Area-based socio-economic disadvantage and tuberculosis incidence.

OBJECTIVE: To examine neighborhood-level influences on tuberculosis (TB) incidence in a multilevel population-based sample. DESIGN: All incident TB cases in Washington State, United States (n = 2161), reported between 1 January 2000 and 31 December 2008 were identified. Multivariate Poisson analysis was used at the ZIP Code tabulation area (ZCTA) level, which allowed for further exploration of area-specific influences on TB incidence. RESULTS: A significant association was found between indices of socio-economic position (SEP) and TB incidence in Washington State, with a clear gradient of higher rates observed among lower ZCTA socio-economic quartiles. Compared to the wealthiest SEP quartile, the relative incidence of TB in successively lower quartiles was respectively 2.7, 4.1 and 10.4 (P trend <0.001). In multivariate analyses, the addition of area-level race, ethnicity and country of birth significantly attenuated this association (adjusted incidence rate ratios 2.3, 2.6, 5.7; P trend <0.001). CONCLUSION: This study found a significant inverse association between area measures of socio-economic status (SES) and TB incidence across ZCTAs in Washington State, even after adjusting for individual age and sex and area-based race, ethnicity and foreign birth. These results emphasize the importance of neighborhood context and the need to target prevention efforts to low-SES neighborhoods.

The influence of types of decision support on physicians' decision making.

OBJECTIVE: To determine whether physicians' post-test probability estimates are influenced by receiving test characteristics and impact their subsequent clinical decisions. DESIGN: Questionnaire based randomised controlled trial. SETTING: Mailed survey with a vignette describing an infant whose pretest likelihood of pertussis was 30% and direct fluorescent-antibody (DFA) test was negative for pertussis. SUBJECTS: Nationally representative sample of US paediatricians (n = 1502). INTERVENTIONS: Random receipt of no additional information (controls), the DFA's sensitivity and specificity (TC group) or the test's sensitivity and specificity with their definitions (TCD group). MAIN OUTCOME MEASURES: Estimated post-test probability (PTP) of pertussis, PTP of 0.50, "nearly correct" PTP (+/-5%), intended erythromycin management and intended hospital disposition. ANALYSES: Chi2 and t tests. RESULTS: Despite the negative DFA result, 67% of the 635 (49.7%) participants who responded estimated a PTP higher than the pretest probability of 30%; the overall mean estimated PTP was 0.41 (SD 0.26) (correct answer: 0.18). The TCD group's mean PTP was significantly higher than controls' mean PTP (0.45 vs 0.38, p<0.001), while the TC and control groups' mean PTP did not differ significantly (0.41 vs 0.38, p = 0.16). With decision support significantly more TC and TCD participants compared to controls estimated the PTP as 0.50 (38% vs 17%, p<0.001; 41% vs 17%, p<0.001, respectively) and also estimated a nearly correct PTP more often (20% vs 13%, p = 0.06; 19% vs 13%, p = 0.08, respectively). The mean PTP of participants intending to discontinue erythromycin therapy or discharge the patient home was significantly lower than that of participants who intended continuing erythromycin or hospitalisation (0.20 vs 0.43, p<0.001; 0.40 vs 0.49, p = 0.005, respectively). CONCLUSIONS: Paediatricians differed in their response to information about test characteristics. For many, it increased errors in estimating post-test probability; for others, it reduced errors. Estimated post-test probability was logically associated with intended clinical management.

Education, cognitive function, and severity of neuropathology in Alzheimer disease.

BACKGROUND: Education may modulate the degree to which the neuropathology of Alzheimer disease (AD) is expressed as impaired cognitive performance. METHODS: We studied 2,051 participants age 65+ years at 27 AD Centers who died and underwent autopsy. All took the Mini-Mental State Examination (MMSE) within 2 years before death. Braak & Braak stage, neuritic plaque density, and Consortium to Establish a Registry for Alzheimer's Disease and National Institute on Aging (NIA)/Reagan diagnostic classifications quantified AD neuropathologic severity. Multivariate analyses modeled MMSE in relation to education and neuropathologic severity, adjusting for age at death, Lewy body pathology, and vascular dementia. RESULTS: Higher education was associated with higher MMSE scores when AD neuropathology was absent or mild. But with more advanced neuropathology, differences in MMSE scores among education levels were attenuated. For example, among patients without AD by NIA/Reagan criteria, fitted MMSE scores ranged from 19.6 for patients with less than high school education to 25.9 with education beyond high school. But among patients with neuropathologically advanced AD, the range of scores by education was only 7.1 to 8.6. CONCLUSIONS: We found no evidence of larger education-related differences in cognitive function when Alzheimer disease (AD) neuropathology was more advanced. Higher Mini-Mental State Examination scores among more educated persons with mild or no AD may reflect better test-taking skills or cognitive reserve, but these advantages may ultimately be overwhelmed by AD neuropathology.

An alternative method for estimating efficacy of the AN1792 vaccine for Alzheimer disease.

BACKGROUND: In a randomized trial of AN1792 vaccine against A beta in Alzheimer disease (AD), only 20% of vaccine recipients had an anti-AN1792 antibody response. The trialists sought to estimate the efficacy of the vaccine among antibody responders by comparing outcomes among antibody responders in the vaccine group with outcomes among all placebo recipients. METHODS: We describe why the method used may be biased. An alternative approach to estimating efficacy is described that compares outcomes between responders in the vaccine group and potential responders in the placebo group. Although potential responders cannot be identified individually, the distribution of outcomes among them can be inferred indirectly, under certain assumptions. Three methods for assessing vaccine effects are compared using data on the ventricular volume boundary shift integral (BSI) from the AN1792 trial and in simulations. RESULTS: Mean (+/- standard error) increase in BSI relative to controls was 0.16 (+/-0.065) by intent-to-treat, 0.61 (+/-0.116) in the published comparison, and 0.81 (+/-0.320) in the proposed approach. Simulations show that the published method can often yield biased estimates, while the proposed method does not. CONCLUSIONS: Published results from the AN1792 trial may have underestimated the effect of vaccine on progression of cerebral atrophy among patients with an antibody response to the vaccine. For this and future similar trials, we suggest that intent-to-treat results always be reported, and that efficacy estimates be based on the proposed potential-outcomes method.

Hypothesis: a motor neuron toxin produced by a clostridial species residing in gut causes ALS.

We hypothesize that a yet-to-be-identified motor neuron toxin produced by a clostridial species causes sporadic amyotrophic lateral sclerosis (ALS) in susceptible individuals. This clostridial species would reside undetected in the gut and chronically produce a toxin that targets the motor system, like the tetanus and botulinum toxins. After gaining access to the lower motor neuron, the toxin would be transported back to the cell body, as occurs with the tetanus toxin, and destroy the lower motor neuron - the essential feature of ALS. Again like the tetanus toxin, some of the toxin would cross to neighboring cells and to the upper motor neuron and similarly destroy these motor neurons. Weakness would relentlessly progress until not enough motor neurons remained to sustain life. If this hypothesis were correct, treatment with appropriate antibiotics or antitoxins might slow or halt progression of disease, and immunization might prevent disease.

Intracranial meningioma and ionizing radiation in medical and occupational settings.

In a population-based case-control study of 200 cases and 400 controls in western Washington State, the authors assessed associations between meningioma and ionizing radiation in medical and occupational settings. No significant associations were observed for diagnostic studies or occupational settings, but associations were observed for radiation therapy to head or neck (odds ratio 3.7, 95% CI 1.5 to 9.5), especially for neoplastic conditions. Only four patients (2%) had meningiomas that followed high-dose cranial radiation.

Dimensions of oral-health-related quality of life.

Oral-health-related quality of life (OHRQoL) is expected to have multiple dimensions. It was the aim of this study to investigate the dimensional structure of OHRQoL measured by the Oral Health Impact Profile (German version) (OHIP-G) and to derive a summary score for the instrument. Subjects (N = 2050; age, 16-79 yrs) came from a national survey. We used rotated principal-components analysis to derive a summary score and to explore the dimensional structure of OHIP-G. The first principal component explained 50% of the variance in the data. The sum of OHIP-G item responses was highly associated with the first principal component (r = 0.99). This simple but informative OHIP-G summary score may indicate that simple sums are also potentially useful scores for other OHRQoL instruments. Four dimensions (psychosocial impact, orofacial pain, oral functions, appearance) were found. These OHIP-G dimensions may serve as a parsimonious set of OHRQoL dimensions in general.

A prospective study of household smoking bans and subsequent cessation related behaviour: the role of stage of change.

OBJECTIVE: To assess the degree to which smokers living with a full household ban on smoking change their cessation related behaviour. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study; follow up of a population based cohort of 1133 smokers, identified from a 1997 telephone survey of adult Oregonians. After a median of 21 months, 565 were located and reinterviewed. MAIN OUTCOME MEASURES: Quit attempts, time until relapse, and smoking cessation, defined as seven day and 90 day sustained abstinence at follow up. RESULTS: A full ban at baseline was associated with a doubling of the odds of a subsequent quit attempt (odds ratio (OR) = 2.0, 95% confidence interval (CI), 1.0 to 3.9). Among respondents in the preparation stage at baseline (intention to quit in the next month with a quit attempt in the previous year), a full ban was associated with a lower relapse rate (hazard ratio = 0.5 (95% CI, 0.2 to 0.9)), while for those in precontemplation/contemplation (no intention to quit or intention to quit within the next six months, respectively), there was no significant association between full ban and relapse rate. For respondents in preparation, those with a full ban had over four times the odds of being in cessation for seven or more days before the follow up call (OR = 4.4 (1.1 to 18.7)), but for those in precontemplation/contemplation, full bans were unrelated to cessation. CONCLUSIONS: Full household bans may facilitate cessation among smokers who are preparing to quit by increasing quit attempts. They may also prolong time to relapse among those smokers.

Prognosis in amyotrophic lateral sclerosis: a population-based study.

BACKGROUND: Accurate information on prognosis of ALS is useful to patients, families, and clinicians. METHODS: In a population-based study of ALS in western Washington, the authors assembled a cohort of 180 patients with incident ALS between 1990 and 1994. Information on potential prognostic factors was collected during an in-person interview. Patients also completed the Medical Outcomes Study Short Form 36 (SF-36). Vital status through December 1999 was known for all patients. RESULTS: Median survival was 32 months from onset of symptoms and 19 months from diagnosis. The 5-year survival after diagnosis was 7%. Older age and female sex were strongly associated with poor survival. In multivariable Cox proportional hazards regression models, factors significantly and independently associated with a worse prognosis included older age, any bulbar features at onset, shorter time from symptom onset to diagnosis, lack of a marital partner, and residence in King County. Recursive partitioning identified age, time from symptom onset to diagnosis, and marital status as the strongest predictors of survival. Good summary scores for physical health on the SF-36, but not for mental health, were significantly associated with longer survival than poor scores. CONCLUSION: These findings are consistent with other population-based studies of ALS and confirm its pernicious nature. Older age, female sex, any bulbar features at onset, short time from symptom onset to diagnosis, lack of a marital partner, and disease severity are key prognostic factors. Serial measurement of severity would likely improve predictions.

History of head trauma and risk of intracranial meningioma: population-based case-control study.

A population-based case-control study in western Washington state was performed to assess the relation between head trauma and meningioma. Based on 200 case and 400 control subjects, head trauma was associated with an increased risk of meningioma (odds ratio = 1.83; 95% CI = 1.28, 2.62), especially head traumas occurring 10 to 19 years before reference date (odds ratio = 4.33; 95% CI = 2.06, 9.10). A dose-response relationship was present for number, but not severity, of head traumas. Whether the associations observed in this study are causal remains unclear.

Is household antibiotic use a risk factor for antibiotic-resistant pneumococcal infection?

We used microbiology and pharmacy data from health-maintenance organizations to determine whether antibiotic use by a household member increases the risk of penicillin-non-susceptible pneumococcal disease. Though it has been well established that an individual's antibiotic use increases one's risk of antibiotic-resistant infection, it is unclear whether the risk is increased if a member of one's household is exposed to antibiotics. We therefore conducted a case-control study of patients enrolled in health maintenance organizations in Western Washington and Northern California. Cases were defined as individuals with penicillin-non-susceptible pneumococcal infection; controls were individuals with penicillin-susceptible pneumococcal infection. Socioeconomic variables were obtained by linking addresses with 1997 census block group data. One-hundred and thirty-four cases were compared with 798 controls. Individual antibiotic use prior to diagnosis increased the odds of penicillin non-susceptibility, with the strongest effect seen for beta-lactam use within 2 months (OR 1.8, 95% CI 1.2, 2.8). When household antibiotic use by persons other than the patient were considered, at 4 months prior to diagnosis there was a trend towards an association between penicillin non-susceptibility and beta-lactam antibiotic use, and a possible association in a small subgroup of patients with eye and ear isolates. However, no significant overall pattern of association was seen. We conclude that though antibiotic use of any kind within 2 months prior to diagnosis is associated with an increased risk of penicillin-non-susceptible pneumococcal disease, there is no significant overall pattern of association between household antibiotic use and penicillin-non-susceptible pneumococcal infection.

Common bile duct injury during laparoscopic cholecystectomy and the use of intraoperative cholangiography: adverse outcome or preventable error?

BACKGROUND: Common bile duct (CBD) injury is a serious complication of laparoscopic cholecystectomy (LC). Predictors of this adverse outcome have not been well documented. HYPOTHESIS: Surgeon experience and the use of intraoperative cholangiography (IOC) are associated with a decreased rate of major CBD injury during LC. DESIGN: A retrospective population-based cohort study. SETTING: Washington State hospital discharge database reports from 1991 through 1998. PATIENTS: Discharge reports were searched for International Classification of Diseases, Ninth Revision, procedure codes consistent with LC and then evaluated for procedure codes for CBD repair and reconstruction within 90 days of LC. MAIN OUTCOME MEASURE: The rate of CBD injury in patients undergoing LC based on the surgeon's experience and IOC use. RESULTS: In all, 30 630 LCs and 76 major CBD injuries (2.5/1000 operations) were identified in this analysis. There were no significant differences between injured and noninjured patients in demographics, disease, payer status, or hospital variables. A CBD injury occurred in 3.2 of 1000 LCs in the early case order of surgeons compared with 1.7 per 1000 at later points (P = .01) (relative risk, 1.81; 95% confidence interval, 1.44-2.88). The rate of injury in LCs performed without IOC was 3.3 per 1000 compared with 2.0 per 1000 in LCs with IOC (P = .02) (relative risk, 1.7; 95% confidence interval, 1.1-2.6). Surgeon's experience and IOC use were independent predictors of injury. CONCLUSIONS: The rate of CBD injury is significantly lower when IOC is used. This effect is magnified during the early experience of surgeons. Systematic use of IOC may significantly reduce the rate of CBD injury.

Adolescents' use of emergency contraception provided by Washington State pharmacists.

STUDY OBJECTIVE: To increase knowledge about adolescents who obtained emergency contraceptive pills (ECP) directly from a pharmacist without first contacting a physician. DESIGN: Cross-sectional self-administered survey. SETTING: Fifteen randomly selected pharmacies providing ECP in western Washington State. PARTICIPANTS: Adolescents 15-21 years old (n = 126) who obtained ECP directly from a pharmacist. OUTCOME MEASURES: Responses to a 20-item questionnaire examining adolescents' reasons for seeking care from a pharmacist, need for additional medical evaluation, risk for not receiving additional medical care, and satisfaction with care provided by the pharmacist. RESULTS: The most common reasons for using the pharmacy were convenience (44%), lack of knowledge about alternatives (38%), and privacy (31%). If the pharmacy service were not available, 58% said they would see a doctor, 22% said they would wait to see if they got pregnant, and 20% did not know. Based on self-report, 81% of adolescents needed a new method of ongoing contraception, an evaluation for sexually transmitted disease, or both. Among these adolescents, 36% had risk factors for not receiving this care. Adolescents were satisfied with the pharmacy service; 94% said they would recommend the service to a friend. CONCLUSIONS: ECP provision by pharmacists is a useful way to increase access to emergency contraception. However, many adolescents using ECP need additional medical care. Programs designed to increase ECP access should use these opportunities to link adolescents with more comprehensive reproductive health care services.

Has misdiagnosis of appendicitis decreased over time? A population-based analysis.

CONTEXT: Misdiagnosis of presumed appendicitis is an adverse outcome that leads to unnecessary surgery. Computed tomography, ultrasonography, and laparoscopy have been suggested for use in patients with equivocal signs of appendicitis to decrease unnecessary surgery. OBJECTIVE: To determine if frequency of misdiagnosis preceding appendectomy has decreased with increased availability of computed tomography, ultrasonography, and laparoscopy. DESIGN, SETTING, AND PATIENTS: Retrospective, population-based cohort study of data from a Washington State hospital discharge database for 85 790 residents assigned International Classification of Diseases, Ninth Revision procedure codes for appendectomy, and United States Census Bureau data for 1987-1998. MAIN OUTCOME MEASURE: Population-based age- and sex-standardized incidence of appendectomy with acute appendicitis (perforated or not) or with a normal appendix. RESULTS: Among 63 707 nonincidental appendectomy patients, 84.5% had appendicitis (25.8% with perforation) and 15.5% had no associated diagnosis of appendicitis. After adjusting for age and sex, the population-based incidence of unnecessary appendectomy and of appendicitis with perforation did not change significantly over time. Among women of reproductive age, the population-based incidence of misdiagnosis increased 1% per year (P =.005). The incidence of misdiagnosis increased 8% yearly in patients older than 65 years (P<.001) but did not change significantly in children younger than 5 years (P =.17). The proportion of patients undergoing laparoscopic appendectomy who were misdiagnosed was significantly higher than that of open appendectomy patients (19.6% vs 15.5%; P<.001). CONCLUSION: Contrary to expectation, the frequency of misdiagnosis leading to unnecessary appendectomy has not changed with the introduction of computed tomography, ultrasonography, and laparoscopy, nor has the frequency of perforation decreased. These data suggest that on a population level, diagnosis of appendicitis has not improved with the availability of advanced diagnostic testing.

Drowsiness, counter-measures to drowsiness, and the risk of a motor vehicle crash.

OBJECTIVES: Knowledge of how different indicators of drowsiness affect crash risk might be useful to drivers. This study sought to estimate how drowsiness related factors, and factors that might counteract drowsiness, are related to the risk of a crash. METHODS: Drivers on major highways in a rural Washington county were studied using a matched case-control design. Control (n=199) drivers were matched to drivers in crashes (n=200) on driving location, travel direction, hour, and day of the week. RESULTS: Crash risk was greater among drivers who felt they were falling asleep (adjusted relative risk (aRR) 14.2, 95% confidence interval (CI) 1.4 to 147) and those who drove longer distances (aRR 2.2 for each additional 100 miles, 95% CI 1.4 to 3.3). Risk was also greater among drivers who had slept nine or fewer hours in the previous 48 hours, compared with those who had slept 12 hours. Crash risk was less for drivers who used a highway rest stop (aRR 0.5, 95% CI 0.3 to 1.0), drank coffee within the last two hours (aRR 0.5, 95% CI 0.3 to 0.9), or played a radio while driving (aRR 0.6, 95% CI .4 to 1.0). CONCLUSION: Drivers may be able to decrease their risk of crashing if they: (1) stop driving if they feel they are falling asleep; (2) use highway rest stops; (3) drink coffee; (4) turn on a radio; (5) get at least nine hours sleep in the 48 hours before a trip; and (6) avoid driving long distances by sharing the driving or interrupting the trip.

Lessons from a trial of acupuncture and massage for low back pain: patient expectations and treatment effects.

STUDY DESIGN: A subanalysis of data derived from a randomized clinical trial was performed. OBJECTIVE: To evaluate the association of a patient's expectation for benefit from a specific treatment with improved functional outcome. SUMMARY OF BACKGROUND DATA: Psychosocial factors, ambiguous diagnoses, and lack of a clearly superior treatment have complicated the management of patients with chronic low back pain. The authors hypothesized that patient expectation for benefit from a specific treatment is associated with improved functional outcomes when that treatment is administered. METHODS: In a randomized trial, 135 patients with chronic low back pain who received acupuncture or massage were studied. Before randomization, study participants were asked to describe their expectations regarding the helpfulness of each treatment on a scale of 0 to 10. The primary outcome was level of function at 10 weeks as measured by the modified Roland Disability scale. RESULTS: After adjustment for baseline characteristics, improved function was observed for 86% of the participants with higher expectations for the treatment they received, as compared with 68% of those with lower expectations (P = 0.01). Furthermore, patients who expected greater benefit from massage than from acupuncture were more likely to experience better outcomes with massage than with acupuncture, and vice versa (P = 0.03). CONCLUSIONS: The results of this study suggest that patient expectations may influence clinical outcome independently of the treatment itself. In contrast, general optimism about treatment, divorced from a specific treatment, is not strongly associated with outcome. These results may have important implications for clinical trial design and recruitment, and may help to explain the apparent success of some conventional and alternative therapies in trials that do not control for patient expectations. The findings also may be important for therapy choices made in the clinical setting.

Formal education and back pain: a review.

OBJECTIVES: To summarise the scientific evidence on the relation between educational status and measures of the frequency and the consequences of back pain and of the outcomes of interventions among back pain patients, and to outline possible mechanisms that could explain such an association if found. DESIGN: Sixty four articles published between 1966 and 2000 that documented the association of formal education with back pain were reviewed. MAIN RESULTS: Overall, the current available evidence points indirectly to a stronger association of low education with longer duration and/or higher recurrence of back pain than to an association with onset. The many reports of an association of low education with adverse consequences of back pain also suggest that the course of a back pain episode is less favourable among persons with low educational attainment. Mechanisms that could explain these associations include variations in behavioural and environmental risk factors by educational status, differences in occupational factors, compromised "health stock" among people with low education, differences in access to and utilisation of health services, and adaptation to stress. Although lower education was not associated with the outcomes of interventions in major studies, it is difficult, in light of the current limited available evidence, to draw firm conclusions on this association. CONCLUSION: Scientific evidence supports the hypothesis that less well educated people are more likely to be affected by disabling back pain. Further study of this association may help advance our understanding of back pain as well as understanding of the relation between socioeconomic status and disease as a general phenomenon.