Laura S. Gold

Impaired lung function and lung cancer incidence in a cohort of Swedish construction workers

Background: Although impaired lung function in general has been associated with an increased risk of lung cancer, past studies typically have not attempted to investigate separately the obstructive and restrictive components of respiratory impairment. To deal with this question further, data from a large (n = 176 997) cohort of male Swedish construction workers, for whom spirometry measurements before follow-up were available, were analysed. Methods: Cancer incidence for 1971–2001 was obtained through linkage with the national cancer registry. Using a modification of the Global Initiative for Chronic Obstructive Lung Disease criteria for chronic obstructive pulmonary disease (COPD), subjects were classified into five categories of lung function: normal, mild COPD, moderate COPD, severe COPD and restrictive lung disease (RLD). Rate ratios (RR) and 95% confidence intervals (CI) for lung cancer across lung function categories were calculated using Poisson regression, adjusted for age and smoking. Other end points (histological types of lung cancer, non-lung tobacco-related cancers, other cancers, total mortality) were also investigated. Results: 834 incident cases of lung cancer were identified. Increased rates of lung cancer were observed for both COPD (mild: RR 1.5, 95% CI 1.2 to 1.9; moderate/severe: RR 2.2, 95% CI 1.8 to 2.7) and RLD (RR 2.0, 95% CI 1.6 to 2.5) relative to normal lung function. These associations did not meaningfully change on applying follow-up lag times of 5, 10 and 15 years after spirometry. When analysed by histological type, associations with both COPD and RLD were stronger for squamous cell carcinoma and small cell carcinoma, and weaker for adenocarcinoma. Both COPD and RLD were associated with increased rates of total mortality. Conclusions: Obstructive and restrictive impairments in lung function are associated with increased lung cancer risk.

Ventricular fibrillation in King County, Washington: a 30-year perspective.

AIM We determined the effect of four major program changes over a 30-year period on survival from witnessed cardiac arrest (CA) with ventricular fibrillation (VF) as the rhythm causing collapse. METHODS We conducted an investigation of emergency medical services (EMS)-treated CA occurring between 1978 and 2007. Data were obtained from a registry maintained by the King County Emergency Medical Services Division. Using Utstein style definitions, we measured changes in patient survival in light of four programs that were implemented during the span of the study: defibrillation by emergency medical technicians (EMTs), dispatcher-assisted cardiopulmonary resuscitation (CPR), public access defibrillation, and a CPR-defibrillation protocol that replaced delivery of three sequential shocks with administration of one shock followed by 2 min of CPR. RESULTS Overall survival from witnessed VF during the study period was 34%. While demographic characteristics of patients in CA remained constant, we observed greater rates of survival in the years following the program changes, 1983-2006, compared to survival in the period before the changes, 1977-1982. The greatest increase in survival occurred following the CPR-defibrillation protocol change in 2005. CONCLUSION Despite adverse temporal trends, the four program changes appear to have contributed to increasing survival rates from out-of-hospital cardiac arrests in King County.

Reliability of the Cerebral Performance Category to classify neurological status among survivors of ventricular fibrillation arrest: a cohort study.

BackgroundThe Cerebral Performance Category (CPC) score is widely used in research and quality assurance to assess neurologic outcome following cardiac arrest. However, little is known about the inter- and intra-reviewer reliability of the CPC.MethodsWe undertook an investigation to assess the inter-reviewer and source document reliability of the CPC among a cohort of survivors from out-of-hospital ventricular fibrillation cardiac arrest (n = 131) in a large metropolitan area between November 1, 2003 and December 31, 2005. Subjects with a CPC of 1 or 2 were classified as favorable outcome and those with CPC 3 or greater were classified as unfavorable outcome. One abstractor first used the discharge summary alone to determine the CPC. All 3 abstractors independently reviewed the entire hospital record. Reliability was assessed by determining the proportion of determinations that agreed between abstractors and the respective kappa statistics. We also evaluated the implications for determining survival with favorable neurological outcome when survival to hospital discharge was 20% and 30%.ResultsWhen the entire hospital record was used to determine CPC, favorable neurologic outcome (CPC 1 or 2) was recorded in 92% by abstractor 1, 89% by abstractor 2, and 74% by abstractor 3. Agreement was 96% (kappa = 0.78) between abstractors 1 and 2, 84% (kappa = 0.49) between abstractors 2 and 3, 82% (kappa = 0.38) between abstractors 1 and 3. The 3-way kappa was 0.50. Agreement was 90% (kappa = 0.71) between the discharge summary alone and the entire hospital record. If the results from review of the entire record are applied to a circumstance where survival to discharge is 20%, favorable neurologic status would occur in 18.4% for abstractor 1, 17.8% for abstractor 2, and 14.8% for abstractor 3. For survival to hospital discharge of 30%, favorable neurologic status would occur in 27.6% for abstractor 1, 26.7% for abstractor 2, and 22.2% for abstractor 3.ConclusionsIn this cohort study of survivors of out-of-hospital ventricular fibrillation cardiac arrest, the use of the CPC to classify favorable versus unfavorable neurological status at hospital discharge produced variable inter- and intra-reviewer agreement. The findings provide useful context to interpret outcome evaluations that report CPC.

Metabolic gene variants and risk of non-Hodgkin's lymphoma.

Genes involved in metabolism of environmental chemical exposures exhibit sequence variability that may mediate the risk of non-Hodgkins lymphoma. We evaluated associations between non-Hodgkins lymphoma and 15 variants in AHR, CYP1A1, CYP1A2, CYP1B1, CYP2C9, CYP2E1, GSTP1, GSTM3, EPHX1, NQO1, and PON1. Cases were identified from four Surveillance, Epidemiology, and End Results registries in the United States, and population-based controls were identified through random-digit dialing and Medicare eligibility files. Metabolic gene variants were characterized for the 1,172 (89% of total) cases and 982 (93%) controls who provided biological samples for genotyping. Subjects who were heterozygous or homozygous for the cytochrome P450 gene variant CYP1B1 V432L G allele were at slightly greater risk of non-Hodgkins lymphoma [odds ratio (OR), 1.27; 95% confidence interval (95% CI), 0.97-1.65]; these results were consistent across B-cell lymphoma subtypes and among both non-Hispanic White and Black subjects, although not statistically significant. The CYP2E1 −1054T allele was associated with decreased risk of non-Hodgkins lymphoma (CT and TT genotypes combined OR, 0.59; 95% CI, 0.37-0.93), and this pattern was observed among all histologic subtypes. The numbers of cases of particular subtypes were rather small for stable estimates, but we noted that the PON1 L55M AA allele, associated with slightly increased risk of non-Hodgkins lymphoma (variant homozygotes OR, 1.36; 95% CI, 0.96-1.95), was most strongly associated with follicular non-Hodgkins lymphoma and T-cell lymphoma, with ORs for variant homozygotes of 2.12 and 2.93, respectively. There was no overall association with non-Hodgkins lymphoma for the other gene variants we examined. The modest effects we observed may reflect the context of exposures within the general population represented in our study. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1647–53)

Association of Early Imaging for Back Pain With Clinical Outcomes in Older Adults

IMPORTANCE In contrast to the recommendations for younger adults, many guidelines allow for older adults with back pain to undergo imaging without waiting 4 to 6 weeks. However, early imaging may precipitate interventions that do not improve outcomes. OBJECTIVE To compare function and pain at the 12-month follow-up visit among older adults who received early imaging with those who did not receive early imaging after a new primary care visit for back pain without radiculopathy. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort of 5239 patients 65 years or older with a new primary care visit for back pain (2011-2013) in 3 US health care systems. We matched controls 1:1 using propensity score matching of demographic and clinical characteristics, including diagnosis, pain severity, pain duration, functional status, and prior resource use. EXPOSURES Diagnostic imaging (plain films, computed tomography [CT], magnetic resonance imaging [MRI]) of the lumbar or thoracic spine within 6 weeks of the index visit. MAIN OUTCOME AND MEASURES PRIMARY OUTCOME back or leg pain-related disability measured by the modified Roland-Morris Disability Questionnaire (score range, 0-24; higher scores indicate greater disability) 12 months after enrollment. RESULTS Among the 5239 patients, 1174 had early radiographs and 349 had early MRI/CT. At 12 months, neither the early radiograph group nor the early MRI/CT group differed significantly from controls on the disability questionnaire. The mean score for patients who underwent early radiography was 8.54 vs 8.74 among the control group (difference, -0.10 [95% CI, -0.71 to 0.50]; mixed model, P = .36). The mean score for the early MRI/CT group was 9.81 vs 10.50 for the control group (difference,-0.51 [-1.62 to 0.60]; mixed model, P = .18). CONCLUSIONS AND RELEVANCE Among older adults with a new primary care visit for back pain, early imaging was not associated with better 1-year outcomes. The value of early diagnostic imaging in older adults for back pain without radiculopathy is uncertain.

Associations of patient outcomes with level of asthma control.

BACKGROUND Despite effective medications, asthma remains a significant burden to the US health care system. OBJECTIVE To determine whether partly and uncontrolled asthma in respondents to the Asthma Insights and Management (AIM) survey was associated with adverse outcomes (such as visits to health care professionals and medication use) compared with well-controlled asthma. METHODS The AIM survey, conducted in 2009, included 2,500 patients with asthma who were 12 years or older. We classified patients into levels of control and compared use of health care services and limitations of activities in patients whose asthma was well controlled vs those with partly and uncontrolled asthma. RESULTS Patients who reported lower income and educational status and lacked health insurance were less likely to have had well-controlled asthma. Respondents with uncontrolled asthma were more likely to report ever use of oral steroids (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.9-3.2) and over-the-counter medicine (OR, 2.7; 95% CI, 2.0-3.7) compared with patients whose asthma was well controlled. Respondents with partly and uncontrolled asthma were also significantly more likely to report ever visiting physicians, specialists, or the emergency department or being hospitalized for asthma compared with those whose asthma was well controlled (ORs ranging from 2.1 to 5.6). Finally, respondents whose asthma was uncontrolled had increased odds (ORs ranging from 14 to 34) of reporting that asthma limited their activities compared with respondents whose asthma was well controlled. CONCLUSION Patients with partly and uncontrolled asthma defined by international guidelines reported use of significantly more health care resources and greater limitations of their daily activities compared with patients whose asthma was well controlled.

The relationship between time to arrival of emergency medical services (EMS) and survival from out-of-hospital ventricular fibrillation cardiac arrest

AIM We examined the relationship between time from collapse to arrival of emergency medical services (EMS) and survival to hospital discharge for out-of-hospital ventricular fibrillation cardiac arrests in order to determine meaningful interpretations of this association. METHODS We calculated survival rates in 1-min intervals from collapse to EMS arrival. Additionally, we used logistic regression to determine the absolute probability of survival per minute of delayed EMS arrival. We created a logistic regression model with spline terms for the time variable to examine the decline in survival in intervals that are hypothesized to be physiologically relevant. RESULTS The observed data showed survival declined, on average, by 3% for each minute that EMS was delayed following collapse. Survival rates did not decline appreciably if the time between collapse and arrival of EMS was 4 min or less but they declined by 5.2% per minute between 5 and 10 min. EMS arrival 11-15 min after collapse showed a less steep decline in survival of 1.9% per minute. The spline model that incorporated changes in slope in the time interval variable modeled this relationship more accurately than a model with a continuous term for time (p=0.01). CONCLUSIONS The results of our analyses show that survival from out-of-hospital cardiac arrest does not decline at a constant rate following collapse. Models that incorporate changes that reflect the physiological alterations that occur following cardiac arrests are a more accurate way to describe changes in survival rates over time than models that include only a continuous term for time.

The relationship between multiple myeloma and occupational exposure to six chlorinated solvents

Objectives Few studies have examined whether exposure to chlorinated solvents is associated with multiple myeloma. We evaluated associations between multiple myeloma and occupational exposure to six chlorinated solvents: 1,1,1-trichloroethane, trichloroethylene (TCE), methylene chloride (DCM), perchloroethylene, carbon tetrachloride and chloroform. Methods In-person interviews obtained occupational histories and information on jobs with likely solvent exposure. We assigned exposure metrics of probability, frequency, intensity and confidence using job-exposure matrices modified by job-specific questionnaire information. We used logistic regression to estimate ORs and 95% CIs for associations between multiple myeloma and ever exposure to each, and any, chlorinated solvent and analysed whether associations varied by duration and cumulative exposure. We also considered all occupations that were given the lowest confidence scores as unexposed and repeated all analyses. Results Risk of multiple myeloma was elevated for subjects ever exposed to 1,1,1-trichloroethane (OR (95% CI): 1.8 (1.1 to 2.9)). Ever exposure to TCE or DCM also entailed elevated, but not statistically significant, risks of multiple myeloma; these became statistically significant when occupations with low confidence scores were considered unexposed (TCE: 1.7 (1.0 to 2.7); DCM: 2.0 (1.2 to 3.2)). Increasing cumulative exposure to perchloroethylene was also associated with increasing multiple myeloma risk. We observed non-significantly increased multiple myeloma risks with exposure to chloroform; however, few subjects were exposed. Conclusions Evidence from this relatively large case-control study suggests that exposures to certain chlorinated solvents may be associated with increased incidence of multiple myeloma; however, the study is limited by relatively low participation (52%) among controls.

Procainamide and Survival in Ventricular Fibrillation Out-of-hospital Cardiac Arrest

OBJECTIVES Procainamide is an antiarrhythmic drug of unproven efficacy in cardiac arrest. The association between procainamide and survival from out-of-hospital cardiac arrest was investigated to better determine the drugs potential role in resuscitation. METHODS The authors conducted a 10-year study of all witnessed, out-of-hospital, ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) cardiac arrests treated by emergency medical services (EMS) in King County, Washington. Patients were considered eligible for procainamide if they received more than three defibrillation shocks and intravenous (IV) bolus lidocaine. Four logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) describing the relationship between procainamide and survival. RESULTS Of the 665 eligible patients, 176 received procainamide, and 489 did not. On average, procainamide recipients received more shocks and pharmacologic interventions and had lengthier resuscitations. Adjusted for their clinical and resuscitation characteristics, procainamide recipients had a lower likelihood of survival to hospital discharge (OR = 0.52; 95% CI = 0.36 to 0.75). Further adjustment for receipt of other cardiac medications during resuscitation negated this apparent adverse association (OR = 1.02; 95% CI = 0.66 to 1.57). CONCLUSIONS In this observational study of out-of-hospital VF and pulseless VT arrest, procainamide as second-line antiarrhythmic treatment was not associated with survival in models attempting to best account for confounding. The results suggest that procainamide, as administered in this investigation, does not have a large impact on outcome, but cannot eliminate the possibility of a smaller, clinically relevant effect on survival.

Associations of common variants in genes involved in metabolism and response to exogenous chemicals with risk of multiple myeloma

BACKGROUND We examined risk of multiple myeloma (MM) associated with variants in genes involved in metabolism and response to exogenous chemicals [cytochrome P450 enzymes (CYP1B1, CYP2C9), epoxide hydrolase (EPHX1), paraoxonase 1 (PON1), arylhydrocarbon hydroxylase receptor (AHR), and NAD(P)H:quinone oxidoreductase (NQO1)]. METHODS This study included 279 MM cases and 782 controls in a pooled analysis of two population-based case-control studies. One common variant from each candidate gene was genotyped using DNA from blood or buccal cells. We estimated risk of MM associated with each genotype, controlling for race, gender, study site, and age, using odds ratios (OR) and 95% confidence intervals (CI). RESULTS Evaluations of the CYP1B1 V432L variant (rs1056836) suggested increased risk of MM among persons with the CG and GG genotypes compared to the CC genotype [OR (95% CI)=1.4 (1.0-2.0)]. Similar results were seen in analyses stratified by race and gender. We did not find any associations between MM and the CYP2C9, EPHX1, NQO1, or PON1 genes. CONCLUSIONS CYP1B1 activates chemicals such as polycyclic aromatic hydrocarbons and dioxins to create oxidized, reactive intermediates, and higher gene activity has been shown for the G allele. We conducted the largest analysis to date on MM and these genetic variants and our results provide preliminary evidence that variation in CYP1B1 may influence susceptibility to MM.