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Objective: Respiratory distress syndrome (RDS), requiring mechanical ventilation and exogenous surfactant treatment, and patent ductus arteriosus (PDA), are common co-morbidities in very premature infants. The effects of intra-tracheal surfactant administration on the cardiovascular and pulmonary systems in very premature infants with RDS and PDAs are not well characterized. We evaluated the effects of poractant alfa and beractant, surfactants with different rapidity of onset and duration of action, in very premature infants with RDS. To assess whether there were differences in PDA hemodynamics in very premature infants with RDS treated with poractant alfa and beractant during the first week of life and to assess whether poractant alfa or beractant had a direct effect on PDAs and PDA hemodynamics following the second dose of surfactant., Study Design: We studied 50 in-born, very premature infants with RDS, 24 0 of 7 to 29 6 of 7 weeks gestation, treated with poractant alfa or beractant, in an open label, 1:1, randomized clinical trial. A subgroup of 16 patients with severe RDS, treated with a second dose of surfactant, had echocardiographical assessments before and 20 to 30 min after the second dose of surfactant., Result: There were 25 infants treated with poractant alfa (27.1±1.6 weeks, birth weight 930±231 g) and 25 treated with beractant (26.7±1.7 weeks, P=0.407 and birth weight 898±282 g, P=0.666). Clinically significant PDAs were diagnosed and treated in 8 of 25 (32%) of the poractant alfa and 19 of 25 (76%) of the beractant group (P=0.002). Indomethacin treatment was slightly earlier (3.4±2.5 days) in the poractant alfa than in the beractant group (5.1±4.9 days, P=0.038). Right ventricle pressure (RVP)/systolic arterial pressure (SAP) ratio in the first week was slightly lower in the poractant alfa (64±20%) than in the beractant (78±26%, P=0.048) group. Following a second dose of surfactant, neither poractant alfa nor beractant changed PDA flow. These hemodynamic observations were associated with less respiratory support in the poractant alfa group, allowing earlier extubation (13 of 25 at 48 h and 15 of 25 at 72 h), than in the beractant group (6 of 25 at 48 h, P=0.044, and 8 of 25 at 72 h, P=0.049)., Conclusion: The more rapid improvement in pulmonary function in the poractant alfa-treated infants was associated with a lower RVP/SAP ratio and a corresponding earlier treatment with indomethacin. Neither surfactant had a significant direct effect on PDA hemodynamics. The lower frequency of clinically significant PDAs in the poractant alfa compared with the beractant group may represent an indirect effect of the differences in the pulmonary improvement induced by the two surfactants.

Objective: Comparison of the differences between availability of animal-derived surfactant preparations used to treat premature infants is incomplete. The objective of this study was to assess the short-term treatment efficacy of the two most commonly used surfactant preparations in the United States, beractant (100 mg kg(-1) initial and subsequent doses) and poractant alfa (200 mg kg(-1) initial and 100 mg kg(-1) subsequent doses), in very premature, mechanically ventilated infants <30 weeks gestation with respiratory distress syndrome (RDS)., Study Design: Inborn infants at two institutions, open label, 1:1, randomized controlled trial. Level of respiratory support for first 72 h of life. Morbidities of prematurity observed during the neonatal intensive care unit hospitalization., Result: We studied 52 infants 24 0/7 to 29 6/7 weeks gestation; 25 received poractant alfa (27.1±1.6 weeks, birth weight of 930±231 g) and 27 received beractant (26.7±1.7 weeks, P=0.343 and birth weight 900±271 g, P=0.668). Respiratory support for the first 72 h of life was lower in the poractant alfa than beractant group for mean airway pressure (MAP, P=0.003) and respiratory index (MAP × FiO(2), P=0.032). Infants in the poractant alfa group had a greater number of infants extubated at 48 (13/25 vs 6/27, P=0.027) and 72 h (15/25 vs 8/27, P=0.029) than the beractant group. Although the study was not powered to detect morbidities of prematurity, the prevalence of PDA and air leaks was less in the infants treated with poractant alfa than in those treated with beractant. Rates of bronchopulmonary dysplasia (8/23 vs 11/22, P=0.303) or death (2/25 [corrected] vs 5/27, P=0.272) were similar in the infants treated with poractant alfa and beractant, respectively., Conclusion: This study suggests significant short-term benefits to the use of the larger initial dose of poractant alfa than beractant in very premature infants with RDS. Further studies involving a larger number of preterm infants are needed to assess long-term effects.

High-dose melphalan chemotherapy and autologous peripheral blood stem cell transplantation (HDM/SCT) has been shown to result in a durable hematologic response and prolonged overall survival in systemic amyloid light-chain (AL) amyloidosis as well as multiple myeloma. However, little is known about the myeloma associated with AL amyloidosis (MM/AL). In this retrospective study, we evaluated 87 patients with MM/AL from 1994 to 2007. Sixteen of these patients underwent HDM/SCT at Boston University Medical Center. Three patients (19%) died from treatment-related mortality. The overall median survival for all 87 patients was 22 months by Kaplan-Meier estimates. However, this was improved to 54.5 months for those who received HDM/SCT compared to 21 months for those who did not receive HDM/SCT. A hematologic complete response was achieved by 25% (4/16) of patients at 6 months after HDM/SCT. Hematologic relapses occurred in 60% of patients at a median of 1 year after HDM/SCT. In conclusion, HDM/SCT can prolong overall survival in patients with MM/AL who are eligible to receive it.

Objectives: To investigate the separate and combined effects of caregiver status and high stress on mortality risk over 8 years in elderly women., Design: Prospective cohort study conducted in four U.S. communities followed from 1999/01 (baseline) to December 31, 2007., Setting: Home-based interviews., Participants: Three hundred seventy-five caregiver and 694 noncaregiver participants from the Caregiver-Study of Osteoporotic Fractures (Caregiver-SOF) who participated in the baseline Caregiver-SOF interview., Measurements: Caregiver status was based on SOF respondents' self-report of performing one or more instrumental or basic activities of daily living for a relative or friend with impairments. Two measures of stress were used: Perceived Stress Scale and stress related to caregiving tasks. All-cause mortality was the outcome., Results: Caregivers were more stressed than noncaregivers; 19.7% of caregivers and 27.4% of noncaregivers died. Mortality was lower in caregivers than noncaregivers (adjusted hazard ratio, (AHR)=0.74, 95% confidence interval (CI)=0.56-0.89). High-stress respondents had greater mortality risk than low-stress respondents over the first 3 years of follow-up (AHR=1.81, 95% CI=1.16-2.82) but not in later years. Likewise, high-stress caregivers and noncaregivers had higher mortality risk than low-stress noncaregivers, although low-stress caregivers had significantly lower mortality than did noncaregivers, whether perceived stress or caregiving-related stress was measured (AHR=0.67 and 0.57). Similar results were observed in analyses comparing spouse caregivers with married noncaregivers., Conclusion: Short-term effects of stress, not caregiving per se, may increase the risk of health decline in older caregivers.

Background: Chronic stress may lead to health decline through metabolic syndrome. Thus, persons in stressful caregiving situations who also have more indicators of metabolic syndrome may experience more decline than other caregivers or noncaregivers., Methods: The sample included 921 women (338 caregivers and 583 noncaregivers) from the Caregiver-Study of Osteoporotic Fractures study. Participants had home-based baseline and 1-year follow-up interviews between 1999 and 2003. At baseline, caregivers were categorized as long term ((3)4 years) versus short term (<4 years), and caring for someone with Alzheimer's disease/dementia or not. A metabolic risk composite score was the sum of four indicators: body mass index (3)30, and diagnosis or using medications for hypertension, diabetes, or high cholesterol. Walking speed (m/second) was measured at both interviews., Results: Walking speed declined for the total sample (adjusted mean = -0.005 m/second, +/-0.16) over an average of 1.04 years (+/-0.16). Overall, caregiving was not associated with decline. Increasing metabolic risk score was associated with greater decline for the total sample and long-term and dementia caregivers, but not other caregivers or noncaregivers. Metabolic risk score modified the adjusted associations between years of caregiving and dementia caregiving with walking speed decline (p values for interaction terms were 0.039 and 0.057, respectively). The biggest declines were in long-term caregivers and dementia caregivers who also had 3-4 metabolic indicators (-0.10 m/second and -0.155 m/second, respectively)., Conclusions: Walking speed declined the most among older women who had both stressful caregiving situations and more metabolic syndrome indicators, suggesting these caregiver subgroups may have increased risk of health decline.

Introduction: We tested the hypothesis that REM sleep contributes to core features of cognitive dysfunction of anxious depression including negative self-appraisals, biased memory processing and unpleasant dream content., Methods: After a habituation night in a sleep lab, a convenience sample of 35 healthy college students and 20 depressed/anxious students were awakened 10 min into a REM sleep episode and then 10 min into a NREM sleep episode. Awakenings were counterbalanced to control circadian effects. After each awakening participants reported a dream and then completed memory recall, mood and self-appraisal tasks., Results: Self-appraisals of depressed/anxious participants were significantly less positive and significantly more negative after awakenings from REM sleep vs NREM sleep. Appraisal of the REM sleep dream self was negative for depressed/anxious subjects only. Recall of negative memories was significantly more frequent after REM vs NREM sleep awakenings for both depress/anxious and healthy participants. REM sleep dreams were associated with greater frequencies of negative emotion, greater aggression and victimization rates than dreams in NREM sleep for depressed/anxious participants., Limitations: Depressed/anxious participants were classified as such on the basis of mood scales rather than clinical interview. All participants were drawn from a volunteer college student population and thus our results may not be applicable to some elderly clinical populations., Conclusions: REM appears to facilitate cognitive distortions of anxious depression., (Copyright (c) 2009 Elsevier B.V. All rights reserved.)

Purpose: Symptomatic atherosclerotic disease of the popliteal artery presents challenges for endovascular therapy. We evaluated the technical success, complications, and midterm outcomes of atherectomy and angioplasty involving the popliteal segment., Methods: We conducted a retrospective review of outcomes of popliteal artery intervention using atherectomy or angioplasty performed between 2003 and 2008., Results: A total of 56 patients (36% women, age 72.8 +/- 12.2 years, 77% critical limb ischemia) underwent popliteal atherectomy (n = 18) or angioplasty (n = 38). These patients had similar clinical characteristics, TransAtlantic Intersociety Consensus (TASC)/ TASC II classification, mean lesion length, and runoff scores. We observed a trend toward higher rates of technical success defined as <30% residual stenosis after atherectomy compared to angioplasty (94% vs 71%, P = .08). While angioplasty was associated with a higher frequency of arterial dissection (23% vs 0%, P = .003), atherectomy was associated with a higher rate of thromboembolic events (22% vs 0%, P = 0.01). Adjunctive stenting was used more frequently following angioplasty compared to atherectomy (45% vs 6%, P = .005). Thrombolysis was used to treat embolization in 4 patients in the atherectomy group. The improvement in the ankle-brachial index (ABI) was similar between the 2 treatment groups. Primary patency of the popliteal artery at 3, 6, and 12 months was 94%, 88%, and 75% in the atherectomy group and 89%, 82%, and 73% in the angioplasty group (P = not significant [NS]). There were no significant differences in limb salvage and freedom from reintervention at 1 year between the atherectomy and angioplasty groups., Conclusions: Our experience with popliteal artery endovascular therapy indicates a distinct pattern of procedural complications with atherectomy compared to angioplasty but similar midterm patency, limb salvage, and freedom from intervention.

Purpose: Direct comparison of transposed arteriovenous fistulas (tAVF) and arteriovenous grafts (AVG) has been hampered by inherent differences in patient characteristics between tAVF and AVG groups. In this study, using matching to control patient variables, we evaluated our outcomes with upper arm tAVF and upper arm prosthetic AVG., Methods: A retrospective review of all newly created upper arm tAVF and AVG was performed. One hundred ninety upper arm tAVF were group matched for age, gender, race, diabetes, and history of previous failed access with 168 AVG chosen from a pool of 476 concurrently performed AVG procedures. Complication, patency, and intervention rates were compared using multivariate analysis., Results: Mean follow up for our cohort was 29.1 months. Transposed fistulae consisted of 119 basilic vein and 71 cephalic vein transpositions, which were found to have similar demographic parameters, complication rates, and patency rates. There were no differences in 30 day mortality, 24 hour thrombosis, bleeding requiring exploration, or ischemic steal requiring intervention between the tAVF and AVG groups. More AVG developed infection requiring operative exploration than tAVF (7.9% vs 1.6%, respectively. P = .004). Primary patency for tAVF was higher than for AVG: 48% vs 14% at five years (P < .0001). Secondary patency rate for tAVF was also higher than for AVG: 57% vs 19% at five years (P < .0001). Nine percent of tAVF compared with 53% of AVG required one or more surgical and/or percutaneous revisions to maintain secondary patency (P < .0001). Multivariate analysis revealed that utilization of a tAVF was associated with a reduced risk of primary (Hazard Ratio [HR] 0.47, 95% Confidence Interval [CI] 0.35-0.64, P < .0001) and secondary failure (HR 0.59, 95% CI 0.42-0.81, P = .0001)., Conclusions: Transposed arteriovenous fistulas have significantly higher primary and secondary patency rates, require fewer revisions, and are less likely to develop a significant infection than AVG. This study supports the contention that as long as a patient is a candidate for a tAVF based on anatomic criteria, a tAVF should be considered before an AVG.

Background: Transthyretin (TTR) mutations known to cause cardiac amyloidosis include V122I, found almost exclusively in African Americans at a prevalence of 3-3.9%. This retrospective study describes TTR V122I-associated cardiac amyloid disease (ATTR) in a major amyloid referral clinic population., Methods: Self-identified African Americans with amyloidosis (n = 156) were screened for TTR V122I by serum isoelectric focusing; mutant TTR was confirmed by DNA sequencing or mass spectrometry. Cardiac findings in ATTR V122I and immunoglobulin light chain (AL) amyloidoses were compared., Results: TTR V122I was identified in 36/156 (23.1%) of evaluated patients and included 5 homozygotes; the allele frequency was 0.013. One compound heterozygote (F44L/V122I) and 4 patients who had AL and the mutant TTR allele were characterized. In patients negative for V122I, AL was the most frequent diagnosis (86/120). Cardiomyopathy was present in 100% of patients with ATTR and 84% of patients with AL (P = .01). In patients with dominant cardiac involvement, better survival occurred in ATTR (n = 30) compared to AL (n = 31), (27 vs 5 months, P < .01) although the mean age in ATTR was higher (70.3 vs 56.2 years, P < .01). Congestive heart failure symptoms and electrocardiographic findings were similar in ATTR and AL, but significant differences in echocardiographic measurements were observed., Conclusions: ATTR V122I and AL are equally prevalent as the cause of cardiomyopathy in African Americans referred for a diagnosis of amyloidosis. Available therapy for AL underscores the need for early and accurate determination of amyloid type.

Background: Black Americans have higher mortality from breast cancer than white Americans. This study explores the influence of socioeconomic factors and black race on treatment and mortality for early-stage breast cancer., Methods: A cohort of 21,848 female black and white, non-Hispanic subjects from the Massachusetts Cancer Registry diagnosed with stage I or II breast cancer between 1999-2004 was studied. Subjects with tumors larger than 5 cm were excluded. We used mixed modeling methods to assess the impact of race on guideline concordant care (GCC), defined as receipt of mastectomy or breast conserving surgery plus radiation. Cox proportional hazard regression was used to assess disease-specific mortality., Results: Blacks were less likely to receive GCC after adjusting for age and clinical variables (OR: 0.75; 95% CI: 0.61, 0.92). Marital status and insurance were predictors of receipt of GCC. After adjustment for all covariates, there were no longer significant differences between black and white women regarding the receipt of GCC. Nevertheless, black women were more likely to die of early-stage breast cancer than white women after adjusting for clinical, treatment, socioeconomic variables, and reporting hospital (HR: 1.6; 95% CI: 1.1-2.1)., Conclusions: Socioeconomic factors are mediators of racial differences in treatment outcomes. Significant racial differences exist in disease-specific mortality for women with early-stage breast cancer. Attention to reducing socioeconomic barriers to care may influence racial differences in breast cancer treatment and mortality.

It is unknown whether caregivers who perform more caregiving tasks have a greater decline in health from higher stress or less decline because of better health, staying active, or psychological factors. This 1999-2004 US study examined caregiving intensity and 2-year change in performance-based functioning among 901 elderly women from the Caregiver-Study of Osteoporotic Fractures sample. Caregivers were categorized as high (n = 167) or low (n = 166) intensity based on how many activities of daily living they performed for the care recipient. Caregiving intensity status and physical performance score (sum of quartiles of walking pace, grip strength, and chair-stand speed; range, 0-9) were assessed at baseline and at 2 annual follow-up interviews. At baseline, high-intensity caregivers reported the most stress but had the best physical functioning; noncaregivers (n = 568) had the poorest physical functioning (adjusted scores = 5.09 vs. 4.54, P = 0.03). Low-intensity caregivers declined more than noncaregivers over 2 years, but high-intensity caregivers did not (adjusted difference = -0.33, P = 0.07 vs. 0.03, P = 0.89). Among respondents with the same caregiving status at baseline and 1-year interviews, high-intensity caregivers maintained the highest physical performance throughout follow-up. Higher levels of physical performance persisted over 2 years among high-intensity caregivers, which did not support the traditional stress hypothesis.

High-dose melphalan chemotherapy and autologous peripheral blood stem cell transplantation has been shown to result in durable hematologic response and prolonged overall survival in systemic AL amyloidosis. In this retrospective study, we evaluated clinical and hematologic responses in 69 patients with predominant liver involvement who were treated with high-dose intravenous melphalan and autologous stem cell transplantation from 1998 to 2006. Nine patients (13%) died from treatment-related mortality, similar to patients without hepatic involvement. The overall survival was 81% at one year and 61% at five years, by Kaplan-Meier estimates. A hematologic complete response was achieved by 53% (31/58) of patients at one year. A hepatic response occurred in 57% (33/58) at one year after high-dose intravenous melphalan and autologous stem cell transplantation and 63% (19/30) at two years after high-dose intravenous melphalan and autologous stem cell transplantation. In conclusion, hepatic disease improves in almost 2/3 patients treated with high-dose intravenous melphalan and autologous stem cell transplantation who have a complete or partial hematologic response to treatment.

Background: Few bowel-preparation rating scales have been validated. Most scales were intended for comparing oral purgatives and fail to account for washing and/or suctioning by the endoscopist. This limits their utility in studies of colonoscopy outcomes, such as polyp-detection rates., Objective: To develop a valid and reliable scale for use in colonoscopy outcomes research., Setting: Academic medical center., Methods: We developed the Boston bowel preparation scale (BBPS), a 10-point scale that assesses bowel preparation after all cleansing maneuvers are completed by the endoscopist. We assessed interobserver and intraobserver reliability by using video footage of colonoscopies viewed on 2 separate occasions by 22 clinicians. We then applied the BBPS prospectively during screening colonoscopies and compared BBPS scores with clinically meaningful outcomes, including polyp-detection rates and procedure times., Results: The intraclass correlation coefficient (a measure of interobserver reliability) for BBPS scores was 0.74. The weighted kappa (a measure of intraobserver reliability) for scores was 0.77 (95% CI, 0.66-0.87). During 633 screening colonoscopies, the mean (SD) BBPS score was 6.0 +/- 1.6. Higher BBPS scores (> or =5 vs <5) were associated with a higher polyp-detection rate (40% vs 24%, P < .02). BBPS scores were inversely correlated with colonoscope insertion (r = -0.16, P < .003) and withdrawal (r = -0.23, P < .001) times., Limitations: Single-center study., Conclusions: The BBPS is a valid and reliable measure of bowel preparation. It may be well suited to colonoscopy outcomes research because it reflects the colon's cleanliness during the inspection phase of the procedure.

Background: This article presents the development and application of a method to diagnose and measure subjective incompetence, the clinical hallmark of demoralization., Methods: The subjects (n = 112) were patients with cancer at a consultation clinic of a cancer center. They completed a questionnaire on general background information, the Brief Cope Scale, and a newly developed scale to measure subjective incompetence. The development and psychometric properties of this scale were studied. Data analysis included both univariate and bivariate statistical tests and an examination of the intercorrelations between the subjective incompetence scores and the scores on the Brief Cope Scale., Results: The scale for subjective incompetence was found to have adequate reliability and validity., Conclusions: The proposed scale will allow us to determine if the distinction between depression and demoralization has practical implications and to what extent and to further clarify the role of demoralization in the etiology and pathogenesis of both physical illnesses and mental disorders. The combined use of this scale with the existing criteria and scales for demoralization will highlight the role of subjective incompetence in converting what might have been a normal response to stress into an abnormal state requiring intervention., (Copyright 2009 S. Karger AG, Basel.)

Objective: The goal was to determine the impact on medication prescribing errors of adding a pediatric medication list (quicklist) to a computerized physician order entry system in a pediatric emergency department., Methods: The quicklist is a drug dosing support tool that targets the most common medications in our clinical setting. We performed a retrospective comparison of orders from 420 randomly selected visits before and after quicklist introduction. Error rates were analyzed with respect to urgency level, physician training level, and patient age. The quicklist was examined for frequency of use and error rates., Results: The 840 patient visits (420 before intervention and 420 after intervention) generated 724 medication orders, which contained 156 medication prescribing errors (21%). The groups did not differ with respect to urgency level, physician training level, or patient age. There were significant decreases in the rate of errors per 100 visits, from 24 to 13 errors per 100 visits, and in the rate of errors per 100 orders, from 31 to 14 errors per 100 orders. The decrease in the error rates did not vary according to urgency score, age group, or physician training level. The quicklist was used in 30% of the orders in the postintervention group. In this group, the error rate was 1.9 errors per 100 orders when the quicklist was used, compared with 18.3 errors per 100 orders when the list was not used. Errors of wrong formulation, allergy, drug-drug interaction, and rule violations were eliminated., Conclusion: The introduction of the quicklist was followed by a significant reduction in medication prescribing errors. A list with dosing support for commonly used pediatric medications may help adapt computerized physician order entry systems designed for adults to serve pediatric populations more effectively.

Objective: Our objective was to compare the effects of oral vs. transdermal estrogen therapy on C-reactive protein (CRP), IL-6, E- and P-selectin, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule-1, serum amyloid A, transferrin, prealbumin, IGF-I, SHBG, thyroxine-binding globulin (TBG), and cortisol-binding globulin (CBG) in naturally menopausal women., Design: This was a randomized, open-label crossover clinical trial. A 6-wk withdrawal from prior hormone therapy (baseline) was followed in randomized order by 12-wk oral conjugated equine estrogens (CEEs) (0.625 mg/d) and 12-wk transdermal estradiol (E2) (0.05 mg/d), with oral micronized progesterone (100 mg/d) given continuously during both regimens., Results: A total of 27 women enrolled, and 25 completed both treatment periods. Nine parameters changed significantly during oral CEE (median percent change from baseline; P value): CRP (192%; P <0.001); E-selectin (-16.3%; P = 0.003); P-selectin (-15.3%; P = 0.012); ICAM-1 (-5%; P = 0.015); transferrin (5.3%; P = 0.024); IGF-I (-30.5%; P < 0.001); SHBG (113%; P < 0.001); TBG (38%; P < 0.001); and CBG (20%; P < 0.001). With transdermal E2, only three parameters changed significantly and to a lesser degree: ICAM-1 (-2.1%; P = 0.04); IGF-I (-12.5%; P < 0.001); and SHBG (2.6%; P = 0.042). During oral CEE the intrasubject changes in CRP correlated strongly with the changes in serum amyloid A (r = 0.805; P < 0.001), and were only weakly associated with the changes in SHBG (r = 0.248; nonsignificant), TBG (0.430; P = 0.031), and CBG (r = 0.072; nonsignificant). The log-log relationship between CRP and IL-6 observed at baseline showed a parallel shift during oral CEE, suggesting an amplified hepatic response or a greater sensitivity to IL-6 stimulation., Conclusion: Compared with oral CEE, transdermal E2 exerts minimal effects on CRP and the other inflammation and hepatic parameters.

Long-term survival and outcome were determined for 80 patients with immunoglobulin light chain (AL) amyloidosis treated with high-dose melphalan and stem cell transplantation (HDM/SCT) more than 10 years ago. Seventeen (21%) patients died within the first year of treatment, of treatment-related complications (14%) or progressive disease (8%). Of the 63 surviving evaluable patients at one year, 32 (51%) achieved a complete hematologic response (CR). For all 80 patients, the median survival was 57 months (4.75 yrs). The median survival exceeds 10 years for patients achieving a CR after HDM/SCT, compared with 50 months for those not achieving a CR (P < .001). In conclusion, HDM/SCT leads to durable remissions and prolonged survival, particularly for those patients who achieve a hematologic CR.

Objective: To characterize symptoms and signs of AL amyloidosis that may bring patients to the attention of rheumatologists, evaluate Ig V(L) gene usage in this subgroup of patients, and assess the impact of soft tissue and bone involvement and V(L) gene usage on survival., Methods: Clinical features of soft tissue and bone involvement were assessed in 191 patients with AL amyloidosis. V(L) gene sequencing was carried out to determine light-chain family, rate of somatic mutation, and evidence of antigen selection. The association of soft tissue and bone involvement with V(L) gene usage was assessed by logistic regression analysis, and survival time was analyzed using log rank tests and Cox regression models., Results: Soft tissue and bone involvement occurred in 42.9% of the patients, and 9.4% had dominant soft tissue and bone involvement. The most common manifestations were submandibular gland enlargement, macroglossia, and carpal tunnel syndrome. Dominant soft tissue and bone involvement was significantly associated with V(L)kappaI gene usage. Mutation rate and evidence of antigen selection in the V(L) genes were not found to be confounding factors, providing evidence against a contribution of autoimmunity in this type of AL amyloidosis. Survival time was initially longer in patients with dominant soft tissue and bone involvement than in patients with other dominant organ involvement; however, this difference diminished over time., Conclusion: Amyloid infiltration into soft tissue, joints, periarticular structures, and bones can bring patients with AL amyloidosis to the attention of rheumatologists. Recognition of the presenting symptoms is essential for accurate diagnosis and appropriate treatment, since the long-term outlook for untreated patients with dominant soft tissue and bone involvement is not better than that for patients with other dominant features of AL amyloidosis.

Objective: To compare the changes induced by oral versus transdermal estrogen therapy on the total and free serum concentrations of testosterone (T), thyroxine (T4), and cortisol (C) and the concentrations of their serum binding globulins sex hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin in naturally menopausal women., Design: Randomized, open-label, crossover. Interventions included a 6-week withdrawal from previous hormone therapy (baseline), followed in randomized order by 12 weeks of oral conjugated equine estrogens (CEE) (0.625 mg/d) and 12 weeks of transdermal estradiol (TD E2) (0.05 mg/d), with oral micronized progesterone (100 mg/d) given continuously during both transdermal estrogen therapy regimens., Results: Twenty-seven women were enrolled in the study, and 25 completed both treatment periods. The mean(SD) percentage changes from baseline of sex hormone-binding globulin, total T, and free T with oral CEE were +132.1% (74.5%), +16.4% (43.8%), and -32.7% (25.9%), respectively, versus +12.0% (25.1%), +1.2% (43.7%), and +1.0% (45.0%) with TD E2. The mean (SD) percentage changes of thyroxine-binding globulin, total T4, and free T4 with oral CEE were +39.9% (20.1%), +28.4% (29.2%), and -10.4% (22.3%), respectively, versus +0.4% (11.1%), -0.7% (16.5%), and +0.2% (26.6%) with TD E2. The mean (SD) percentage changes of cortisol-binding globulin, total C, and free C with oral CEE were +18.0% (19.5%), +29.2% (46.3%), and +50.4% (126.5%), respectively, versus -2.2% (11.3%), -6.7% (30.8%), and +1.8% (77.1%) with TD E2. Concentrations of all hormones and binding globulins were significantly different (P < or = 0.003) during administration of oral versus transdermal estrogen therapy, except for free T4 and free C., Conclusions: Compared with oral CEE, TD E2 exerts minimal effects on the total and free concentrations of T, T4, and C and their binding proteins.

Clinical outcomes of patients with AL amyloidosis treated with high-dose melphalan and stem cell transplantation (HDM/SCT) are tightly linked to the achievement of a hematologic complete response (HCR). We conducted a prospective trial to determine whether a second cycle of HDM/SCT could induce HCR in patients in whom the plasma cell dyscrasia persisted following initial treatment with HDM/SCT. Sixty-two patients were enrolled. Nine patients (15%) were removed from the protocol. Of the 53 patients continuing in this study, four died within 100 days of treatment (8%), and 27 (55%) achieved an HCR at 6 months after the first cycle of HDM/SCT. Of the 22 patients who did not achieve an HCR after initial treatment, 17 received a second HDM/SCT, 1 died within 100 days of treatment (6%), while 5 (31%) achieved an HCR. Thus, the HCR rate was 67% (32/48) for surviving patients on study, 60% (32/53) for all patients who received initial cycle of HDM/SCT, and 56% (35/62) by intention-to-treat. The median survival for all patients enrolled on the trial has not yet been reached. Thus, tandem cycles of HDM/SCT can increase the proportion of patients who achieve an HCR.

Background: Despite the high prevalence of HIV in correctional settings, the duration of therapy and response to various highly active antiretroviral therapy (HAART) regimens in this setting is unknown., Method: Using a retrospective cohort study (1997-2002) of HIV-infected prisoners in Connecticut that linked demographic, pharmacy, and laboratory data, we compared HIV-1 RNA (VL) and CD4 lymphocyte responses to four treatment strategies at baseline and at the end of incarceration., Results: Using an analysis of 1,044 incarceration periods or 1,099 subjects for whom 6 months of continuous data were available, HAART regimens that included a triple NRTI, two NRTIs + either a PI or NNRTI, or a three-class (NRTI+NNRTI+PI) strategy demonstrated no difference in virological and immunological outcomes. The proportion of subjects who were initiated with NRTI, NNRTI, PI, or three-class regimens were 14%, 32%, 46%, and 8%, respectively. For all study groups, the mean change from baseline in CD4 and VL was +74 cells/muL and -0.93 log(10) copies/mL (p < .0001), respectively. Overall, 59% of subjects had an HIV-1 RNA level below the level of detection (<400 copies/mL) by the end of their incarceration. Using Kaplan-Meier curves to examine the time to change in the initial HAART strategy over the incarceration period, the three-class strategy was significantly more likely to be changed earlier than all others (p < .05)., Conclusion: Although the three-class strategy was less durable, initiating HAART with any strategy resulted in similar and impressive virological and immunological outcomes by the end of incarceration, further supporting prison as an important site for the initiation and provision of effective antiretroviral therapy.

Introduction: Although autogenous brachial-basilic upper arm transpositions (BVT) have been extensively utilized, there has been significant disparity in published patency rates. Very little is known about the efficacy of autogenous brachial-cephalic upper arm transpositions (CVT). We evaluated our experience with transposed upper arm arteriovenous fistulas (tAVF) in order to assess patency and identify factors that affect efficacy. We then compared our tAVF patients with a cohort of upper arm arteriovenous grafts (AVG)., Methods: A retrospective review was conducted of tAVF performed at our institution from 1998 to 2004. The tAVF group consisted of 119 BVT and 71 CVT procedures. We compared these with 164 AVG. tAVF were placed only for veins >/=2.5 mm in diameter by duplex ultrasonography., Results: Mean follow-up was 28 months. With the exception of mean vein diameter, the patients in the BVT and CVT groups had similar demographic parameters and complication rates. Primary and secondary patency rates were 52% and 62% at 5 years for BVT and 40% and 46% at 5 years for CVT, respectively (P = NS). Multivariate analysis revealed that hemodialysis dependence at the time of fistula placement and history of previous upper arm access independently affected primary patency. History of upper torso dialysis catheters independently affected secondary patency. Comparison of the tAVF and AVG groups revealed that tAVF patients were significantly younger, more likely to be male, less likely to be African American (AA) and less likely to have a history of previous AV access. The primary patency rate for tAVF was significantly higher than for AVG: 48% vs 14% at 5 years (P < .001). The secondary patency rate for tAVF was also significantly higher than for AVG: 57% vs 17% at 5 years (P < .001). Among the tAVF procedures, 9% required one or more revisions to maintain secondary patency, compared to 51% with the AVG group (P < .001). Multivariate analysis revealed that presence of AVG and a history of previous upper arm access negatively affected primary and secondary patency., Conclusions: Autogenous BVT and CVT have similar, high patency rates. Transposed upper arm arteriovenous fistulas have higher patency rates than upper arm AVG and require significantly fewer revisions. Our data strongly support the contention that as long as the patient is a candidate for an upper arm tAVF, based on anatomical criteria, a tAVF should always be considered before an AVG.

Erdosteine has positive effects on mucus rheology and transport due to the active metabolite (Metabolite I) which contains a free thiol group. Erdosteine inhibits bacterial adhesiveness and has antioxidant properties. A synergistic effect of erdosteine with various antibiotics has been demonstrated in pharmacological and clinical studies. The present study was multicenter, randomized, double-blind and placebo-controlled. The aims of the study were to compare a combination of erdosteine with amoxicillin against an amoxicillin-placebo combination in pediatric patients with acute lower respiratory tract disease. A total of 158 patients (78 in the erdosteine group and 80 in the placebo group) were treated for 7 +/- 2 days. The efficacy parameters were cough (primary), polypnea, rhonchi, rales and body temperature (all measured at baseline, on Day 3 and at the end of treatment). Safety was assessed by strictly monitoring the occurrence of adverse events and using standard laboratory parameters. The results of the intention-to-treat analysis showed that the severity of cough was decreased by 47% at Day 3 in the erdosteine group with a statistically significant difference compared to placebo, the difference was still significant at the final visit. The decrease in the severity of rales was significantly greater at Day 3 in the erdosteine group than in the placebo group. The incidence of polypnea and rhonchi in the two groups showed similar decreases, an improvement mainly due to the antibiotic. No adverse events occurred and no adverse changes in laboratory parameters were observed. It is concluded that the combination of erdosteine and amoxicillin is a safe medication which is clinically superior to that of the antibiotic combined with placebo, especially in regard to the effects on cough.

People seem to think that a unit of some entity (with certain constraints) is the appropriate and optimal amount. We refer to this heuristic as unit bias. We illustrate unit bias by demonstrating large effects of unit segmentation, a form of portion control, on food intake. Thus, people choose, and presumably eat, much greater weights of Tootsie Rolls and pretzels when offered a large as opposed to a small unit size (and given the option of taking as many units as they choose at no monetary cost). Additionally, they consume substantially more M&M's when the candies are offered with a large as opposed to a small spoon (again with no limits as to the number of spoonfuls to be taken). We propose that unit bias explains why small portion sizes are effective in controlling consumption; in some cases, people served small portions would simply eat additional portions if it were not for unit bias. We argue that unit bias is a general feature in human choice and discuss possible origins of this bias, including consumption norms.

Background: The use of outpatient psychiatric services has been shown to be a complex function of sociodemographic, clinical, and pathway variables. The relative contribution of each variable or groups of variables in explaining the variability in the use of outpatient psychiatric services, however, remains poorly documented., Methods: The subjects (N=382) were all patients admitted to an outpatient psychiatric clinic serving mostly a minority and low-income population. The charts of the patients were reviewed for sociodemographic, clinical, and pathway variables and the number of outpatient visits. The pathway variables studied were source of referral and most recent psychiatric treatment service used. Both bivariate and multivariate statistics were used to analyze the data., Results: Pathway variables were better predictors of the number of outpatient visits than clinical variables after controlling for sociodemographic variables., Conclusion: Patients recently hospitalized may be sicker or have fewer social supports and therefore require more outpatient visits. Recent treatment history stands out as an important variable in the prediction of the number of outpatient mental health visits. More research is needed to examine the influence of pathway variables on treatment decisions.

Responses to highly active antiretroviral therapy (HAART) in correctional settings and their sustained benefit in prisoners after release are currently not known. To examine the human immunodeficiency virus type 1 (HIV-1) RNA level (VL) and CD4 lymphocyte response to HAART during incarceration and upon reentry to the correctional system, we conducted a retrospective cohort study of longitudinally linked demographic, pharmacy, and laboratory data from the Connecticut prison system. During incarceration, the mean CD4 lymphocyte count increased by 74 lymphocytes/ mu L, and the mean VL decreased by 0.93 log10 copies/mL (P<.0001). Fifty-nine percent of the subjects achieved a VL of <400 copies/mL at the end of each incarceration period. For the 27% of subjects who were reincarcerated, the mean CD4 lymphocyte count decreased by 80 lymphocytes/ mu L, and the mean VL increased by 1.14 log10 (P<.0001). Although HAART use resulted in impressive VL and CD4 lymphocyte outcomes during the period of incarceration, recidivism to prison was high and was associated with a poor outcome. More effective community-release programs are needed for incarcerated patients with HIV disease.