Patients' estimates of their sleep times: reliability and impact on diagnosis of obstructive sleep apnoea.

BACKGROUND: Home polysomnography (PSG) is an alternative method for diagnosis of obstructive sleep apnoea (OSA). Some types 3 and 4 PSG do not monitor sleep and so rely on patients' estimation of total sleep time (TST). AIM: To compare patients' subjective sleep duration estimation with objective measures in patients who underwent type 2 PSG for probable OSA. METHODS: A prospective clinical audit of 536 consecutive patients of one of the authors between 2006 and 2013. A standard questionnaire was completed by the patients the morning after the home PSG to record the time of lights being turned off and estimated time of sleep onset and offset. PSG was scored based on the guidelines of the American Academy of Sleep Medicine. RESULTS: Median estimated sleep latency (SL) was 20 min compared with 10 min for measured SL (P < 0.0001). There was also a significant difference between the estimated and measured sleep offset time (median difference = -1 min, P = 0.01). Estimated TST was significantly shorter than the measured TST (median difference = -18.5 min, P = 0.002). No factors have been identified to affect patients' accuracy of sleep perception. Only 2% of patients had a change in their diagnosis of OSA based on calculated apnoea-hypopnoea index. CONCLUSIONS: Overall estimated TST in the patients with probable OSA was significantly shorter than measured with significant individual variability. Collectively, inaccurate sleep time estimation had not resulted in significant difference in the diagnosis of OSA.

Microbial risk assessment for recreational use of the Chicago area waterway system.

A microbial risk assessment was conducted to estimate the human health risks from incidental contact recreational activities such as canoeing, boating and fishing in the Chicago Area Waterway System (CAWS) receiving secondary treated, but non-disinfected, effluent from three municipal water reclamation plants. Actual concentrations of the pathogens (pathogenic E. coli [estimated], Giardia, Cryptosporidium, adenovirus, norovirus, enteric virus) detected from the waterway field data collection at locations upstream and downstream of the effluent outfall during dry and wet weather conditions within the recreation season were included in the risk assessment. The results under the current treatment scheme with no disinfection indicated that the total expected gastrointestinal illness (GI) rate per 1000 incidental contact recreational exposure events during combined weather (dry and wet) conditions ranged from 0.10 to 2.78 in the CAWS, which is below the eight illnesses per 1000 swimmers considered tolerable by the United States Environmental Protection Agency. Wet weather conditions contribute to elevated pathogen load to the CAWS; therefore this study determined that disinfecting the effluents of three major WRPs that discharge to the CAWS would result in an extremely small reduction in the aggregate recreation season risk to incidental contact recreators.

Dry and wet weather microbial characterization of the Chicago area waterway system.

The Chicago Area Waterway System (CAWS) is a man-made channel, which serves the Chicago area for the drainage of urban storm water and the conveyance of secondary treated effluent from the Metropolitan Water Reclamation District of Greater Chicago's (District) North Side, Stickney and Calumet water reclamation plants (WRPs). A microbial characterization of the CAWS upstream and downstream of the WRPs and from the WRP outfall was initiated by collecting dry and wet weather samples and analyzing for indicators and pathogens. During dry weather, indicator bacteria (fecal coliform [FC], E. coli [EC], enterococci [EN]) were the most abundant microbial species detected in the CAWS compared to pathogens (Salmonella spp [SA], enteric viruses [EV], adenovirus [AV], norovirus [NV] and Giardia and Cryptosporidium). Pseudomonas aeruginosa [PA] levels in the outfall samples were either lower or equivalent to the CAWS. The wet weather samples had a higher frequency of detection of indicator bacteria and pathogens compared to dry weather samples. Overall, the concentrations of pathogens in the CAWS, representing the weather conditions experienced in a recreational year, were relatively low. The study concluded that the presence of pathogens in the CAWS downstream of the WRPs were due to secondary loading of the waterway under wet weather conditions from combined sewer overflows (CSOs) and other discharges.

Heat shock proteins and acquired resistance to uranium nephrotoxicity.

Previous studies have demonstrated that prior exposures to uranium can produce acquired resistance to uranium nephrotoxicity. In this study, the potential role for heat shock proteins (Hsps) in acquired resistance to uranium nephrotoxicity was explored. Pretreatment of male Sprague-Dawley rats with a conditioning dose of uranyl acetate (5 mg/kg, i.p.) was found to diminish the severity of proximal convoluted tubule necrosis and azotemia produced by a subsequent, higher uranyl acetate dose (10 mg/kg, i.p., 10 days after the conditioning dose). Kidney homogenates from rats euthanized at the end of the conditioning period were found to contain elevated levels of Hsp25, Hsp32, and Hsp70i, but not Hsc70. Immunochemical staining of renal sections for Hsp25 and Hsp70i revealed that these proteins were prominently expressed in tubular epithelial cells in uranyl acetate pretreated animals. Morphological characteristics and staining for proliferating cell nuclear antigen (PCNA) indicated that the cells expressing high levels of Hsps were regenerating. In RK3E and LLC-PK1 renal epithelial cells in culture, Hsp induction by thermal pretreatment did not afford protection from uranyl acetate cytotoxicity. Further, treatment of RK3E and LLC-PK1 cells with uranyl acetate did not result in induction of Hsps, as occurs with other nephrotoxic heavy metals. These observations suggest that while stress proteins are elevated in acquired resistance to uranyl acetate in vivo, they are not responsible for diminished uranium nephrotoxicity but are an epiphenomenon of tubular epithelial regeneration.

Efficacy, safety, and adherence with a twice-daily combination lamivudine/zidovudine tablet formulation, plus a protease inhibitor, in HIV infection.

OBJECTIVE: A randomized, open-label, multicenter study to establish clinical equivalence (non-inferiority) of a regimen employing a lamivudine 150 mg/zidovudine 300 mg combination tablet, administered twice daily, plus a marketed protease inhibitor, compared with a conventional regimen of 150 mg lamivudine twice daily, 600 mg zidovudine daily, and a protease inhibitor, in antiretroviral-experienced patients infected with HIV-1. PATIENTS: Adults who were seropositive for HIV-1 infection with plasma HIV-1 RNA levels < 10000 copies/ml (Roche Amplicor polymerase chain reaction assay, lower limit of quantitation (LLOQ) 400 copies/ml) and CD4+ cell counts > or = 300 x 10(6)/l). All patients had been receiving the conventional lamivudine/zidovudine/protease inhibitor regimen for > or = 10 weeks immediately prior to the study. INTERVENTION: Patients were randomized to the conventional regimen (n = 113) or combination tablet regimen (n = 110) for 16 weeks. The primary study endpoint was treatment failure, defined as an increase in HIV-1 RNA > or = 0.5 log10 above baseline in patients with viral load > LLOQ at randomization and as HIV-1 RNA increasing to > or = 1250 copies/ml in patients with viral load < LLOQ at randomization. RESULTS: The combination tablet regimen was associated with a 3.5% greater success rate than the conventional regimen (96.4 versus 92.9%), with four and eight patients failing treatment due to increases in HIV-1 RNA levels, respectively. The lower limit of the associated confidence interval for the difference was -2.4%, which was well within the -10% margin predefined as clinically unimportant. This establishes the clinical equivalence (non-inferiority) of the combination tablet regimen to the conventional regimens regarding virologic response. The combination tablet and conventional regimens were similar with respect to percentage of patients maintaining HIV-1 RNA levels < LLOQ at the end of study or improving from baseline to undetectability (94 versus 91%; P= 0.063), overall incidence of drug-related adverse events (21 versus 19%) (P=0.868), and mean area under the curve for CD4+ cell counts [treatment difference, 5.9 cells (95% confidence interval, -15.8 to 27.6 x 10(6) cells/l)]. A self-reported adherence questionnaire indicated that patients in the combination tablet group were less likely to miss doses of nucleoside analogue medication at weeks 8 (P= 0.007) and 16 (P= 0.046). CONCLUSIONS: The combination lamivudine/zidovudine tablet/protease inhibitor regimen is clinically equivalent (non-inferior) to the conventional regimen with respect to virologic response and may offer adherence advantages.

The National Nosocomial Infections Surveillance System: plans for the 1990s and beyond.

The National Nosocomial Infections Surveillance (NNIS) System is an ongoing collaborative surveillance system among the Centers for Disease Control (CDC) and United States hospitals to obtain national data on nosocomial infections. This system provides comparative data for hospitals and can be used to identify changes in infection sites, risk factors, and pathogens, and develop efficient surveillance methods. Data are collected prospectively using four surveillance components: hospital-wide, intensive care unit, high-risk nursery, and surgical patient. The limitations of NNIS data include the variability in case-finding methods, infrequency or unavailability of culturing, and lack of consistent methods for post-discharge surveillance. Future plans include more routine feedback of data, studies on the validity of NNIS data, new components, a NNIS consultant group, and more rapid data exchange with NNIS hospitals. Increasing the number of NNIS hospitals and cooperating with other agencies to exchange data may allow NNIS data to be used better for generating benchmark nosocomial infection rates. The NNIS system will continue to evolve as it seeks to find more effective and efficient ways to measure the nosocomial infection experience and assess the influence of patient risk, changes in the delivery of hospital care, and changes in infection control practices on these measures.

Surgical wound infection rates by wound class, operative procedure, and patient risk index. National Nosocomial Infections Surveillance System.

To perform a valid comparison of rates among surgeons, among hospitals, or across time, surgical wound infection (SWI) rates must account for the variation in patients' underlying severity of illness and other important risk factors. From January 1987 through December 1990, 44 National Nosocomial Infections Surveillance System hospitals reported data collected under the detailed option of the surgical patient surveillance component protocol, which includes definitions of eligible patients, operations, and nosocomial infections. Pooled mean SWI rates (number of infections per 100 operations) within each of the categories of the traditional wound classification system were 2.1, 3.3, 6.4, and 7.1, respectively. A risk index was developed to predict a surgical patient's risk of acquiring an SWI. The risk index score, ranging from 0 to 3, is the number of risk factors present among the following: (1) a patient with an American Society of Anesthesiologists preoperative assessment score of 3, 4, or 5, (2) an operation classified as contaminated or dirty-infected, and (3) an operation lasting over T hours, where T depends upon the operative procedure being performed. The SWI rates for patients with scores of 0, 1, 2, and 3 were 1.5, 2.9, 6.8, and 13.0, respectively. The risk index is a significantly better predictor of SWI risk than the traditional wound classification system and performs well across a broad range of operative procedures.

Nosocomial infection rates in adult and pediatric intensive care units in the United States. National Nosocomial Infections Surveillance System.

To determine which intensive care unit (ICU) infection rate may be best for interhospital and intrahospital comparisons and to assess the influence of invasive devices and type of ICU on infection rates, we analyzed data from the National Nosocomial Infections Surveillance System. From October 1986 to December 1990, 79 hospitals reported 2,334 hospital-months of data from 196 hospital units. The median overall infection rate was 9.2 infections per 100 patients. However, this infection rate had a strong positive correlation with average length of ICU stay (r = 0.60, p less than 0.0001). When patient-days was used in the denominator, the median overall nosocomial infection rate was 23.7 infections per 1,000 patient-days. Although there was a marked reduction in the correlation with average length of stay, this rate had a strong positive correlation with device utilization (r = 0.59, p less than 0.0001). To attempt to control for average length of stay and device utilization, we examined device-associated nosocomial infection rates. Central line-associated bloodstream infection rates, catheter-associated urinary tract infection rates, and ventilator-associated pneumonia rates varied by ICU type. The distributions of device-associated infection rates were different between some ICU types and were not different between others (coronary and medical ICUs or medical-surgical and surgical ICUs). Comparison of device-associated infection rates and overall device utilization identified hospital units with outlier infection rates or device utilization. These data show that: (1) choice of denominator is critical when calculating ICU infection rates; (2) device-associated infection rates vary by ICU type; and (3) intrahospital and interhospital comparison of ICU infection rates may best be made by comparing ICU-type specific, device-associated infection rates.

Comparison of rates of nosocomial infections in neonatal intensive care units in the United States. National Nosocomial Infections Surveillance System.

To determine nosocomial infection (NI) rates among neonatal intensive care units (NICUs) that are useful for interhospital comparison, we analyzed data reported in 1986-1990 from 35 hospitals that have level III NICUs and used standard National Nosocomial Infections Surveillance protocols and NI site definitions. Overall rates of NI were calculated as the number of NI per 100 patients (overall NI patient rates) or the number of NI per 1,000 NICU patient-days (overall NI patient-day rates). A strong positive association was found between overall NI patient rates and the neonates' average length of stay, a marker for duration of exposure to important risk factors. No correlation was found between overall NI patient-day rates and average length of stay. However, a strong positive correlation between overall NI patient-day rates and a measure of device utilization (total device-days/total patient-days x 100) was found. Additionally, a positive correlation between overall NI patient rates and device utilization was found. Stratification among the three birthweight groups (less than 1,500 g, 1,500-2,500 g, greater than 2,500 g) did not eliminate the need to control for variations in these factors among NICUs. Device-associated, device-day infection rates, calculated as the number of umbilical or central line-associated blood-stream infections per 1,000 umbilical or central line-days and the number of ventilator-associated pneumonias per 1,000 ventilator days, were not correlated with a unit's site-specific device utilization. These data suggest that calculation of device-associated NI rates in NICUs using device-days as the denominator helps to control for the duration of exposure to the primary risk factor and will be more meaningful for purposes of interhospital comparison.

Nosocomial infections in elderly patients in the United States, 1986-1990. National Nosocomial Infections Surveillance System.

We analyzed 101,479 nosocomial infections in 75,398 adult patients (greater than 15 years) that were reported to the National Nosocomial Infections Surveillance (NNIS) system between 1986 and 1990 by 89 hospitals using the NNIS hospital-wide surveillance component. Overall, 54% of the infections occurred in elderly patients (greater than or equal to 65 years). In the elderly, 44% of the infections were urinary tract infections (UTIs), 18% were pneumonias, 11% were surgical wound infections (SWIs), 8% were bloodstream infections (BSIs), and the remainder were infections at other sites. When we compared the infections in elderly patients with those in younger adult patients, ages 15 to 64 years, a far greater percentage of the infections in elderly patients were UTIs, and there were more pneumonias than SWIs. Elderly and younger patients with ventilator-associated pneumonia were about 1.5 times more likely to develop a secondary BSI than those with pneumonia not associated with ventilator use. When the pathogens isolated from the infections were compared to those reported to the NNIS system in 1984, the percentage that were coagulase-negative staphylococci had increased in both elderly and younger patients. The patient died in 12% of all of the infections. Surveillance personnel reported that 54% of the infections in elderly infected patients who died were related to death compared with 59% in younger infected patients who died. When the infection was related to the patient's death, it was most often pneumonia or a BSI. The risk of an infection-related death was significantly higher when the infected patient developed a secondary BSI. Infection prevention efforts should target infections that occur frequently, are amenable to intervention, and have an adverse outcome.

Secular trends in nosocomial primary bloodstream infections in the United States, 1980-1989. National Nosocomial Infections Surveillance System.

More than 25,000 primary bloodstream infections (BSIs) were identified by 124 National Nosocomial Infections Surveillance System hospitals performing hospital-wide surveillance during the 10-year period 1980-1989. These hospitals reported 6,729 hospital-months of data, during which time approximately 9 million patients were discharged. BSI rates by hospital stratum (based on bed size and teaching affiliation) and pathogen groups were calculated. In 1989, the overall BSI rates for small (less than 200 beds) nonteaching, large nonteaching, small (less than 500 beds) teaching, and large teaching hospitals were 1.3, 2.5, 3.8, and 6.5 BSIs per 1,000 discharges, respectively. Over the period 1980-1989, significant increases (p less than 0.0001) were observed within each hospital stratum, in the overall BSI rate and the BSI rate due to each of the following pathogen groups: coagulase-negative staphylococci, Staphylococcus aureus, enterococci, and Candida species. In contrast, the BSI rate due to gram-negative bacilli remained stable over the decade, in all strata. Except for small nonteaching hospitals, the greatest increase in BSI rates was observed in coagulase-negative staphylococci (the percentage increase ranged between 424% and 754%), followed by Candida species (219-487%). In small nonteaching hospitals, the greatest increase was for S. aureus (283%), followed by enterococci (169%) and coagulase-negative staphylococci (161%). Our analysis documents the emergence over the last decade of coagulase-negative staphylococci as one of the most frequently occurring pathogens in BSI.

Nosocomial infections among neonates in high-risk nurseries in the United States. National Nosocomial Infections Surveillance System.

BACKGROUND: Nosocomial infections result in considerable morbidity and mortality among neonates in high-risk nurseries (HRNs). PURPOSE: To examine the epidemiology of nosocomial infections among neonates in level III HRNs. METHODS: Data were collected from 99 hospitals with HRNs participating in the National Nosocomial Infections Surveillance system, which uses standard surveillance protocols and nosocomial infection site definitions. The data included information on maternal acquisition of and risk factors for infection, such as device exposure, birth weight category (< or = 1000, 1001 through 1500, 1501 through 2500, and > 2500 g), mortality, and the relationship of the nosocomial infection to death. RESULTS: From October 1986 through September 1994, these hospitals submitted data on 13 179 nosocomial infections. The bloodstream was the most frequent site of nosocomial infection in all birth weight groups. Nosocomial pneumonia was the second most common infection site, followed by the gastrointestinal and eye, ear, nose, and throat sites. The most common nosocomial pathogens among all neonates were coagulase-negative staphylococci, Staphylococcus aureus, enterococci, Enterobacter sp, and Escherichia coli. Group B streptococci were associated with 46% of bloodstream infections that were maternally acquired; coagulase-negative staphylococci were associated with 58% of bloodstream infections that were not maternally acquired, most of which (88%) were associated with umbilical or central intravenous catheters. CONCLUSIONS: Bloodstream infections, the most frequent nosocomial infections in all birth weight groups, should be a major focus of surveillance and prevention efforts in HRNs. For bloodstream infections, stratification of surveillance data by maternal acquisition will help focus prevention efforts for group B streptococci outside the HRN. Within the nursery, bloodstream infection surveillance should focus on umbilical or central intravenous catheter use, a major risk factor for infection.

Impact of HIV type 1 drug resistance mutations and phenotypic resistance profile on virologic response to salvage therapy.

This study examines the association between presence of drug resistance mutations and phenotypic resistance at baseline to virologic response to salvage therapy in a community setting. The study population consisted of 58 antiretroviral drug-experienced patients with HIV-1 infection who had recently switched therapy because of virologic failure. Drug resistance mutations in the reverse transcriptase- and protease-coding regions and phenotypic susceptibility to 13 antiretroviral drugs were assessed at baseline. Plasma HIV-1 RNA levels were assessed at baseline and at subsequent clinic visits. Results showed that three variables were significant in predicting virologic response: HIV-1 levels at baseline, number of protease mutations, and phenotypic sensitivity score for the regimen at baseline. For four drugs there was a significant association between the presence of specific drug resistance mutations and >10-fold phenotypic resistance to that drug. With phenotypic resistance defined as >4-fold resistance, the association between specific drug resistance mutations and phenotypic resistance was significant for seven drugs. Overall, these data show that phenotypic susceptibility and absence of drug resistance mutations, particularly protease mutations, are significant predictors of virologic response. For several drugs, specific combinations of drug resistance mutations are associated with decreased phenotypic susceptibility and might provide useful clinical guidelines in selecting therapeutic options.

Methicillin-resistant Staphylococcus aureus in U.S. hospitals, 1975-1991.

OBJECTIVES: Analyze changes that have occurred among U.S. hospitals over a 17-year period, 1975 through 1991, in the percentage of Staphylococcus aureus resistant to beta-lactam antibiotics and associated with nosocomial infections. DESIGN: Retrospective review. The percentage of methicillin-resistant S aureus (MRSA) was defined as the number of S aureus isolates resistant to either methicillin, oxacillin, or nafcillin divided by the total number of S aureus isolates for which methicillin, oxacillin, or nafcillin susceptibility test results were reported to the National Nosocomial Infections Surveillance (NNIS) System. SETTING: NNIS System hospitals. RESULTS: Of the 66,132 S aureus isolates that were tested for susceptibility to methicillin, oxacillin, or nafcillin during 1975 through 1991, 6,986 (11%) were resistant to methicillin, oxacillin, or nafcillin. The percentage MRSA among all hospitals rose from 2.4% in 1975 to 29% in 1991, but the rate of increase differed significantly among 3 bed-size categories: < 200 beds, 200 to 499 beds, and > or = 500 beds. In 1991, for hospitals with < 200 beds, 14.9% of S aureus isolates were MRSA; for hospitals with 200 to 499 beds, 20.3% were MRSA; and for hospitals with > or = 500 beds, 38.3% were MRSA. The percentage MRSA in each of the bed-size categories rose above 5% at different times: in 1983, for hospitals with > or = 500 beds; in 1985, for hospitals with 200 to 499 beds; and in 1987, for hospitals with < 200 beds. CONCLUSIONS: This study suggests that hospitals of all sizes are facing the problem of MRSA, the problem appears to be increasing regardless of hospital size, and control measures advocated for MRSA appear to require re-evaluation. Further study of MRSA in hospitals would benefit our understanding of this costly pathogen.

Evidence of interhospital transmission of extended-spectrum beta-lactam-resistant Klebsiella pneumoniae in the United States, 1986 to 1993. The National Nosocomial Infections Surveillance System.

BACKGROUND: In addition to single-hospital outbreaks, interhospital transmission of extended-spectrum beta-lactam-resistant (ESBLR) Klebsiella pneumoniae has been suspected in some reports. However, these studies lacked sufficient epidemiological information to confirm such an occurrence. METHODS: We reviewed the surveillance data reported to the National Nosocomial Infections Surveillance (NNIS) System during 1986 to 1993 for K pneumoniae isolates and their susceptibility to either ceftazidime, cefotaxime, ceftriaxone, or aztreonam. Pulsed-field gel electrophoresis (PFGE) was used to study available ESBLR K pneumoniae isolates. RESULTS: Among 8,319 K pneumoniae isolates associated with nosocomial infections, 727 (8.7%) were resistant or had intermediate-level resistance to at least one of these antibiotics. One hospital (hospital A) accounted for 321 isolates (44.2%) of ESBLR K pneumoniae. During 1986 to 1993, the percentage of K pneumoniae isolates that were ESBLR increased from 0 to 57.7% in hospital A, from 0 to 35.6% in NNIS hospitals 0 to 20 miles from hospital A (area B), and from 1.6 to 7.3% in NNIS hospitals more than 20 miles from hospital A, including hospitals located throughout the United States. Analysis of PFGE restriction profiles showed a genetic relationship between a cluster of isolates from hospital A and some isolates from one hospital in area B, and consecutive admission in these two hospitals was confirmed for two patients from whom isolates were available. CONCLUSIONS: These data provide evidence of interhospital transmission of ESBLR K pneumoniae in one region of the United States and stress the interrelationship between hospitals when trying to control antimicrobial resistance.

Characteristics of hospitals and infection control professionals participating in the National Nosocomial Infections Surveillance System 1999.

The National Nosocomial Infections Surveillance (NNIS) system is the oldest and largest monitoring system for health care-acquired infections in the United States. This report describes both the characteristics of NNIS hospitals compared with those of US hospitals with 100 beds or more and their infection control programs. Overall, NNIS hospitals tend to have more hospital beds than the average for-comparable US hospitals. The majority of NNIS hospitals have affiliations with academic medical centers, and most have substantial intensive care units. Even though infection control professionals in NNIS hospitals spend most of their time in inpatient settings, 40% of their time is also spent in a variety of other settings, including home health, outpatient surgery or clinics, extended care facilities, employee health and quality management, and other clinical or administrative activities. As described in this report, the infrastructure of the NNIS system offers a national resource on which to build improved voluntary patient safety monitoring efforts, as outlined in the recent Institute of Medicine report on medical errors.

Reevaluating cancer risk estimates for short-term exposure scenarios.

Estimates of cancer risk from short-term exposure to carcinogens generally rely on cancer potency values derived from chronic, lifetime-exposure studies and assume that exposures of limited duration are associated with a proportional reduction in cancer risk. The validity of this approach was tested empirically using data from both chronic lifetime and stop-exposure studies of carcinogens conducted by the National Toxicology Program. Eleven compounds were identified as having data sufficient for comparison of relative cancer potencies from short-term versus lifetime exposure. The data were modeled using the chronic data alone, and also using the chronic and the stop-exposure data combined, where stop-exposure doses were adjusted to average lifetime exposure. Maximum likelihood estimates of the dose corresponding to a 1% added cancer risk (ED(01)) were calculated along with their associated 95% upper and lower confidence bounds. Statistical methods were used to evaluate the degree to which adjusted stop-exposures produced risks equal to those estimated from the chronic exposures. For most chemical/cancer endpoint combinations, inclusion of stop-exposure data reduced the ED(01), indicating that the chemical had greater apparent potency under stop-exposure conditions. For most chemicals and endpoints, consistency in potency between continuous and stop-exposure studies was achieved when the stop-exposure doses were averaged over periods of less than a lifetime-in some cases as short as the exposure duration itself. While the typical linear adjustments for less-than-lifetime exposure in cancer risk assessment can theoretically result in under- or overestimation of risks, empirical observations in this analysis suggest that an underestimation of cancer risk from short-term exposures is more likely.

Effect of temperature and humidity on the formation of dibutylurea in benlate fungicide.

Benomyl [methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate] is the active ingredient in DuPont Benlate fungicides. The formation of N, N'-dibutylurea (DBU), a phytotoxic degradation product of benomyl, in Benlate formulations was evaluated by analyzing Benlate samples maintained under simulated storage conditions and assessing the effects of temperature and humidity on sample moisture content, benomyl degradation, and the rate of DBU formation. Benomyl degraded during storage by the elimination of n-butylisocyanate (BIC) to form methyl 2-benzimidazole carbamate (MBC; carbendazim). Liberated BIC could then proceed to react with water to form DBU (first-order rate constant of 8.4 x 10(-)(4) s (-)(1)). The degradation of benomyl and subsequent formation of DBU were dependent on the temperature and highly dependent on the humidity of the storage environment. At the lower humidity storage conditions the rates of DBU formation were significantly higher in the dry flowable (DF) formulation than in the wettable powder (WP) formulation. The initial moisture content of Benlate DF samples was higher than those of Benlate WP samples, although the Benlate WP samples absorbed more moisture upon incubation. These results may yield insight on the appearance of high levels of DBU found in some boxes and bags of Benlate DF and Benlate WP formulations.

Correlation between self-reported adherence to highly active antiretroviral therapy (HAART) and virologic outcome.

The Patient Medication Adherence Questionnaire Version 1.0 (PMAQ-V1.0) is a patient-reported adherence instrument to assess medication-taking behaviors and identify barriers to adherence with antiretroviral therapy. To assess the correlation between adherence and virologic outcome, the PMAQ-V1.0 was administered to 194 antiretroviral-experienced adults with HIV infection enrolled in a 16-week evaluation of protease inhibitor-containing regimens featuring a lamivudine/zidovudine combination tablet. At baseline, plasma HIV-1 RNA levels were less than 10,000 copies/mL and CD4(+)-cell counts were equal to or greater than 300 x 10(6)/L; patients had been receiving a conventional regimen of lamivudine + zidovudine (separately) plus a protease inhibitor for at least 10 weeks immediately prior to the study. Forty-eight percent of patients who reported missing at least one dose of a nucleoside reverse-transcriptase inhibitor (NRTI) during the study had detectable plasma HIV-1 RNA, compared with 26% of patients who reported no missed doses (P = .002). Patients who missed at least one dose of an NRTI or protease inhibitor were 2.5 times more likely to have quantifiable HIV-1 RNA than those who reported no missed doses. Patients who reported fewer barriers and more motivators to adherence had better virologic outcomes (P = .001). Several dimensions of the PMAQ-V1.0 did not function as well as hypothesized. In this study, self-reported adherence derived from the PMAQ-V1.0 predicted virologic outcomes, but further refinement of the dimensions appears warranted.