Brentuximab vedotin plus AVD for Hodgkin lymphoma: incidence and management of peripheral neuropathy in a multisite cohort.

Brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is increasingly used for frontline treatment of stage III/IV classical Hodgkin lymphoma (cHL). Peripheral neuropathy (PN) was the most common and treatment-limiting side effect seen in clinical trials but has not been studied in a nontrial setting, in which clinicians may have different strategies for managing it. We conducted a multisite retrospective study to characterize PN in patients who received BV + AVD for newly diagnosed cHL. One hundred fifty-three patients from 10 US institutions were eligible. Thirty-four patients (22%) had at least 1 ineligibility criteria for ECHELON-1, including stage, performance status, and comorbidities. PN was reported by 80% of patients during treatment; 39% experienced grade (G) 1, 31% G2, and 10% G3. In total, BV was modified in 44% of patients because of PN leading to BV discontinuation in 23%, dose reduction in 17%, and temporary hold in 4%. With a median follow-up of 24 months, PN resolution was documented in 36% and improvement in 33% at the last follow-up. Two-year progression-free survival (PFS) for the advanced-stage patients was 82.7% (95% confidence interval [CI], 0.76-0.90) and overall survival was 97.4% (95% CI, 0.94-1.00). Patients who discontinued BV because of PN did not have inferior PFS. In the nontrial setting, BV + AVD was associated with a high incidence of PN. In our cohort, which includes patients who would not have been eligible for the pivotal ECHELON-1 trial, BV discontinuation rates were higher than previously reported, but 2-year outcomes remain comparable.

Biosynthesis of Guanitoxin Enables Global Environmental Detection in Freshwater Cyanobacteria.

Harmful cyanobacterial blooms (cyanoHABs) cause recurrent toxic events in global watersheds. Although public health agencies monitor the causal toxins of most cyanoHABs and scientists in the field continue developing precise detection and prediction tools, the potent anticholinesterase neurotoxin, guanitoxin, is not presently environmentally monitored. This is largely due to its incompatibility with widely employed analytical methods and instability in the environment, despite guanitoxin being among the most lethal cyanotoxins. Here, we describe the guanitoxin biosynthesis gene cluster and its rigorously characterized nine-step metabolic pathway from l-arginine in the cyanobacterium Sphaerospermopsis torques-reginae ITEP-024. Through environmental sequencing data sets, guanitoxin (gnt) biosynthetic genes are repeatedly detected and expressed in municipal freshwater bodies that have undergone past toxic events. Knowledge of the genetic basis of guanitoxin biosynthesis now allows for environmental, biosynthetic gene monitoring to establish the global scope of this neurotoxic organophosphate.

The household economic burden of non-communicable diseases in 18 countries

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of death globally. In 2014, the United Nations committed to reducing premature mortality from NCDs, including by reducing the burden of healthcare costs. Since 2014, the Prospective Urban and Rural Epidemiology (PURE) Study has been collecting health expenditure data from households with NCDs in 18 countries. METHODS: Using data from the PURE Study, we estimated risk of catastrophic health spending and impoverishment among households with at least one person with NCDs (cardiovascular disease, diabetes, kidney disease, cancer and respiratory diseases; n=17 435), with hypertension only (a leading risk factor for NCDs; n=11 831) or with neither (n=22 654) by country income group: high-income countries (Canada and Sweden), upper middle income countries (UMICs: Brazil, Chile, Malaysia, Poland, South Africa and Turkey), lower middle income countries (LMICs: the Philippines, Colombia, India, Iran and the Occupied Palestinian Territory) and low-income countries (LICs: Bangladesh, Pakistan, Zimbabwe and Tanzania) and China. RESULTS: The prevalence of catastrophic spending and impoverishment is highest among households with NCDs in LMICs and China. After adjusting for covariates that might drive health expenditure, the absolute risk of catastrophic spending is higher in households with NCDs compared with no NCDs in LMICs (risk difference=1.71%; 95% CI 0.75 to 2.67), UMICs (0.82%; 95% CI 0.37 to 1.27) and China (7.52%; 95% CI 5.88 to 9.16). A similar pattern is observed in UMICs and China for impoverishment. A high proportion of those with NCDs in LICs, especially women (38.7% compared with 12.6% in men), reported not taking medication due to costs. CONCLUSIONS: Our findings show that financial protection from healthcare costs for people with NCDs is inadequate, particularly in LMICs and China. While the burden of NCD care may appear greatest in LMICs and China, the burden in LICs may be masked by care foregone due to costs. The high proportion of women reporting foregone care due to cost may in part explain gender inequality in treatment of NCDs. (AU)

Salmonella and Escherichia coli O157:H7 prevalence in cattle and on carcasses in a vertically integrated feedlot and harvest plant in Mexico.

To determine the prevalence of Salmonella and Escherichia coli O157:H7 in cattle feedlots and the impact of subsequent contamination on carcasses in a Mexican Federal Inspection Type Standards harvest facility, 250 animals were tagged and sampled in each step of the slaughter process. Samples were taken from hides and fecal grabs, and composite samples were taken from three anatomical carcass sites (hindshank, foreshank, and inside round) during the slaughter process, at preevisceration (PE), prior to entering the hot box (PHB), and after 24 h of dry chilling (DC). Additionally, 250 fecal samples were collected from the feedlot (FL), holding pens (HP), and intestinal feces (IF), and water samples were taken from the HP area. E. coli O157:H7 and Salmonella detection were carried out with the BAX System, immunomagnetic separation, and conventional methods. Overall Salmonella prevalence was 52.5%. The highest prevalence (92.4%) was found on hides, followed by feces from the HP (91.0%), FL (55.56%), PE (49.0%), IF (46.8%), and PHB (24.8%), for all sampling periods combined. The lowest prevalence of 6.0% was found after DC. The overall prevalence of E. coli O157:H7 was as follows: 11.7% for hides, 5.2% for IF, 2.7% for FL, 2.0% for HP, 0.8% for PE, 0.4% for PHB, and 0.4% for the cooler. High prevalence of Salmonella in IF and on hides present a significant risk factor for contamination by Salmonella at the different processing steps. These results serve as a warning as to the risks of contamination in meats for these pathogens and the importance of following good manufacturing practices during beef production processes.

Long-term renal and cardiovascular outcomes in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants by baseline estimated GFR.

BACKGROUND AND OBJECTIVES: CKD is common among older patients. This article assesses long-term renal and cardiovascular outcomes in older high-risk hypertensive patients, stratified by baseline estimated GFR (eGFR), and long-term outcome efficacy of 5-year first-step treatment with amlodipine or lisinopril, each compared with chlorthalidone. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a long-term post-trial follow-up of hypertensive participants (n=31,350), aged ≥55 years, randomized to receive chlorthalidone, amlodipine, or lisinopril for 4-8 years at 593 centers. Participants were stratified by baseline eGFR (ml/min per 1.73 m(2)) as follows: normal/increased (≥90; n=8027), mild reduction (60-89; n=17,778), and moderate/severe reduction (<60; n=5545). Outcomes were cardiovascular mortality (primary outcome), total mortality, coronary heart disease, cardiovascular disease, stroke, heart failure, and ESRD. RESULTS: After an average 8.8-year follow-up, total mortality was significantly higher in participants with moderate/severe eGFR reduction compared with those with normal and mildly reduced eGFR (P<0.001). In participants with an eGFR <60, there was no significant difference in cardiovascular mortality between chlorthalidone and amlodipine (P=0.64), or chlorthalidone and lisinopril (P=0.56). Likewise, no significant differences were observed for total mortality, coronary heart disease, cardiovascular disease, stroke, or ESRD. CONCLUSIONS: CKD is associated with significantly higher long-term risk of cardiovascular events and mortality in older hypertensive patients. By eGFR stratum, 5-year treatment with amlodipine or lisinopril was not superior to chlorthalidone in preventing cardiovascular events, mortality, or ESRD during 9-year follow-up. Because data on proteinuria were not available, these findings may not be extrapolated to proteinuric CKD.

Blood pressure control in Hispanics in the antihypertensive and lipid-lowering treatment to prevent heart attack trial.

Historically, blood pressure control in Hispanics has been considerably less than that of non-Hispanic whites and blacks. We compared determinants of blood pressure control among Hispanic white, Hispanic black, non-Hispanic white, and non-Hispanic black participants (N=32 642) during follow-up in a randomized, practice-based, active-controlled trial. Hispanic blacks and whites represented 3% and 16% of the cohort, respectively; 33% were non-Hispanic black and 48% were non-Hispanic white. Hispanics were less likely to be controlled (<140/90 mm Hg) at enrollment, but within 6 to 12 months of follow-up, Hispanics had a greater proportion <140/90 mm Hg compared with non-Hispanics. At 4 years of follow-up, blood pressure was controlled in 72% of Hispanic whites, 69% of Hispanic blacks, 67% of non-Hispanic whites, and 59% of non-Hispanic blacks. Compared with non-Hispanic whites, Hispanic whites had a 20% greater odds of achieving BP control by 2 years of follow-up (odds ratio: 1.20; 95% CI: 1.10 to 1.31) after controlling for demographic variables and comorbidities, Hispanic blacks had a similar odds of achieving BP control (odds ratio: 1.04; 95% CI: 0.86 to 1.25), and non-Hispanic blacks had a 27% lower odds (odds ratio: 0.73; 95% CI: 0.69 to 0.78). We conclude that in all patients high levels of blood pressure control can be achieved with commonly available medications and that Hispanic ethnicity is not associated with inferior control in the setting of a clinical trial in which hypertensive patients had equal access to medical care, and medication was provided at no cost.

Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT).

CONTEXT: Blood pressure control (<140/90 mm Hg) rates for hypertension fall far short of the US national goal of 50% or more. Achievable control rates in varied practice settings and geographic regions and factors that predict improved blood pressure control are not well identified. OBJECTIVE: To determine the success and predictors of blood pressure control in a large hypertension trial involving a multiethnic population in diverse practice settings. DESIGN: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial is a randomized, double-blind, active-controlled clinical trial with a mean follow-up of 4.9 years. Participant enrollment began in February 1994 and follow-up was completed in March 2002. SETTING: A total of 623 centers in the United States, Canada, and the Caribbean. PARTICIPANTS: A total of 33,357 participants (aged > or =55 years) with hypertension and at least one other coronary heart disease risk factor. INTERVENTIONS: Participants were randomly assigned to receive (double-blind) chlorthalidone, 12.5-25 mg/d (n=15,255), amlodipine 2.5-10 mg/d (n=9048), or lisinopril 10-40 mg/d (n=9054) after other medication was discontinued. Doses were increased within these ranges and additional drugs from other classes were added as needed to achieve blood pressure control (<140/90 mm Hg). MAIN OUTCOME MEASURES: The outcome measures for this report are systolic and diastolic blood pressure, the proportion of participants achieving blood pressure control (<140/90 mm Hg), and the number of drugs required to achieve control in all three groups combined. RESULTS: Mean age was 67 years, 47% were women, 35% black, 36% diabetic; 90% were on antihypertensive drug treatment at entry. At the first of two pre-randomization visits, blood pressure was <140/90 mm Hg in only 27.4% of participants. After 5 years of follow-up, the percent controlled improved to 66%. Systolic blood pressure was <140 mm Hg in 67% of participants, diastolic blood pressure was <90 mm Hg in 92%, the mean number of drugs prescribed was 2.0+/-1.0, and the percent on > or =2 drugs was 63%. Blood pressure control varied by geographic regions, practice settings, and demographic and clinical characteristics of participants. CONCLUSIONS: These data demonstrate that blood pressure may be controlled in two thirds of a multiethnic hypertensive population in diverse practice settings. Systolic blood pressure is more difficult to control than diastolic blood pressure, and at least two antihypertensive medications are required for most patients to achieve blood pressure control. It is likely that the majority of people with hypertension could achieve a blood pressure <140/90 mm Hg with the antihypertensive medications available today.

Reducing blood donor exposures in low birth weight infants by the use of older, unwashed packed red blood cells.

We performed a prospective, randomized masked trial to determine whether the use of dedicated units of packed red blood cells equipped with seven satellite bags would reduce donor exposures in infants with birth weights < 1500 gm. We also examined the use of unwashed and older red blood cells. Red blood cells given to the study group were used without washing and until their expiration date (35 to 42 days). Changes in blood pH, potassium, ionized calcium, and hemoglobin were determined with each transfusion and compared with data collected from a control group that received washed, younger red blood cells. There was a 64% reduction in donor exposures in the study group. Changes in infants' blood pH and calcium levels with transfusion were the same in the two groups. There was a clinically unimportant difference in potassium levels. A greater rise in hemoglobin values occurred when washed cells were used. There was no correlation between changes in the blood levels measured and the age of unwashed cells infused. We conclude that the use of red blood cells from satellite bag-equipped dedicated units decreases donor exposures, and that the practices of using only younger red blood cells and of saline washing of red blood cells before infusion, are unwarranted.

Polynuclear aromatic hydrocarbon contaminants in oysters from the Gulf of Mexico (1986-1990).

Polynuclear aromatic hydrocarbon (PAH) contaminant concentrations in 870 composite oyster samples from coastal and estuarine areas of the Gulf of Mexico analyzed as part of National Oceanographic and Atmospheric Administration's (NOAA's) National Status and Trends (NS&T) Mussel Watch Program exhibit a log-normal distribution. There are two major populations in the data. The cumulative frequency function was used to deconvolute the data distribution into two probability density functions and calculate summary statistics for each population. The first population consists of sites with lower PAH concentration probably due to background contamination (i.e. stormwater runoff, atmospheric deposition). The second population are sites with higher concentrations of PAHs associated with local point sources of PAH input (i.e. small oil spills, etc.). The temporal pattern for the mean concentration of the populations from the Gulf of Mexico is consistent with large-scale climatic factors such as the El Niño cycles which affect the precipitation regime.

Entamoeba histolytica: naturally occurring infections in baboons.

Entamoeba chattoni frequently occurs as an intestinal infection in non-human primates. It has been isolated from both wild and captive animals. Morphologically this amoeba resembles E. histolytica. E. histolytica has also been isolated from non-human primates on a number of occasions but these isolations have been from captive animals. In recent years identification of E. histolytica has been enhanced by the introduction of iso-enzyme electrophoresis methods. This technology has been widely applied to amoebae isolated from humans from many parts of the world. Limited work using iso-enzyme electrophoresis on non-human primates in captivity has confirmed the earlier parasitological studies mentioned above as both E. histolytica and E. chattoni were isolated; furthermore zymodeme (strain or species based on the characteristic iso-enzyme electrophoretic pattern) analysis demonstrated that these two organisms could be readily distinguished by this method. The importance of establishing whether E. histolytica occurs in wild primates as a true zoonosis was emphasised by these studies, particularly from the point of view of potential disease transmission. A study of baboons (Papio ursinus) in South African game reserves has been initiated and three surveys have been conducted in the Kruger National Park; these baboons are considered to live in isolation from humans. Of the 210 isolations attempted 65-75% yielded E. chattoni while E. histolytica were cultured from the faeces of 1-3% of the baboons. Although the prevalence rates varied in each of the 3 study locations both species of amoeba were found in baboons from all of them. All the E. histolytica isolated thus far have been non-pathogenic zymodemes.(ABSTRACT TRUNCATED AT 250 WORDS)