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1.  Impact of supplementary private health insurance on stomach cancer care in Korea: a cross-sectional study 
Background
Korea achieved universal health insurance coverage in only 12 years; however, insufficient government funding has resulted in high out-of-pocket payments and, in turn, a demand for supplementary private health insurance (PHI). Supplementary PHI provides a fixed amount of benefits in the event of critical illness (e.g., cancer or stroke), surgery, or hospitalization. In this study, we tried to identify factors that influence the decision to purchase supplementary PHI and investigate the impacts of PHI on various aspects of cancer care.
Methods
In a cross-sectional study of 391 patients with gastric cancer, we collected data on demographic and clinical variables, coverage by PHI at the time of diagnosis, and patients' cancer care experiences from surgery databases and patient questionnaires. Two separate multivariate logistic regression models were used 1) to determine whether various sociodemographic and clinical variables influence the purchase of supplementary PHI, and 2) to determine if there is a difference in various outcome measures between individuals with and without PHI.
Results
We studied 187 subjects (49.6%) who were covered under PHI at the time of diagnosis. Subjects who purchased PHI tended to be younger (aOR = 5.01, 95% C.I. = 2.05 – 12.24), and more educated (aOR = 2.67, 95% C.I. = 1.04 – 6.86). Supplementary PHI coverage was significantly associated with financial independence (aOR = 2.07, 95% CI = 1.19 – 3.61), but not with other aspects of cancer care, such as access to healthcare, quality of care, communication and patient autonomy.
Conclusion
Our findings demonstrate that supplementary PHI neither serves as a safety net for vulnerable patients nor improves cancer care experience, except for maintaining the financial independence of beneficiaries.
doi:10.1186/1472-6963-9-133
PMCID: PMC2726135  PMID: 19643032
2.  The role and uptake of private health insurance in different health care systems: are there lessons for developing countries? 
Background
Social and national health insurance schemes are being introduced in many developing countries in moving towards universal health care. However, gaps in coverage are common and can only be met by out-of-pocket payments, general taxation, or private health insurance (PHI). This study provides an overview of PHI in different health care systems and discusses factors that affect its uptake and equity.
Methods
A representative sample of countries was identified (United States, United Kingdom, The Netherlands, France, Australia, and Latvia) that illustrates the principal forms and roles of PHI. Literature describing each country’s health care system was used to summarize how PHI is utilized and the factors that affect its uptake and equity.
Results
In the United States, PHI is a primary source of funding in conjunction with tax-based programs to support vulnerable groups; in the UK and Latvia, PHI is used in a supplementary role to universal tax-based systems; in France and Latvia, complementary PHI is utilized to cover gaps in public funding; in The Netherlands, PHI is supplementary to statutory private and social health insurance; in Australia, the government incentivizes the uptake of complementary PHI through tax rebates and penalties. The uptake of PHI is influenced by age, income, education, health care system typology, and the incentives or disincentives applied by governments. The effect on equity can either be positive or negative depending on the type of PHI adopted and its role within the wider health care system.
Conclusion
PHI has many manifestations depending on the type of health care system used and its role within that system. This study has illustrated its common applications and the factors that affect its uptake and equity in different health care systems. The results are anticipated to be helpful in informing how developing countries may utilize PHI to meet the aim of achieving universal health care.
doi:10.2147/CEOR.S40386
PMCID: PMC3593711  PMID: 23494071
social health insurance; developing countries; private health insurance; health care systems
3.  Service Use, Charge, and Access to Mental Healthcare in a Private Kenyan Inpatient Setting: The Effects of Insurance 
PLoS ONE  2014;9(3):e90297.
The gap in Kenya between need and treatment for mental disorders is wide, and private providers are increasingly offering services, funded in part by private health insurance (PHI). Chiromo, a 30-bed psychiatric hospital in Nairobi, forms part of one of the largest private psychiatric providers in East Africa.
The study evaluated the effects of insurance on service use and charge, questioning implications on access to care. Data derive from invoices for 455 sequential patients, including 12-month follow-up. Multi-linear and binary logistic regressions explored the effect of PHI on readmission, cumulative length of stay, and treatment charge.
Patients were 66.4% male with a mean age of 36.8 years. Half were employed in the formal sector. 70% were admitted involuntarily. Diagnoses were: substance use disorder 31.6%; serious mental disorder 49.5%; common mental disorder 7%; comorbid 7%; other 4.9%. In addition to daily psychiatric consultations, two-thirds received individual counselling or group therapy; half received lab tests or scans; and 16.2% received ECT. Most took a psychiatric medicine. Half of those on antipsychotics were given only brands.
Insurance paid in full for 28.8% of patients. Mean length of stay was 11.8 days and, in 12 months, 16.7 days (median 10.6). 22.2% were readmitted within 12 months. Patients with PHI stayed 36% longer than those paying out-of-pocket and had 2.5 times higher odds of readmission. Mean annual charge per patient was Int$ 4,262 (median Int$ 2,821). Insurers were charged 71% more than those paying out-of-pocket - driven by higher fees and longer stays.
Chiromo delivers acute psychiatric care each year to approximately 450 people, to quality and human rights standards higher than its public counterpart, but at considerably higher cost. With more efficient delivery and wider insurance coverage, Chiromo might expand from its occupancy of 56.6% to reach a larger population in need.
doi:10.1371/journal.pone.0090297
PMCID: PMC3961252  PMID: 24651115
4.  Prospective, Multi-Center Evaluation of the Beckman Coulter Prostate Health Index Using WHO Calibration 
The Journal of urology  2012;189(5):1702-1706.
Purpose
Reported prostate-specific antigen (PSA) values may differ substantially between assays with the Hybritech and World Health Organization (WHO) standardization. [-2]proPSA (p2PSA) and the Beckman Coulter prostate health index (phi) are newly approved serum markers, which are associated with prostate cancer risk and aggressiveness. Our objective was to study the influence of assay standardization on these markers.
Materials and Methods
PSA, % free PSA (%fPSA), and p2PSA were measured using the Hybritech calibration in 892 men undergoing prostate biopsy from a prospective multicenter study. Phi was calculated as: [p2PSA/ fPSA) × (square root of PSA)]. Performance characteristics of phi for prostate cancer detection were then determined using re-calculated WHO calibration PSA values.
Results
The median phi was significantly higher in men with prostate cancer compared to those with negative biopsies using the WHO values (47.4 vs 39.8, p<0.001). Phi offered improved discrimination of prostate cancer detection on biopsy (AUC 0.704) compared to %fPSA or total PSA using the WHO calibration.
Conclusions
Phi can be calculated using Hybritech or WHO standardized assays, and significantly improved the prediction of biopsy outcome over %fPSA or PSA alone.
doi:10.1016/j.juro.2012.11.149
PMCID: PMC4273580  PMID: 23206426
prostate cancer screening; proPSA; phi; prostate health index; assay
5.  Predicting Progressive Hemorrhagic Injury after Traumatic Brain Injury: Derivation and Validation of a Risk Score Based on Admission Characteristics 
Journal of Neurotrauma  2012;29(12):2137-2142.
Abstract
Previous studies have demonstrated that patients with traumatic brain injury (TBI) who also have progressive hemorrhagic injury (PHI), have a higher risk of clinical deterioration and worse outcomes than do TBI patients without PHI. Therefore, the early prediction of PHI occurrence is useful to evaluate the status of patients with TBI and to improve outcomes. The objective of this study was to develop and validate a prognostic model that uses information available at admission to determine the likelihood of PHI after TBI. Retrospectively collected data were used to develop a PHI prognostic model with a logistic regression analysis. The prediction model was validated in 114 patients from a separate hospital. Eight independent prognostic factors were identified: age ≥57 years (5 points), intra-axial bleeding/brain contusion (4 points), midline shift≥5 mm (6 points), platelet (PLT) count<100×109/L (10 points), PLT count≥100 but <150×109/L (4 points), prothrombin time>14 sec (7 points), D-dimer≥5 mg/L (12 points), and glucose≥10 mmol/L (10 points). Each patient was assigned a number of points proportional to the regression coefficient. We calculated risk scores for each patient and defined three risk groups: low risk (0–13 points), intermediate risk (14–22 points), and high risk (23–54 points). In the development cohort, the PHI rates after TBI for these three groups were 10.3%, 47.3%, and 85.2%, respectively. In the validation cohort, the corresponding PHI rates were 10.9%, 47.3%, and 86.9%. The C-statistic for the point system was 0.864 (p=0.509 by the Hosmer-Lemeshow test) in the development cohort, and 0.862 (p=0.589 by the Hosmer-Lemeshow test) in the validation cohort. In conclusion, a relatively simple risk score using admission predictors accurately predicted the risk for PHI after TBI.
doi:10.1089/neu.2011.2233
PMCID: PMC3419842  PMID: 22568757
prognostic model; progressive hemorrhagic injury; risk score; traumatic brain injury; validation
6.  Birth Size and Breast Cancer Risk: Re-analysis of Individual Participant Data from 32 Studies 
PLoS Medicine  2008;5(9):e193.
Background
Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size–breast cancer association.
Methods and Findings
Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02–1.09) and parental recall when the participants were children (1.02; 95% CI 0.99–1.05), but not in those based on adult self-reports, or maternal recall during the woman's adulthood (0.98; 95% CI 0.95–1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000–3.499 kg, the risk was 0.96 (CI 0.80–1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00–1.25) in those who weighed ≥ 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03–1.10] and 1.09 [95% CI 1.03–1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution.
Conclusions
This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood.
Editors' Summary
Background.
Last year, more than one million women discovered that they had breast cancer. In the US, nearly 200,000 women will face the same diagnosis this year and 40,000 will die because of breast cancer. Put another way, about one in eight US women will have breast cancer during her lifetime. Like all cancers, breast cancer begins when cells acquire genetic changes that allow them to divide uncontrollably and to move around the body (metastasize). This uncontrolled division leads to the formation of a lump that can be detected by mammography (a breast X-ray) or by manual examination of the breasts. Breast cancer is treated by surgical removal of the lump or, if the cancer has started to spread, by removal of the whole breast (mastectomy). Surgery is usually followed by radiotherapy, chemotherapy, and other treatments designed to kill any remaining cancer cells. Unlike some cancers, the outlook for women with breast cancer is good. In the US, for example, nearly 90% of affected women are still alive five years after their diagnosis.
Why Was This Study Done?
Scientists have identified several factors that increase a woman's risk of developing breast cancer by comparing the characteristics of populations of women with and without breast cancer. Well-established risk factors include increasing age, not having children, and having a late menopause, but another potential risk factor for breast cancer is birth size. A baby's weight, length, and head circumference at birth (three related measures of birth size) depend on the levels of hormones (including estrogen, a hormone that often affects breast cancer growth) and other biological factors to which the baby is exposed during pregnancy—its prenatal environment. The idea that prenatal environment might also affect breast cancer risk in later life was first proposed in 1990, but the findings of studies that have tried to investigate this possibility have been inconsistent. Here, the researchers re-analyze individual participant data from a large number of studies into women's health conducted in Europe, Northern America, and China to get more precise information about the association between birth size and breast cancer risk.
What Did the Researchers Do and Find?
The researchers identified 32 published and unpublished studies that had collected information on birth size and on the occurrence of breast cancer. They then obtained the individual participant data from these studies, which involved more than 22,000 women who had developed breast cancer and more than 600,000 women who had not. Their analyses of these data show that birth weight was positively associated with breast cancer risk in those studies where this measurement was recorded at birth or based on parental recall during the study participant's childhood (but not in those studies in which birth weight was self-reported or maternally recalled during the participant's adulthood). For example, women with recorded birth weights of more than 4 kg or more had a 12% higher chance of developing breast cancer than women who weighed 3–3.5 kg at birth. Birth length and head circumference were also positively associated with breast cancer risk, but birth length was the strongest single predictor of risk. Finally, the amount by which birth size affected breast cancer risk was not affected by allowing for other established risk factors.
What Do These Findings Mean?
These findings provide strong evidence that birth size—in particular, birth length—is a marker of a woman's breast cancer risk in adulthood although the mechanisms underlying this association are unclear. The researchers note that the observed effect of birth size on breast cancer risk is of a similar magnitude to that of other more established risk factors and estimate that 5% of all breast cancers in developed countries could be caused by a high birth size. Because practically all the studies included in this pooled analysis were done in developed countries, these findings may not hold for developing countries. Further investigations into how the prenatal environment may affect breast cancer risk might identify new ways to prevent this increasingly common cancer.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050193.
This study is further discussed in a PLoS Medicine Perspective by Trichopoulos and Lagiou
The US National Cancer Institute provides detailed information for patients and health professionals on all aspects of breast cancer, including information on risk factors for breast cancer (in English and Spanish)
The MedlinePlus Encyclopedia provides information for patients about breast cancer; Medline Plus also provides links to many other breast cancer resources (in English and Spanish)
The UK charity Cancerbackup also provides detailed information about breast cancer
Cancer Research UK is the UK's leading charity dedicated to cancer research
doi:10.1371/journal.pmed.0050193
PMCID: PMC2553821  PMID: 18828667
7.  Active or Passive Exposure to Tobacco Smoking and Allergic Rhinitis, Allergic Dermatitis, and Food Allergy in Adults and Children: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(3):e1001611.
In a systematic review and meta-analysis, Bahi Takkouche and colleagues examine the associations between exposure to tobacco smoke and allergic disorders in children and adults.
Please see later in the article for the Editors' Summary
Background
Allergic rhinitis, allergic dermatitis, and food allergy are extremely common diseases, especially among children, and are frequently associated to each other and to asthma. Smoking is a potential risk factor for these conditions, but so far, results from individual studies have been conflicting. The objective of this study was to examine the evidence for an association between active smoking (AS) or passive exposure to secondhand smoke and allergic conditions.
Methods and Findings
We retrieved studies published in any language up to June 30th, 2013 by systematically searching Medline, Embase, the five regional bibliographic databases of the World Health Organization, and ISI-Proceedings databases, by manually examining the references of the original articles and reviews retrieved, and by establishing personal contact with clinical researchers. We included cohort, case-control, and cross-sectional studies reporting odds ratio (OR) or relative risk (RR) estimates and confidence intervals of smoking and allergic conditions, first among the general population and then among children.
We retrieved 97 studies on allergic rhinitis, 91 on allergic dermatitis, and eight on food allergy published in 139 different articles. When all studies were analyzed together (showing random effects model results and pooled ORs expressed as RR), allergic rhinitis was not associated with active smoking (pooled RR, 1.02 [95% CI 0.92–1.15]), but was associated with passive smoking (pooled RR 1.10 [95% CI 1.06–1.15]). Allergic dermatitis was associated with both active (pooled RR, 1.21 [95% CI 1.14–1.29]) and passive smoking (pooled RR, 1.07 [95% CI 1.03–1.12]). In children and adolescent, allergic rhinitis was associated with active (pooled RR, 1.40 (95% CI 1.24–1.59) and passive smoking (pooled RR, 1.09 [95% CI 1.04–1.14]). Allergic dermatitis was associated with active (pooled RR, 1.36 [95% CI 1.17–1.46]) and passive smoking (pooled RR, 1.06 [95% CI 1.01–1.11]). Food allergy was associated with SHS (1.43 [1.12–1.83]) when cohort studies only were examined, but not when all studies were combined.
The findings are limited by the potential for confounding and bias given that most of the individual studies used a cross-sectional design. Furthermore, the studies showed a high degree of heterogeneity and the exposure and outcome measures were assessed by self-report, which may increase the potential for misclassification.
Conclusions
We observed very modest associations between smoking and some allergic diseases among adults. Among children and adolescents, both active and passive exposure to SHS were associated with a modest increased risk for allergic diseases, and passive smoking was associated with an increased risk for food allergy. Additional studies with detailed measurement of exposure and better case definition are needed to further explore the role of smoking in allergic diseases.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The immune system protects the human body from viruses, bacteria, and other pathogens. Whenever a pathogen enters the body, immune system cells called T lymphocytes recognize specific molecules on its surface and release chemical messengers that recruit and activate other types of immune cells, which then attack the pathogen. Sometimes, however, the immune system responds to harmless materials (for example, pollen; scientists call these materials allergens) and triggers an allergic disease such as allergic rhinitis (inflammation of the inside of the nose; hay fever is a type of allergic rhinitis), allergic dermatitis (also known as eczema, a disease characterized by dry, itchy patches on the skin), and food allergy. Recent studies suggest that all these allergic (atopic) diseases are part of a continuous state called the “atopic march” in which individuals develop allergic diseases in a specific sequence that starts with allergic dermatitis during infancy, and progresses to food allergy, allergic rhinitis, and finally asthma (inflammation of the airways).
Why Was This Study Done?
Allergic diseases are extremely common, particularly in children. Allergic rhinitis alone affects 10%–30% of the world's population and up to 40% of children in some countries. Moreover, allergic diseases are becoming increasingly common. Allergic diseases affect the quality of life of patients and are financially costly to both patients and health systems. It is important, therefore, to identify the factors that cause or potentiate their development. One potential risk factor for allergic diseases is active or passive exposure to tobacco smoke. In some countries up to 80% of children are exposed to second-hand smoke so, from a public health point of view, it would be useful to know whether exposure to tobacco smoke is associated with the development of allergic diseases. Here, the researchers undertake a systematic review (a study that uses predefined criteria to identify all the research on a given topic) and a meta-analysis (a statistical approach for combining the results of several studies) to investigate this issue.
What Did the Researchers Do and Find?
The researchers identified 196 observational studies (investigations that observe outcomes in populations without trying to affect these outcomes in any way) that examined the association between smoke exposure and allergic rhinitis, allergic dermatitis, or food allergy. When all studies were analyzed together, allergic rhinitis was not associated with active smoking but was slightly associated with exposure to second-hand smoke. Specifically, compared to people not exposed to second-hand smoke, the pooled relative risk (RR) of allergic rhinitis among people exposed to second-hand smoke was 1.10 (an RR of greater than 1 indicates an increased risk of disease development in an exposed population compared to an unexposed population). Allergic dermatitis was associated with both active smoking (RR = 1.21) and exposure to second-hand smoke (RR = 1.07). In the populations of children and adolescents included in the studies, allergic rhinitis was associated with both active smoking and exposure to second-hand smoke (RRs of 1.40 and 1.09, respectively), as was allergic dermatitis (RRs of 1.36 and 1.06, respectively). Finally food allergy was associated with exposure to second-hand smoke (RR = 1.43) when cohort studies (a specific type of observational study) only were examined but not when all the studies were combined.
What Do These Findings Mean?
These findings provide limited evidence for a weak association between smoke exposure and allergic disease in adults but suggest that both active and passive smoking are associated with a modestly increased risk of allergic diseases in children and adolescents. The accuracy of these findings may be affected by the use of questionnaires to assess smoke exposure and allergic disease development in most of the studies in the meta-analysis and by the possibility that individuals exposed to smoke may have shared other characteristics that were actually responsible for their increased risk of allergic diseases. To shed more light on the role of smoking in allergic diseases, additional studies are needed that accurately measure exposure and outcomes. However, the present findings suggest that, in countries where many people smoke, 14% and 13% of allergic rhinitis and allergic dermatitis, respectively, among children may be attributable to active smoking. Thus, the elimination of active smoking among children and adolescents could prevent one in seven cases of allergic rhinitis and one in eight cases of allergic dermatitis in such countries.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001611.
The UK National Health Service Choices website provides information about allergic rhinitis, hay fever (including personal stories), allergic dermatitis (including personal stories), and food allergy (including personal stories)
The US National Institute of Allergy and Infectious Disease provides information about allergic diseases
The UK not-for-profit organization Allergy UK provides information about all aspects of allergic diseases and a description of the atopic march
MedlinePlus encyclopedia has pages on allergic rhinitis and allergic dermatitis (in English and Spanish)
MedlinePlus provides links to further resources about allergies, eczema, and food allergy (in English and Spanish)
doi:10.1371/journal.pmed.1001611
PMCID: PMC3949681  PMID: 24618794
8.  Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) Significantly Improve Prostate Cancer Detection at Initial Biopsy in a Total PSA Range of 2–10 ng/ml 
PLoS ONE  2013;8(7):e67687.
Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2–10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2–10 ng/ml at initial biopsy, outperforming currently used %fPSA.
doi:10.1371/journal.pone.0067687
PMCID: PMC3701535  PMID: 23861782
9.  Napa Immunization Study: Immunization Rates for Children with Publicly Funded Insurance Compared with those with Private Health Insurance in a Suburban Medical Office 
The Permanente Journal  2011;15(4):12-22.
Introduction: Healthy People 2020 set a goal to increase the proportion of children who receive the recommended doses of Diphtheria Tetanus and Pertussis, polio, measles mumps and rubella, Haemophilus influenzae type b, hepatitis B, varicella and pneumococcal conjugate vaccines to 80% from the 2009 baseline rate of 69%. The purpose of this study is to compare the recommended immunization rates for low-income children insured through publicly funded health insurance (PFI) to the rates for children with private health insurance (PHI) in a suburban medical office.
Methods: The immunization rates and health access measures of 109 children ages 24 to 48 months who had PFI were compared with 300 children of the same age with PHI in the same medical practice.
Results: Overall immunization rates for the study population were very high and exceeded the Healthy People 2020 goals for full immunization. Children with PFI had lower rates of immunization and fluoride prescriptions; however the differences were only significant in the cohort of children age two years. By three years of age, the immunization rates and the fluoride prescription rates were similar. There were no significant differences in health outcomes for Spanish-speaking compared with English-speaking children.
Discussion: Barriers to successful immunization practices and strategies to overcome those barriers are discussed.
Conclusion: The successful immunization practices and secondary outcomes in this study are a reflection of the integrated care model in this practice that facilitates comprehensive, coordinated, and accessible care for patients and allows physicians and support staff to practice culturally sensitive and compassionate care—the definition of a medical home.
PMCID: PMC3267555  PMID: 22319411
10.  Timing of Orchiopexy in the United States: A Quality-of-Care Indicator 
Urology  2012;80(5):1121-1126.
Objective
To investigate whether orchiopexies are occurring later than recommended by American Academy of Pediatrics 1996 guidelines (around age one). Adherence to guidelines is poorly studied.
Methods
Main Cohort: 4,103 boys insured from birth (Innovus i3, insurance claims database) Complementary cohort: 17,010 insured and non-insured boys (Pediatric Health Information System, PHIS)
Inclusion criteria: age ≤5 years at time of ICD-9-defined cryptorchidism diagnosis Primary outcome: timely surgery (orchiopexy by age 18 months)
Results
In Innovus, 87% of boys who underwent an orchiopexy had a timely orchiopexy. Of those who did not undergo surgery (n=2738), 90% had at least one subsequent well-care visit. Those who underwent timely surgery were referred to a surgeon at a younger age compared with those who underwent late surgery (4.1 months vs. 16.1 months, p<.00005). Predictors of timely surgery were number of well-care visits (OR 1.5, 95% CI 1.3–1.7), continuity of primary care (OR 1.9, 95% CI 1.3–2.7), and use of laparoscopy (OR 4.5, 95% CI 1.4–14.9). Family/internal medicine as referring provider was predictive of delayed surgery (OR 0.5, 95% CI 0.3–0.8). In PHIS, 61% of those with private insurance had timely surgery compared with 54% of those without private insurance (p< 0.0001).
Conclusions
We found an unexpectedly high adherence to guidelines in our continuously insured since birth Innovus population. Primary care continuity and well-care visits were associated with timely surgery. Further studies can confirm these findings in non-privately insured patients with the ultimate goal of instituting quality improvement initiatives.
doi:10.1016/j.urology.2012.08.008
PMCID: PMC3753094  PMID: 23107402
cryptorchidism; health services research; orchiopexy; pediatrics; quality indicators; healthcare
11.  Waiting times for elective treatments according to insurance status: A randomized empirical study in Germany 
Background
Health insurance coverage for all citizens is often considered a requisite for reducing disparities in health care accessibility. In Germany, health insurees are covered either by statutory health insurance (SHI) or private health insurance (PHI). Due to a 20%–35% higher reimbursement of physicians for patients with PHI, it is often claimed that patients with SHI are faced with longer waiting times when it comes to obtaining outpatient appointments. There is little empirical evidence regarding outpatient waiting times for patients with different health insurance status in Germany.
Methods
We called 189 specialist practices in the region of Cologne, Leverkusen, and Bonn. Practices were selected from publicly available telephone directories (Yellow Pages 2006/2007) for the specified region. Data were collected for all practices within each of five specialist fields. We requested an appointment for one of five different elective treatments (allergy test plus pulmonary function test, pupil dilation, gastroscopy, hearing test, MRT of the knee) by calling selected practices. The caller was randomly assigned the status of private or statutory health insuree. The total period of data collection amounted to 4.5 weeks in April and May 2006.
Results
Between 41.7% and 100% of the practices called were included according to specialist field. We excluded practices that did not offer the requested treatment, were closed for more than one week, did not answer the call, did not offer fixed appointments ("open consultation hour") or did not accept any newly registered patients. Waiting time difference between private and statutory policyholders was 17.6 working days (SHI 26.0; PHI 8.4) for allergy test plus pulmonary function test; 17.0 (25.2; 8.2) for pupil dilation; 24.8 (36.7; 11.9) for gastroscopy; 4.6 (6.8; 2.2) for hearing test and 9.5 (14.1; 4.6) for the MRT of the knee. In relative terms, the difference in working days amounted to 3.08 (95%-KI: 1,88 bis 5,04) and proved significant.
Conclusion
Even with comprehensive health insurance coverage for almost 100% of the population, Germany shows clear differences in access to care, with SHI patients waiting 3.08 times longer for an appointment than PHI patients. Wide-spread anecdotal reports of shorter waiting times for PHI patients were empirically supported. Discrepancies in access to care not only depend on accessibility to comprehensive health insurance cover, but also on the level of reimbursement for the physician. Higher reimbursements for the provider when it comes to comparable health problems and diagnostic treatments could lead to improved access to care. We conclude that incentives for adjusting access to care according to the necessity of treatment should be implemented.
doi:10.1186/1475-9276-7-1
PMCID: PMC2246139  PMID: 18184426
12.  Association between esophageal cancer risk and EPHX1 polymorphisms: A meta-analysis 
AIM: To summarize the relationship between p.Tyr113His and p.His139Arg polymorphisms in microsomal epoxide hydrolase (EPHX1) and risk for esophageal cancer (EC).
METHODS: The MEDLINE/PubMed and EMBASE databases were searched for studies of the association between EPHX1 polymorphisms and EC risk that were published from the database inception date to April 2013. A total of seven case-control studies, including seven on p.Tyr113His (cases, n = 1118; controls, n = 1823) and six on p.His139Arg (cases, n = 861; controls, n = 1571), were included in the meta-analysis. After data extraction by two investigators working independently, the meta-analyses were carried out with STATA 11.0 software. Pooled odds ratios and 95%CI were calculated using a fixed-effects model or a random-effects model, as appropriate.
RESULTS: The pooled EPHX1 p.Tyr113His polymorphism data showed no significant association with EC in any of the genetic models (OR = 1.00, 95%CI: 0.70-1.48 for Tyr/His vs Tyr/Tyr; OR = 1.10, 95%CI: 0.77-1.57 for His/His vs Tyr/Tyr; OR = 1.06, 95%CI: 0.75-1.49 for a dominant model; OR = 1.09, 95%CI: 0.89-1.34 for a recessive model). Similar results were obtained from the p.His139Arg polymorphism analysis (Arg/His vs His/His: OR = 1.02, 95%CI: 0.84-1.23; Arg/Arg vs His/His: OR = 0.96, 95%CI: 0.60-1.54; OR = 1.03, 95%CI: 0.78-1.37 for the dominant model; OR = 0.97, 95%CI: 0.61-1.56 for the recessive model). Subgroup analyses for ethnicity, subtype of EC, and source of controls (population-based or hospital-based) showed trends that were consistent with the pooled analysis (reported above), with no significant associations found.
CONCLUSION: This meta-analysis suggests that the p.Tyr113His and p.His139Arg polymorphisms in EPHX1 may not be associated with EC development.
doi:10.3748/wjg.v20.i17.5124
PMCID: PMC4009551  PMID: 24803829
Esophageal cancer; Squamous cell carcinoma; Adenocarcinoma; EPHX1; Polymorphism; Meta-analysis
13.  Hepatitis C Virus Testing in Adults Living with HIV: A Need for Improved Screening Efforts 
PLoS ONE  2014;9(7):e102766.
Objectives
Guidelines recommend hepatitis C virus (HCV) screening for all people living with HIV (PLWH). Understanding HCV testing practices may improve compliance with guidelines and can help identify areas for future intervention.
Methods
We evaluated HCV screening and unnecessary repeat HCV testing in 8,590 PLWH initiating care at 12 U.S. HIV clinics between 2006 and 2010, with follow-up through 2011. Multivariable logistic regression examined the association between patient factors and the outcomes: HCV screening (≥1 HCV antibody tests during the study period) and unnecessary repeat HCV testing (≥1 HCV antibody tests in patients with a prior positive test result).
Results
Overall, 82% of patients were screened for HCV, 18% of those screened were HCV antibody-positive, and 40% of HCV antibody-positive patients had unnecessary repeat HCV testing. The likelihood of being screened for HCV increased as the number of outpatient visits rose (adjusted odds ratio 1.02, 95% confidence interval 1.01–1.03). Compared to men who have sex with men (MSM), patients with injection drug use (IDU) were less likely to be screened for HCV (0.63, 0.52–0.78); while individuals with Medicaid were more likely to be screened than those with private insurance (1.30, 1.04–1.62). Patients with heterosexual (1.78, 1.20–2.65) and IDU (1.58, 1.06–2.34) risk compared to MSM, and those with higher numbers of outpatient (1.03, 1.01–1.04) and inpatient (1.09, 1.01–1.19) visits were at greatest risk of unnecessary HCV testing.
Conclusions
Additional efforts to improve compliance with HCV testing guidelines are needed. Leveraging health information technology may increase HCV screening and reduce unnecessary testing.
doi:10.1371/journal.pone.0102766
PMCID: PMC4102540  PMID: 25032989
14.  Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. 
Journal of Clinical Investigation  1981;68(6):1456-1467.
The quantitative contributions of pancreatic responsiveness and insulin sensitivity to glucose tolerance were measured using the "minimal modeling technique" in 18 lean and obese subjects (88-206% ideal body wt). The individual contributions of insulin secretion and action were measured by interpreting the dynamics of plasma glucose and insulin during the intravenous glucose tolerance test in terms of two mathematical models. One, the insulin kinetics model, yields parameters of first-phase (phi 1) and second-phase (phi 2) responsivity of the beta-cells to glucose. The other glucose kinetics model yields the insulin sensitivity parameters, SI. Lean and obese subjects were subdivided into good (KG greater than 1.5) and lower (KG less than 1.5) glucose tolerance groups. The etiology of lower glucose tolerance was entirely different in lean and obese subjects. Lean, lower tolerance was related to pancreatic insufficiency (phi 2 77% lower than in good tolerance controls [P less than 0.03]), but insulin sensitivity was normal (P greater than 0.5). In contrast, obese lower tolerance was entirely due to insulin resistance (SI diminished 60% [P less than 0.01]); pancreatic responsiveness was not different from lean, good tolerance controls (phi 1: P greater than 0.06; phi 2: P greater than 0.40). Subjects (regardless of weight) could be segregated into good and lower tolerance by the product of second-phase beta-cell responsivity and insulin sensitivity (phi 2 . SI). Thus, these two factors were primarily responsible for overall determination of glucose tolerance. The effect of phi 1 was to modulate the KG value within those groups whose overall tolerance was determined by phi 2 . SI. This phi 1 modulating influence was more pronounced among insulin sensitive (phi 1 vs. KG, r = 0.79) than insulin resistant (obese, low tolerance; phi 1 vs. KG, r = 0.91) subjects. This study demonstrates the feasibility of the minimal model technique to determine the etiology of impaired glucose tolerance.
PMCID: PMC370948  PMID: 7033284
15.  Gaps in the Existing Public Health Informatics Training Programs: A Challenge to the Development of a Skilled Global Workforce 
The objective of this study was to explore public health informatics (PHI) training programs that currently exist to meet the growing demand for a trained global workforce. We used several search engines, scientific databases, and the websites of informatics organizations; sources included PubMed, Google, the American Medical Informatics Organization, and the International Medical Informatics Organization. The search was conducted from May to July 2011 and from January to February 2012 using key words such as informatics, public health informatics, or biomedical informatics along with academic programs, training, certificate, graduate programs, or postgraduate programs. Course titles and catalog descriptions were gathered from the program or institution websites. Variables included PHI program categories, location and mode of delivery, program credits, and costs. Each course was then categorized based on its title and description as available on the Internet. Finally, we matched course titles and descriptions with the competencies for PHIs determined by Centers for Disease Control and Prevention (CDC). Descriptive analysis was performed to report means and frequency distributions for continuous and categorical variables. Stratified analysis was performed to explore average credits and cost per credit among both the public and private institutions. Fifteen PHI programs were identified across 13 different institutions, the majority of which were US-based. The average number of credits and the associated costs required to obtain PHI training were much higher in private as compared to public institutions. The study results suggest that a need for online contextual and cost-effective PHI training programs exists to address the growing needs of professionals worldwide who are using technology to improve public health in their respective countries.
PMCID: PMC3510646  PMID: 23209452
public health informatics; training; global workforce
16.  Health promotion activity in primary care: performance of models and associated factors 
Open Medicine  2009;3(3):149-164.
Background
Lifestyle behaviours have significant health and economic consequences. Primary care providers play an important role in promoting healthy behaviours. We compared the performance of primary care models in delivering health promotion and identified practice factors associated with its delivery.
Methods
Surveys were conducted in 137 randomly selected primary care practices in 4 primary care models in Ontario, Canada: 35 community health centres, 35 fee-for-service practices, 35 family health networks and 32 health service organizations. A total of 4861 adult patients who were visiting their family practice participated in the study. Qualitative nested case studies were also conducted at 2 practices per model. A 7-item question was used to evaluate health promotion. The main outcome was whether at least 1 of the 7 health promotion items was discussed at the survey visit. Multilevel logistic regressions were used to compare the models and determine performance-related practice factors.
Results
The rate of health promotion was significantly higher in community health centres than in the other models (the unadjusted difference ranged between 8% and 13%). This finding persisted after controlling for patient and family physician profiles. Factors independently positively associated with health promotion were as follows: reason for visit (for a general checkup: adjusted odds ratio [AOR] 3.34, 95% confidence interval [CI] 2.81–3.97; for care for a chronic disease: AOR 2.03, 95% CI 1.69–2.43), patients having and seeing their own provider (for those not: AOR 0.58, 95% CI 0.43–0.78), number of nurses in the practice (AOR 1.07, 95% CI 1.02–1.12), percentage of female family physicians (AOR 1.38, 95% CI 1.15–1.66), smaller physician panel size (AOR 0.92, 95% CI 0.85–1.01) and longer booking interval (AOR 1.03, 95% CI 1.01–1.04). Providers in interdisciplinary practices viewed health promotion as an integral part of primary care, whereas other providers emphasized the role of relational continuity in effective health promotion.
Conclusion
We have identified several attributes associated with health promotion delivery. These results may assist practice managers and policy-makers in modifying practice attributes to improve health promotion in primary care.
PMCID: PMC3090121  PMID: 21603049
17.  Lack of agreement between tonometric and gastric juice partial carbon dioxide tension 
Critical Care  2000;4(4):249-254.
Our goal was to compare measurement of tonometered saline and gastric juice partial carbon dioxide tension (PCO2). In this prospective observational study, 112 pairs of measurements were simultaneously obtained under various hemodynamic conditions, in 15 critical care patients. Linear regression analysis showed a significant correlation between the two methods of measuring PCO2 (r 2 = 0.43; P < 0.0001). However, gastric juice PCO2 was systematically higher (mean difference 51 mmHg). The 95% limits of agreement were 315 mmHg and the dispersion increased as the values of PCO2 increased. Tonometric and gastric juice PCO2 cannot be used interchangeably. Gastric juice PCO2 measurement should be interpreted with caution.
Introduction:
In recent years there has been growing interest in tonometric estimation of gastric intramucosal pH (pHi). More recently, attention has focused on the gradient between intraluminal and arterial PCO2. pHi appears to be a useful diagnostic and prognostic tool in critically ill patients, and may also be used as a therapeutic guide. However, intraluminal PCO2 is the parameter measured to calculate pHi, and it is assumed as equivalent to the PCO2 of the upper layers of the gastric mucosa.
Direct measurement of PCO2 in gastric juice might offer advantages over tonometry. Tonometer costs could be saved, and equilibration time would no longer be necessary. Additionally, preanalytic factors that account for poor reproducibility, such as inadequate volume of saline in the tonometer, errors in the dwell time of the sample or in the technique used to aspirate saline, mixing of the sample with tonometer dead space and delay in analysis, could be prevented. Nevertheless, to our knowledge few experimental or clinical studies have examined PCO2 in gastric juice. Moreover, no comparison with simultaneous tonometric samples has been performed. Our goal was to compare simultaneous measurement of PCO2 in gastric juice and in saline samples from a tonometer. Data from the present study show that gastric juice PCO2 is systematically higher. Furthermore, differences widen at high PCO2 values, and data dispersion becomes even more striking. Therefore, tonometric PCO2 and gastric juice PCO2 are not interchangeable.
Patients and methods:
The present study was approved by the local ethics committee, and informed consent was obtained from the next of kin of each patient.
We studied 15 consecutive mechanically ventilated patients from a medical/surgical intensive care unit, in whom tonometric monitoring was indicated by attending physicians. All patients were receiving 50 mg intravenous ranitidine every 8 h. Gastric tonometers were filled with saline, which was extracted after 90 min of equilibration time. At the same time, gastric juice was anaerobically extracted from the aspiration port of the tonometer. The initial 20 ml was discarded. PCO2 in both samples was measured using a blood gas analyzer (AVL 945; AVL List GMBH, Gratz, Austria). These measurements were taken at various time points in each patient, and under various haemodynamic and oxygen transport conditions, All measurements were performed with the patient fasted. Correlation between the two measurements was examined using the Bland-Altman technique.
We also performed an in vitro study to quantify the precision and bias for the AVL 945. For this purpose, a stable PCO2 in saline solution was achieved by bubbling 5% carbon dioxide calibration gas.
Results:
We performed 112 pairs of measurements in 15 patients. Table 1 shows clinical data and the first values of arterial, tonometered and gastric juice PCO2 for each patient. Regression analysis demonstrated a significant correlation between both methods of measuring PCO2 (r 2 =0.43; gastric juice PCO2 = -28.79 + [2.55 × tonometric PCO2]; P < 0.0001; Fig. 1). However, the bias calculated as the mean difference of gastric juice and tonometric PCO2 was 51 mmHg. The 95% limits of agreement were 315 mmHg (Fig. 2). For mean PCO2 values lesser than 100 mmHg, the bias and the 95% limits of agreement were 19 and 102 mmHg, respectively. As mean PCO2 increased, the scattering of differences widened (r 2 =0.71; P < 0.0001).
In an effort to prevent the bias related to multiple measurements per patient, we performed Bland-Altman analysis with the first measurement of each patient. After this the results remained similar (bias 55 mmHg, 95% limits of agreement 216 mmHg).
The AVL 945 blood gas analyzer showed a negative bias of 0.97 mmHg and a precision of 2.13 mmHg. This bias was considered negligible, so no further correction was made to saline tonometric values.
Discussion:
The results of the present study show that tonometric PCO2 and gastric juice PCO2 are not interchangeable. Gastric juice PCO2 is systematically higher. At high PCO2 values the differences widen, and data dispersion becomes even more marked.
There is no clear cause for these observations. A possible explanation might be that tonometric PCO2 is generated over a time interval, whereas gastric juice PCO2 might reflect rapid changes in mucosal metabolism. Different equilibrium time could also account for data dispersion, but not for the positive bias for gastric juice. Rapid changes should occur in both directions.
Another potential confounding factor is the ability of blood gas analyzers to measure PCO2 in gastric juice. Measurement of PCO2 in 0.9% saline is an important source of error in the estimation of pHi. Variation in PCO2 values may occur with different PCO2 equilibration solutions. For example, bias is -66.5% when the Nova Stat Profile 7 blood gas analyzer (Nova Biomedical, Waltham, MA, USA) measures concentration of 1.95% of CO2 equilibrated in normal saline. However, bias changes to +45.4% when 1.95% CO2 is equilibrated in human albumin solution 4.5%.
It would not be surprising if gastric juice components such as proteins, mucopolisaccharides and others interfere with CO2 solubility and its subsequent measurement by blood gas analyzers. In this way, intersubject and intrasubject variation in gastric juice composition could also account for data dispersion. Fiddian-Green et al [1] measured PCO2 in gastric contents of anaesthetized dogs. They isolated the stomach from the oesophagus and the duodenum with ligatures, and washed it through a catheter with saline. Then, they instilled 250 ml 0.9% saline and took samples to measure PCO2 and to estimate pHi. Simultaneously, mucosa pH was recorded with a microglass probe. They found a statistically significant correlation between both methods. However, data dispersion in the graph was considerable.
We were able to exclude analyzer underestimation of PCO2 in saline as the cause for the present results. In vitro performance of the AVL 945 in blood was good. It showed a negative bias less than 1 mmHg and a precision of about 2 mmHg.
We cannot infer from the present data the technique that should be the gold standard for measuring PCO2 in gastric mucosa. However, the studies that have established the normal values for pHi, prognostic changes and its uses as a therapeutic index have been performed with tonometry. Hence, more data are needed for the routine measurement of PCO2 in gastric juice.
Correlation between gastric juice and tonometric PCO2. We performed 112 pairs of measurements of gastric juice and tonometric PCO2 in 15 critical care patients under different haemodynamic and oxygen transport conditions. The linear regression coefficient is significant. However, the slope value indicates systematic overestimation of gastric juice PCO2 in relation to saline PCO2.
Bland-Altman analysis of the differences between gastric juice and tonometric PCO2. The bias calculated as the mean difference of gastric juice and tonometric PCO2 was 51 mmHg. The 95% limits of agreement were 315 mmHg. The bias and the scattering of differences widened as PCO2 increased.
Clinical characteristics and first value of arterial, tonometer and gastric juice PCO2
ARDS, acute respiratory distress syndrome.
PMCID: PMC29045  PMID: 11056754
gastric tonometry; intramucosal partial carbon dioxide tension; intramucosal pH
18.  Chronic disease and sitting time in middle-aged Australian males: findings from the 45 and Up Study 
Background
Compared to females, males experience a range of health inequities including higher rates of diabetes and cardiovascular disease. Although sitting time is emerging as a distinct risk factor for chronic disease, research on the association of sitting time and chronic disease in middle-aged Australian males is limited.
Methods
A sample of 63,048 males aged 45-64 years was drawn from the baseline dataset of the 45 and Up Study – a longitudinal cohort study on healthy ageing with 267,153 participants from across New South Wales, Australia’s most populous state. Baseline data on self-reported chronic disease (heart disease, cancer, diabetes, high blood pressure, combined chronic diseases), sitting time, physical activity (Active Australia Survey), and a range of covariates were used for cross-sectional analyses. Crude (OR), partially and fully adjusted odds ratios (AOR) and 95% confidence intervals (CI) were calculated using binary logistic regression.
Results
Compared to those sitting <4 hours/day, participants reporting 4 to <6, 6 to <8, and ≥8 hours were significantly more likely to report ever having any chronic disease (AOR 1.06, 95% CI 1.00 – 1.12, p = 0.050; AOR 1.10, 95% CI 1.03 – 1.16, p = 0.003; AOR 1.09, 95% CI 1.03 – 1.15, p = 0.002, respectively). Participants who reported 6 to <8 hours and ≥8 hours of sitting were also significantly more likely to report ever having diabetes than those reporting <4 hours/day (AOR 1.15, 95% CI 1.03 – 1.28, p = 0.016; AOR 1.21, 95% CI 1.09 – 1.33, p <0.001, respectively).
Conclusions
Our findings suggest that higher volumes of sitting time are significantly associated with diabetes and overall chronic disease, independent of physical activity and other potentially confounding factors. Prospective studies using valid and reliable measures into domain-specific sitting time in middle-aged males are required to understand and explain the direction of these relationships.
doi:10.1186/1479-5868-10-20
PMCID: PMC3571940  PMID: 23394382
Physical activity; Sedentary behaviour; Sedentary lifestyle; Chronic disease; Heart disease; Cancer; Diabetes; Blood pressure
19.  A Multi-Center Study of [−2]Pro-Prostate-Specific Antigen (PSA) in Combination with PSA and Free PSA for Prostate Cancer Detection in the 2.0 to 10.0 ng/mL PSA Range 
The Journal of urology  2011;185(5):1650-1655.
Purpose
PSA and free PSA (fPSA) have limited specificity for detecting clinically significant, curable prostate cancer (PCa), leading to unnecessary biopsies and detection and treatment of some indolent tumors. [−2]proPSA (p2PSA) may improve specificity for detecting clinically significant PCa. Our objective was to evaluate p2PSA, fPSA, and PSA in a mathematical formula (prostate health index [phi] = [−2]proPSA / fPSA) × PSA1/2) to enhance specificity for detecting overall and high-grade PCa.
Materials and Methods
We enrolled 892 men in a prospective multi-institutional trial with no history of PCa, normal rectal examination, a PSA of 2–10 ng/mL, and ≥6- core prostate biopsy. We examined the relationship of serum PSA, %fPSA and phi with biopsy results. The primary endpoints were the specificity and AUC using phi to detect overall and Gleason ≥7 prostate cancer on biopsy compared with %fPSA.
Results
For the 2–10 ng/mL PSA range, at 80–95% sensitivity, the specificity and AUC (0.703) of phi exceeded those of PSA and %fPSA. Increasing phi was associated with a 4.7-fold increased risk of PCa and 1.61-fold increased risk of Gleason ≥7 disease on biopsy. The AUC for phi (0.724) exceeded that of %fPSA (0.670) in discriminating between PCa with Gleason ≥ 4+3 vs. lower grade disease or negative biopsies. Phi results were not associated with age and prostate volume.
Conclusions
Phi may be useful in PCa screening to reduce unnecessary biopsies in men age ≥50 years with PSA 2–10 ng/mL and negative DRE, with minimal loss in sensitivity.
doi:10.1016/j.juro.2010.12.032
PMCID: PMC3140702  PMID: 21419439
20.  An Evaluation of Personal Health Information Remnants in Second-Hand Personal Computer Disk Drives 
Background
The public is concerned about the privacy of their health information, especially as more of it is collected, stored, and exchanged electronically. But we do not know the extent of leakage of personal health information (PHI) from data custodians. One form of data leakage is through computer equipment that is sold, donated, lost, or stolen from health care facilities or individuals who work at these facilities. Previous studies have shown that it is possible to get sensitive personal information (PI) from second-hand disk drives. However, there have been no studies investigating the leakage of PHI in this way.
Objectives
The aim of the study was to determine the extent to which PHI can be obtained from second-hand computer disk drives.
Methods
A list of Canadian vendors selling second-hand computer equipment was constructed, and we systematically went through the shuffled list and attempted to purchase used disk drives from the vendors. Sixty functional disk drives were purchased and analyzed for data remnants containing PHI using computer forensic tools.
Results
It was possible to recover PI from 65% (95% CI: 52%-76%) of the drives. In total, 10% (95% CI: 5%-20%) had PHI on people other than the owner(s) of the drive, and 8% (95% CI: 7%-24%) had PHI on the owner(s) of the drive. Some of the PHI included very sensitive mental health information on a large number of people.
Conclusions
There is a strong need for health care data custodians to either encrypt all computers that can hold PHI on their clients or patients, including those used by employees and subcontractors in their homes, or to ensure that their computers are destroyed rather than finding a second life in the used computer market.
doi:10.2196/jmir.9.3.e24
PMCID: PMC2047285  PMID: 17942386
Privacy; confidentiality; security; data disclosure
21.  The inadvertent disclosure of personal health information through peer-to-peer file sharing programs 
Objective
There has been a consistent concern about the inadvertent disclosure of personal information through peer-to-peer file sharing applications, such as Limewire and Morpheus. Examples of personal health and financial information being exposed have been published. We wanted to estimate the extent to which personal health information (PHI) is being disclosed in this way, and compare that to the extent of disclosure of personal financial information (PFI).
Design
After careful review and approval of our protocol by our institutional research ethics board, files were downloaded from peer-to-peer file sharing networks and manually analyzed for the presence of PHI and PFI. The geographic region of the IP addresses was determined, and classified as either USA or Canada.
Measurement
We estimated the proportion of files that contain personal health and financial information for each region. We also estimated the proportion of search terms that return files with personal health and financial information. We ascertained and discuss the ethical issues related to this study.
Results
Approximately 0.4% of Canadian IP addresses had PHI, as did 0.5% of US IP addresses. There was more disclosure of financial information, at 1.7% of Canadian IP addresses and 4.7% of US IP addresses. An analysis of search terms used in these file sharing networks showed that a small percentage of the terms would return PHI and PFI files (ie, there are people successfully searching for PFI and PHI on the peer-to-peer file sharing networks).
Conclusion
There is a real risk of inadvertent disclosure of PHI through peer-to-peer file sharing networks, although the risk is not as large as for PFI. Anyone keeping PHI on their computers should avoid installing file sharing applications on their computers, or if they have to use such tools, actively manage the risks of inadvertent disclosure of their, their family's, their clients', or patients' PHI.
doi:10.1136/jamia.2009.000232
PMCID: PMC3000774  PMID: 20190057
22.  Utilization of DXA Bone Mineral Densitometry in Ontario 
Executive Summary
Issue
Systematic reviews and analyses of administrative data were performed to determine the appropriate use of bone mineral density (BMD) assessments using dual energy x-ray absorptiometry (DXA), and the associated trends in wrist and hip fractures in Ontario.
Background
Dual Energy X-ray Absorptiometry Bone Mineral Density Assessment
Dual energy x-ray absorptiometry bone densitometers measure bone density based on differential absorption of 2 x-ray beams by bone and soft tissues. It is the gold standard for detecting and diagnosing osteoporosis, a systemic disease characterized by low bone density and altered bone structure, resulting in low bone strength and increased risk of fractures. The test is fast (approximately 10 minutes) and accurate (exceeds 90% at the hip), with low radiation (1/3 to 1/5 of that from a chest x-ray). DXA densitometers are licensed as Class 3 medical devices in Canada. The World Health Organization has established criteria for osteoporosis and osteopenia based on DXA BMD measurements: osteoporosis is defined as a BMD that is >2.5 standard deviations below the mean BMD for normal young adults (i.e. T-score <–2.5), while osteopenia is defined as BMD that is more than 1 standard deviation but less than 2.5 standard deviation below the mean for normal young adults (i.e. T-score< –1 & ≥–2.5). DXA densitometry is presently an insured health service in Ontario.
Clinical Need
 
Burden of Disease
The Canadian Multicenter Osteoporosis Study (CaMos) found that 16% of Canadian women and 6.6% of Canadian men have osteoporosis based on the WHO criteria, with prevalence increasing with age. Osteopenia was found in 49.6% of Canadian women and 39% of Canadian men. In Ontario, it is estimated that nearly 530,000 Ontarians have some degrees of osteoporosis. Osteoporosis-related fragility fractures occur most often in the wrist, femur and pelvis. These fractures, particularly those in the hip, are associated with increased mortality, and decreased functional capacity and quality of life. A Canadian study showed that at 1 year after a hip fracture, the mortality rate was 20%. Another 20% required institutional care, 40% were unable to walk independently, and there was lower health-related quality of life due to attributes such as pain, decreased mobility and decreased ability to self-care. The cost of osteoporosis and osteoporotic fractures in Canada was estimated to be $1.3 billion in 1993.
Guidelines for Bone Mineral Density Testing
With 2 exceptions, almost all guidelines address only women. None of the guidelines recommend blanket population-based BMD testing. Instead, all guidelines recommend BMD testing in people at risk of osteoporosis, predominantly women aged 65 years or older. For women under 65 years of age, BMD testing is recommended only if one major or two minor risk factors for osteoporosis exist. Osteoporosis Canada did not restrict its recommendations to women, and thus their guidelines apply to both sexes. Major risk factors are age greater than or equal to 65 years, a history of previous fractures, family history (especially parental history) of fracture, and medication or disease conditions that affect bone metabolism (such as long-term glucocorticoid therapy). Minor risk factors include low body mass index, low calcium intake, alcohol consumption, and smoking.
Current Funding for Bone Mineral Density Testing
The Ontario Health Insurance Program (OHIP) Schedule presently reimburses DXA BMD at the hip and spine. Measurements at both sites are required if feasible. Patients at low risk of accelerated bone loss are limited to one BMD test within any 24-month period, but there are no restrictions on people at high risk. The total fee including the professional and technical components for a test involving 2 or more sites is $106.00 (Cdn).
Method of Review
This review consisted of 2 parts. The first part was an analysis of Ontario administrative data relating to DXA BMD, wrist and hip fractures, and use of antiresorptive drugs in people aged 65 years and older. The Institute for Clinical Evaluative Sciences extracted data from the OHIP claims database, the Canadian Institute for Health Information hospital discharge abstract database, the National Ambulatory Care Reporting System, and the Ontario Drug Benefit database using OHIP and ICD-10 codes. The data was analyzed to examine the trends in DXA BMD use from 1992 to 2005, and to identify areas requiring improvement.
The second part included systematic reviews and analyses of evidence relating to issues identified in the analyses of utilization data. Altogether, 8 reviews and qualitative syntheses were performed, consisting of 28 published systematic reviews and/or meta-analyses, 34 randomized controlled trials, and 63 observational studies.
Findings of Utilization Analysis
Analysis of administrative data showed a 10-fold increase in the number of BMD tests in Ontario between 1993 and 2005.
OHIP claims for BMD tests are presently increasing at a rate of 6 to 7% per year. Approximately 500,000 tests were performed in 2005/06 with an age-adjusted rate of 8,600 tests per 100,000 population.
Women accounted for 90 % of all BMD tests performed in the province.
In 2005/06, there was a 2-fold variation in the rate of DXA BMD tests across local integrated health networks, but a 10-fold variation between the county with the highest rate (Toronto) and that with the lowest rate (Kenora). The analysis also showed that:
With the increased use of BMD, there was a concomitant increase in the use of antiresorptive drugs (as shown in people 65 years and older) and a decrease in the rate of hip fractures in people age 50 years and older.
Repeat BMD made up approximately 41% of all tests. Most of the people (>90%) who had annual BMD tests in a 2-year or 3-year period were coded as being at high risk for osteoporosis.
18% (20,865) of the people who had a repeat BMD within a 24-month period and 34% (98,058) of the people who had one BMD test in a 3-year period were under 65 years, had no fracture in the year, and coded as low-risk.
Only 19% of people age greater than 65 years underwent BMD testing and 41% received osteoporosis treatment during the year following a fracture.
Men accounted for 24% of all hip fractures and 21 % of all wrist fractures, but only 10% of BMD tests. The rates of BMD tests and treatment in men after a fracture were only half of those in women.
In both men and women, the rate of hip and wrist fractures mainly increased after age 65 with the sharpest increase occurring after age 80 years.
Findings of Systematic Review and Analysis
Serial Bone Mineral Density Testing for People Not Receiving Osteoporosis Treatment
A systematic review showed that the mean rate of bone loss in people not receiving osteoporosis treatment (including postmenopausal women) is generally less than 1% per year. Higher rates of bone loss were reported for people with disease conditions or on medications that affect bone metabolism. In order to be considered a genuine biological change, the change in BMD between serial measurements must exceed the least significant change (variability) of the testing, ranging from 2.77% to 8% for precisions ranging from 1% to 3% respectively. Progression in BMD was analyzed, using different rates of baseline BMD values, rates of bone loss, precision, and BMD value for initiating treatment. The analyses showed that serial BMD measurements every 24 months (as per OHIP policy for low-risk individuals) is not necessary for people with no major risk factors for osteoporosis, provided that the baseline BMD is normal (T-score ≥ –1), and the rate of bone loss is less than or equal to 1% per year. The analyses showed that for someone with a normal baseline BMD and a rate of bone loss of less than 1% per year, the change in BMD is not likely to exceed least significant change (even for a 1% precision) in less than 3 years after the baseline test, and is not likely to drop to a BMD level that requires initiation of treatment in less than 16 years after the baseline test.
Serial Bone Mineral Density Testing in People Receiving Osteoporosis Therapy
Seven published meta-analysis of randomized controlled trials (RCTs) and 2 recent RCTs on BMD monitoring during osteoporosis therapy showed that although higher increases in BMD were generally associated with reduced risk of fracture, the change in BMD only explained a small percentage of the fracture risk reduction.
Studies showed that some people with small or no increase in BMD during treatment experienced significant fracture risk reduction, indicating that other factors such as improved bone microarchitecture might have contributed to fracture risk reduction.
There is conflicting evidence relating to the role of BMD testing in improving patient compliance with osteoporosis therapy.
Even though BMD may not be a perfect surrogate for reduction in fracture risk when monitoring responses to osteoporosis therapy, experts advised that it is still the only reliable test available for this purpose.
A systematic review conducted by the Medical Advisory Secretariat showed that the magnitude of increases in BMD during osteoporosis drug therapy varied among medications. Although most of the studies yielded mean percentage increases in BMD from baseline that did not exceed the least significant change for a 2% precision after 1 year of treatment, there were some exceptions.
Bone Mineral Density Testing and Treatment After a Fragility Fracture
A review of 3 published pooled analyses of observational studies and 12 prospective population-based observational studies showed that the presence of any prevalent fracture increases the relative risk for future fractures by approximately 2-fold or more. A review of 10 systematic reviews of RCTs and 3 additional RCTs showed that therapy with antiresorptive drugs significantly reduced the risk of vertebral fractures by 40 to 50% in postmenopausal osteoporotic women and osteoporotic men, and 2 antiresorptive drugs also reduced the risk of nonvertebral fractures by 30 to 50%. Evidence from observational studies in Canada and other jurisdictions suggests that patients who had undergone BMD measurements, particularly if a diagnosis of osteoporosis is made, were more likely to be given pharmacologic bone-sparing therapy. Despite these findings, the rate of BMD investigation and osteoporosis treatment after a fracture remained low (<20%) in Ontario as well as in other jurisdictions.
Bone Mineral Density Testing in Men
There are presently no specific Canadian guidelines for BMD screening in men. A review of the literature suggests that risk factors for fracture and the rate of vertebral deformity are similar for men and women, but the mortality rate after a hip fracture is higher in men compared with women. Two bisphosphonates had been shown to reduce the risk of vertebral and hip fractures in men. However, BMD testing and osteoporosis treatment were proportionately low in Ontario men in general, and particularly after a fracture, even though men accounted for 25% of the hip and wrist fractures. The Ontario data also showed that the rates of wrist fracture and hip fracture in men rose sharply in the 75- to 80-year age group.
Ontario-Based Economic Analysis
The economic analysis focused on analyzing the economic impact of decreasing future hip fractures by increasing the rate of BMD testing in men and women age greater than or equal to 65 years following a hip or wrist fracture. A decision analysis showed the above strategy, especially when enhanced by improved reporting of BMD tests, to be cost-effective, resulting in a cost-effectiveness ratio ranging from $2,285 (Cdn) per fracture avoided (worst-case scenario) to $1,981 (Cdn) per fracture avoided (best-case scenario). A budget impact analysis estimated that shifting utilization of BMD testing from the low risk population to high risk populations within Ontario would result in a saving of $0.85 million to $1.5 million (Cdn) to the health system. The potential net saving was estimated at $1.2 million to $5 million (Cdn) when the downstream cost-avoidance due to prevention of future hip fractures was factored into the analysis.
Other Factors for Consideration
There is a lack of standardization for BMD testing in Ontario. Two different standards are presently being used and experts suggest that variability in results from different facilities may lead to unnecessary testing. There is also no requirement for standardized equipment, procedure or reporting format. The current reimbursement policy for BMD testing encourages serial testing in people at low risk of accelerated bone loss. This review showed that biannual testing is not necessary for all cases. The lack of a database to collect clinical data on BMD testing makes it difficult to evaluate the clinical profiles of patients tested and outcomes of the BMD tests. There are ministry initiatives in progress under the Osteoporosis Program to address the development of a mandatory standardized requisition form for BMD tests to facilitate data collection and clinical decision-making. Work is also underway for developing guidelines for BMD testing in men and in perimenopausal women.
Conclusion
Increased use of BMD in Ontario since 1996 appears to be associated with increased use of antiresorptive medication and a decrease in hip and wrist fractures.
Data suggest that as many as 20% (98,000) of the DXA BMD tests in Ontario in 2005/06 were performed in people aged less than 65 years, with no fracture in the current year, and coded as being at low risk for accelerated bone loss; this is not consistent with current guidelines. Even though some of these people might have been incorrectly coded as low-risk, the number of tests in people truly at low risk could still be substantial.
Approximately 4% (21,000) of the DXA BMD tests in 2005/06 were repeat BMDs in low-risk individuals within a 24-month period. Even though this is in compliance with current OHIP reimbursement policies, evidence showed that biannual serial BMD testing is not necessary in individuals without major risk factors for fractures, provided that the baseline BMD is normal (T-score < –1). In this population, BMD measurements may be repeated in 3 to 5 years after the baseline test to establish the rate of bone loss, and further serial BMD tests may not be necessary for another 7 to 10 years if the rate of bone loss is no more than 1% per year. Precision of the test needs to be considered when interpreting serial BMD results.
Although changes in BMD may not be the perfect surrogate for reduction in fracture risk as a measure of response to osteoporosis treatment, experts advised that it is presently the only reliable test for monitoring response to treatment and to help motivate patients to continue treatment. Patients should not discontinue treatment if there is no increase in BMD after the first year of treatment. Lack of response or bone loss during treatment should prompt the physician to examine whether the patient is taking the medication appropriately.
Men and women who have had a fragility fracture at the hip, spine, wrist or shoulder are at increased risk of having a future fracture, but this population is presently under investigated and under treated. Additional efforts have to be made to communicate to physicians (particularly orthopaedic surgeons and family physicians) and the public about the need for a BMD test after fracture, and for initiating treatment if low BMD is found.
Men had a disproportionately low rate of BMD tests and osteoporosis treatment, especially after a fracture. Evidence and fracture data showed that the risk of hip and wrist fractures in men rises sharply at age 70 years.
Some counties had BMD utilization rates that were only 10% of that of the county with the highest utilization. The reasons for low utilization need to be explored and addressed.
Initiatives such as aligning reimbursement policy with current guidelines, developing specific guidelines for BMD testing in men and perimenopausal women, improving BMD reports to assist in clinical decision making, developing a registry to track BMD tests, improving access to BMD tests in remote/rural counties, establishing mechanisms to alert family physicians of fractures, and educating physicians and the public, will improve the appropriate utilization of BMD tests, and further decrease the rate of fractures in Ontario. Some of these initiatives such as developing guidelines for perimenopausal women and men, and developing a standardized requisition form for BMD testing, are currently in progress under the Ontario Osteoporosis Strategy.
PMCID: PMC3379167  PMID: 23074491
23.  Associations between Stroke Mortality and Weekend Working by Stroke Specialist Physicians and Registered Nurses: Prospective Multicentre Cohort Study 
PLoS Medicine  2014;11(8):e1001705.
In a multicenter observational study, Benjamin Bray and colleagues evaluate whether weekend rounds by stroke specialist physicians, or the ratio of registered nurses to beds on weekends, is associated with patient mortality after stroke.
Please see later in the article for the Editors' Summary
Background
Observational studies have reported higher mortality for patients admitted on weekends. It is not known whether this “weekend effect” is modified by clinical staffing levels on weekends. We aimed to test the hypotheses that rounds by stroke specialist physicians 7 d per week and the ratio of registered nurses to beds on weekends are associated with mortality after stroke.
Methods and Findings
We conducted a prospective cohort study of 103 stroke units (SUs) in England. Data of 56,666 patients with stroke admitted between 1 June 2011 and 1 December 2012 were extracted from a national register of stroke care in England. SU characteristics and staffing levels were derived from cross-sectional survey. Cox proportional hazards models were used to estimate hazard ratios (HRs) of 30-d post-admission mortality, adjusting for case mix, organisational, staffing, and care quality variables. After adjusting for confounders, there was no significant difference in mortality risk for patients admitted to a stroke service with stroke specialist physician rounds fewer than 7 d per week (adjusted HR [aHR] 1.04, 95% CI 0.91–1.18) compared to patients admitted to a service with rounds 7 d per week. There was a dose–response relationship between weekend nurse/bed ratios and mortality risk, with the highest risk of death observed in stroke services with the lowest nurse/bed ratios. In multivariable analysis, patients admitted on a weekend to a SU with 1.5 nurses/ten beds had an estimated adjusted 30-d mortality risk of 15.2% (aHR 1.18, 95% CI 1.07–1.29) compared to 11.2% for patients admitted to a unit with 3.0 nurses/ten beds (aHR 0.85, 95% CI 0.77–0.93), equivalent to one excess death per 25 admissions. The main limitation is the risk of confounding from unmeasured characteristics of stroke services.
Conclusions
Mortality outcomes after stroke are associated with the intensity of weekend staffing by registered nurses but not 7-d/wk ward rounds by stroke specialist physicians. The findings have implications for quality improvement and resource allocation in stroke care.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In a perfect world, a patient admitted to hospital on a weekend or during the night should have as good an outcome as a patient admitted during regular working hours. But several observational studies (investigations that record patient outcomes without intervening in any way; clinical trials, by contrast, test potential healthcare interventions by comparing the outcomes of patients who are deliberately given different treatments) have reported that admission on weekends is associated with a higher mortality (death) rate than admission on weekdays. This “weekend effect” has led to calls for increased medical and nursing staff to be available in hospitals during the weekend and overnight to ensure that the healthcare provided at these times is of equal quality to that provided during regular working hours. In the UK, for example, “seven-day working” has been identified as a policy and service improvement priority for the National Health Service.
Why Was This Study Done?
Few studies have actually tested the relationship between patient outcomes and weekend physician or nurse staffing levels. It could be that patients who are admitted to hospital on the weekend have poor outcomes because they are generally more ill than those admitted on weekdays. Before any health system introduces potentially expensive increases in weekend staffing levels, better evidence that this intervention will improve patient outcomes is needed. In this prospective cohort study (a study that compares the outcomes of groups of people with different baseline characteristics), the researchers ask whether mortality after stroke is associated with weekend working by stroke specialist physicians and registered nurses. Stroke occurs when the brain's blood supply is interrupted by a blood vessel in the brain bursting (hemorrhagic stroke) or being blocked by a blood clot (ischemic stroke). Swift treatment can limit the damage to the brain caused by stroke, but of the 15 million people who have a stroke every year, about 6 million die within a few hours and another 5 million are left disabled.
What Did the Researchers Do and Find?
The researchers extracted clinical data on 56,666 patients who were admitted to stroke units in England over an 18-month period from a national stroke register. They obtained information on the characteristics and staffing levels of the stroke units from a biennial survey of hospitals admitting patients with stroke, and information on deaths among patients with stroke from the national register of deaths. A quarter of the patients were admitted on a weekend, almost half the stroke units provided stroke specialist physician rounds seven days per week, and the remainder provided rounds five days per week. After adjustment for factors that might have affected outcomes (“confounders”) such as stroke severity and the level of acute stroke care available in each stroke unit, there was no significant difference in mortality risk between patients admitted to a stroke unit with rounds seven days/week and patients admitted to a unit with rounds fewer than seven days/week. However, patients admitted on a weekend to a stroke unit with 1.5 nurses/ten beds had a 30-day mortality risk of 15.2%, whereas patients admitted to a unit with 3.0 nurses/ten beds had a mortality risk of 11.2%, a mortality risk difference equivalent to one excess death per 25 admissions.
What Do These Findings Mean?
These findings show that the provision of stroke specialist physician rounds seven days/week in stroke units in England did not influence the (weak) association between weekend admission for stroke and death recorded in this study, but mortality outcomes after stroke were associated with the intensity of weekend staffing by registered nurses. The accuracy of these findings may be affected by the measure used to judge the level of acute care available in each stroke unit and by residual confounding. For example, patients admitted to units with lower nursing levels may have shared other unknown characteristics that increased their risk of dying after stroke. Moreover, this study considered the impact of staffing levels on mortality only and did not consider other relevant outcomes such as long-term disability. Despite these limitations, these findings support the provision of higher weekend ratios of registered nurses to beds in stroke units, but given the high costs of increasing weekend staffing levels, it is important that controlled trials of different models of physician and nursing staffing are undertaken as soon as possible.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001705.
This study is further discussed in a PLOS Medicine Perspective by Meeta Kerlin
Information about plans to introduce seven-day working into the National Health Service in England is available; the 2013 publication “NHS Services—Open Seven Days a Week: Every Day Counts” provides examples of how hospitals across England are working together to provide routine healthcare services seven days a week; a “Behind the Headlines” article on the UK National Health Service Choices website describes a recent observational study that investigated the association between admission to hospital on the weekend and death, and newspaper coverage of the study's results; the Choices website also provides information about stroke for patients and their families, including personal stories
A US nurses' site includes information on the association of nurse staffing with patient safety
The US National Institute of Neurological Disorders and Stroke provides information about all aspects of stroke (in English and Spanish); its Know Stroke site provides educational materials about stroke prevention, treatment, and rehabilitation, including personal stories (in English and Spanish); the US National Institute of Health SeniorHealth website has additional information about stroke
The Internet Stroke Center provides detailed information about stroke for patients, families, and health professionals (in English and Spanish)
doi:10.1371/journal.pmed.1001705
PMCID: PMC4138029  PMID: 25137386
24.  Association between Cutaneous Nevi and Breast Cancer in the Nurses' Health Study: A Prospective Cohort Study 
PLoS Medicine  2014;11(6):e1001659.
Using data from the Nurses' Health Study, Jiali Han and colleagues examine the association between number of cutaneous nevi and the risk for breast cancer.
Please see later in the article for the Editors' Summary
Background
Cutaneous nevi are suggested to be hormone-related. We hypothesized that the number of cutaneous nevi might be a phenotypic marker of plasma hormone levels and predict subsequent breast cancer risk.
Methods and Findings
We followed 74,523 female nurses for 24 y (1986–2010) in the Nurses' Health Study and estimate the relative risk of breast cancer according to the number of cutaneous nevi. We adjusted for the known breast cancer risk factors in the models. During follow-up, a total of 5,483 invasive breast cancer cases were diagnosed. Compared to women with no nevi, women with more cutaneous nevi had higher risks of breast cancer (multivariable-adjusted hazard ratio, 1.04, 95% confidence interval [CI], 0.98–1.10 for 1–5 nevi; 1.15, 95% CI, 1.00–1.31 for 6–14 nevi, and 1.35, 95% CI, 1.04–1.74 for 15 or more nevi; p for continuous trend = 0.003). Over 24 y of follow-up, the absolute risk of developing breast cancer increased from 8.48% for women without cutaneous nevi to 8.82% (95% CI, 8.31%–9.33%) for women with 1–5 nevi, 9.75% (95% CI, 8.48%–11.11%) for women with 6–14 nevi, and 11.4% (95% CI, 8.82%–14.76%) for women with 15 or more nevi. The number of cutaneous nevi was associated with increased risk of breast cancer only among estrogen receptor (ER)–positive tumors (multivariable-adjusted hazard ratio per five nevi, 1.09, 95% CI, 1.02–1.16 for ER+/progesterone receptor [PR]–positive tumors; 1.08, 95% CI, 0.94–1.24 for ER+/PR− tumors; and 0.99, 95% CI, 0.86–1.15 for ER−/PR− tumors). Additionally, we tested plasma hormone levels according to the number of cutaneous nevi among a subgroup of postmenopausal women without postmenopausal hormone use (n = 611). Postmenopausal women with six or more nevi had a 45.5% higher level of free estradiol and a 47.4% higher level of free testosterone compared to those with no nevi (p for trend = 0.001 for both). Among a subgroup of 362 breast cancer cases and 611 matched controls with plasma hormone measurements, the multivariable-adjusted odds ratio for every five nevi attenuated from 1.25 (95% CI, 0.89–1.74) to 1.16 (95% CI, 0.83–1.64) after adjusting for plasma hormone levels. Key limitations in this study are that cutaneous nevi were self-counted in our cohort and that the study was conducted in white individuals, and thus the findings do not necessarily apply to other populations.
Conclusions
Our results suggest that the number of cutaneous nevi may reflect plasma hormone levels and predict breast cancer risk independently of previously known factors.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
One woman in eight will develop breast cancer during her lifetime. Breast cancer begins when cells in the breast acquire genetic changes that allow them to divide uncontrollably (which leads to the formation of a lump in the breast) and to move around the body (metastasize). The treatment of breast cancer, which is diagnosed using mammography (a breast X-ray) or manual breast examination and biopsy, usually involves surgery to remove the lump, or the whole breast (mastectomy) if the cancer has started to metastasize. After surgery, women often receive chemotherapy or radiotherapy to kill any remaining cancer cells and may also be given drugs that block the action of estrogen and progesterone, female sex hormones that stimulate the growth of some breast cancer cells. Globally, half a million women die from breast cancer each year. However, in developed countries, nearly 90% of women affected by breast cancer are still alive five years after diagnosis.
Why Was This Study Done?
Several sex hormone–related factors affect breast cancer risk, including at what age a woman has her first child (pregnancy alters sex hormone levels) and her age at menopause, when estrogen levels normally drop. Moreover, postmenopausal women with high circulating levels of estrogen and testosterone (a male sex hormone) have an increased breast cancer risk. Interestingly, moles (nevi)—dark skin blemishes that are a risk factor for the development of melanoma, a type of skin cancer—often darken or enlarge during pregnancy. Might the number of nevi be a marker of hormone levels, and could nevi counts therefore be used to predict an individual's risk of breast cancer? In this prospective cohort study, the researchers look for an association between number of nevi and breast cancer risk among participants in the US Nurses' Health Study (NHS). A prospective cohort study enrolls a group of people, determines their baseline characteristics, and follows them over time to see which characteristics are associated with the development of certain diseases. The NHS, which enrolled 121,700 female nurses aged 30–55 years in 1976, is studying risk factors for cancer and other chronic diseases in women.
What Did the Researchers Do and Find?
In 1986, nearly 75,000 NHS participants (all of whom were white) reported how many nevi they had on their left arm. Over the next 24 years, 5,483 invasive breast cancers were diagnosed in these women. Compared to women with no nevi, women with increasing numbers of nevi had a higher risk of breast cancer after adjustment for known breast cancer risk factors. Specifically, among women with 1–5 nevi, the hazard ratio (HR) for breast cancer was 1.04, whereas among women with 15 or more nevi the HR was 1.35. An HR compares how often a particular event occurs in two groups with different characteristics; an HR greater than one indicates that a specific characteristic is associated with an increased risk of the event. Over 24 years of follow-up, the absolute risk of developing breast cancer was 8.48% in women with no nevi but 11.4% for women with 15 or more nevi. Notably, postmenopausal women with six or more nevi had higher blood levels of estrogen and testosterone than women with no nevi. Finally, in a subgroup analysis, the association between number of nevi and breast cancer risk disappeared after adjustment for hormone levels.
What Do These Findings Mean?
These findings support the hypothesis that the number of nevi reflects sex hormone levels in women and may predict breast cancer risk. Notably, they show that the association between breast cancer risk and nevus number was independent of known risk factors for breast cancer, and that the risk of breast cancer increased with the number of nevi in a dose-dependent manner. These findings also suggest that a hormonal mechanism underlies the association between nevus number and breast cancer risk. Because this study involved only white participants, these findings may not apply to non-white women. Moreover, the use of self-reported data on nevus numbers may affect the accuracy of these findings. Finally, because this study is observational, these findings are insufficient to support any changes in clinical recommendations for breast cancer screening or diagnosis. Nevertheless, these data and those in an independent PLOS Medicine Research Article by Kvaskoff et al. support the need for further investigation of the association between nevi and breast cancer risk and of the mechanisms underlying this relationship.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001659.
An independent PLOS Medicine Research Article by Kvaskoff et al. also investigates the relationship between nevi and breast cancer risk
The US National Cancer Institute provides comprehensive information about cancer (in English and Spanish), including detailed information for patients and professionals about breast cancer; it also has a fact sheet on moles
Cancer Research UK, a not-for profit organization, provides information about cancer, including detailed information on breast cancer
The UK National Health Service Choices website has information and personal stories about breast cancer; the not-for profit organization Healthtalkonline also provides personal stories about dealing with breast cancer
More information about the Nurses' Health Study is available
doi:10.1371/journal.pmed.1001659
PMCID: PMC4051600  PMID: 24915186
25.  Factors associated with self-reported, pesticide-related visits to health care providers in the agricultural health study. 
Environmental Health Perspectives  1998;106(7):415-420.
To investigate factors associated with pesticide-related visits to health care providers (i.e., doctor or hospital visits), responses to self-administered questionnaires received from 35,879 licensed restricted-use pesticide applicators participating in the Agricultural Health Study were analyzed. (In Iowa, applicators are actually certified, whereas in North Carolina they are licensed; for ease of reference, the term license will be used for both states in this paper.) The cohort reported a total of more than 10.9 million pesticide-application days. These applications were associated with one or more pesticide-related health care visits by 2,214 applicators (7.0% of the applicator cohort for whom health care visit data were available). The odds of a pesticide-related health care visit were increased for commercial applicators compared to private applicators [odds ratio (OR = 1.77; 95% confidence interval (CI), 1.52-2.06) and for applicators who used insecticides 70 times or more in their lifetime compared to those who used insecticides less frequently (OR = 1.43; CI, 1.26-1.63). After adjusting for the number of applications in a logistic regression model, significantly higher odds of health care visits were observed among North Carolina applicators compared to Iowa applicators (OR = 1.35; CI, 1.17-1.52), among applicators who mixed their own pesticides (OR = 1.65; CI, 1. 22-2.23), and among applicators who personally repaired their pesticide application equipment at least once per year (OR = 1.12; CI, 1.06-1.25). Significantly lower odds were found among female versus male applicators (OR = 0.68; CI, 0.46-0.99) and among applicators who graduated from high school versus those who did not (OR = 0.82; CI, 0.71-0.94 for high school graduates and OR = 0.79; CI, 0.68-0.91 for those with at least some college). Several methods of pesticide application to crops, seed, or stored grain were also associated with significantly elevated odds ratios of health care visits. These observations suggest that several steps can be taken to reduce the number of health care visits resulting from occupational exposure to pesticides. The implications of this pattern of pesticide-related health care visits may have etiologic implications for cancer and other chronic diseases.
Images
PMCID: PMC1533128  PMID: 9637799

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