Risk factors for cefepime nonsusceptible Gram-negative infections in allogeneic hematopoietic cell transplant recipients.

PURPOSE: Allogeneic hematopoietic cell transplant recipients undergo myelosuppressive chemotherapy to allow engraftment of stem cells and are at particularly high risk for bacterial infections and adverse outcomes. Patients undergoing hematopoietic cell transplant are at increased risk for healthcare-associated infections, including infections with multidrug-resistant pathogens. Cefepime is a commonly prescribed antibiotic for empiric therapy in hematopoietic cell transplant patients, but there is minimal data describing cefepime resistance rates, risk factors for resistance, and clinical outcomes associated with cefepime-resistant infections. METHODS: Adult (≥18 years old) allogeneic hematopoietic cell transplant recipients with a culture positive for a gram-negative rod between January 2010 and January 2016 were spilt into two groups: cefepime susceptible and cefepime nonsusceptible . The primary objective of this study was to identify risk factors for cefepime nonsusceptible through multivariable logistic regression. RESULTS: A total of 107 patients were included (27 cefepime nonsusceptible, 80 cefepime-susceptible), yielding a 25.2% nonsusceptibility rate. Multivariable analysis yielded age >60 years old, Klebsiella spp. infection, Acinetobacter spp. infection, healthcare exposures within 90 days, acute gastrointestinal graft-vs-host-disease, and chronic graft-vs-host-disease at multiple locations as significant risk factors for cefepime nonsusceptible. The receiver operating characteristic area under the curve of the model was 0.851. Thirty-day all-cause mortality (29.6% versus 16.3%, p = 0.13) and length of hospitalization (19 versus 12.5 days, p = 0.0650) were numerically higher in the cefepime nonsusceptible group. CONCLUSIONS: Hematopoietic cell transplant patients with acute gastrointestinal graft versus host disease, extensive chronic graft-vs-host-disease, advanced age, previous healthcare exposures, or infections with Klebsiella and Acinetobacter are at increased risk for cefepime nonsusceptible. Patients infected with cefepime nonsusceptible pathogens may have higher rates of mortality and length of hospitalization.

A real-time Global Warming Index.

We propose a simple real-time index of global human-induced warming and assess its robustness to uncertainties in climate forcing and short-term climate fluctuations. This index provides improved scientific context for temperature stabilisation targets and has the potential to decrease the volatility of climate policy. We quantify uncertainties arising from temperature observations, climate radiative forcings, internal variability and the model response. Our index and the associated rate of human-induced warming is compatible with a range of other more sophisticated methods to estimate the human contribution to observed global temperature change.

Baseline body mass index among children and adults undergoing allogeneic hematopoietic cell transplantation: clinical characteristics and outcomes.

Obesity is an important public health problem that may influence the outcomes of hematopoietic cell transplantation (HCT). We studied 898 children and adults receiving first-time allogeneic hematopoietic SCTs between 2004 and 2012. Pretransplant body mass index (BMI) was classified as underweight, normal weight, overweight or obese using the WHO classification or age-adjusted BMI percentiles for children. The study population was predominantly Caucasian, and the median age was 51 years (5 months-73 years). The cumulative 3-year incidence of nonrelapse mortality (NRM) in underweight, normal weight, overweight and obese patients was 20%, 19%, 20% and 33%, respectively. Major causes of NRM were acute and chronic GVHD. The corresponding incidence of relapse was 30%, 41%, 37% and 30%, respectively. Three-year OS was 59%, 48%, 47% and 43%, respectively. Multivariate analysis showed that obesity was associated with higher NRM (hazard ratio (HR) 1.43, P=0.04) and lower relapse (HR 0.65, P=0.002). Pretransplant plasma levels of ST2 and TNFR1 biomarkers were significantly higher in obese compared with normal weight patients (P=0.04 and P=0.05, respectively). The increase in NRM observed in obese patients was partially offset by a lower incidence of relapse with no difference in OS.

Risk factors for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients.

BACKGROUND: Recurrent Clostridium difficile infection (CDI) represents a significant burden on the healthcare system and is associated with poor outcomes in hematopoietic stem cell transplant (HSCT) patients. Data are limited evaluating recurrence rates and risk factors for recurrence in HSCT patients. METHODS: HSCT patients who developed CDI between January 2010 and December 2012 were divided into 2 groups: non-recurrent CDI (nrCDI) and recurrent CDI (rCDI). Risk factors for rCDI were compared between groups. Rate of recurrence in HSCT patients was compared to that in other hospitalized patients. RESULTS: CDI was diagnosed in 95 of 711 HSCT patients (22 rCDI and 73 nrCDI). Recurrence rates were similar in HSCT patients compared with other hospitalized patients (23.2% vs. 22.9%, P > 0.99). Patients in the rCDI group developed the index case of CDI significantly earlier than the nrCDI group (3.5 days vs. 7.0 days after transplant, P = 0.05). On univariate analysis, patients with rCDI were more likely to have prior history of CDI and neutropenia at the time of the index CDI case. Neutropenia at the time of the index CDI case was the only independent predictor of rCDI (78.8 vs. 34.8%, P = 0.006) on multivariate analysis. CONCLUSIONS: The rate of rCDI was similar between HSCT and other hospitalized patients, and the majority of patients developed the index case of CDI within a week of transplantation. Neutropenia at the index CDI case may be associated with increased rates of rCDI.

Systemic absorption of oral vancomycin in a peripheral blood stem cell transplant patient with severe graft-versus-host disease of the gastrointestinal tract.

Oral vancomycin is often considered the drug of choice for severe Clostridium difficile-associated disease due to both its efficacy and pharmacokinetics. The potential for absorption is not well described in patients with impaired gastrointestinal (GI) mucosa. We describe a case of significant and potentially toxic absorption of oral vancomycin in a peripheral blood stem cell transplant patient with grade IV graft-versus-host disease (GVHD) of the GI tract. In patients with GI GVHD clinicians need to be aware of the potential for oral absorption and, in select cases, monitoring of levels may be appropriate.

The climateprediction.net BBC climate change experiment: design of the coupled model ensemble.

Perturbed physics experiments are among the most comprehensive ways to address uncertainty in climate change forecasts. In these experiments, parameters and parametrizations in atmosphere-ocean general circulation models are perturbed across ranges of uncertainty, and results are compared with observations. In this paper, we describe the largest perturbed physics climate experiment conducted to date, the British Broadcasting Corporation (BBC) climate change experiment, in which the physics of the atmosphere and ocean are changed, and run in conjunction with a forcing ensemble designed to represent uncertainty in past and future forcings, under the A1B Special Report on Emissions Scenarios (SRES) climate change scenario.

Probabilistic climate forecasts and inductive problems.

The development of ensemble-based 'probabilistic' climate forecasts is often seen as a promising avenue for climate scientists. Ensemble-based methods allow scientists to produce more informative, nuanced forecasts of climate variables by reflecting uncertainty from various sources, such as similarity to observation and model uncertainty. However, these developments present challenges as well as opportunities, particularly surrounding issues of experimental design and interpretation of forecast results. This paper discusses different approaches and attempts to set out what climateprediction.net and other large ensemble, complex model experiments might contribute to this research programme.

Low-dose cidofovir treatment of BK virus-associated hemorrhagic cystitis in recipients of hematopoietic stem cell transplant.

In recipients of hematopoietic stem cell transplants (HSCTs), BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC). In our institution, HSCT recipients with BKV-associated HC are treated with 1 mg/kg of cidofovir weekly. We identified HSCT recipients with BKV-associated HC, treated with weekly cidofovir. Microbiological response was defined as at least a one log reduction in urinary BKV viral load; clinical response was defined as improvement in symptoms and stability or reduction in the grade of cystitis. Nineteen allogeneic HSCT patients received a mean of 4.5 weekly doses of cidofovir. HC occurred at a mean of 68.7 days after transplant. A clinical response was detected in 16/19 (84%) patients, and 9/19 (47%) had a measurable microbiological response (8/10 nonresponders had a BKV viral load above the upper limit of the assay before treatment). Fourteen out of nineteen (74%) patients had no significant increase in serum creatinine. Five patients with renal dysfunction resolved after completion of the therapy and removal of other nephrotoxic agents. We conclude that weekly low-dose cidofovir appears to be a safe treatment option for BKV-associated HC. Although the efficacy of low-dose cidofovir is not proven, a prospective trial is warranted.

Uncertainty in predictions of the climate response to rising levels of greenhouse gases.

The range of possibilities for future climate evolution needs to be taken into account when planning climate change mitigation and adaptation strategies. This requires ensembles of multi-decadal simulations to assess both chaotic climate variability and model response uncertainty. Statistical estimates of model response uncertainty, based on observations of recent climate change, admit climate sensitivities--defined as the equilibrium response of global mean temperature to doubling levels of atmospheric carbon dioxide--substantially greater than 5 K. But such strong responses are not used in ranges for future climate change because they have not been seen in general circulation models. Here we present results from the 'climateprediction.net' experiment, the first multi-thousand-member grand ensemble of simulations using a general circulation model and thereby explicitly resolving regional details. We find model versions as realistic as other state-of-the-art climate models but with climate sensitivities ranging from less than 2 K to more than 11 K. Models with such extreme sensitivities are critical for the study of the full range of possible responses of the climate system to rising greenhouse gas levels, and for assessing the risks associated with specific targets for stabilizing these levels.

Human skeletal allograft collection--room for improvement?

AIM: To assess the efficiency of skeletal allograft collection from patients undergoing primary joint arthroplasty at a District General Orthopaedic Unit. METHODS: A two cycle audit was performed. Between cycles procedural changes were implemented to improve the efficiency of allograft collection. The discard rate of donated allograft was also assessed during each cycle. RESULTS: Initially 80 patients were identified. Eight (8/ 80) did not donate allograft due to medical contraindications. Two (2/80) patients underwent intra-operative autologous born grafting. Allograft was not collected from 22 (22/70) suitable patients. As such only 68.6% of suitable bone was collected by the West of Scotland Blood Transfusion Service (WSBTS). Subsequently 100 patients were studied. Twenty-eight (28/100) patients did not donate allograft due to medical contra-indications. Two (2/100) patients underwent intraoperative autologous bone grafting. Eight (8/70) allografts were discarded as a result of logistical problems. As such 88.9% of suitable allograft was collected. Initially 29% of all allograft donated was rejected due to poor patient selection. This subsequently fell to 9.4%. CONCLUSION: By auditing the collection process a significant improvement (c2 = 7.17 df = 1 p = 0.001) in the efficiency of allograft collection was achieved. This was complemented by a significant reduction (c2 = 6.09 df = 1 p = 0.05) in the proportion of unsuitable allograft donated to the WSBTS.

Interactive effects of dietary sodium and chloride on the incidence of spontaneous cardiomyopathy (round heart) in turkeys.

Two pen trials were conducted in Utah, altitude 1,630 m, with Large White female turkey poults to evaluate effects of dietary Na and chloride (Cl) concentrations on live performance and deaths caused by spontaneous cardiomyopathy (STC, "round heart") from 0 to 35 d of age. A randomized block 2 x 2 factorial arrangement with four replicate pens per treatment was used. Pen size was 3.8 x 5.6 m. In each trial, four starter diets were formulated from a common basal diet (corn-soy-meat) to obtain the following sodium and chloride concentrations: High Na (0.24%):High Cl (0.40%); High Na (0.24%):Low Cl (0.16%); Low Na (0.14%):High Cl (0.40%); and Low Na (0.14%):Low Cl (0.16%). Supplements were NaCl, NaHCO3, NH4Cl, or combinations. After laboratory analysis, true values of Na were slightly lower than expected, Cl was near expected values to slightly low, and K was 1.145%. Body weight and feed conversion ratio at 35 d of age were unaffected in both trials. In both experiments, STC mortality was significantly reduced by the Low Na:High Cl treatment compared to the other treatments. In conclusion, a diet containing 0.10 to 0.12% Na and 0.38 to 0.40% Cl, significantly improved poult livability by reducing STC mortality without adverse effects on poult weight or feed conversion ratio.

Intravesicular instillation of E-aminocaproic acid for patients with adenovirus-induced hemorrhagic cystitis.

Hemorrhagic cystitis (HC) is a known complication of allogenic BMT. We report a case of a 28-year-old female with CML in chronic phase, which was treated with a matched unrelated donor (MUD) transplant, complicated by hemorrhagic cystitis on day +42 after the transplant. Adenovirus was isolated from the urine and she was treated with ribavirin, 1 g twice a day for 8 days. We report the use of Amicar (E-aminocaproic acid), 2.5 g solution as bladder instillation to treat the intractable hematuria.

Efficacy of ondansetron and prochlorperazine for the prevention of postoperative nausea and vomiting after total hip replacement or total knee replacement procedures: a randomized, double-blind, comparative trial.

BACKGROUND: Limited data are available on the efficacy of ondansetron hydrochloride compared with prochlorperazine maleate for the treatment of postoperative nausea and vomiting (PONV). OBJECTIVE: To evaluate the comparative efficacy of ondansetron and prochlorperazine for the prophylaxis of PONV in patients undergoing total hip replacement or total knee replacement procedures. METHODS: A randomized, double-blind, comparative trial was conducted at a tertiary care, university hospital. Seventy-eight patients undergoing elective total hip or total knee replacement procedures received a single dose of ondansetron hydrochloride (n = 37), 4 mg intravenously, or prochlorperazine maleate (n = 41), 10 mg intramuscularly, at the end of the surgical procedure. Rescue therapy was administered every 4 hours as needed during the initial 48 hours. Primary outcome measures were the incidences and severity of PONV. Secondary outcome measures included the number of rescue antiemetic doses required, number of physical therapy cancellations because of PONV, length of hospital stay, and cost of antiemetic agents administered. RESULTS: The incidence of nausea was significantly greater in the ondansetron group compared with the prochlorperazine group (81% vs 56%; odds ratio, 3.4; 95% confidence interval, 1.2-9.4) as was the severity of nausea (P = .04). Multivariate analysis identified administration of ondansetron, history of PONV, obesity, and female sex as risk factors for a nausea event. The incidence of vomiting tended to be greater in the ondansetron group (49% vs 32%; odds ratio, 2.0; 95% confidence interval, 0.8-5.0). The need for rescue antiemetic therapy was also greater in the ondansetron group (46% vs 27%; odds ratio, 2.3; 95% confidence interval, 0.9-6.0). The mean antiemetic drug cost per patient was significantly greater for the ondansetron group ($47.56 vs $2.47; P<.001). However, the proportion of patients who were unable to participate in physical therapy because of PONV and the median length of hospital stay were similar in both groups. CONCLUSION: Prochlorperazine is associated with superior efficacy and significant cost savings compared with ondansetron for the prevention of PONV in patients undergoing total hip and total knee replacement procedures.

Spontaneous apoptosis of endometrial tissue is impaired in women with endometriosis.

OBJECTIVE: To evaluate spontaneous apoptosis in single-cell suspensions of eutopic and ectopic endometrium from women with endometriosis and in eutopic endometrium from fertile controls without endometriosis. DESIGN: Paired specimens of eutopic and ectopic endometrial tissue from patients with endometriosis and eutopic endometrium from controls were assessed for spontaneous apoptosis. SETTING: Institute for the Study and Treatment of Endometriosis and university-based research laboratories. PATIENT(S): Fertile controls (n = 10) and women with untreated endometriosis (n = 16). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Spontaneous apoptosis assessed with an ELISA-based cell death detection kit. RESULT(S): Spontaneous apoptosis (monitored by absorbance) of eutopic endometrium from patients with endometriosis and fertile controls was 0.63 +/- 0.1 and 1.43 +/- 0.11, respectively. Among patients with endometriosis, spontaneous apoptosis of ectopic endometrium was 0.26 +/- 0.06. Decreased apoptosis of ectopic versus eutopic endometrium was observed independent of cycle phase. CONCLUSION(S): The susceptibility of endometrial tissue to spontaneous apoptosis is significantly lower in women with endometriosis than in fertile controls. We suggest that decreased susceptibility of endometrial tissue to apoptosis contributes to the etiology or pathogenesis of endometriosis.

Genotypic variation, clinical and histological characteristics of chronic hepatitis C detected at blood donor screening.

Since blood donor screening for the hepatitis C virus (HCV) began in 1991 a large number of seropositive subjects have been detected and several reports have suggested a high prevelance of liver disease. The aim of this study was to evaluate the severity of liver disease in HCV-positive blood donors in terms of the clinical, biochemical and histological abnormalities and to investigate the relationships between these features and the mode of transmission, duration of infection and viral genotype. We evaluated 54 consecutive blood donors who were positive for HCV both on serological testing and polymerase chain reaction. Twenty-three (43%) had a history of intravenous drug abuse and 17 (31%) had received blood transfusions. In only two (4%) was no risk factor identified. The mean duration of infection in those with a clear history of HCV exposure was 12 years. Eighty-three percent were HCV genotypes 1 or 3. All had abnormal liver biopsies with chronic hepatitis and several patients had periportal or portal-portal fibrous septa, but there was none with architectural distortion or cirrhosis. There was no correlation between severity of liver disease and duration of HCV infection, mode of transmission or viral genotype. In the majority of HCV carriers detected at donor screening there is a chronic hepatitis with bridging necrosis in one third, but the degree of fibrosis is minimal and cirrhosis was not present in our patients. The long period of infection of many patients suggests that irreversible liver injury does not necessarily develop at an early stage despite persistent infection.

Recurrent outbreaks of a cutaneous form of Pasteurella multocida infection in turkeys.

Cutaneous infection caused by Pasteurella multocida was diagnosed in a flock of seven thousand 17-to-22-week old male turkeys. The affected grow-out facility had an annual outbreak of fowl cholera, in which a cutaneous infection ventral and lateral to the tail was the predominant lesion. P. multocida serotypes 1 and 14 were the predominant isolates. The exact source of the infection was not determined.

Occlusive laryngotracheitis in turkeys following drinking water administration of gentian violet.

Acute respiratory signs and increased mortality due to suffocation occurred in a flock of 5-week-old male turkey poults following water administration of gentian violet. Gross lesions of laryngeal edema and occlusion of the tracheal opening with caseous plugs were present. Microscopic lesions in the tracheas consisted of vascular congestion, mucosal degeneration, and necrosis. The condition was reproduced experimentally in turkey poults by giving drinking water containing gentian violet.