Immunotherapy following relapse of acute leukaemia after T-cell-replete allogeneic peripheral blood progenitor cell transplantation: importance of new onset chronic graft-versus-host disease.

INTRODUCTION: To further define the relative impact of immunotherapy and subsequent development of graft-versus-host disease (GVHD) on survival in patients with relapsed acute leukaemia postallogeneic hematopoietic stem cell transplant (SCT), we performed a single-centre retrospective analysis of 32 actively treated patients between 2003 and 2011. METHODS: A total of 13 patients were identified who were treated actively with cessation of immunosuppression ± Fludarabine, Cytarabine, G-CSF (FLAG) induction, but no donor leucocyte infusion (DLI) (non-DLI group) and 19 patients received the same step-wise therapy plus G-CSF mobilized DLI (G-DLI group). RESULTS: Groups were not statistically different with regards to baseline characteristics; however, the G-DLI group contained more sibling donors as opposed to unrelated donors than the non-DLI group. With a median follow-up of 47 months, the median overall survival (OS) of the non-DLI and G-DLI groups was not statistically different (8 months vs. 9 months, respectively, P = 0.5). Survival at 3 years was <10% in both groups. Univariate analysis identified response to FLAG, and new onset chronic GVHD as the only factors associated with improved OS. CONCLUSION: Second donor stem cell infusions are unwarranted in the treatment of relapse after allogeneic SCT and therapeutic strategies should focus on cytoreduction followed by immune modulation with the aim of invoking chronic GVHD.

Concordance of a positive tuberculin skin test and an interferon gamma release assay in bacille Calmette-Guérin vaccinated persons.

BACKGROUND: False-positive tuberculin skin test (TST) results due to prior bacille Calmette-Guérin (BCG) vaccination may lead to unnecessary treatment of presumed latent tuberculosis infection (LTBI). Recently approved interferon-gamma release assays (IGRAs) are more specific for LTBI in this group. METHODS: A total of 316 BCG-vaccinated foreign-born individuals with a positive TST had a commercially available IGRA (QuantiFERON®-TB Gold In-Tube) performed as part of a two-step procedure to determine the need for isoniazid therapy. Baseline demographic information and TST size were recorded and analyzed for characteristics associated with an increased likelihood of having a positive IGRA. RESULTS: Increasing age, male sex, origin from a country with a high prevalence of tuberculosis (TB), shorter time since arrival in the United States, and increasing TST size were all independently associated with a positive IGRA. CONCLUSION: Patient characteristics and TST size can help determine those at highest risk for LTBI. A two-step procedure for LTBI screening should be considered for foreign-born persons with prior BCG vaccination and a positive TST.

Disparities of health in African Americans.

As a cohort of the vulnerable populations, African Americans have the poorest health status indicators of all ethnic groups. Using a vulnerable populations theoretical framework, the reasons for the disparities are discussed.

A firm trial of interdisciplinary rounds on the inpatient medical wards: an intervention designed using continuous quality improvement.

OBJECTIVES: In August 1993 a group of house staff and nursing staff at MetroHealth Medical Center formed a quality improvement team to evaluate the process of medical care on the inpatient wards. Using standard continuous quality improvement (CQI) methods, a team of medical interns, nurses, and other health professionals involved in patient care on the medicine inpatient service designed interdisciplinary, daily work rounds to improve the care of patients on the inpatient wards. METHODS: The authors conducted a randomized, controlled firm trial of the impact of interdisciplinary rounds on the inpatient medicine services. The trial lasted 6 months (November 1993-April 1994) and included 1,102 admissions randomly assigned to experimental or control teams by the pre-existing firm system. Of the 1,102 admissions included in the study, 535 were randomized to medical services with traditional rounds and 567 to medical services with interdisciplinary rounds. The outcomes studied included length of stay (LOS), total hospital charges, provider satisfaction, and ancillary service efficiency. RESULTS: Unadjusted analysis for log-transformed data showed lower length of stay and total charges for the interdisciplinary group. The mean LOS for interdisciplinary rounds was 5.46 days, compared with 6.06 days for traditional care (P = 0.006), whereas mean total charges were $6,681 and $8,090 (P = 0.002) for the two groups, respectively. After multivariate regression analysis using a propensity score that included gender, age, marital status, admission source, diagnosis-related group (DRG) weight, and primary diagnosis by International Classification of Diseases, Ninth Revision (ICD-9) cluster, these differences remained statistically significant. CONCLUSIONS: Previous studies of interdisciplinary teams have failed to show statistically significant cost savings. This study involving more patients shows both cost and LOS decreases with the use of interdisciplinary teams. At the end of the 6-month trial, interdisciplinary rounds were instituted on all medicine inpatient services.

Medical leadership in an era of managed care and continual improvement.

Because clinicians control more than 70% of the total costs of medical care, the success of managed care systems in containing expenditures depends to a large degree on their leadership. Clinicians must make cultural changes and develop core competencies and technical skills to promote the continuous improvement needed for the success of managed care.

Physiological responses to submaximal exercise at the mid-follicular, ovulatory and mid-luteal phases of the menstrual cycle.

This study examined the responses of eumenorrheic women to 60 min of submaximal exercise at the mid-follicular (MF), ovulatory (OV) and mid-luteal (ML) phases of the menstrual cycle. Blood metabolite-hormonal measures, cardiorespiratory responses and ratings of perceived exertion (RPE) (local, legs only; and total, entire body) were monitored at 15-min intervals throughout exercise. No significant effects for phase were observed in the blood measures or the cardiorespiratory responses, except for the respiratory exchange ratio (RER). The overall exercise OV RER (0.86 ± 0.02; mean ± SEM) was lower than at MF (0.94 ± 0.02) but not at ML (0.89 ± 0.01). Substrate utilization (%) and oxidation (g/min) calculations indicated that more fat was used during OV than at MF but not ML. Conversely, more carbohydrate was used during MF than OV. Additionally, local RPE was higher in OV than in the MF or ML trials at 30-60 min of exercise. These findings suggest that menstrual cycle hormonal fluctuations influence metabolic substrate usage and effort perception during submaximal exercise in eumenorrheic women.

Comparison of the effects of oat bran and low-fiber wheat on serum lipoprotein levels and blood pressure.

Previous studies have shown that supplementation of the diet with oat bran may lower serum cholesterol levels. However, it is not known whether oat-bran diets lower serum cholesterol levels by replacing fatty foods in the diet or by a direct effect of the dietary fiber contained in oat bran. To determine which is the case, we compared the effect of isocaloric supplements of high-fiber oat bran (87 g per day) and a low-fiber refined-wheat product on the serum lipoprotein cholesterol levels of 20 healthy subjects, 23 to 49 years old. After a one-week base-line period during which they consumed their usual diets, the subjects were given each type of supplement for six-week periods in a double-blind, crossover trial. Mean serum cholesterol levels (+/- SD) were not significantly different during the high-fiber and low-fiber periods: total cholesterol, 4.44 +/- 0.73 and 4.46 +/- 0.64 mmol per liter (172 +/- 28 and 172 +/- 25 mg per deciliter); low-density lipoprotein, 2.69 +/- 0.63 and 2.77 +/- 0.59 mmol per liter (104 +/- 24 and 107 +/- 23 mg per deciliter); and high-density lipoprotein, 1.40 +/- 0.39 and 1.32 +/- 0.39 mmol per liter (54.2 +/- 15.0 and 50.9 +/- 15.2 mg per deciliter), respectively. However, both types of supplements lowered the mean base-line serum cholesterol level, 4.80 +/- 0.80 mmol per liter (186 +/- 31 mg per deciliter), by 7 to 8 percent (95 percent confidence interval for high fiber, 11 to 4 percent, and for low fiber, 11 to 3 percent). The subjects ate less saturated fat and cholesterol and more polyunsaturated fat during both periods of supplementation than at base line. Those changes in dietary fats were sufficient to explain all of the reduction in serum cholesterol levels caused by the high-fiber and low-fiber diets. The average blood pressure was 112/68 mm Hg at base line and did not change during either dietary period. We conclude that oat bran has little cholesterol-lowering effect and that high-fiber and low-fiber dietary grain supplements reduce serum cholesterol levels about equally, probably because they replace dietary fats.

Changes in serum total creatine phosphokinase (CPK) and its isoenzymes caused by experimental ligation of the superior mesenteric artery.

The changes in serum total CPK and its isoenzymes have not been delineated in acute mesenteric infarction. As measurement of serum CPK levels could conceivably be a useful diagnostic test for bowel infarction, this experiment was performed to assess changes in serum CPK levels in bowel infarction in dogs, using sham operation and talc peritonitis as controls. Laparotomies were performed in 20 dogs, and each was as signed randomly to one of three groups: those having laparotomy (LAP), talc peritonitis (PER), and superior mesenteric artery infarction (MAI). Mixed venous blood samples were obtained from all subjects for 30 hours after surgery. All animals were killed, and complete autopsies were performed. Confirmation of infarction and determination of its extent were obtained through both gross and microscopic examination of the gut in canines subjected to arterial infarction. Total serum CPK levels were determined by spectrophotometric analysis. Agarose gel electrophoresis was used to determine the levels of each of the isoenzymes. Significant elevations of CPK and CPK-MM occurred nine hours after injury. CPK-BB reached maximum elevation by six hours, while CPK-MB did not reach its maximum until 24 hours after injury. From data in the study we conclude that total CPK and its isoenzymes become elevated in the serum of canines subjected to experimental superior mesenteric artery infarction. That CPK-BB elevations peak in the first 12 hours after injury and CPK-MB in the second 12 hours after injury may be of particular diagnostic significance.