Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis.

The diagnosis of cystic fibrosis (CF) patients with allergic bronchopulmonary aspergillosis (ABPA) is clinically challenging, due to the absence of an objective biological test. Since blood basophils play a major role in allergic responses, we hypothesised that changes in their surface activation pattern discriminate between CF patients with and without ABPA.We conducted a prospective longitudinal study (Stanford cohort) comparing basophil activation test CD203c levels by flow cytometry before and after activation with Aspergillus fumigatus allergen extract or recombinant Asp f1 in 20 CF patients with ABPA (CF-ABPA) and in two comparison groups: CF patients with A. fumigatus colonisation (AC) but without ABPA (CF-AC; n=13) and CF patients without either AC or ABPA (CF; n=12). Patients were tested every 6 months and when ill with pulmonary exacerbation. We also conducted cross-sectional validation in a separate patient set (Dublin cohort).Basophil CD203c surface expression reliably discriminated CF-ABPA from CF-AC and CF over time. Ex vivo stimulation with A. fumigatus extract or recombinant Asp f1 produced similar results within the Stanford (p<0.0001) and the Dublin cohorts. CF-ABPA patients were likelier to have elevated specific IgE to A. fumigatus and were less frequently co-infected with Staphylococcus aureus.Basophil CD203c upregulation is a suitable diagnostic and stable monitoring biomarker of ABPA in CF.

Cancer in World Trade Center responders: Findings from multiple cohorts and options for future study.

BACKGROUND: Three longitudinal studies of cancer incidence in varied populations of World Trade Center responders have been conducted. METHODS: We compared the design and results of the three studies. RESULTS: Separate analyses of these cohorts revealed excess cancer incidence in responders for all cancers combined and for cancers of the thyroid and prostate. Methodological dissimilarities included recruitment strategies, source of cohort members, demographic characteristics, overlap between cohorts, assessment of WTC and other occupational exposures and confounders, methods and duration of follow-up, approaches for statistical analysis, and latency analyses. CONCLUSIONS: The presence of three cohorts strengthens the effort of identifying and quantifying the cancer risk; the heterogeneity in design might increase sensitivity to the identification of cancers potentially associated with exposure. The presence and magnitude of an increased cancer risk remains to be fully elucidated. Continued long-term follow up with minimal longitudinal dropout is crucial to achieve this goal.

Mortality among World Trade Center rescue and recovery workers, 2002-2011.

BACKGROUND: Rescue and recovery workers responding to the 2001 collapse of the World Trade Center (WTC) sustained exposures to toxic chemicals and have elevated rates of multiple morbidities. METHODS: Using data from the World Trade Center Health Program and the National Death Index for 2002-2011, we examined standardized mortality ratios (SMR) and proportional cancer mortality ratios (PCMR) with indirect standardization for age, sex, race, and calendar year to the U.S. general population, as well as associations between WTC-related environmental exposures and all-cause mortality. RESULTS: We identified 330 deaths among 28,918 responders (SMR 0.43, 95%CI 0.39-0.48). No cause-specific SMRs were meaningfully elevated. PCMRs were elevated for neoplasms of lymphatic and hematopoietic tissue (PCMR 1.76, 95%CI 1.06-2.75). Mortality hazard ratios showed no linear trend with exposure. CONCLUSIONS: Consistent with a healthy worker effect, all-cause mortality among responders was not elevated. There was no clear association between intensity and duration of exposure and mortality. Surveillance is needed to monitor the proportionally higher cancer mortality attributed to lymphatic/hematopoietic neoplasms.

The association between body mass index and gastroesophageal reflux disease in the World Trade Center Health Program General Responder Cohort.

BACKGROUND: There is increasing concern about the obesity epidemic in the United States. Obesity is a potential risk factor for a number of chronic diseases, including gastroesophageal reflux disease (GERD). This analysis examined whether body mass index (BMI) was associated with physician-diagnosed GERD in World Trade Center (WTC) general responders. METHODS: 19,819 WTC general responders were included in the study. Cox proportional hazards regression models were used to compare time to GERD diagnosis among three BMI groups (normal (<25 kg/m(2) ), overweight (≥25 and <30 kg/m(2) ), and obese (≥30 kg/m(2) )). RESULTS: Among the responders, 43% were overweight and 42% were obese. The hazard ratio for normal versus overweight was 0.81 (95% Confidence Interval (CI), 0.75-0.88); normal versus obese 0.71 (95%CI, 0.66, 0.77); and overweight versus obese 0.88 (95%CI, 0.83-0.92). CONCLUSION: GERD diagnoses rates were higher in overweight and obese WTC responders. Am. J. Ind. Med. 59:761-766, 2016. © 2016 Wiley Periodicals, Inc.

Effect of Palliative Care-Led Meetings for Families of Patients With Chronic Critical Illness: A Randomized Clinical Trial.

IMPORTANCE: Family caregivers of patients with chronic critical illness experience significant psychological distress. OBJECTIVE: To determine whether family informational and emotional support meetings led by palliative care clinicians improve family anxiety and depression. DESIGN, SETTING, AND PARTICIPANTS: A multicenter randomized clinical trial conducted from October 2010 through November 2014 in 4 medical intensive care units (ICUs). Adult patients (aged ≥21 years) requiring 7 days of mechanical ventilation were randomized and their family surrogate decision makers were enrolled in the study. Observers were blinded to group allocation for the measurement of the primary outcomes. INTERVENTIONS: At least 2 structured family meetings led by palliative care specialists and provision of an informational brochure (intervention) compared with provision of an informational brochure and routine family meetings conducted by ICU teams (control). There were 130 patients with 184 family surrogate decision makers in the intervention group and 126 patients with 181 family surrogate decision makers in the control group. MAIN OUTCOMES AND MEASURES: The primary outcome was Hospital Anxiety and Depression Scale symptom score (HADS; score range, 0 [best] to 42 [worst]; minimal clinically important difference, 1.5) obtained during 3-month follow-up interviews with the surrogate decision makers. Secondary outcomes included posttraumatic stress disorder experienced by the family and measured by the Impact of Events Scale-Revised (IES-R; total score range, 0 [best] to 88 [worst]), discussion of patient preferences, hospital length of stay, and 90-day survival. RESULTS: Among 365 family surrogate decision makers (mean age, 51 years; 71% female), 312 completed the study. At 3 months, there was no significant difference in anxiety and depression symptoms between surrogate decision makers in the intervention group and the control group (adjusted mean HADS score, 12.2 vs 11.4, respectively; between-group difference, 0.8 [95% CI, -0.9 to 2.6]; P = .34). Posttraumatic stress disorder symptoms were higher in the intervention group (adjusted mean IES-R score, 25.9) compared with the control group (adjusted mean IES-R score, 21.3) (between-group difference, 4.60 [95% CI, 0.01 to 9.10]; P = .0495). There was no difference between groups regarding the discussion of patient preferences (intervention, 75%; control, 83%; odds ratio, 0.63 [95% CI, 0.34 to 1.16; P = .14]). The median number of hospital days for patients in the intervention vs the control group (19 days vs 23 days, respectively; between-group difference, -4 days [95% CI, -6 to 3 days]; P = .51) and 90-day survival (hazard ratio, 0.95 [95% CI, 0.65 to 1.38], P = .96) were not significantly different. CONCLUSIONS AND RELEVANCE: Among families of patients with chronic critical illness, the use of palliative care-led informational and emotional support meetings compared with usual care did not reduce anxiety or depression symptoms and may have increased posttraumatic stress disorder symptoms. These findings do not support routine or mandatory palliative care-led discussion of goals of care for all families of patients with chronic critical illness. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01230099.

How well do medical oncologists manage chronic cancer pain? A national survey.

BACKGROUND: Cancer pain is usually managed by oncologists, occasionally with input from specialists in hospice and palliative medicine (PLM) or pain medicine (PMD). We evaluated the knowledge of cancer pain management in these three specialty groups. METHODS: Eight vignettes depicting challenging scenarios of patients with poorly controlled pain were developed; each had five or six treatment choices. Respondents indicated choices likely to be safe and efficacious as "true" and choices likely to be unsafe or inefficacious as "false." Two questionnaires were created, each with four vignettes. Three anonymous mailings targeted geographically representative U.S. samples of 570 oncologists, 266 PMD specialists, and 280 PLM specialists, each randomly assigned one version of the questionnaire. Vignette scores were normalized to a 0-100 numeric rating scale (NRS); a score of 50 indicates that the number of correct choices equals the number of incorrect choices (consistent with guessing). RESULTS: Overall response rate was 49% (oncologists, 39%; PMD specialists, 48%; and PLM specialists, 70%). Average vignette score ranges were 53.2-66.5, 45.6-65.6, and 50.8-72.0 for oncologists, PMD specialists, and PLM specialists, respectively. Oncologists scored lower than PLM specialists on both questionnaires and lower than PMD specialists on one. On a 0-10 NRS, oncologists rated their ability to manage pain highly (median 7, with an interquartile range [IQR] of 5-8). Lower ratings were assigned to pain-related training in medical school (median 3, with an IQR of 2-5) and residency/fellowship (median 5, with an IQR of 4-7). Oncologists older than 46-47 years rated their training lower than younger oncologists. CONCLUSION: These data suggest that oncologists and other medical specialists who manage cancer pain have knowledge deficiencies in cancer pain management. These gaps help clarify the need for pain management education.

The occurrence of Graves disease (autoimmune thyrotoxicosis) in endocrinologists at the Mount Sinai Hospital in New York City from 1954 to 2011.

OBJECTIVE: We report on the unique occurrence of Graves disease (thyrotoxicosis) in 7 male endocrinologists at the Mount Sinai Hospital (MSH) in New York City, New York between 1954 and 2011. METHODS: We followed the endocrinologists and fellows assigned to the division over a period of 57 years by survey and personal contact. In the statistical studies, we assumed that the number of cases had a Poisson distribution and computed the exact probability based on the expected values. RESULTS: Seven male endocrinologists had proven thyrotoxicosis during or following their service in the Endocrine Division at MSH. Six had a family history of thyrotoxicosis. None had known iodine 131 (131-I) thyroid contamination. CONCLUSION: The incidence of thyrotoxicosis greatly exceeds the rate predicted. Postulated factors in the causation of this unique occurrence are discussed.

Maternal active and passive smoking and hypertensive disorders of pregnancy: risk with trimester-specific exposures.

BACKGROUND: The inverse association between prenatal smoking and preeclampsia is puzzling, given the increased risks of prematurity and low birthweight associated with both smoking and preeclampsia. We analyzed the Norwegian Mother and Child Birth Cohort (MoBa) to determine whether the associations varied by timing of prenatal smoking. METHODS: We conducted an analysis of 74,439 singleton pregnancies with completed second- and third- trimester questionnaires. Active and passive smoke exposure by trimester were determined by maternal self-report, and covered the period of preconception through approximately 30 weeks' gestation. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Rates of active smoking declined dramatically during pregnancy: for trimester 1, 23%; trimester 2, 9%; and trimester 3, 8%. Active smoking in the third trimester was associated with reduced odds of preeclampsia and gestational hypertension, with the strongest association among continuous smokers (for preeclampsia, OR= 0.57 [95% CI = 0.46-0.70]). Women who quit smoking before the third trimester had approximately the same risk of preeclampsia and gestational hypertension as nonsmokers. There was some evidence of dose-response, with the heaviest smokers (more than eight cigarettes per day) having the lowest risks of preeclampsia (0.48 [0.32-0.73]) and gestational hypertension (0.51 [0.28-0.95]). There was little evidence of an association with passive smoking exposure. CONCLUSION: The association between smoking and preeclampsia varies substantially according to the timing and intensity of exposure. A better understanding of the biologic pathways that underlie these associations may provide important clues to the etiology of preeclampsia and the development of effective clinical interventions.

Characterizing the pregnancy immune phenotype: results of the viral immunity and pregnancy (VIP) study.

PURPOSE: The increased risk of morbidity and mortality from certain microbial infections and the demonstrated improvements in the clinical course of some autoimmune diseases support the existence of pregnancy-related alterations in immune status. Elucidating the changes in innate and adaptive immunity during gestation may improve pregnancy outcomes and facilitate the development of targeted therapies for autoimmune diseases. METHOD: The Viral Immunity and Pregnancy (VIP) study evaluated over 50 subjects longitudinally at three time points during pregnancy and at two time points post-delivery. Leukocyte enumeration was performed; functional responses of NK cells and CD4 T cells were analyzed, and soluble factors such as cytokines, defensins, and steroid hormones were measured in maternal blood. RESULTS: In comparison to the post-partum period, the latter part of pregnancy was characterized by significant increases in blood phagocytes and pDCs and decreases in the number and activity of NK and T cells. Alterations were found in antimicrobial proteins and serum cytokines. CONCLUSIONS: These data show that pregnancy is not a period of immunosuppression but an alteration in immune priorities characterized by a strengthening of innate immune barriers and a concomitant reduction in adaptive/inflammatory immunity in the later stages of pregnancy.

Persistence of multiple illnesses in World Trade Center rescue and recovery workers: a cohort study.

BACKGROUND: More than 50,000 people participated in the rescue and recovery work that followed the Sept 11, 2001 (9/11) attacks on the World Trade Center (WTC). Multiple health problems in these workers were reported in the early years after the disaster. We report incidence and prevalence rates of physical and mental health disorders during the 9 years since the attacks, examine their associations with occupational exposures, and quantify physical and mental health comorbidities. METHODS: In this longitudinal study of a large cohort of WTC rescue and recovery workers, we gathered data from 27,449 participants in the WTC Screening, Monitoring, and Treatment Program. The study population included police officers, firefighters, construction workers, and municipal workers. We used the Kaplan-Meier procedure to estimate cumulative and annual incidence of physical disorders (asthma, sinusitis, and gastro-oesophageal reflux disease), mental health disorders (depression, post-traumatic stress disorder [PTSD], and panic disorder), and spirometric abnormalities. Incidence rates were assessed also by level of exposure (days worked at the WTC site and exposure to the dust cloud). FINDINGS: 9-year cumulative incidence of asthma was 27·6% (number at risk: 7027), sinusitis 42·3% (5870), and gastro-oesophageal reflux disease 39·3% (5650). In police officers, cumulative incidence of depression was 7·0% (number at risk: 3648), PTSD 9·3% (3761), and panic disorder 8·4% (3780). In other rescue and recovery workers, cumulative incidence of depression was 27·5% (number at risk: 4200), PTSD 31·9% (4342), and panic disorder 21·2% (4953). 9-year cumulative incidence for spirometric abnormalities was 41·8% (number at risk: 5769); three-quarters of these abnormalities were low forced vital capacity. Incidence of most disorders was highest in workers with greatest WTC exposure. Extensive comorbidity was reported within and between physical and mental health disorders. INTERPRETATION: 9 years after the 9/11 WTC attacks, rescue and recovery workers continue to have a substantial burden of physical and mental health problems. These findings emphasise the need for continued monitoring and treatment of the WTC rescue and recovery population. FUNDING: Centers for Disease Control and Prevention and National Institute for Occupational Safety and Health.

Meeting standards of high-quality intensive care unit palliative care: clinical performance and predictors.

OBJECTIVES: High-quality care for intensive care unit patients and families includes palliative care. To promote performance improvement, the Agency for Healthcare Research and Quality's National Quality Measures Clearinghouse identified nine evidence-based processes of intensive care unit palliative care (Care and Communication Bundle) that are measured through review of medical record documentation. We conducted this study to examine how frequently the Care and Communication Bundle processes were performed in diverse intensive care units and to understand patient factors that are associated with such performance. DESIGN: Prospective, multisite, observational study of performance of key intensive care unit palliative care processes. SETTINGS: A surgical intensive care unit and a medical intensive care unit in two different large academic health centers and a medical-surgical intensive care unit in a medium-sized community hospital. PATIENTS: Consecutive adult patients with length of intensive care unit stay ≥5 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between November 2007 and December 2009, we measured performance by specified day after intensive care unit admission on nine care process measures: Identify medical decision-maker, advance directive and resuscitation preference, distribute family information leaflet, assess and manage pain, offer social work and spiritual support, and conduct interdisciplinary family meeting. Multivariable regression analysis was used to determine predictors of performance of five care processes. We enrolled 518 (94.9%) patients and 336 (83.6%) family members. Performances on pain assessment and management measures were high. In contrast, interdisciplinary family meetings were documented for <20% of patients by intensive care unit day 5. Performance on other measures ranged from 8% to 43%, with substantial variation across and within sites. Chronic comorbidity burden and site were the most consistent predictors of care process performance. CONCLUSIONS: Across three intensive care units in this study, performance of key palliative care processes (other than pain assessment and management) was inconsistent and infrequent. Available resources and strategies should be utilized for performance improvement in this area of high importance to patients, families, and providers.

Diabetes, glucose control, glucose lowering medications, and cancer risk: a 10-year population-based historical cohort.

BACKGROUND: Both diabetes and glucose-lowering medications have been associated with an increased risk of cancer incidence. This study will compare cancer incidence rates in individuals with and without diabetes; and will investigate, in individuals with diabetes, an association between glucose control and cancer incidence; and between the use of specific glucose-lowering medications, as well as no drug exposure, and cancer incidence. METHODS/DESIGN: This is a population based historical cohort study of all individuals aged 21 years or older (about 2,300,000) who were insured by Clalit Health Services, the largest health maintenance organization in Israel during a ten-year study period. Four study groups will be established according to the status of diabetes and cancer at study entry, Jan 1, 2002: cancer free, diabetes free; cancer free, diabetes prevalent; cancer prevalent, diabetes free; and cancer prevalent, diabetes prevalent. Individuals without diabetes at study entry will be followed for diabetes incidence, and all four groups will be followed for specific cancer incidence, including second primary neoplasms. Glucose control will be assessed by HbA1c and by fasting plasma glucose levels. Time dependent regression models for cancer incidence will account for glucose-lowering medications as they are added and changed over the follow-up period. A large number of demographic and clinical variables will be considered, including: age, gender, BMI, smoking status, concomitant medications, glucose control (assessed by HbA1c and by fasting plasma glucose) and cancer screening tests. DISCUSSION: Strengths of this study include the large population; high quality comprehensive data; comparison to individuals without diabetes, and to those with diabetes but not treated with glucose-lowering medications; and the extensive range of variables available for analysis. The great increases in diabetes prevalence and in treatment options render this study particularly relevant and timely. The Israeli national healthcare system, characterized by high standard and uniform healthcare, offers an advantageous environment for its conduct.

Clinical safety of Food Allergy Herbal Formula-2 (FAHF-2) and inhibitory effect on basophils from patients with food allergy: Extended phase I study.

BACKGROUND: Food allergy is a common and increasing health concern in westernized countries. No effective treatment is available, and accidental ingestion can be life-threatening. Food Allergy Herbal Formula-2 (FAHF-2) blocks peanut-induced anaphylaxis in a murine model of peanut-induced anaphylaxis. It was found to be safe and well tolerated in an acute phase I study of patients with food allergy. OBJECTIVE: We sought to assess the safety of FAHF-2 in an extended phase I clinical trial and determine the potential effects on peripheral blood basophils from patients with food allergy. METHODS: Patients in an open-label study received 3.3 g (6 tablets) of FAHF-2 three times a day for 6 months. Vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiographic data were acquired at baseline and at 2-month intervals. During the course of the study, basophil activation and basophil and eosinophil numbers were evaluated by using CCR3/CD63 staining and flow cytometry. RESULTS: Of 18 patients enrolled, 14 completed the study. No significant drug-associated differences in laboratory parameters, pulmonary function study results, or electrocardiographic findings before and after treatment were found. There was a significant reduction (P < .010) in basophil CD63 expression in response to ex vivo stimulation at month 6. There was also a trend toward a reduction in eosinophil and basophil numbers after treatment. CONCLUSION: FAHF-2 was safe and well tolerated and had an inhibitory effects on basophil numbers in an extended phase I clinical study. A controlled phase II study is warranted.

"Sarcoid like" granulomatous pulmonary disease in World Trade Center disaster responders.

BACKGROUND: More than 20,000 responders have been examined through the World Trade Center (WTC) Medical Monitoring and Treatment Program since September 11, 2001. Studies on WTC firefighters have shown elevated rates of sarcoidosis. The main objective of this study was to report the incidence of "sarcoid like" granulomatous pulmonary disease in other WTC responders. METHODS: Cases of sarcoid like granulomatous pulmonary disease were identified by: patient self-report, physician report and ICD-9 codes. Each case was evaluated by three pulmonologists using the ACCESS criteria and only "definite" cases are reported. RESULTS: Thirty-eight patients were classified as "definite" cases. Six-year incidence was 192/100,000. The peak annual incidence of 54 per 100,000 person-years occurred between 9/11/2003 and 9/11/2004. Incidence in black responders was nearly double that of white responders. Low FVC was the most common spirometric abnormality. CONCLUSIONS: Sarcoid like granulomatous pulmonary disease is present among the WTC responders. While the incidence is lower than that reported among firefighters, it is higher than expected.

Cancer in General Responders Participating in World Trade Center Health Programs, 2003-2013.

BACKGROUND: Following the September 11, 2001, attacks on the World Trade Center (WTC), thousands of workers were exposed to an array of toxins known to cause adverse health effects, including cancer. This study evaluates cancer incidence in the WTC Health Program General Responder Cohort occurring within 12 years post exposure. METHODS: The study population consisted of 28 729 members of the General Responder Cohort enrolled from cohort inception, July 2002 to December 31, 2013. Standardized incidence ratios (SIRs) were calculated with cancer case inclusion and follow-up starting post September 11, 2001 (unrestricted) and, alternatively, to account for selection bias, with case inclusion and follow-up starting 6 months after enrollment in the WTC Health Program (restricted). Case ascertainment was based on linkage with six state cancer registries. Under the restricted criterion, hazard ratios were estimated using multivariable Cox proportional hazards models for all cancer sites combined and for prostate cancer. RESULTS: Restricted analyses identified 1072 cancers in 999 responders, with elevations in cancer incidence for all cancer sites combined (SIR = 1.09, 95% confidence interval [CI] = 1.02 to 1.16), prostate cancer (SIR = 1.25, 95% CI = 1.11 to 1.40), thyroid cancer (SIR = 2.19, 95% CI = 1.71 to 2.75), and leukemia (SIR = 1.41, 95% CI = 1.01 to 1.92). Cancer incidence was not associated with any WTC exposure index (composite or individual) for all cancer sites combined or for prostate cancer. CONCLUSION: Our analyses show statistically significant elevations in cancer incidence for all cancer sites combined and for prostate and thyroid cancers and leukemia. Multivariable analyses show no association with magnitude or type of exposure.

BRCA1 promoter methylation is associated with increased mortality among women with breast cancer.

Promoter-CpG island hypermethylation has been proposed as an alternative mechanism to inactivate BRCA1 in the breast where somatic mutations of BRCA1 are rare. To better understand breast cancer etiology and progression, we explored the association between BRCA1 promoter methylation status and prognostic factors as well as survival among women with breast cancer. Promoter methylation of BRCA1 was assessed in 851 archived tumor tissues collected from a population-based study of women diagnosed with invasive or in situ breast cancer in 1996-1997, and who were followed for vital status through the end of 2002. About 59% of the tumors were methylated at the promoter of BRCA1. The BRCA1 promoter methylation was more frequent in invasive cancers (P = 0.02) and among premenopausal cases (P = 0.05). BRCA1 promoter methylation was associated with increased risk of breast cancer-specific mortality (age-adjusted HR 1.71; 95% CI: 1.05-2.78) and all-cause mortality (age-adjusted HR 1.49; 95% CI: 1.02-2.18). Neither dietary methyl intakes in the year prior to the baseline interview nor the functional polymorphisms in one-carbon metabolism were associated with BRCA1 methylation status. Our study is the first epidemiological investigation on the prognostic value of BRCA1 promoter methylation in a large population-based cohort of breast cancer patients. Our results indicate that BRCA1 promoter methylation is an important factor to consider in predicting breast cancer survival.

Epidemiologic research on man-made disasters: strategies and implications of cohort definition for World Trade Center worker and volunteer surveillance program.

Studies of long-term health consequences of disasters face unique methodologic challenges. The authors focused on studies of the health of cleanup and recovery workers, who are often poorly enumerated at the outset and difficult to follow over time. Comparison of the experience at the World Trade Center disaster with 4 past incidents of chemical and radiation releases at Seveso, Italy; Bhopal, India; Chernobyl, Ukraine; and Three Mile Island, USA, provided useful contrasts. Each event had methodologic advantages and disadvantages that depended on the nature of the disaster and the availability of records on area residents, and the emergency-response and cleanup protocol. The World Trade Center Worker Monitoring Program has well-defined eligibility criteria but lacks information on the universe of eligible workers to characterize response proportions or the potential for distortion of reported health effects. Nonparticipation may result from lack of interest, lack of awareness of the program, availability of another source of medical care, medical conditions precluding participation, inability to take time off from work, moving out of the area, death, or shift from initially ineligible to eligible status. Some of these considerations suggest selective participation by the sickest individuals, whereas others favor participation by the healthiest. The greatest concern with the validity of inferences regarding elevated health risks relative to external populations is the potential for selective enrollment among those who are affected. If there were a large pool of nonparticipating workers and those who suffered ill health were most motivated to enroll, the rates of disease among participants would be substantially higher than among all those eligible for the program. Future disaster follow-up studies would benefit substantially by having access to accurate estimates of the number of workers and information on the individuals who contributed to the cleanup and recovery effort.

Communication about chronic critical illness.

BACKGROUND: Despite poor outcomes, life-sustaining treatments including mechanical ventilation are continued for a large and growing population of patients with chronic critical illness. This may be owing in part to a lack of understanding resulting from inadequate communication between clinicians and patients and families. Our objective was to investigate the informational needs of patients with chronic critical illness and their families and the extent to which these needs are met. METHODS: In this prospective observational study conducted at 5 adult intensive care units in a large, university-affiliated hospital in New York, New York, 100 patients with chronic critical illness (within 3-7 days of elective tracheotomy for prolonged mechanical ventilation) or surrogates for incapacitated patients were surveyed using an 18-item questionnaire addressing communication about chronic critical illness. Main outcome measures included ratings of importance and reports of whether information was received about questionnaire items. RESULTS: Among 125 consecutive, eligible patients, 100 (80%) were enrolled; questionnaire respondents included 2 patients and 98 surrogates. For all items, more than 78% of respondents rated the information as important for decision making (>98% for 16 of 18 items). Respondents reported receiving no information for a mean (SD) of 9.0 (3.3) of 18 items, with 95% of respondents reporting not receiving information for approximately one-quarter of the items. Of the subjects rating the item as important, 77 of 96 (80%) and 69 of 74 (93%) reported receiving no information about expected functional status at hospital discharge and prognosis for 1-year survival, respectively. CONCLUSIONS: Many patients and their families may lack important information for decision making about continuation of treatment in the chronic phase of critical illness. Strategies for effective communication in this clinical context should be investigated and implemented.

PRO 2000 elicits a decline in genital tract immune mediators without compromising intrinsic antimicrobial activity.

OBJECTIVE: Vaginal microbicides should protect against infection without disrupting the mucosal environment or its mediators of host defense. The objective of this study was to examine the effect of 14 daily applications of 0.5% PRO 2000 or placebo gel on mediators of mucosal immunity and intrinsic antimicrobial activity. DESIGN AND METHODS: A randomized, prospective, double-blind, placebo-controlled study was conducted among 24 healthy, abstinent women. Levels of cytokines, chemokines, defensins, and other protective factors and intrinsic antimicrobial activity were determined in cervicovaginal lavage samples collected on study days 0, 7, 14, and 21. RESULTS: No increase in pro-inflammatory cytokines was observed. Rather cytokines and protective factors including interleukin (IL)-1 receptor antagonist, immunoglobulins and human beta-defensin 2 were lower in the drug compared with the placebo group. All of the mediators returned towards baseline on day 21. Women who were cycling had lower levels of most proteins on study days 7 and/or 14 compared with women on oral contraceptives; however, the magnitude of decline was greater in women who received PRO 2000 compared with placebo gel. The reduction in protective factors was not associated with a loss in the intrinsic anti-viral (HIV or herpes simplex virus) activity or anti-bacterial activity (Escherichia coli or Staphylococcus aureus). CONCLUSION: In contrast to experience with nonoxynol-9, PRO 2000 did not trigger an inflammatory response in cervicovaginal secretions. There was a modest reduction in mucosal immune mediators, but this loss was not associated with a reduction in intrinsic antimicrobial activity.