed as specific for the thymus, since such primary fluorescence was absent from other simultaneously investigated organs, such as the adrenal.

Dimerisation of levonorgestrel in solid state ultraviolet light irradiation.

UV-irradiation of levonorgestrel (1) in the crystalline state under a nitrogen atmosphere yielded its dimer, [17 alpha[1R-(1 alpha,2 beta,4a beta,4b alpha,10a alpha)]]-13-ethyl-17- [4- (2-ethyl-1,2,3,4a,4b,5,6,7,9,10,10a-dodecahydro-7-oxo-1-phenant renyl)-1- methylen-2-oxo-butoxy]-18,19-dinorpregna-4-en-20-in-3-one(3) , as the principal photoproduct. It was characterized from its spectral and analytical data. The single crystal X-ray crystallographic data of 1 indicated the possibility of its photochemical dimerisation.

Photostability studies of ouabain, alpha-acetyldigoxin and digoxin in solid state.

Ouabain, alpha-acetyldigoxin and digoxin were subjected to irradiation using different light sources in crystalline state and their respective yields of photoproducts were determined densitometrically. alpha-Acetyldigoxin was found to be less stable than digoxin yielding a higher percentage of photoproducts under each light source examined. Ouabain showed photostability under the conditions of investigation.

Slow-release sodium fluoride in the management of postmenopausal osteoporosis. A randomized controlled trial.

OBJECTIVE: To test whether intermittent treatment with slow-release sodium fluoride and continuous calcium citrate supplementation inhibits vertebral fractures without causing fluoride complications. DESIGN: A placebo-controlled, randomized trial. SETTING: Outpatient setting of specialty clinics in Dallas and Temple, Texas. INTERVENTIONS: Slow-release sodium fluoride (25 mg twice daily) in repeated 14-month cycles (12 months on treatment followed by 2 months off treatment) compared with placebo. Both groups took calcium citrate (400 mg calcium twice daily) continuously. PATIENTS: 110 patients with postmenopausal osteoporosis were randomly assigned to two groups. In the slow-release sodium fluoride group, 48 of 54 patients completed more than 1 cycle of treatment (mean, 2.44 cycles/patient), whereas 51 of 56 patients in the placebo group completed at least 1 cycle (mean, 2.14 cycles/patient) in this interim analysis. MEASUREMENTS: Vertebral fracture rate and lumbar bone mineral content. Vertebral fractures were quantified from yearly radiographs. Bone mass was determined annually by densitometry. RESULTS: In the sodium fluoride group, the mean L2 to L4 bone mineral content increased by 4% to 6% in each cycle and the mean femoral neck bone density increased by 4.1% and 2.1% during the first two cycles, but the radial bone density did not change. The placebo group showed no statistical change in bone mass at any site. Compared with the placebo group, the sodium fluoride group had a lower individual new vertebral fracture rate (0.057/patient cycle compared with 0.204/patient cycle, P = 0.017), a higher fracture-free rate (83.3% compared with 64.7%, P = 0.042), and a lower group fracture rate (0.085/patient cycle compared with 0.239/patient cycle, P = 0.006). The side-effect profile was similar for the two groups; no patient developed microfractures, hip fractures, or blood loss anemia. CONCLUSIONS: Intermittent slow-release sodium fluoride plus continuous calcium citrate, administered for about 2.5 years, inhibits new vertebral fractures, increases the mean spinal bone mass without decreasing the radial shaft bone density, and is safe to use.

Prognostic indicators in children with IgA nephropathy--report of the Southwest Pediatric Nephrology Study Group.

Investigators in 13 pediatric nephrology centers reviewed clinical and pathological features in 218 children and adolescents with IgA nephropathy (IgAN), with particular emphasis on 80 patients who had follow-up periods of at least 4 years. Potential prognostic markers in the 80 children were compared between 12 (15%) who developed end-stage renal disease (ESRD) versus 68 who did not. The relationship between clinical and pathological features and the subsequent development of ESRD was examined using stepwise linear discriminant analysis in addition to standard univariate analysis. Seven variables were found to be predictive of ESRD: the presence of glomerular sclerotic changes, especially when this was associated with proliferation or sclerosis in 20% or more of the glomeruli; black race; hypertension at biopsy; proteinuria at biopsy; age at presentation; crescents; male sex. Using the resulting discriminant function, development of ESRD could be correctly predicted in 95% of the subjects. We conclude that ESRD is more common in American children with IgAN than was realized previously. Risk factors previously documented in adult studies have been confirmed, especially the presence of glomerular sclerosis, proteinuria, and hypertension.

Dietary protein and growth in infants with chronic renal insufficiency: a report from the Southwest Pediatric Nephrology Study Group and the University of California, San Francisco.

This report describes growth and nutrition data from the feasibility phase of a clinical trial that was designed to evaluate the effect of diet protein modification in infants with chronic renal insufficiency (CRI). The purpose of the proposed trial was to compare the safety (effect on growth in length) and efficacy [effect on glomerular filtration rate (GFR)] of a diet with a low protein: energy (P:E) ratio versus a control diet in such patients. Twenty-four infants with GFRs less than 55 ml/min per 1.73 m2 were randomly assigned at 8 months of age to receive either a low-protein (P:E ratio 5.6%) or control protein (P:E ratio 10.4%) formula, which resulted in average protein intakes of 1.4 and 2.4 g/kg per day in the low and control groups, respectively. Overall energy intakes over a 10-month period of study averaged 92% +/- 12% recommended dietary allowance (RDA) for length in the low-protein group and 92 +/- 15% RDA in the control group. Weight for age standard deviation scores (SDS) were comparably low in both groups at the time of randomization (low-protein--2.0 +/- 1.3, control -1.9 +/- 1.1) and at the end of the study (low -1.9 +/- 1.2, control -1.7 +/- 0.9). Length for age SDS at entry tended to be lower in the low-protein group but were not significantly different in the two groups (low -2.2 +/- 1.4 vs. control -1.7 +/- 1.4). However, at 18 months the low-protein group had a significantly lower SDS for length (-2.6 +/- 1.2 vs. -1.7 +/- 1.4).(ABSTRACT TRUNCATED AT 250 WORDS)