Prevalence and burden of dyspnoea among COPD patients in Japan.

BACKGROUND AND AIMS: Dyspnoea is the most common symptom of chronic obstructive pulmonary disease (COPD) significantly affecting activity, impairing patients' well-being and contributing to the economic burden of COPD. The objective of this study was to estimate the prevalence of dyspnoea and its impact on COPD management costs in Japan. METHODS: A cross-sectional survey was conducted among 82 internal medicine physicians and 85 respiratory specialists representing 420 patients with COPD in Japan. Information was collected on demographic and clinical characteristics, dyspnoea (mMRC scale), and healthcare resource use. Dyspnoea prevalence was estimated among all patients and those on specific COPD treatments. The economic burden was derived from two cohorts based on their level of dyspnoea that were matched by propensity scores balancing their demographic and disease burden characteristics. RESULTS: Moderate-severe dyspnoea (mMRC score ≥ 2) was reported by 37.5% of COPD patients and ranging from 21.5% among patients treated with a mono bronchodilator to 59.8% among patients treated with triple therapy. Descriptive analysis showed that dyspnoeic patients have higher annual costs attributable to consultations (€2999 vs. €1906), medications (€1139 vs. €716), exacerbations (€674 vs. €36), other resources (€1789 vs. €140) and in total (€6348 vs. €2797) (p < 0.0001 for all comparisons) compared to patients with mild or no dyspnoea (mMRC score < 2). The total costs remained significantly higher in a propensity-matched cohort adjusted for severity and cardiovascular comorbidity [€6776.1 vs. €4461.3, p = 0.0236]. CONCLUSION: Moderate-severe dyspnoea is common among consulting COPD patients in Japan and is a significant cost driver for the healthcare system.

Sarcocystis fayeri-Induced Granulomatous and Eosinophilic Myositis in 2 Related Horses.

This report describes 2 genetically related paint mares, case Nos. 1 and 2, presented to the Oklahoma State University Boren Veterinary Medical Teaching Hospital for chronic weight loss and abnormal gait, respectively. Notable findings in both cases included marked persistent eosinophilia and multiple intramuscular lateral thoracic masses. Histologic examination of masses revealed eosinophilic, centrally necrotic granulomas and marked eosinophilic myositis. Granulomas in case No. 1 also contained intralesional Sarcocystis sp material, and adjacent muscle fibers contained intact protozoal cysts. Case No. 1 developed severe refractory muscle pain and recurrent esophageal dysphagia. At necropsy, disseminated, grossly visible granulomas were present throughout all examined striated muscles. Nested polymerase chain reaction of the 18S rRNA gene revealed >99% homology with Sarcocystis fayeri. Sarcocystis spp are apicomplexan protozoa that infect striated muscle of many omnivorous species, typically without inciting clinical disease. Sarcocystosis should be considered a rare cause of granulomatous eosinophilic myositis and choke in horses.

In vitro effects of Epstein-Barr virus on peripheral blood mononuclear cells from patients with rheumatoid arthritis and normal subjects.

Peripheral blood mononuclear cells from 10 patients with rheumatoid arthritis and 9 control subjects were cultured in vitro for 30 days with and without infection by Epstein-Barr virus. All cultures showed polyclonal stimulation of B cells as indicated by rising levels of IgM in the culture supernates, reaching maximal at 18-24 days, and with no quantitative or kinetic difference between the RA and control cells. IgM anti-IgG was also produced in both groups and maximally at 18-24 days, but in greater quantity by the RA lymphocytes. The anti-IgG made by the RA lymphocytes was more easily absorbed by solid phase IgG than was the anti-IgG made by the normal lymphocytes and thus was judged to be of higher affinity. RA lymphocytes uninfected with EBV had higher transformation scores than did the normal controls and developed spontaneously into permanent cell lines in six instances.

Retrospective multicentre study of methicillin-resistant Staphylococcus aureus infections in 115 horses.

REASONS FOR PERFORMING STUDY: Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging veterinary and zoonotic pathogen, associated with increasing reports of disease in horses. OBJECTIVES: To provide an overview of the characteristics of clinical MRSA infections in horses. METHODS: A retrospective case study was performed on 115 horses admitted to 6 participating veterinary teaching hospitals in Canada and the United States between 2000 and 2006, and diagnosed with clinical MRSA infection. Descriptive statistics, univariate and multivariable analyses for community- (CA) vs. hospital-associated (HA) MRSA infections, and survival vs. nonsurvival at discharge were performed. RESULTS: The age range of MRSA-infected horses was zero (born in hospital) to 31 years. HA (58/114, 50.9%) and CA infections (56/114, 49.1%) were equally common. Infection of surgical incisions was most frequently reported (44/115, 38.0%). Overall 93/111 (83.8%) cases survived to discharge. Previous hospitalisation and treatment with gentamicin were associated significantly with CA-MRSA, whereas infected incision sites were associated significantly with HA-MRSA. Factors significantly associated with nonsurvival included i.v. catheterisation, CA-MRSA infection and dissemination of infection to other body sites. CONCLUSIONS: Equine MRSA infections have a broad range of clinical presentations, appear to be primarily opportunistic and the overall prognosis for survival to discharge is good. POTENTIAL RELEVANCE: These results should help direct future research with regard to investigation of risk factors for equine MRSA infection in community and hospital populations.

Cytokine dysregulation in aged horses and horses with pituitary pars intermedia dysfunction.

BACKGROUND: Equine pituitary pars intermedia dysfunction (PPID) is the result of a loss of dopaminergic inhibition of the pars intermedia secondary to neurodegeneration of periventricular hypothalamic neurons. The pathologic events contributing to development of neurodegeneration or clinical signs in equids with PPID are unknown. Chronic inflammation may contribute to initiation or progression of PPID. HYPOTHESIS: Horses with PPID have a distinct systemic cytokine profile compared with that of normal adult or aged horses. The cytokine profile of healthy aged horses differs from that of adult horses. ANIMALS: Aged horses with PPID, healthy aged-matched controls, and adult controls (n = 14 per group). METHODS: Total leukocyte cytokine expression was determined by quantitative polymerase chain reaction (PCR), and tumor necrosis factor (TNF)-alpha plasma concentration was determined by enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cell (PBMC) TNF-alpha response after endotoxin (lipopolysaccharide [LPS]) treatment was assessed by ELISA. RESULTS: Aged healthy horses had increased expression of interleukin (IL)-6, IL-8, and interferon-gamma as well as PBMC TNF-alpha release after LPS stimulation compared with healthy adult horses. In contrast, aged horses with PPID had increased IL-8 expression, but expression of other cytokines was similar to that of healthy adult horses, not age-matched controls. CONCLUSIONS AND CLINICAL IMPORTANCE: Aged horses show evidence of a proinflammatory state that may contribute to development of age-associated diseases. Horses with PPID have increased expression of IL-8, which may influence the ability of horses with PPID to respond to bacterial pathogens. The general decrease in proinflammatory cytokine expression observed in horses with PPID may be the outcome of high plasma concentrations of anti-inflammatory hormones.

Lack of correlation of N-myc gene amplification with prognosis in localized neuroblastoma: a Pediatric Oncology Group study.

Multiple copies of N-myc proto-oncogene are only rarely detected in localized neuroblastomas (NBs), and the prognostic relevance of amplification in this subset of patients is not clear. We analyzed a series of 850 children with NB admitted to a Pediatric Oncology Group NB Biology Study and identified six patients with localized NBs harboring N-myc gene amplification. Three patients whose tumors showed favorable histology by Shimada classification and low-risk histological features according to the Joshi classification have remained disease-free, whereas two of three patients with unfavorable histology tumors have developed recurrent disease. Although earlier studies have indicated that N-myc amplification is associated with diploid DNA content, flow cytometric analysis revealed that only two of the localized tumors contained stem lines with diploid DNA content. Loss of chromosome 1p was not detected by fluorescence in situ hybridization in the two tumors examined. N-myc protein was detected by immunohistochemical studies in four of the five NBs analyzed. However, N-myc protein was not visualized in one of the tumors with stroma-rich histology, and Western blot analysis revealed only low levels of N-myc protein expression in another NB with favorable histology. These studies indicate that the presence of N-myc amplification in localized NBs does not necessarily portend an adverse outcome. Furthermore, the biological features of this subset of N-myc-amplified NBs appear to differ from those of more advanced N-myc-amplified tumors.

Evidence for validity of a national physician and patient-reported, cross-sectional survey in China and UK: the Disease Specific Programme.

OBJECTIVE: Diabetes represents a significant challenge for Chinese healthcare providers. Healthcare decision-making is generally based on many data sources, including randomised controlled and real-world studies; however, good-quality data from Chinese diabetes patients are scarce. We performed an initial validation to assess the representativeness of one source of real-world data-the Diabetes Adelphi Disease Specific Programme (DSP) in China. SETTING: China, UK. PARTICIPANTS: The Chinese DSP included 2060 patients with previously diagnosed type 2 diabetes mellitus (T2DM) sampled by 200 physicians. The reference Chinese population comprised 238 639 patients with previously diagnosed T2DM. The UK DSP contained 1481 patients with T2DM sampled by 125 physicians; the reference UK population comprised 289 patients with diabetes. PRIMARY AND SECONDARY OUTCOMES: The primary outcome was comparison of unweighted China DSP and reference data for sex, body mass index (BMI), blood pressure (BP), patients achieving glycosylated haemoglobin (HbA1c)<7%, total cholesterol, coronary heart disease and dyslipidaemia. The secondary outcome was comparison of weighted UK DSP and reference data for BMI, BP, mean HbA1c, total cholesterol, smoking and insulin status. RESULTS: Comparison of unweighted China DSP and reference data revealed statistical equivalence for BMI, systolic BP, proportion of patients achieving HbA1c <7%, total cholesterol, coronary heart disease and dyslipidaemia. Sex, age, diabetes duration, diastolic BP and mean HbA1c level were not equivalent, although differences were generally small. Weighting of data did not substantially affect the results. A similar pattern was observed for UK data. CONCLUSIONS: This study provides evidence that the methodology used for the China and UK parts of the Diabetes DSP produces representative samples that are comparable with other independent sources of patient treatment outcomes data, which may ultimately inform public health decision-making. Although this method could be used in other countries, the current validation applies to UK and China. Further research is required for other countries.

Therapy of refractory or recurrent childhood acute myeloid leukemia using amsacrine and etoposide with or without azacitidine: a Pediatric Oncology Group randomized phase II study.

PURPOSE: A randomized study compared the combination of amsacrine (100 mg/m2/d on days 1 to 5) and etoposide (200 mg/m2/d on days 1 to 3) with the same two agents plus azacitidine (250 mg/m2/d on days 4 to 50) for the therapy of induction-resistant or relapse childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: One hundred sixty-seven assessable children with AML who either had failed to respond to primary induction therapy (group 1, n = 41) or had relapsed (group 2, n = 126) were randomized. RESULTS: Overall, there were 56 complete responses (34%; SE 4%). Among primary refractory patients (group 1), the complete response rate was higher with the three-drug regimen (18% vs 53%, P = .03). In the relapsed patients (group 2), there was no difference in complete response rates related to treatment (31% vs 35%, P = .3). There were 17 early deaths. The major toxicities for both regimens were myelosuppression and infection. CONCLUSION: The overall complete response rate of 34% in this patient population is indicative of effective antileukemic activity. For patients with relapsed leukemia, the addition of azacitidine to etoposide and amsacrine did not improve response. The suggested advantage of the three-drug regimen for induction failures warrants further investigation.

Treatment of metastatic osteosarcoma at diagnosis: a Pediatric Oncology Group Study.

PURPOSE: To estimate the duration of survival (S) of patients with metastatic osteosarcoma (MOS) at diagnosis treated with a multiagent, ifosfamide-containing chemotherapeutic and surgical regimen and to evaluate the toxicity of this regimen. PATIENTS AND METHODS: Thirty patients aged younger than 30 years received two courses of ifosfamide followed by surgery on the primary tumor and metastatic sites. Patients then received a postsurgical multiagent chemotherapeutic regimen that consisted of high-dose methotrexate (HDMTX), ifosfamide, doxorubicin, and cisplatin. RESULTS: The 5-year event-free survival (EFS) rate was 46.7% (95% confidence interval [CI]; 28.5 to 64.9) and 5-year S rate was 53.3% (95% CI; 35.1 to 71.5). Three patients with bone metastases and one patient with lymph node metastases died. Twenty-six patients presented with pulmonary metastatic nodules only. Eight of these patients had at least eight nodules at diagnosis and had an estimated 5-year EFS rate of 25.0% compared with 66.7% for the 18 patients with less than eight nodules (P=.06). Fourteen patients presented with bilateral lung metastases and had a 5-year EFS rate of 35.7% compared with the 12 patients who presented with unilateral involvement and had a 5-year EFS rate of 75.0% (P=.03). The hematopoietic toxicity experienced by the patients during the entire regimen was relatively mild. Seven patients had renal toxicity characterized by hypophosphatemia and/or hypokalemia. CONCLUSION: This ifosfamide-containing regimen is tolerable and effective in the treatment of patients with osteosarcoma (OS) who present with lung metastases. However, better regimens are required for this group of patients.

Prognostic significance of age, MYCN oncogene amplification, tumor cell ploidy, and histology in 110 infants with stage D(S) neuroblastoma: the pediatric oncology group experience--a pediatric oncology group study.

PURPOSE: Although a high rate of spontaneous regression is observed in infants with stage D(S) neuroblastoma (NB), survival is not uniform. To determine the prognostic relevance of age at diagnosis, therapy, and tumor biology in infants with stage D(S) NB, we reviewed the Pediatric Oncology Group (POG) experience. PATIENTS AND METHODS: A review of patients diagnosed with stage D(S) NB registered on POG protocols was performed. Survival according to age at diagnosis, treatment, and tumor biology was determined. RESULTS: Between 1987 and 1996, 110 infants with stage D(S) NB had an estimated 3-year survival rate of 85% +/- 4%; survival rate was 71% +/- 8% for infants 2 months of age or younger, and 68% +/- 12%, 44% +/- 33%, and 33% +/- 19% for patients with diploid, MYCN-amplified, and unfavorable histology tumors, respectively. Survival rates were similar for patients who received adjuvant chemotherapy versus those who did not (82% +/- 5% v 93% +/- 6%, respectively; P = .187). Furthermore, there was no statistical difference in survival rate for patients who underwent complete resection of their primary tumor compared with those who underwent partial resection or biopsy only (90% +/- 5% v 78% +/- 7%, respectively; P = .083). CONCLUSION: Our review confirmed that the survival of infants with stage D(S) NB is excellent. However, subsets of patients with poor prognosis can be identified by young age and unfavorable biologic factors. More effective therapy is needed for the group of stage D(S) infants who show unfavorable clinical and biologic features.

Effect of repeated oral administration of hypertonic electrolyte solution on equine gastric mucosa.

REASONS FOR PERFORMING STUDY: Electrolyte supplementation is common in horses during endurance competitions, but the effect on the gastric mucosa is unknown. HYPOTHESIS: Repeated oral administration of hypertonic electrolyte solution is associated with exacerbation of gastric ulcers in mature horses. METHODS: The study design was a randomised, blinded, crossover trial. Fourteen horses were divided randomly into equal groups and administered either 60 ml water (placebo) or 56.7 g commercial electrolyte supplement mixed with 60 ml water by dose syringe orally once an hour for 8 h. The minimum concentration of individual constituent electrolytes/28.35 g dry commercial product used was: sodium (5528 mg); chloride (11,886 mg); potassium (3657 mg); calcium (754 mg); and magnesium (153 mg). Gastric lesions were scored prior to and after oral treatments, and analysis of variance procedures were then performed. RESULTS: Administration of hypertonic electrolytes resulted in a significant increase in mean ulcer number (P = 0.0174) and severity (P = 0.0006) scores in the nonglandular stomach. Mean ulcer number score was 3.6 and mean ulcer severity score 2.7 after hypertonic electrolyte treatment. CONCLUSIONS: Oral hypertonic electrolyte administration to horses in this model was associated with exacerbation of gastric ulcers. POTENTIAL RELEVANCE: Our findings suggest that one schedule of electrolyte supplementation used commonly in endurance horses may be harmful to the gastric mucosa.

Lathyrus hirsutus (Caley Pea) intoxication in a herd of horses.

BACKGROUND: Caley Pea (Lathyrus hirsutus) is potentially toxic to horses, but large case series are not reported. OBJECTIVES: To describe the clinical signs of horses intoxicated with Lathyrus hirsutus and speculate on the neuroanatomical lesion localization and pathogenesis based upon the observed clinical signs. ANIMALS: Twenty-two of 25 horses ranging in age from 6 to 34 months were affected. Five affected horses were presented to the OSUCHVS for evaluation and treatment after having been attended at the ranch by a local veterinarian (ALA). An additional horse that had been euthanized was also presented for necropsy. METHODS: A case series is presented. Diagnostic evaluation included: physical examination, complete blood count, serum biochemistry, CSF analysis, EMG, ERG, upper airway endoscopy, muscle biopsy, and serum vitamin E analysis. The grain ration consumed by the affected horses was analyzed for ionophores and cultured for fungi: the hay was examined for toxic plants. RESULTS: Bermuda grass hay consumed by the horses contained large quantities of mature Lathyrus hirsutus. Acute clinical signs conform to earlier descriptions of Lathyrus hirsutus intoxication in cattle. Residual neurologic signs were characterized by incoordination in the rhythmicity of multiple gaits. Evidence of mild neurogenic muscle atrophy was recognized in 1 of 5 horses biopsied. CONCLUSIONS AND CLINICAL IMPORTANCE: Caley Pea intoxication may occur within days of seed pod consumption. The neurologic signs are unique and suggest involvement of the upper motor neuron system and regions of the spinal cord influencing voluntary motor movement. Drought conditions during plant growth may increase the risk of toxicosis.

Phase II study of 13-cis-retinoic acid in pediatric patients with acute nonlymphocytic leukemia--a Pediatric Oncology Group study.

Forty-one patients with refractory acute non-lymphocytic leukemia (ANLL) in relapse were treated with 13-cis-retinoic acid (cRA) as salvage therapy. The cRA was given as a single oral dose of 100 mg/m2/day for 4 weeks. One patient achieved a complete remission and two patients achieved a partial remission with reduction of the bone marrow blast count from 40 to 20% after the first course. We recommend further study of cRA in combination with other agents in the treatment of ANLL in children.

Calcium intake: covariates and confounders.

One common nutrient postulated to be protective against osteoporosis, hypertension, and colon cancer is dietary calcium. We report here nutrient patterns by calcium intake in older adult residents of a geographically defined community in Southern California. The analysis included all 426 men and 531 women aged 50-79 y with complete 24-h diet data. Nutrient-density-adjusted calcium intake was divided into tertiles: low intake (less than 284 mg/1000 kcal), mid intake (284-440 mg/1000 kcal), and high intake (greater than 440 mg/1000 kcal). The distribution of the reported 24-h nutrient density of protein, fat, fiber, caffeine, trace minerals, vitamin D, and vitamin C was examined in relation to the calcium-intake tertiles. In both men and women, the adjusted intakes of protein, saturated fatty acids, vitamin D, magnesium, and phosphorus were significantly higher in the high-calcium-intake group than in the low- and mid-calcium-intake groups. In both men and women, alcohol intake was significantly lower in the high-calcium-intake group. Studies postulating a protective role for calcium will need to consider the multicolinearity in the Western diet.

Dissociation of item and order spatial memory in rats following medial prefrontal cortex lesions.

In order to test whether there is a correspondence in function of prefrontal cortex in rats and humans, rats with medial prefrontal cortex lesions were tested for item and order memory for a list of items (spatial locations in a maze). Results indicate that for order memory rats with medial prefrontal cortex lesions cannot remember the order of presentation of four or eight specific spatial locations. This inability to remember order information can be seen even when animals with lesions have to remember only two spatial locations, can self-order the sequence of four or eight spatial locations, or have been presented with the same study phase on every trial. In contrast, for item memory animals with medial prefrontal cortex lesions retain the first item of the list in the variable study phase situation and remember all the items of the list in a constant study phase situation. However, there are also deficits for the last items within a list in the variable study phase situation for both win-stay and win-shift procedures. This deficit might be a function of an impairment in the utilization of appropriate temporal strategies, which normally would facilitate recognition memory in the win-stay and win-shift tasks. In general, the data suggest a partial, but not complete, dissociation of item-order memory. Furthermore, the data suggest that the medial prefrontal cortex is involved in temporal structuring of information.

Quality of life in patients with multiple injuries--basic issues, assessment, and recommendations.

BACKGROUND: While the primary goal of trauma care continues to be the preservation of life, interest has begun to focus on disability and quality of life of those who survive. Numerous instruments have been developed to measure personal well-being, impairment, or subjective life-satisfaction. But there is no consensus regarding which instruments are most appropriate to use in multiply injured patients, and comparison of results are difficult. OBJECTIVE: The objective of this multinational conference was to arrive at a consensus regarding the measurement of quality of life in survivors of multiple trauma. Specifically we sought to identify the best time intervals for measurement and a minimum set of instruments. METHOD: The group reviewed instruments currently in use for quality of life measurement in multiply injured patients. A structured discussion covered the following topics: definition of the population, the concept of quality of life, the importance of different domains of quality of life at different time points, the type of measures and their validity, consistency, and practicability, the mode of administration, subject burden, and availability of population norms. RESULTS: The group suggested three time points, after 3, 12 and 24 months, for the assessment of quality of life after multiple injury. The Glasgow Outcome Scale (GOS) was suggested as an overall global outcome measure including death and vegetative state. The EuroQol was proposed to permit economic analysis, and the SF-36 as a validated global quality of life measure. CONCLUSION: While most selected measures are psychometrically sound, many have had limited use in the setting of multiple injuries. Researchers and clinicians may use these suggestions as a source of information when developing a measurement strategy.

High-risk behavior and the public burden for funding the costs of acute injury.

OBJECTIVE: To determine if high-risk behavior is associated with increased injury severity and cost and if public agencies bear a disproportionate burden of that cost. DESIGN: Case comparison study utilizing patient data collected over a 10-year period. SETTING: Five level 1 and 2 trauma centers in an urban-suburban community with a population of 2.4 million. PARTICIPANTS: Trauma registry data from 37,304 consecutive hospitalized adult patients with trauma. Financial data were reported and analyzed on 28,842 of these. MAIN OUTCOME MEASURES: Incidence of alcohol intoxication, other drug use, use of vehicular protective devices, and firearm violence injuries in patients with private vs public health care sponsorship. Length of hospital stay, injury severity, and hospital unit charges were assessed for high-risk behavior. RESULTS: High-risk behavior was more prevalent among trauma patients relying on public funding to cover the costs of their injuries (P < .001). Total hospital unit charges were 28% and 35% higher for motorists not wearing seat belts and motorcyclists not wearing helmets, respectively. Injury severity and length of stay were also higher (P < .001). CONCLUSIONS: High-risk behavior is associated with increased injury severity and cost. Trauma victims exhibiting high-risk behavior more often depend on public agencies to cover the cost of acute injury. Failure to establish and enforce laws and policies designed to reduce or prevent injury may generate enormous trauma care costs, borne to a large extent by public agencies. Further restriction of certain types of high-risk behavior and the institution of "users' fees," taxes, or penalties may be necessary to reduce the disproportionate public agency cost generated by this activity.

The epidemiology of traumatic death. A population-based analysis.

Despite the proliferation of trauma systems, there are no population-based data describing the epidemiology of traumatic death. To provide these data, we reviewed all trauma deaths occurring in San Diego (California) County during 1 year. There were 625 traumatic deaths during the study (27.3 deaths per 100,000 population per year). Motor vehicle trauma was the most common cause of injury leading to death (N = 344 [55.2%]; 15.0 annual deaths per 100,000 population). Central nervous system injuries were the most common cause of death (48.5%, or 13.2 deaths per 100,000 population per year). Sepsis was responsible for only 2.5% of the overall mortality. Based on life-table data, traumatic death resulted in an annual loss of 1091 years of life per 100,000 and an annual loss of 492 years of productivity per 100,000. Injury continues to account for an enormous loss of life despite improvements in survival wrought by trauma systems.