Changes in primary care provider utilization by phase of care for women diagnosed with breast cancer: a CanIMPACT longitudinal cohort study.

BACKGROUND: Primary care providers (PCPs) have always played an important role in cancer diagnosis. There is increasing awareness of the importance of their role during treatment and survivorship. We examined changes in PCP utilization from pre-diagnosis to survival for women diagnosed with breast cancer, factors associated with being a high user of primary care, and variation across four Canadian provinces. METHODS: The cohorts included women 18+ years of age diagnosed with stage I-III invasive breast cancer in years 2007-2012 in British Columbia (BC), Manitoba (MB), Ontario (ON), and Nova Scotia (NS) who had surgery plus adjuvant chemotherapy and were alive 30+ months after diagnosis (N = 19,589). We compared the rate of PCP visits in each province across phases of care (pre-diagnosis, diagnosis, treatment, and survival years 1 to 4). RESULTS: PCP use was greatest during treatment and decreased with each successive survival year in all provinces. The unadjusted difference in PCP use between treatment and pre-diagnosis was most pronounced in BC where PCP use was six times higher during treatment than pre-diagnosis. Factors associated with being a high user of primary care during treatment included comorbidity and being a high user of care pre-diagnosis in all provinces. These factors were also associated with being a higher user of care during diagnosis and survival. CONCLUSIONS: Contrary to the traditional view that PCPs focus primarily on cancer prevention and early detection, we found that PCPs are involved in the care of women diagnosed with breast cancer across all phases of care.

Cross-Canada differences in early-stage breast cancer treatment and acute-care use.

Background: Chemotherapy has improved outcomes in early-stage breast cancer, but treatment practices vary, and use of acute care is common. We conducted a pan-Canadian study to describe treatment differences and the incidence of emergency department visits (edvs), edvs leading to hospitalization (edvhs), and direct hospitalizations (hs) during adjuvant chemotherapy. Methods: The cohort consisted of women diagnosed with early-stage breast cancer (stages i-iii) during 2007-2012 in British Columbia, Manitoba, Ontario, or Nova Scotia who underwent curative surgery. Parallel provincial analyses were undertaken using linked clinical, registry, and administrative databases. The incidences of edvs, edvhs, and hs in the 6 months after treatment initiation were examined for patients treated with adjuvant chemotherapy. Results: The cohort consisted of 50,224 patients. The proportion of patients who received chemotherapy varied by province, with Ontario having the highest proportion (46.4%), and Nova Scotia, the lowest proportion (38.0%). Age, stage, receptor status, comorbidities, and geographic location were associated with receipt of chemotherapy in all provinces. Ontario had the highest proportion of patients experiencing an edv (36.1%), but the lowest proportion experiencing h (6.4%). Conversely, British Columbia had the lowest proportion of patients experiencing an edv (16.0%), but the highest proportion experiencing h (26.7%). The proportion of patients having an edvh was similar across provinces (13.9%-16.8%). Geographic location was associated with edvs, edvhs, and hs in all provinces. Conclusions: Intra- and inter-provincial differences in the use of chemotherapy and acute care were observed. Understanding variations in care can help to identify gaps and opportunities for improvement and shared learnings.

Evidence of advanced stage colorectal cancer with longer diagnostic intervals: a pooled analysis of seven primary care cohorts comprising 11 720 patients in five countries.

BACKGROUND: The benefits from expedited diagnosis of symptomatic cancer are uncertain. We aimed to analyse the relationship between stage of colorectal cancer (CRC) and the primary and specialist care components of the diagnostic interval. METHODS: We identified seven independent data sets from population-based studies in Scotland, England, Canada, Denmark and Spain during 1997-2010 with a total of 11 720 newly diagnosed CRC patients, who had initially presented with symptoms to a primary care physician. Data were extracted from patient records, registries, audits and questionnaires, respectively. Data sets were required to hold information on dates in the diagnostic interval (defined as the time from the first presentation of symptoms in primary care until the date of diagnosis), symptoms at first presentation in primary care, route of referral, gender, age and histologically confirmed stage. We carried out reanalysis of all individual data sets and, using the same method, analysed a pooled individual patient data set. RESULTS: The association between intervals and stage was similar in the individual and combined data set. There was a statistically significant convex (∩-shaped) association between primary care interval and diagnosis of advanced (i.e., distant or regional) rather than localised CRC (P=0.004), with odds beginning to increase from the first day on and peaking at 90 days. For specialist care, we saw an opposite and statistically significant concave (∪-shaped) association, with a trough at 60 days, between the interval and diagnosis of advanced CRC (P<0.001). CONCLUSIONS: This study provides evidence that longer diagnostic intervals are associated with more advanced CRC. Furthermore, the study cannot define a specific 'safe' waiting time as the length of the primary care interval appears to have negative impact from day one.

Use of physician services during the survivorship phase: a multi-province study of women diagnosed with breast cancer.

INTRODUCTION: Oncologists have traditionally been responsible for providing routine follow-up care for cancer survivors; in recent years, however, primary care providers (pcps) are taking a greater role in care during the follow-up period. In the present study, we used a longitudinal multi-province retrospective cohort study to examine how primary care and specialist care intersect in the delivery of breast cancer follow-up care. METHODS: Various databases (registry, clinical, and administrative) were linked in each of four provinces: British Columbia, Manitoba, Ontario, and Nova Scotia. Population-based cohorts of breast cancer survivors were identified in each province. Physician visits were identified using billings or claims data and were classified as visits to primary care (total, breast cancer-specific, and other), oncology (medical oncology, radiation oncology, and surgery), and other specialties. The mean numbers of visits by physician type and specialty, or by combinations thereof, were examined. The mean numbers of visits for each follow-up year were also examined by physician type. RESULTS: The results showed that many women (>64%) in each province received care from both primary care and oncology providers during the follow-up period. The mean number of breast cancer-specific visits to primary care and visits to oncology declined with each follow-up year. Interprovincial variations were observed, with greater surgeon follow-up in Nova Scotia and greater primary care follow-up in British Columbia. Provincial differences could reflect variations in policies and recommendations, relevant initiatives, and resources or infrastructure to support pcp-led follow-up care. CONCLUSIONS: Optimizing the role of pcps in breast cancer follow-up care might require strategies to change attitudes about pcp-led follow-up and to better support pcps in providing survivorship care.

Waiting Time Intervals for Non-small Cell Lung Cancer Diagnosis and Treatment in Alberta: Quantification of Intervals and Identification of Risk Factors Associated with Delays.

AIMS: Very little is known regarding the time required to diagnose and treat patients with non-small cell lung cancer (NSCLC) in Canada. We sought to quantify diagnostic and treatment intervals for NSCLC care in Alberta and identify risk factors for delays. MATERIALS AND METHODS: The Alberta Cancer Registry identified all cases of stage I-III NSCLC diagnosed and treated in Alberta, Canada from 2004 to 2011. Diagnostic data were obtained from physician billing, inpatient/outpatient hospital data and electronic medical records to quantify the duration of diagnostic and treatment intervals and their sum (system interval). Multivariable logistic regression was carried out to identify factors associated with delays. RESULTS: Of the 3009 eligible patients included, the median and 90th percentile system interval was 78 (95% confidence interval 76-80) and 185 days (95% confidence interval 178-195), respectively. The treatment interval was longer than the diagnostic interval, with medians of 51 (95% confidence interval 49-53) and 38 (95% confidence interval 36-40) days, respectively. After adjustment, age > 60 years and treatment by modalities other than supportive care (especially surgery) were associated with delays. Factors associated with prompt care included high acuity presentations and stage III disease. CONCLUSION: The majority of Albertans with potentially curable NSCLC exceeded guidelines for the timeliness of their care.

Survival in stage I-III breast cancer patients by surgical treatment in a publicly funded health care system.

BACKGROUND: Recent investigations of breast cancer survival in the United States suggest that patients who receive mastectomy have poorer survival than those who receive breast-conserving surgery (BCS) plus radiotherapy, despite clinically established equivalence. This study investigates breast cancer survival in the publicly funded health care system present in Alberta, Canada. PATIENTS AND METHODS: Surgically treated stage I-III breast cancer cases diagnosed in Alberta from 2002 to 2010 were included. Demographic, treatment and mortality information were collected from the Alberta Cancer Registry. Unadjusted overall and breast cancer-specific mortality was assessed using Kaplan-Meier and cumulative incidence curves, respectively. Cox proportional hazards models were used to calculate stage-specific mortality hazard estimates associated with surgical treatment received. RESULTS: A total of 14 939 cases of breast cancer (14 633 patients) were included in this study. The unadjusted 5-year all-cause survival probabilities for patients treated with BCS plus radiotherapy, mastectomy, and BCS alone were 94% (95% CI 93% to 95%), 83% (95% CI 82% to 84%) and 74% (95% CI 70% to 78%), respectively. Stage II and III patients who received mastectomy had a higher all-cause (stage II HR = 1.36, 95% CI 1.13-1.48; stage III HR = 1.74, 95% CI 1.24-2.45) and breast cancer-specific (stage II HR = 1.39, 95% CI 1.09-1.76; stage III HR = 1.79, 95% CI 1.21-2.65) mortality hazard compared with those who received BCS plus radiotherapy, adjusting for patient and clinical characteristics. BCS alone was consistently associated with poor survival. CONCLUSIONS: Stage II and III breast cancer patients diagnosed in Alberta, Canada, who received mastectomy had a significantly higher all-cause and breast cancer-specific mortality hazard compared with those who received BCS plus radiotherapy. We suggest greater efforts toward educating and encouraging patients to receive BCS plus radiotherapy rather than mastectomy when it is medically feasible and appropriate.

Using administrative data to estimate time to breast cancer diagnosis and percent of screen-detected breast cancers ­ a validation study in Alberta, Canada.

Appropriate use of administrative data enables the assessment of care quality at the population level. Our objective was to develop/validate methods for assessing quality of breast cancer diagnostic care using administrative data, specifically by identifying relevant medical tests to estimate the percentage screen/symptom-detected cancers and time to diagnosis. Two databases were created for all women diagnosed with a first-ever breast cancer in years 2007-2010 in Alberta, Canada, with dates of medical tests received in years 2006-2010. One purchased database had test results and was used to determine the 'true' first relevant test of a cancer diagnosis. The other free administrative database had test types but no test results. Receiver operating characteristic curves and concordance rates were used to assess estimates of percent screen/symptom-detected breast cancers; Log-rank test was used to assess time to diagnosis obtained from the two databases. Using a look-back period of 4-6 months from cancer diagnosis to identify relevant tests resulted in over 94% concordance, sensitivity and specificity for classifying patients into screen/symptom-detected group; good agreement between the distributions of time to diagnosis was also achieved. Our findings support the use of administrative data to accurately identify relevant tests for assessing the quality of breast cancer diagnostic care.

The relationship between lingual and hypoglossal nerve function and quality of life in head and neck cancer.

Sensorimotor impairment of the tongue has the potential to affect speech and swallowing. The purpose of this study was to critically examine the effects of nerve preservation and reinnervation after reconstruction of the base of tongue on patient-perceived outcomes of quality of life (QoL) related to speech and swallowing through completion of the EORTC QLQ-H&N35 standardised questionnaire. Thirty participants with a diagnosis of base of tongue cancer underwent primary resection and reconstruction with a radial forearm free flap, which may or may not have included nerve repair to the lingual nerve, hypoglossal nerve or both. Eight QoL domains sensitive to changes in motor and sensory nerve function were included in the analysis. Transected lingual and hypoglossal nerves were associated with difficulty in swallowing, social eating, dry mouth and social contact. There were fewer problems reported when these nerves were either repaired or left intact. There were no significant differences between patient nerve status and QoL outcomes for speech, sticky saliva and use of feeding tubes. This study was the first to examine the impact of sensory or motor nerve transection and reconstruction on health-related QoL outcomes.

Sarcopenia is associated with postoperative infection and delayed recovery from colorectal cancer resection surgery.

BACKGROUND: Skeletal muscle depletion (sarcopenia) predicts morbidity and mortality in the elderly and cancer patients. METHODS: We tested whether sarcopenia predicts primary colorectal cancer resection outcomes in stage II-IV patients (n=234). Sarcopenia was assessed using preoperative computed tomography images. Administrative hospitalisation data encompassing the index surgical admission, direct transfers for inpatient rehabilitation care and hospital re-admissions within 30 days was searched for International Classification of Disease (ICD)-10 codes for postoperative infections and inpatient rehabilitation care and used to calculate length of stay (LOS). RESULTS: Overall, 38.9% were sarcopenic; 16.7% had an infection and 9.0% had inpatient rehabilitation care. Length of stay was longer for sarcopenic patients overall (15.9 ± 14.2 days vs 12.3 ± 9.8 days, P=0.038) and especially in those ≥ 65 years (20.2 ± 16.9 days vs 13.1 ± 8.3 days, P=0.008). Infection risk was greater for sarcopenic patients overall (23.7% vs 12.5%; P=0.025), and especially those ≥ 65 years (29.6% vs 8.8%, P=0.005). Most (90%) inpatient rehabilitation care was in patients ≥ 65 years. Inpatient rehabilitation was more common in sarcopenic patients overall (14.3% vs 5.6%; P=0.024) and those ≥ 65 years (24.1% vs 10.7%, P=0.06). In a multivariate model in patients ≥ 65 years, sarcopenia was an independent predictor of both infection (odds ratio (OR) 4.6, (95% confidence interval (CI) 1.5, 13.9) P<0.01) and rehabilitation care (OR 3.1 (95% CI 1.04, 9.4) P<0.04). CONCLUSION: Sarcopenia predicts postoperative infections, inpatient rehabilitation care and consequently a longer LOS.

Referral rate to oncologists and its variation by hospital for colorectal cancer patients.

BACKGROUND: Recent population-based studies in Alberta, Canada, found that approximately 50% of patients with stage III colon or stages II/III rectal adenocarcinoma did not receive guideline-recommended treatment (surgery plus chemotherapy or chemoradiation); a primary reason was not having an oncologist consult. We assessed the relationship between the hospital where the surgery was performed and the probability of a patient not having an oncologist consult. METHODS: All patients diagnosed with stage III colon or stage II/III rectal adenocarcinoma between 2002 and 2005 in Alberta who had surgery were identified from the Alberta Cancer Registry and included in the study. Multivariable logistic regression modeling with hospitals as random effects was used to estimate cancer-type-specific odds ratios of not having an oncologist consult for each hospital, adjusted for age, sex, and comorbidities, relative to the overall nonconsultation rate. RESULTS: Overall, 21% of stage III colon, 25% of stage II rectal, and 13% of stage III rectal adenocarcinoma patients did not have an oncologist consult. Rates varied appreciably across hospitals and between cancer types within hospitals, even after the case-mix adjustment (adjusted odds ratios of nonconsultation ranged from 0.4 to 8.1). Small hospitals that performed 12 or fewer surgeries had nearly 100% consultation rates. CONCLUSIONS: The variation in oncologist-consult rates, particularly for stage II rectal cancer patients, is concerning. We are presenting the findings to the surgical community and discussing interventions to improve oncologist-consult rates.

Adherence to treatment guidelines in stage II/III rectal cancer in Alberta, Canada.

AIMS: Evidence suggests that pre- and/or postoperative treatment benefits patients with stage II/III rectal cancer. This study aimed to quantify treatment patterns and adherence to treatment guidelines, and to identify barriers to having a consultation with an oncologist and barriers to receiving treatment in stage II/III rectal cancer, in a publicly funded medical care system. MATERIALS AND METHODS: Patients with surgically treated stage II/III rectal adenocarcinoma, diagnosed from 2002 to 2005 in Alberta, a Canadian province with a population of 3 million, were included. Demographic and treatment information from the Alberta Cancer Registry were linked to data from electronic medical records, hospital discharge data and the 2001 Canadian Census. The study outcomes were 'not having an oncologist consultation' and 'not receiving guideline-based treatment'. The relative risks of the two outcomes in association with patient characteristics were estimated using multivariable log-binomial regression. RESULTS: Of a total of 910 surgically treated stage II/III rectal adenocarcinoma patients, 748 (82%) had a consultation with an oncologist and 414 (45.5%) received treatment. Pre-/post-surgical treatment modalities and timing varied; 96 (10.5%) received neoadjuvant treatment only, 389 (42.7%) received adjuvant treatment only, 119 (13.1%) received both, and 306 (33.6%) had surgery alone. Factors related to not having a consultation with an oncologist included older age, co-morbidities, cancer stage II and region of residence. Older age was the most significantly associated factor with not receiving treatment (relative risk=2.23; 95% confidence interval: 1.89, 2.64). CONCLUSIONS: Disparities exist in the receipt of treatment in stage II/III rectal cancer. Factors such as age, region of residence and stage should not be barriers to consulting an oncologist to discuss or receive treatment. The reasons for these disparities need to be identified and addressed.

Utilization of oncology services and receipt of treatment: a comparison between patients with breast, colon, rectal, or lung cancer.

BACKGROUND: Higher awareness could translate into better care for patients with breast cancer than for those with other cancers. This study examines utilization of two key oncology services across cancer sites: consultation with an oncologist and receipt of treatment. PATIENTS AND METHODS: All residents of Alberta, Canada, who were diagnosed in 2005 with breast, colon, rectal, or lung cancer and had a disease stage that should be treated with chemotherapy, radiation therapy, or hormonal therapy were included. Data were obtained from the Alberta Cancer Registry and electronic cancer medical records. Percentages of patients who had a consultation and who received treatment were compared. Multivariable log-binomial regression models were used to identify patient characteristics associated with not having the outcomes. RESULTS: A much higher percentage of patients with breast cancer had consultations and received treatment (92% and 83%, respectively) than those with colon (83% and 59%), rectal (86% and 73%), or lung (77% and 66%) cancer. Age, disease stage, region of residence, and surgery status are related to having a consultation and/or receiving treatment but the relationship varies by cancer site. CONCLUSION: Efforts are needed to eliminate disparities in utilization of key cancer services across cancer sites.

Palliative radiotherapy for women with breast cancer.

AIMS: Palliative radiotherapy (PRT) plays an important role in women with metastatic breast cancer. However, not all cancer patients with an indication for PRT receive it. The aim of this study was to measure the use of PRT for women who have died of breast cancer in the Canadian province of Alberta, and to identify factors that might affect this use. MATERIALS AND METHODS: All women who died of breast cancer in Alberta between 2000 and 2004 were identified from the Alberta Cancer Registry. PRT, defined as any radiotherapy given with palliative intent, was abstracted from the radiotherapy databases of the treatment facilities of the Alberta Cancer Board (ACB). The variables evaluated were: age at death, regional health authority (RHA), driving distance to nearest radiotherapy facility, receipt of initial treatment at an ACB facility, receipt of radiotherapy as part if initial treatment, residence in a city with an ACB facility, residence in a city with radiotherapy facilities or visiting radiation oncologists, median household income, and municipality population. Backwards stepwise logistic regression was used to determine the final set of predictor variables for the use of PRT. RESULTS: In total, 1906 women were identified as having died of breast cancer between 2000 and 2004, inclusive. Of these, 50.4% received at least one course of PRT. Factors associated with not receiving PRT in the final multiple logistic regression model for women who lived outside of the cities with radiotherapy facilities were: age>75 years, community size>10,000, median income<$47,000, and residence in RHA 4. For women living in cities with radiotherapy facilities, only age was significant. CONCLUSIONS: There are many factors that influence the receipt of PRT in Alberta that are unrelated to patient need. The education of physicians and patients, as well as the establishment of more radiotherapy facilities, will help to improve the use of PRT.

Breast cancer risk and "delayed" primary Epstein-Barr virus infection.

Parallel to its established causal association with both infectious mononucleosis (IM) and young adulthood Hodgkin disease (YAHD), we propose a hypothesis that "delayed" primary EBV infection (i.e., primary infection occurring during adolescence or adulthood) is associated with elevated breast cancer risk. We evaluated this hypothesis with two investigations, one descriptive and the other analytic. The descriptive study used international/United States cancer registry data to assess the association between incidence rates of breast cancer and those of YAHD. The incidence rates of the seemingly unrelated neoplasms were strongly correlated (correlation coefficients of 0.74 and 0.88 for international and United States data, respectively; these were higher than the correlation coefficients of YAHD with two other cancers that we considered). Populations with higher incidence rates corresponded to those with higher likelihood of delayed primary EBV infection. The analytical study was based on a population-based case-control study of breast cancer in middle-aged women. Age-adjusted odds ratios of breast cancer in women who reported a history of IM, relative to women who did not, increased monotonically from 0.55 [95% confidence interval (CI), 0.05-6.17] for women with 0-9 years of age at IM onset to 2.67 (CI, 1.04-6.89) for women with > or =25 years of age at IM onset (P = 0.016). An older age at tonsillectomy, another surrogate of delayed EBV exposure, was also associated with increased risk of breast cancer: odds ratios, 0.92 (CI, 0.57-1.48) and 1.76 (CI, 1.15-2.69) for women with tonsillectomy at 0-4 years of age and > or =15 years of age, respectively (P = 0.018). Adjusting for additional potential confounders did not modify the associations appreciably. The implications of the findings and a potential biological mechanism are presented.

An empirical evaluation of various priors in the empirical Bayes estimation of small area disease risks.

Empirical and fully Bayes estimation of small area disease risks places a prior distribution on area-specific risks. Several forms of priors have been used for this purpose including gamma, log-normal and non-parametric priors. Spatial correlation among area-specific risks can be incorporated in log-normal priors using Gaussian Markov random fields or other models of spatial dependence. However, the criterion for choosing one prior over others has been mostly logical reasoning. In this paper, we evaluate empirically the various priors used in the empirical Bayes estimation of small area disease risks. We utilize a Spanish mortality data set of a 12-year period to give the underlying true risks, and estimate the true risks using only a 3-year portion of the data set. Empirical Bayes estimates are shown to have substantially smaller mean squared errors than Poisson likelihood-based estimates. However, relative performances of various priors differ across a variety of mortality outcomes considered. In general, the non-parametric prior provides good estimates for lower-risk areas, while spatial priors provide good estimates for higher-risk areas. Ad hoc composite estimates averaging the estimates from the non-parametric prior and those from a spatial log-normal prior appear to perform well overall. This suggests that an empirical Bayes prior that strikes a balance between these two priors, if one can construct such a prior, may prove to be useful for the estimation of small area disease risks.

Antibody to human immunodeficiency virus type 1 (HIV-1) gp160 in mucosal specimens of asymptomatic HIV-1-infected volunteers parenterally immunized with an experimental recombinant HIV-1 IIIB gp160 vaccine. The National Institute of Allergy and Infectious Diseases-sponsored AIDS Vaccine Evaluation Group.

Twenty-two human immunodeficiency virus type 1 (HIV-1)-infected, asymptomatic volunteers with CD4 cell counts of >600 cells/mm3 who were enrolled in a phase I immunotherapy trial comparing two schedules of immunization of an HIV-1 IIIB-based recombinant gp160 (rgp160) experimental vaccine were evaluated for rgp160-specific antibodies in parotid saliva, genital secretions, and serum. When the study was unblinded, it was determined that five volunteers had received rgp160 on a month 0, 1, 2, 3, 4, and 5 immunization schedule, seven volunteers had received rgp160 on a month 0, 1, 2, and 5 schedule, five had received alum/deoxycholate placebo, and seven had received a licensed hepatitis B virus vaccine. Five volunteers consented to the donation of parotid saliva but not genital secretions. Prior to immunization, parotid saliva specimens were available for 11 of 22 volunteers, seminal plasma (SP) specimens were available for 7 of 22 volunteers, cervicovaginal lavage (CVL) specimens were available for 5 of 22 volunteers, and serum was available for 22 of 22 volunteers. These baseline specimens and specimens collected at 1 and 7 months after the final immunizations were assessed by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) and IgA antibodies specific for HIV-1 LAI rgp160 or HIV-1 MN rgp160. No augmentation in HIV rgp160-specific IgG or IgA antibody production in either parotid saliva or serum specimens of vaccinees compared to that in controls was observed after immunization. There were insufficient numbers of SP or CVL specimens available for statistical comparisons between vaccinees and controls. Overall, anti-LAI rgp160 IgG antibodies were detected in the parotid saliva specimens of 20 of 22 volunteers, the seminal plasma specimens of 11 of 11 volunteers, and the CVL specimens of 6 of 6 volunteers and in 21 of 22 serum specimens. Fewer volunteers expressed anti-LAI rgp160 IgA antibodies in mucosal or serum specimens: 11 of 22 parotid saliva specimens, 3 of 11 SP specimens, 3 of 5 CVL samples, and 12 of 22 sera.

Wood-burning stoves and lower respiratory illnesses in Navajo children.

BACKGROUND: Acute lower respiratory illnesses (ALRI) have been associated with exposure to domestic smoke. To examine further this association, a case-control study was conducted among Navajo children seen at the Public Health Service Indian Hospital at Fort Defiance, AZ. METHODS: Cases, children hospitalized with an ALRI (n = 45), were ascertained from the inpatient logs during October, 1992, through March, 1993. Controls, children who had a health record at the same hospital and had never been hospitalized for ALRI, were matched 1:1 to cases on date of birth and gender. Home interviews of parents of subjects during March and April, 1993, elicited information on heating and cooking fuels and other household characteristics. Indoor air samples were collected for determination of time-weighted average concentrations of respirable particles (i.e. < 10 microns in diameter). RESULTS: Age of cases at the time of admission ranged from 1 to 24 months (median, 7 months); 60% of the cases were male. Matched pair analysis revealed an increased risk of ALRI for children living in households that cooked with any wood (odds ratio (OR), 5.0; 95% confidence interval (CI), 0.6 to 42.8), had indoor air concentrations of respirable particles > or = 65 micrograms/m3 (i.e. 90th percentile) (OR 7.0, 95% CI 0.9 to 56.9), and where the primary caretaker was other than the mother (OR 9, 95% CI 1.1 to 71.4). Individual adjustment for potential confounders resulted in minor change (i.e. < 20%) in these results. Indoor air concentration of respirable particles was positively correlated with cooking and heating with wood (P < 0.02) but not with other sources of combustion emissions. CONCLUSIONS: Cooking with wood-burning stoves was associated with higher indoor air concentrations of respirable particles and with an increased risk of ALRI in Navajo children.

Immunoglobulin G subclass responses of children during infection with Onchocerca volvulus.

To characterize the patterns of immunoglobulin G (IgG) subclass and IgE reactivity during the early stages of onchocerciasis, sera were collected from 224 children (age groups, 2 to 5, 6 to 10, and 11 to 15 years) residing in a region of Sierra Leone where Onchocerca volvulus is endemic, and these samples were tested by enzyme-linked immunosorbent assay for their reactivity to adult antigens (OvAg) and against four recombinant proteins (OV11, OV27, OV29, and OV16). Over 88% of the samples contained detectable levels of anti-OvAg IgG. In samples from microfilaria (MF)-positive children, IgG4 responses were significantly elevated and constituted on average 39, 35 and 28% of the total IgG responses for the age groups of 2 to 5, 6 to 10, and 11 to 15 years, respectively. For MF-negative individuals, the mean contributions of IgG4 to the total IgG response were 11% (2 to 5 years), 27% (6 to 10 years), and 56% (11 to 15 years). OvAg-specific IgE was detectable in the sera from both MF-negative and MF-positive individuals. To increase the specificity of the response, recombinant antigens OV11, OV27, and OV29 were tested individually or as a cocktail. Nearly 50% of the MF-negative children and 85% of the MF-positive children had detectable levels of IgG against at least one of the recombinant antigens. Only a small portion of the IgG against the recombinant peptides was IgG4. The prevalence of IgG against OV16 in samples from MF-negative children was 51%, and that for MF-positive children was 75%. The general profile of the humoral immune responses mounted by both MF-positive and a large percentage of the MF-negative children during the initial phases of infection with O. volvulus is similar to the profile reported for adults harboring chronic O. volvulus infections. These results suggest that very quickly after infection, the interactions between parasite and host result in an immunological environment that may contribute to the maintenance of a long-term, chronic infection.

The extracellular domain of HER2/neu is a potential immunogen for active specific immunotherapy of breast cancer.

The proto-oncogene HER2/neu encodes a protein tyrosine kinase (p185HER2) that is homologous to the human epidermal growth factor receptor. Amplification and/or overexpression of HER2/neu occurs in multiple human malignancies and appears to be integrally involved in progression of some breast and ovarian cancers. Because of this fact, HER2/neu is an intriguing target for specific cancer therapeutic strategies. One such strategy is active specific immunotherapy, in which the immune system is targeted at specific antigens expressed by tumor cells. We have employed a transfected cell line that secretes the extracellular domain of p185HER2 as a source of HER2-derived immunogen in a guinea pig model. The immunized animals developed a cellular immune response, as monitored by delayed-type hypersensitivity, and antisera derived from immunized animals specifically inhibited the in vitro growth of human breast tumor cells overexpressing p185HER2. These data provide support for an immunotherapeutic approach to cancers characterized by overexpression of the HER2/neu proto-oncogene.