Improving the quality of care and patient experience of care during the diagnosis of lupus: a qualitative study of primary care.

Purpose To better understand diagnostic delay and doctor-patient communication during the diagnosis of systemic lupus erythematous in patients without malar rash, we conducted a qualitative study of primary care providers' perceptions. Methods We conducted in-depth interviews with a purposive sample of eight primary care physicians in Kaiser Permanente Northern California. Telephone interviews were recorded, transcribed, reviewed, and coded for domains and themes. Results We identified five domains related to diagnosis: initial assessment and tests, initial diagnosis and empiric treatment, timeliness of diagnosis, communicating with the patient, and opportunities for improvement. In the absence of malar rash, the lupus manifestations are common while the disease is rare. Once the primary care provider believes that the disease may be autoimmune, they work with a rheumatologist, but this could take months. Initially, the physician assesses whether the condition is self-limiting or responds to empiric treatments. Over time, as empiric treatments fail or additional lupus manifestations emerge, the primary care provider makes a referral. Doctor-patient communication is critical to help the physician make sense of the symptoms, maintain trust, and assure the patient that he or she is receiving appropriate care. Patient persistence and communication are critically important. Continuing education was deemed essential by each physician. Conclusion In the absence of malar rash, a lupus diagnosis can be difficult. Enhanced doctor-patient communication, patient persistence, physician access to rheumatology and continuing education of primary care might improve time to diagnosis and the patient's experience with primary care. This knowledge is transferable to other rare, complex diseases.

Initiation of TNF inhibitor therapy and change in physiologic measures in psoriasis.

BACKGROUND: Psoriasis may predispose to cardiovascular disease and diabetes. However, the role of tumor necrosis factor (TNF) inhibitor in mediating this risk is controversial. OBJECTIVE: To assess this relationship, we estimated change in metabolic physiologic measures before and after initiation of TNF inhibitor therapy compared with methotrexate (MTX) therapy among psoriasis patients. METHODS: We conducted a retrospective cohort study, 2007-2012, using computerized clinical data for 1274 new users of TNF inhibitor and 979 new users of MTX therapy to compare change in blood pressure, lipids, triglycerides, fasting plasma glucose and body mass index (BMI) before and after start of TNF inhibitors or MTX. The study was restricted to new users. We computed within-person change in each measure, so that each patient served as their own control. In addition, we compared TNF inhibitor patients to MTX patients, by computing the adjusted difference in their group means. In secondary analyses, we examined phototherapy as a comparator. RESULTS: Among starters of TNF inhibitor and MTX therapy, within-person change in physiologic measures at 6 months did not differ significantly. We observed no important or significant changes in any of the physiologic measures with initiation of TNF inhibitor compared with MTX. The same results were found in subgroup analyses focused on men, and on those with hypertension, diabetes mellitus, or obesity. The same results were observed with phototherapy, except that diastolic blood pressure declined by 0.6 mmHg within person during the 6 months after starting phototherapy (P < 0.05). CONCLUSIONS: The study provides no evidence for improvement of physiologic measures associated with the metabolic syndrome resulting from TNF inhibitor use for psoriasis.

Mycobacterial diseases and antitumour necrosis factor therapy in USA.

OBJECTIVE: In North America, tuberculosis and nontuberculous mycobacterial (NTM) disease rates associated with antitumour necrosis factor α (anti-TNFα) therapy are unknown. METHODS: At Kaiser Permanente Northern California, the authors searched automated pharmacy records to identify inflammatory disease patients who received anti-TNF therapy during 2000-2008 and used validated electronic search algorithms to identify NTM and tuberculosis cases occurring during anti-TNF drug exposure. RESULTS: Of 8418 anti-TNF users identified, 60% had rheumatoid arthritis (RA). Among anti-TNF users, 18 developed NTM and 16 tuberculosis after drug start. Anti-TNF associated rates of NTM and tuberculosis were 74 (95% CI: 37 to 111) and 49 (95% CI: 18 to 79) per 100 000 person-years, respectively. Rates (per 100, 000 person-years) for NTM and tuberculosis respectively for etanercept were 35 (95% CI: 1 to 69) and 17 (95% CI: 0 to 41); infliximab, 116 (95% CI: 30 to 203) and 83 (95% CI: 10 to 156); and adalimumab, 122 (95% CI: 3 to 241) and 91 (95% CI: 19 to 267). Background rates for NTM and tuberculosis in unexposed RA-patients were 19.2 (14.2 to 25.0) and 8.7 (5.3 to 13.2), and in the general population were 4.1 (95% CI 3.9 to 4.4) and 2.8 (95% CI 2.6 to 3.0) per 100, 000 person-years. Among anti-TNF users, compared with uninfected individuals, NTM case-patients were older (median age 68 vs 50 years, p<0.01) and more likely to have RA (100% vs 60%, p<0.01); whereas, tuberculosis case-patients were more likely to have diabetes (37% vs 16%, p=0.02) or chronic renal disease (25% vs 6%, p=0.02). CONCLUSIONS: Among anti-TNF users in USA, mycobacterial disease rates are elevated, and NTM is associated with RA.

Occupational exposure to bisphenol-A (BPA) and the risk of self-reported male sexual dysfunction.

BACKGROUND: Animal studies have suggested that bisphenol-A (BPA) is a potential human endocrine disrupter; but evidence from human studies is needed. METHODS: We conducted an occupational cohort study to examine the effect of occupational exposure to BPA on the risk of male sexual dysfunction. Current workers from BPA-exposed and control factories were recruited. The exposed workers were exposed to very high BPA levels in their workplace. Male sexual function was ascertained through in-person interviews using a standard male sexual function inventory. RESULTS: BPA-exposed workers had consistently higher risk of male sexual dysfunction across all domains of male sexual function than the unexposed workers. After controlling for matching variables and potential confounders, exposed workers had a significantly increased risk of reduced sexual desire [odds ratios (OR) = 3.9, 95% confidence interval: 1.8-8.6), erectile difficulty (OR = 4.5, 95% CI 2.1-9.8), ejaculation difficulty (OR = 7.1, 95% CI 2.9-17.6), and reduced satisfaction with sex life (OR = 3.9, 95% CI 2.3-6.6). A dose-response relationship was observed with an increasing level of cumulative BPA exposure associated with a higher risk of sexual dysfunction. Furthermore, compared with the unexposed workers, BPA-exposed workers reported significantly higher frequencies of reduced sexual function within 1 year of employment in the BPA-exposed factories. CONCLUSIONS: Our findings provide the first evidence that exposure to BPA in the workplace could have an adverse effect on male sexual dysfunction.

Ovarian cancer incidence among Asian migrants to the United States and their descendants.

PURPOSE: We sought clues to the etiology of ovarian cancer by comparing the incidence rates among Chinese, Japanese, and Filipino migrants to the United States and among their descendants with rates among U.S.-born whites. METHODS: Information on age, race, and birthplace was obtained for each resident of Hawaii, San Francisco/Oakland, and western Washington identified by the Surveillance, Epidemiology, and End Results (SEER) cancer registry operating in each of those areas with incident ovarian cancer diagnosed during the period from 1973 to 1986. The number of women-years at risk was estimated from a special tabulation of the 1980 census. RESULTS: Among U.S. residents aged 20-79 years, the annual incidence of epithelial ovarian cancer among U.S.-born women of Asian descent was nearly the same as that of women born in Asia (respective annual rates per 100,000: Chinese, 11.7 versus 12.5; Japanese, 11.5 versus 14.1; and Filipino, 8.1 versus 11.0) and was 10%-50% lower than the rate among U.S.-born white women (15.6 per 100,000). For Chinese and Japanese women, this overall pattern with birthplace largely reflected the experience of those aged 50 years and older; in younger women, the rates were somewhat higher among those born in the United States and were similar to those of white women. CONCLUSION: These findings suggest that some descendants of Asian migrants to the United States retain a factor, genetic or otherwise, that partially protects against the development of ovarian cancer.

Cigarette smoking and risk of non-Hodgkin's lymphoma subtypes.

We examined the hypothesis that cigarette smoking increases the risk of non-Hodgkin's lymphoma (NHL) subtypes in a cohort of approximately 253,000 members of the Kaiser Permanente Medical Care Program, ages 16-84 years, who completed a self-administered questionnaire during the period 1964-1991 that ascertained smoking history. Using information from the Surveillance, Epidemiology, and End Results cancer registry that operates in the area and the Kaiser Permanente cancer registry, we identified 674 incident cases of NHL through 1993. We observed a positive association between smoking and risk of follicular lymphoma (compared with nonsmokers: former smokers, relative risk = 1.9 with 95% confidence interval = 1.2-2.9; current smokers, relative risk = 1.4 with 95% confidence interval = 0.9-2.2), although the strength of the association did not increase consistently with increasing duration and intensity of smoking. We observed no relationship between smoking status and the risks of small cell lymphocytic, diffuse, or high-grade lymphoma, nor was smoking related to the risk of all histological types of NHL combined. These results give limited evidence for a relationship between smoking and the risk of follicular lymphoma.

How accurately does the medical record capture maternal history of cancer?

We sought to assess the reliability of information regarding the maternal history of cancer by comparing the medical records of 214 women with breast cancer, ages 26-59 years and diagnosed in 1974-1995, and of their controls with the medical records of their mothers. Subjects were members of Kaiser Permanente, Northern California, selected for a study of early-life predictors of breast cancer. For any type of cancer identified in the mother's medical record, the proportion noted in the daughter's medical record at least 6 months before the daughter's diagnosis or reference date was 56% among cases and 32% among controls. The odds ratio for the association of maternal cancer history with breast cancer risk was 2.1 using the maternal record and 3.5 using the subject's record. For a maternal history of breast cancer, the proportion noted in the subject's record was 79% among cases and 57% among controls, and the odds ratios were 4.0 and 6.5, respectively. We believe that the case-control difference in missing information was attributable to higher utilization of breast cancer screening among cases. This study illustrates the need to assess the impact of screening differences on the ascertainment of information from the medical records.

Postmenopausal unopposed estrogens. Characteristics of use in relation to the risk of endometrial carcinoma.

To determine whether treatment regimens for unopposed estrogens can be tailored so as to minimize the excess risk of endometrial cancer, results from 19 published studies of the association between unopposed estrogen use and endometrial cancer were compiled. We sought to examine the influence of duration of use, recency, dose, type of estrogen preparation, and periodic interruption of use on cancer incidence. Estrogen use for 5 years or longer was examined in 18 studies and was associated with a large increase in the risk of endometrial cancer in each one (range in relative risk, 1.8 to 36). Use for shorter durations also was observed to increase risk; however, among women who used estrogens for less than 6 months, any increased risk that may exist appears to be very small in size (six studies; range, 0.6 to 1.4). Risk consistently was seen to decrease with increasing time since cessation of use, although there is evidence from seven of eight studies that some residual excess risk remains long after estrogens have been discontinued. In each of 12 studies that examined the influence of dose, all dose levels of conjugated estrogens increased risk of endometrial cancer substantially. Four of five studies found no differences between oral synthetic estrogens and conjugated estrogens with respect to cancer risk, and all of eight studies found no difference between cyclic and continuous regimens. Based on our review, we conclude that apart from minimizing the duration of use, there is no way of taking unopposed postmenopausal estrogens that reduces their potential to cause endometrial cancer.

Risk factors for synchronous primary endometrial and ovarian cancers.

PURPOSE: The incidence of synchronous primary endometrial and ovarian cancer is 2- to 10-fold higher than that expected based on the incidence of each cancer alone. We sought to evaluate reasons for this in a case-control study. METHODS: We combined data on a maternal history of cancer and reproductive and menstrual factors from 56 women with synchronous multiple primary disease who had participated in three population-based studies of gynecologic cancer. For comparison, we analyzed the same information from 280 women with endometrial cancer alone, 280 with ovarian cancer alone, and 280 without a history of either cancer. RESULTS: The reduced risk of multiple primary disease associated with high parity (2 or more births vs 0: OR = 0.37, 95% Cl, 0.19-76) and long-term use of oral contraceptives (12 or more months vs none: OR = 0.60, 95% Cl, 0.24-1.5) tended to be more pronounced than that associated with endometrial cancer alone or with ovarian cancer alone. CONCLUSIONS: Though limited by relatively small numbers, our results suggest that the presence of some common etiologies is a basis for the unusually high co-occurrence of endometrial and ovarian cancers.

Lactose metabolism and time to pregnancy.

OBJECTIVE: To investigate whether, in the absence of galactosemia, relatively high intestinal lactase activity or low activity of an enzyme involved in galactose catabolism reduces fertility, as it does in the presence of galactosemia. DESIGN: Retrospective cohort study. SETTING: Healthy women selected from the community. PATIENTS: Fifty-three married women. INTERVENTION: Urinary galactose after an oral lactose challenge (a measure of intestinal lactase activity), erythrocyte galactose-1-phosphate uridyltransferase (transferase) activity, and transferase polymorphisms by isoelectric focusing. MAIN OUTCOME MEASURE: Pregnancy rate (number of pregnancies divided by number of months at risk) in the 12 months after stopping use of birth control to become pregnant. RESULTS: Relatively high urinary galactose was not related to a decreased rate of pregnancy during the first 12 months (> or = 24.6 compared with < or = 14.3 mg: relative risk [RR] = 1.9; 95% confidence interval [CI] = 0.86 to 4.0). Relatively high transferase activity was not related to an increased rate of pregnancy (> or = 19.5 compared with < or = 17.2 mumol/h per g hemoglobin: RR = 1.1; 95% CI = 0.56 to 2.4). Low-activity transferase polymorphisms were not related to a decreased rate (RR = 1.2; 95% CI = 0.58 to 2.5). CONCLUSION: Our study does not support the hypothesis that the biologic variation in galactose metabolism that exists in the general population influences infertility.

Screening differences and risk of cervical cancer in inflammatory bowel disease.

BACKGROUND: Cervical cancer risk is high among immune suppressed women. AIM: To evaluate inflammatory bowel disease (IBD) with medications and risk of cervical cancer. METHODS: Members of Kaiser Permanente Northern California (KPNC), 15-68 years from 1996 to 2006 with IBD were compared with age-matched women without IBD. Cervical cancer was ascertained using the KPNC Cancer Registry. IBD medications of interest were aminosalicylates (ASA), corticosteroids, immune modulators and infliximab. Odds of cervical cancer were analysed with adjusted logistic regression. The prevalence of Pap smear testing was compared using a log binomial model. RESULTS: Ten cervical cancer cases occurred among 1165 women with IBD and 72 cancers among 12 124 controls. The adjusted odds ratio (OR) of IBD with risk of cervical cancer was 1.45 [95% confidence interval (CI) 0.74-2.84]. Medication ORs were 1.65 for ASA, 2.79 for corticosteroids and 3.45 for immune modulators (all P > 0.05). No cancer case used infliximab. The adjusted absolute increase in Pap smears among IBD women compared to women without IBD was 4% (95% CI 2-5%). CONCLUSIONS: Although a trend of elevated risk for cervical cancer with IBD and IBD medications was observed, it was not statistically significant. Regular cervical cancer screening for women with IBD is recommended.

Incidence of Waldenström's macroglobulinemia.

This study sought to determine the incidence and pattern of occurrence of Waldenström's macroglobulinemia, a plasmacytoid lymphocyte malignancy that involves monoclonal production of the IgM M-component type. Cases with Waldenström's macroglobulinemia have been reported since 1978 to the population-based cancer registry that serves western Washington state, and since 1988 to the eight other cancer registries that participate in the National Cancer Institute's Surveillance, Epidemiology, and End-Results program. Persons less than 85 years old newly diagnosed with Waldenström's macroglobulinemia were identified through 1989. The age-standardized annual incidence rate was 6.1 per million in white men and 2.5 per million in white women (1980 US standard). Only five cases were reported in black women, among whom the age-standardized annual incidence rate was 3.6 per million. No cases were reported among black men (5.8 cases expected, based on the rates in white men); this finding may be due to chance, underdiagnosis of Waldenström's macroglobulinemia in this group, or may reflect a truly low rate. Further investigation of a large, racially diverse population is required to better characterize the epidemiology of this rare disease.

Obesity and multiple myeloma.

An exploratory study was conducted of common clinical conditions as predictors of subsequent cancer in 143,574 outpatients of a health maintenance organization (in California, USA). An association was noted between obesity, diagnosed in 14,388 patients, and the subsequent development of multiple myeloma (MM) in up to 21 years (33 cases observed, 21.3 expected based on the experience of the entire cohort; standardized morbidity ratio = 1.55, 95 percent confidence interval [CI] = 1.06-2.17). This association was evaluated further in a second cohort of 163,561 multiphasic-checkup examinees followed up for as many as 24 years. Body mass index (BMI) at entry examination was associated positively with the incidence of MM in White men (e.g., relative risk [RR] = 1.07, CI = 1.01-1.15 per unit increase in BMI; and RR = 1.68, CI = 0.75-3.78, comparing the highest with lowest quartile). This association was absent in White women, partially confirmed in Black men and women (BMI quartiles two, three, and four showed higher risk than quartile one), and not explained by the presence of diabetes mellitus. The association was reduced or absent with BMI based on reported greatest adult-weight, and in White women was inverse with BMI based on reported lowest adult-weight. Among subjects with more than one checkup, increased risk was associated directly with weight loss among White men and associated inversely with weight gain among Black women. These findings suggest that body build or nutritional status may be involved in the development of MM by mechanisms that are presently unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of childhood height and later risk of breast cancer.

The authors sought to examine the hypothesis that girls who were relatively tall during the prepubescent period (indicative of an affluent diet and good general health) were at increased risk of subsequent breast cancer. They conducted a case-control study of 214 long-term members who were diagnosed with breast cancer during 1973-1995 and who were age 12 years or younger when they first joined Kaiser Permanente and of 214 appropriately matched controls. Information was obtained from the medical records. While the authors observed the expected association of adult height with risk of breast cancer (height at age 15-18 years, tall-for-age vs. short-for-age: odds ratio = 2.2, 95% confidence interval: 1.1, 4.3), the association was no stronger earlier in life (height at age 9-11 years: odds ratio = 1.0, 95% confidence interval: 0.5, 1.8). The study does not support a relation between pubertal skeletal growth and adult risk of breast cancer. However, it is limited by the inclusion of few postmenopausal women.

Transferrin saturation and risk of cancer.

The authors examined the hypothesis that relatively high levels of transferrin saturation increase the risk of cancer. They studied a cohort of prepaid health plan members whose transferrin saturation levels were measured during the period 1969-1971 and who were followed for cancer through 1990. After the exclusion of 10 percent of the subjects who received treatment for one or more of six chronic conditions or who were pregnant when the measurement was made and persons who contributed less than 5 years of follow-up, the authors were left with 38,538 persons who were followed for an average period of 17.7 years. In women, a positive association was observed between transferrin saturation and risk of stomach carcinoma (> or = 34.5% compared with < or = 20.3%: relative risk (RR) = 3.5, 95% confidence interval (CI) 0.98-12). In men, transferrin saturation was inversely associated with risk of colon and rectal carcinoma (> or = 40.7% compared with < or = 26.0%: colon, RR = 0.62, 95% CI 0.35-1.1; rectum, RR = 0.30, 95% CI 0.08-1.1) and with non-Hodgkin's lymphoma (32.1-40.6% compared with < or = 26.0%: RR = 0.31, 95% CI 0.11-0.88; no cases observed with transferrin saturation > or = 40.7%). The authors did not find evidence that the risk of epithelial cancer (all sites combined) was related to transferrin saturation level or to iron deficiency (< or = 15%) or overload (> or = 60%).

Breast cancer incidence in Asian migrants to the United States and their descendants.

We studied breast cancer incidence during the period 1973-1986 in Asian residents of three U.S. geographic areas. The rate in Asian-American women born in China or Japan and in their U.S.-born counterparts was about 50% and 75% that of U.S.-born whites, respectively, and was approximately twice the rate of women residing in Asia. Breast cancer incidence was nearly identical in U.S.- and foreign-born Filipino-Americans, but it was 40% that of U.S.-born whites.