Relationship among chelator adherence, change in chelators, and quality of life in thalassemia.

PURPOSE: Thalassemia, a chronic blood disease, necessitates life-long adherence to blood transfusions and chelation therapy to reduce iron overload. We examine stability of health-related quality of life (HRQOL) in thalassemia and adherence to chelation therapy over time, especially after changes in chelator choice. METHODS: Thalassemia Longitudinal Cohort participants in the USA, UK, and Canada completed the SF-36v2 (ages 14+) and the PF-28 CHQ (parents of children <14 years). Chelation adherence was defined as self-reported percent of doses administered in the last 4 weeks. RESULTS: Two hundred and fifty-eight adults/adolescents (mean 29.7 years) and 133 children (mean 8.5 years) completed a mean of 2.8-years follow-up. Children made few chelator changes, whereas a mean of 2.2 changes was observed among the 37% of adults/adolescents who made chelator changes, mainly due to patient preference or medical necessity. Physical HRQOL improved among those with lower iron burden (better health status) at baseline who made a single change in chelator, but declined among participants with multiple changes and/or high iron burden (worse health status). Mental health improved among participants with lower iron burden, but iron overload was negatively associated with social functioning. Adherence did not significantly change over follow-up except for an increase after a change from deferoxamine (DFO) infusion to oral deferasirox (p = 0.03). Predictors of lower adherence for adults/adolescents at follow-up included side effects, smoking, younger age, problems preparing DFO, increased number of days per week DFO prescribed, and lower physical quality of life . CONCLUSIONS: Strategies to balance medical needs with family, work, and personal life may assist in adherence.

Pain in thalassaemia: the effects of age on pain frequency and severity.

Pain is not a symptom generally associated with thalassaemia. However, providers have noted increasing patient reports of pain, creating an impetus for this prospective, observational assessment of pain in thalassaemia patients. The primary study goals were to assess pain prevalence, severity, location, and potential risk factors. This was a multicentre, prospective study of thalassaemia patients receiving care at 12 Thalassaemia Clinical Research Network sites. Pain was assessed using the Brief Pain Inventory. Two hundred and fifty-two thalassaemia patients ranging in age from 12 to 71 years (mean 28.8) were enrolled. Sixty-four per cent reported experiencing pain during the last 4 weeks, 22% of whom reported pain on a daily basis. Ordinal regression analysis of pain ratings demonstrated significant (P < 0.001) correlation of increased age with increased pain, irrespective of diagnosis, transfusion status, gender, bone density, chelator type or iron overload. Eighty-one per cent reported having pain for 1 year or longer and 31% reported pain for five or more years. Pain is a major cause of morbidity and an unrecognized problem for patients with thalassaemia. Age is the strongest predictor of frequency and severity. Little else is known about the aetiology and predictors of this pain syndrome.

Pain over time and its effects on life in thalassemia.

Pain reports have become increasingly common and problematic in thalassemia. As patients are living longer,there is a growing need to study pain and to explore its impact on patient lives. The Brief Pain Inventory(BPI) was used quarterly to assess pain and pain interference in patients with thalassemia in North America.The Medical Outcomes Study 36-Item Short Form Health Survey and the Hospital Anxiety and Depression Scale were used to assess quality of life, anxiety and depression. Of the 252 participants, 56% reported pain at least once over the course of this study, with 32% reporting severe pain (≥7/10); 16% reported pain at all four visits. Increased pain severity significantly interfered with daily life (P< 0.001; regression analysis) and participants with more sites of pain showed an increase in the amount of daily activities affected by pain(P50.001). Participants reporting more visits with pain reported a significantly higher impact on affective and physical function (P< 0.001). Physical quality of life decreased with increasing numbers of visits with pain (P< 0.001). Those who reported one or more sites of pain showed increased symptoms of both depression(P< 0.001) and anxiety (P50.003). Participants reporting at least two visits with pain had higher symptoms of anxiety (P50.002) and those with at least three visits reported higher symptoms of depression(P50.003). Pain is prevalent in thalassemia and is often a chronic condition that interferes with life. The study highlights the significance of pain in thalassemia and its impact, which should be considered in future research and treatments.

Randomized trial of web-based training to promote counselor use of cognitive behavioral therapy skills in client sessions.

BACKGROUND AND METHODS: The authors designed and delivered an innovative Web course on cognitive behavioral therapy (CBT), a specific empirically based treatment, to a diverse group of addiction counselors and supervisors in 54 addiction units across the country, and conducted a randomized controlled trial of its effectiveness with 127 counselors. The primary focus of the trial was to assess "adequate adherence to CBT practice" after training as judged by raters blinded to training condition who listened to audiotapes of actual client sessions. Counselors who passed were judged to satisfy 2 criteria: (a) low pass or greater on at least 1 of 3 "CBT-generic skills" assessing session structure; and (b) low pass or greater on at least 1 of 3 "CBT-specific skills" related to use of functional analysis, cognitive skills practice, or behavioral skills practice. RESULTS: Although the counselors' use of CBT skills in sessions increased after Web course training, it was not statistically significant and not larger than the gain of control-group counselors trained with a written CBT manual.

Use of electronic data collection to assess pain in thalassaemia: a feasibility study.

AIM: To assess the feasibility of collecting electronic pain data from thalassaemia patients, based on its acceptability and convenience to the participants and study team. METHODS: Participants in the Thalassemia Clinical Research Network Assessment of Pain Survey Study completed the Brief Pain Inventory (BPI) quarterly by paper or phone interview. Participants in a substudy completed the BPI Short Form daily over three non-consecutive transfusion cycles through an automated telephone system. RESULTS: The consent rate for the main study was 93%, with 93% retention. The substudy had 75% retention, with more than 75% of scheduled calls completed. Regular monitoring of enrollment, missed calls, data quality, and the performance of the subcontractor for the automated system was crucial to fulfillment of the study goals. CONCLUSIONS: Use of electronic data collection for patient-reported outcomes was convenient for both patients and study personnel but required human interactions beyond the automated system to maximise data quantity and quality.

The NERI Hypogonadism Screener: psychometric validation in male patients and controls.

OBJECTIVE: Hypogonadism (HG) is a clinical disorder consisting of reduced testosterone (T) levels and characteristic signs and symptoms of low T. Current instruments used to assess hypogonadal symptoms in men lack adequate measurement properties. To present data on the quantitative validation of a new self-report instrument (HG Screener) developed to identify men with symptoms of HG. DESIGN: This is a psychometric validation study conducted at 16 clinical sites across the Unites States. Subjects completed two visits separated by 2-4 weeks. PATIENTS: One hundred and thirty-one men (82 hypogonadal patients with total T≤10·4 nmol/l and 49 controls with total T>10·4 nmol/l) aged 21-75 years were enrolled. MEASUREMENTS: Self-reported assessments including the HG Screener (at both visits) along with seven validated questionnaires. RESULTS: The results of a factor analysis identified five functional factors or domains. The resulting instrument contains 25 items consisting of 18 functional items in five core domains (sexual function, mood, memory, sleep function and fatigue) and seven physical symptom items. Overall, the new instrument was found to have strong psychometric properties, including acceptable discriminant, construct and content validity, as well as good internal consistency and test-retest reliability. CONCLUSIONS: A new screening tool (HG Screener) for identifying men with HG has been developed and validated according to FDA standards. This new instrument possesses acceptable psychometrics and is available for clinical or research use.

Sexual desire, distress, and associated factors in premenopausal women: preliminary findings from the hypoactive sexual desire disorder registry for women.

This article presents data from a validation sample of 390 premenopausal women clinically diagnosed with hypoactive sexual desire disorder (HSDD) enrolled in the HSDD Registry for Women. Participants completed validated measures of sexual distress (e.g., Female Sexual Distress Scale Revised, Question 13) and sexual function including desire (e.g., Female Sexual Function Index). Results showed that lower levels of desire in these women were associated with diminished sexual satisfaction, increased sexually related distress, and fatigue or stress in the women's lives. In addition, the level of distress related to sexual desire decreased with age. The authors conclude that even among women with clinically diagnosed HSDD, the level of sexually related distress varies with situational factors, such as stress and fatigue.

Differences in the diagnosis and management of type 2 diabetes in 3 countries (US, UK, and Germany): results from a factorial experiment.

OBJECTIVES: This article examines the diagnosis and management of type-2 diabetes when exactly the same "patient" is encountered by 192 randomly selected primary care doctors in 3 different health care systems--the United States, United Kingdom, and Germany. METHODS: We conducted a factorial experiment, employing 2 clinically authentic filmed scenarios, to examine country differences in the treatment of diabetes, while controlling the effects of selected characteristics of patients and physicians. The patient in the first scenario presented with (undiagnosed) signs and symptoms strongly suggestive of diabetes, while the second scenario presented an already diagnosed patient with an emerging foot neuropathy. Physicians were asked how they would diagnose and manage the patients after watching the video vignettes using a questionnaire with standardized and open-ended questions. RESULTS: Regarding the first (undiagnosed) case, US doctors would ask significantly more questions than physicians from the UK and Germany (P < 0.001). German physicians would give less advice but would want to see the patient again much sooner (P < 0.001). Regarding the diagnosed case with an emerging foot neuropathy, US physicians would be most active in terms of questioning, testing, prescribing, and advice giving. Again, physicians from Germany would be less active in terms of therapeutic strategies but they would like to see the patient again sooner (P = 0.005). CONCLUSIONS: Although physicians in the 3 countries encountered exactly the same patient, differences in diagnostic and management decisions were evident. The experimental design provides unconfounded estimates of health system differences while simultaneously controlling for the effects of selected patient attributes and physician characteristics.

Sexual desire and the female sexual function index (FSFI): a sexual desire cutpoint for clinical interpretation of the FSFI in women with and without hypoactive sexual desire disorder.

INTRODUCTION: A validated cutpoint for the total Female Sexual Function Index scale score exists to classify women with and without sexual dysfunction. However, there is no sexual desire (SD) domain-specific cutpoint for assessing the presence of diminished desire in women with or without a sexual desire problem. AIMS: This article defines and validates a specific cutpoint on the SD domain for differentiating women with and without hypoactive sexual desire disorder (HSDD). METHODS: Eight datasets (618 women) were included in the development dataset. Four independent datasets (892 women) were used in the validation portion of the study. MAIN OUTCOME MEASURES: Diagnosis of HSDD was clinician-derived. Receiver-operator characteristic (ROC) curves were used to develop the cutpoint, which was confirmed in the validation dataset. RESULTS: The use of a diagnostic cutpoint for classifying women with SD scores of 5 or less on the SD domain as having HSDD and those with SD scores of 6 or more as not having HSDD maximized diagnostic sensitivity and specificity. In the development sample, the sensitivity and specificity for predicting HSDD (with or without other conditions) were 75% and 84%, respectively, and the corresponding sensitivity and specificity in the validation sample were 92% and 89%, respectively. CONCLUSIONS: These analyses support the diagnostic accuracy of the SD domain for use in future observational studies and clinical trials of HSDD.

The presentation of hypoactive sexual desire disorder in premenopausal women.

INTRODUCTION: Little is known about the clinical presentation of hypoactive sexual desire disorder (HSDD) in premenopausal women or their perceptions of sexual problems. AIM: Describe characteristics of premenopausal women with clinically diagnosed acquired, generalized HSDD, and investigate factors perceived to contribute to desire problems. METHODS: Cross-sectional analysis of baseline data from premenopausal women with clinically diagnosed and confirmed HSDD enrolled during the first year of the HSDD Registry for Women (N=400). MAIN OUTCOME MEASURES: Relationship, demographic, and clinical characteristics were assessed by clinician's medical history review and self-administered questionnaire. Sexual desire function was measured by the validated Female Sexual Function Index (FSFI). RESULTS: Over 85% of women cited multiple factors that contributed to ongoing decreased desire (mean 2.9± 2.3 factors, range 0-12). Most commonly cited contributing factors were "stress or fatigue" (60.0%), "dissatisfaction with my physical appearance" (40.8%), and other sexual difficulties (e.g., inability to reach orgasm) (33.5%). Exploratory analyses of the FSFI score confirmed that self-image (P=0.002) and other sexual problems (P<0.001) were significantly associated with decreased desire. Almost all (96%) participants were currently in a partner relationship. Antidepressant medication was currently used by 18.0% of women, hormonal contraceptives by 28.5%, and hormonal medications (for noncontraceptive reasons) by 7.3%. Physical functioning was consistent with general population norms (SF-36 mean±standard deviation, 53.3±7.6 vs. norm of 50±10), while overall mental functioning was slightly lower (SF-36, 44.7±10.6). CONCLUSIONS: Within this sample of premenopausal women with clinically diagnosed HSDD, decreased sexual desire was associated with multiple factors, including poor self-image and stress or fatigue. Clinicians presented with premenopausal women expressing sexual desire problems should assess patients' perceptions of their condition to develop a comprehensive, patient-oriented management plan. Therapy may need to address issues with low self-esteem and mood and offer practical coping mechanisms for stress and fatigue.

Physician cognitive processing as a source of diagnostic and treatment disparities in coronary heart disease: results of a factorial priming experiment.

Literature on health disparities documents variations in clinical decision-making across patient characteristics, physician attributes, and among health care systems. Using data from a vignette-based factorial experiment of 256 primary care providers, we examine the cognitive basis of disparities in the diagnosis and treatment of coronary heart disease (CHD). We explore whether previously observed disparities are due to physicians (1) not fully considering CHD for certain patients or (2) considering CHD but then discounting it. Half of the physicians in the experiment were primed with explicit directions to consider a CHD diagnosis, and half were not. Relative to their unprimed counterparts, primed physicians were more likely to order CHD-related tests and prescriptions. However, the main effects for patient gender and age remained, suggesting that physicians treated these demographic variables as diagnostic features indicating lower risk of CHD for these patients. This finding suggests that physician appeals to perceived base rates have the potential to contribute to the further reification of socially constructed health statistics.

Physician assessments of drug seeking behavior: A mixed methods study.

BACKGROUND: Pain complaints are common, but clinicians are increasingly concerned about overuse of opioid pain medications. This may lead patients with actual pain to be stigmatized as "drug-seeking," or attempting to obtain medications they do not require medically. We assessed whether patient requests for specific opioid pain medication would lead physicians to classify them as drug-seeking and change management decisions. METHODS AND FINDINGS: Mixed-methods analysis of interviews with 192 office-based primary care physicians after viewing video vignettes depicting patients presenting with back pain. For each presentation physicians were randomly assigned to see either an active request for a specific medication or a more general request for help with pain. The main outcome was assignment by the physician of "drug-seeking" as a potential diagnosis among patients presenting with back pain. Additional outcomes included other actions the physician would take and whether the physician would prescribe the medication requested. A potential diagnosis of drug-seeking behavior was included by 21% of physicians seeing a specific request for oxycodone vs. 3% for a general request for help with back pain(p<0.001). In multivariable models an active request was most strongly associated with a physician-assigned diagnosis of drug-seeking behavior(OR 8.10; 95% CI 2.11-31.15;p = 0.002); other major patient and physician characteristics, including gender and race, did not have strong associations with drug-seeking diagnosis. Physicians described short courses of opioid medications as a strategy for managing patients with pain while avoiding opioid overuse. CONCLUSIONS: When patients make a specific request for opioid pain medication, physicians are far more likely to suspect that they are drug-seeking. Physician suspicion of drug-seeking behavior did not vary by patient characteristics, including gender and race. The strategies used to assess patients further varied widely. These findings indicate a need for the development of better clinical tools to support the evaluation and management of patients presenting with pain.

DTPA Fe(III) decreases cytokines and hypotension but worsens survival with Escherichia coli sepsis in rats.

OBJECTIVE: Nonselective inhibition of nitric oxide (NO) with NO synthase antagonists decreases hypotension but worsens outcome clinically. We investigated whether iron (III) complex of diethylenetriaminepentaacetic acid [DTPA Fe(III)], a scavenger of NO as well as other oxidant mediators, has similar divergent effects in E. coli challenged rats. METHODS: Animals with venous and arterial catheters and challenged with intrabronchial or intravenous E. coli were randomized to treatment with DTPA Fe(III) in doses from 3 to 800 mg/kg or placebo. Mean blood pressure (MBP) was measured in all animals and plasma NO, cytokines, and blood and lung leukocyte and bacteria counts in animals administered intrabronchial E. coli and DTPA Fe(III) 50 mg/kg or placebo. Animals received antibiotics and were observed 168 h. RESULTS: Independent of drug regimen or infection site, compared to placebo, DTPA Fe(III) increased MBP although this was greater with high vs. lower doses. Despite increased MBP, DTPA Fe(III) worsened the hazards ratio of survival . At 6 and 24 h DTPA Fe(III) decreased NO but not significantly and decreased four cytokines (tumor necrosis factor-alpha, interleukins 1 and 10, and macrophage inflammatory protein 3alpha) and lung lavage neutrophils. From 6 to 24 h DTPA Fe(III) increased blood bacteria. CONCLUSIONS: DTPA Fe(III) while increasing blood pressure has the potential to worsen outcome in sepsis. Further preclinical testing is required before this agent is applied clinically.

Potential savings from substituting generic drugs for brand-name drugs: medical expenditure panel survey, 1997-2000.

BACKGROUND: Generic substitution is one mechanism of curtailing prescription drug expenditures. Limited information is available about the potential savings associated with generic substitution. OBJECTIVE: To estimate the potential savings associated with broad substitution of generic drugs. DESIGN: Cross-sectional, nationally representative survey of noninstitutionalized adults. SETTING: United States. PARTICIPANTS: Adults included in the Medical Expenditure Panel Survey Household Component, 1997-2000. MEASUREMENTS: Use of a multisource drug (that is, a drug available in a brand-name and > or =1 generic formulation) or a generic drug and the potential cost savings associated with broad generic substitution for all multisource products. RESULTS: Fifty-six percent of all outpatient drugs were multisource products, accounting for 41% of total outpatient drug expenditures. Of these multisource drugs, 61% were dispensed as a generic. If a generic had been substituted for all corresponding brand-name outpatient drugs in 2000, the median annual savings in drug expenditures per person would have been 45.89 dollars (interquartile range, 10.35 dollars to 158.06) for adults younger than 65 years of age and 78.05 dollars (interquartile range, 19.94 dollars to 241.72 dollars) for adults at least 65 years of age. In these age groups, the national savings would have been 5.9 billion dollars (95% CI, 5.5 billion dollars to 6.2 billion dollars) and 2.9 billion dollars (CI, 2.6 billion dollars to 3.1 billion dollars), respectively, representing approximately 11% of drug expenditures. LIMITATIONS: Specific information about an individual's formulary was not available, so the authors could not estimate how much of the potential savings would benefit an individual or his or her health plan. CONCLUSION: Although broad substitution of generic drugs would affect only a modest percentage of drug expenditures, it could result in substantial absolute savings.

Factors affecting Fontan length of stay: Results from the Single Ventricle Reconstruction trial.

BACKGROUND: In the Single Ventricle Reconstruction trial, infants with hypoplastic left heart syndrome (HLHS) who received a right-ventricle-to-pulmonary-artery shunt (RVPAS) versus a modified Blalock-Taussig shunt (MBTS) had lower early postoperative mortality, but more complications at 14 months. We explored the effect of shunt type and other patient, medical, and surgical factors on postoperative length of stay (LOS) after the Fontan operation. METHODS: Fontan postoperative course was ascertained from medical record review. Cox proportional hazards modeling was used to identify factors associated with LOS. RESULTS: Of 327 subjects who underwent Fontan, 323 were analyzed (1 death, 1 biventricular repair, 2 with missing data). Median age and weight at Fontan were 2.8 years (interquartile range [IQR]: 2.3, 3.4) and 12.7 kg (IQR: 11.4, 14.1), respectively. Fontan type was extracardiac in 55% and lateral tunnel in 45%; 87% were fenestrated. The RVPAS and MBTS subjects had similar LOS (median 11 days [IQR: 9, 18] vs 10 days [IQR: 9, 13]; P = .23). Independent risk factors for longer LOS were treatment center (P < .01), LOS at stage II (hazard ratio [HR] 1.02 for each additional day; P < .01), and pre-Fontan complications (HR 1.03 for each additional complication; P = .04). Use of deep hypothermic circulatory arrest at Fontan (HR 0.64; P = .02) was independently associated with shorter LOS. When center was excluded from the model, pre-Fontan complications and use of circulatory arrest were no longer significant; instead, older age at stage II (HR 1.08 for each additional month; P = .01) predicted longer LOS. In 254 subjects who had a pre-Fontan echocardiogram, at least moderate tricuspid regurgitation was independently associated with longer LOS, both with center (HR 1.72; P < .01) and without center in the model (HR 1.49; P = .02). CONCLUSIONS: In this multicenter prospective cohort of subjects with HLHS, Norwood shunt type was not associated with Fontan LOS. Rather, global measures of earlier medical complexity indicate greater likelihood of longer LOS after the Fontan operation.

Prophylactic high-dose N(omega)-monomethyl-L-arginine prevents the late cardiac dysfunction associated with lethal tumor necrosis factor-alpha challenge in dogs.

We investigated nitric oxide (NO) as a possible cause of the cardiac dysfunction associated with high, lethal doses of tumor necrosis factor-alpha (TNF-alpha) in dogs. Eighty-seven awake, 2-year-old (10-12 kg), purpose-bred beagles were randomized to receive an infusion of saline or N-monomethyl-L-arginine (L-NMMA), a nonselective NO synthase (NOS) inhibitor, as a 40 mg kg bolus followed by a 40 mg kg(-1) h(-1) infusion for 3 to 6 h 3 h before (prophylactic) or 3 h after (therapeutic) challenge with TNF-alpha (60 microg kg(-1)) or vehicle. Serial radionuclide-heart scans and thermodilution pulmonary artery catheter hemodynamic measurements were performed. The effects of prophylactic L-NMMA on TNF-alpha-induced cardiac dysfunction as measured by decreases in mean left ventricular (LV) ejection fraction and downward and rightward shifts of LV function plots (peak systolic pressure versus end systolic volume index and LV stroke work index versus end diastolic volume index) were significantly different comparing early (3-6 h) and delayed (24 h) time points (P = 0.02). Prophylactic L-NMMA therapy did not appear to fully prevent early (3-6 h) TNF-alpha-induced cardiac dysfunction, but at 24 h, complete protection was seen. Therapeutic L-NMMA did not appear to fully protect the heart from TNF-alpha-induced early or delayed cardiac dysfunction (P = NS). Similarly, L-NMMA given prophylactically, but not therapeutically, blocked TNF-alpha-induced increases in exhaled NO flow rates and plasma nitrite and nitrate concentrations (both P = 0.02). These data suggest that TNF-alpha initiates two phases of cardiac injury: an early (3-6 h) phase that may be partially NO independent and a delayed (24 h) phase that is NO dependent. The delayed, more persistent dysfunction can be completely blocked by high doses of a nonselective NOS inhibitor administered before TNF-alpha.

Changes in the use of postmenopausal hormone therapy after the publication of clinical trial results.

BACKGROUND: The recent publication of clinical trial results has led to a dramatic shift in the evidence about postmenopausal hormone therapy. OBJECTIVE: To examine whether the publication of clinical trial results, specifically the Heart and Estrogen/progestin Replacement Study (HERS) in 1998 and the Women's Health Initiative (WHI) in 2002, has influenced the use of hormone therapy among postmenopausal women. DESIGN: Observational cohort (1997 to 2003). SETTING: San Francisco Mammography Registry, San Francisco, California. PARTICIPANTS: Postmenopausal women between the ages of 50 and 74 years without a personal history of breast cancer who underwent mammography (151862 mammograms). MEASUREMENTS: Self-reported current use of hormone therapy. RESULTS: Among menopausal women who had mammography, it was estimated that 41% were currently using hormone therapy in 1997. Before the publication of HERS, the use of hormone therapy was increasing at a rate of 1% (95% CI, 0% to 2%) per quarter. After the publication of HERS, use decreased by 1% (CI, -3% to 0%) per quarter. In contrast, the publication of the WHI in 2002 was associated with a more substantial decline in the use of hormone therapy of 18% (CI, -21% to -16%) per quarter. Similar associations were observed for most subgroups of women, including women older than 65 years of age; women with a previous hysterectomy; and women who described their race or ethnicity as white, African American, Latina, Chinese, or Filipina. CONCLUSIONS: The release of the HERS data was temporally associated with a modest decline in the use of hormone therapy. In contrast, the release of the principal findings from the WHI was associated with a more substantial decline in use by postmenopausal women. The reason for the differences in decline may relate to the fact that the WHI results were widely publicized or were more applicable to most postmenopausal women because the WHI study was performed in healthy women.

Sympathetic blockade in a canine model of gram-negative bacterial peritonitis.

We investigated, in a well-established canine model of human sepsis, the effects of two different techniques of sympathetic blockade during bacterial peritonitis on pain relief, hemodynamics, and survival rate. Twenty-two purpose-bred beagles (12-28 months old, weighing 10-12 kg) were studied. Fourteen animals received an epidural infusion of bupivicaine and morphine, and the other eight received either a celiac plexus block (n = 4) or a sham block (n = 4). Eighteen of the 22 animals received an intraperitoneal challenge of Escherichia coli (1-10 x 10(9) CFU kg(-1) body weight). At comparable doses of intraperitoneal-implanted E. coli (2.5-5 x 10(9) CFU kg(-1) body weight), the addition of sympathetic blockade produced a synergistic decrease in survival times (P = 0.002) and mean left ventricular ejection fraction (P = 0.008), and increase in creatinine levels (P = 0.02). There was also a significant increase in tumor necrosis factor (TNF) levels (P = 0.004) and decrease in blood endotoxin clearance (P = 0.006) associated with sympathetic blockade during sepsis. The celiac plexus-blocked animals had no improvement in pain scores, and subjectively looked clinically worse than animals with sepsis without a celiac plexus block. In contrast, the epidural block was effective in blocking the pain and discomfort associated with low lethality doses of intraperitoneal bacteria reflected by no increase in pain scores compared with animals not receiving bacterial challenge. This study shows that during severe bacterial peritonitis, maintenance of sympathetic tone irrespective of pain relief provided is necessary for clearance of bacterial toxins, control of proinflammatory mediator release, hemodynamic stability, and survival.

Impact of initial shunt type on cardiac size and function in children with single right ventricle anomalies before the Fontan procedure: the single ventricle reconstruction extension trial.

BACKGROUND: In children with single right ventricular (RV) anomalies, changes in RV size and function may be influenced by shunt type chosen at the time of the Norwood procedure. OBJECTIVES: The study sought to identify shunt-related differences in echocardiographic findings at 14 months and ≤6 months pre-Fontan in survivors of the Norwood procedure. METHODS: We compared 2-dimensional and Doppler echocardiographic indices of RV size and function, neo-aortic and tricuspid valve annulus dimensions and function, and aortic size and patency at 14.1 ± 1.2 months and 33.6 ± 9.6 months in subjects randomized to a Norwood procedure using either the modified Blalock-Taussig shunt (MBTS) or right ventricle to pulmonary artery shunt (RVPAS). RESULTS: Acceptable echocardiograms were available at both time points in 240 subjects (114 MBTS, 126 RVPAS). At 14 months, all indices were similar between shunt groups. From the 14-month to pre-Fontan echocardiogram, the MBTS group had stable indexed RV volumes and ejection fraction, while the RVPAS group had increased RV end-systolic volume (p = 0.004) and decreased right ventricular ejection fraction (RVEF) (p = 0.004). From 14 months to pre-Fontan, the treatment groups were similar with respect to decline in indexed neo-aortic valve area, >mild neo-aortic valve regurgitation (<5% at each time), indexed tricuspid valve area, and ≥moderate tricuspid valve regurgitation (<20% at each time). CONCLUSIONS: Initial Norwood shunt type influences pre-Fontan RV remodeling during the second and third years of life in survivors with single RV anomalies, with greater RVEF deterioration after RVPAS. Encouragingly, other indices of RV function remain stable before Fontan regardless of shunt type. (Comparison of Two Types of Shunts in Infants with Single Ventricle Defect Undergoing Staged Reconstruction-Pediatric Heart Network; NCT00115934).