Cost-effectiveness analysis of smoking cessation interventions using cell phones in a low-income population.

BACKGROUND: The prevalence of cigarette smoking is significantly higher among those living at or below the federal poverty level. Cell phone-based interventions among such populations have the potential to reduce smoking rates and be cost-effective. METHODS: We performed a cost-effectiveness analysis of three smoking cessation interventions: Standard Care (SC) (brief advice to quit, nicotine replacement therapy and self-help written materials), Enhanced Care (EC) (SC plus cell phone-delivered messaging) and Intensive Care (IC) (EC plus cell phone-delivered counselling). Quit rates were obtained from Project ACTION (Adult smoking Cessation Treatment through Innovative Outreach to Neighborhoods). We evaluated shorter-term outcomes of cost per quit and long-term outcomes using cost per quality-adjusted life year (QALY). RESULTS: For men, EC cost an additional $541 per quit vs SC; however, IC cost an additional $5232 per quit vs EC. For women, EC was weakly dominated by IC-IC cost an additional $1092 per quit vs SC. Similarly, for men, EC had incremental cost-effectiveness ratio (ICER) of $426 per QALY gained vs SC; however, IC resulted in ICER of $4127 per QALY gained vs EC. For women, EC was weakly dominated; the ICER of IC vs SC was $1251 per QALY gained. The ICER was below maximum acceptable willingness-to-pay threshold of $50 000 per QALY under all alternative modelling assumptions. DISCUSSION: Cell phone interventions for low socioeconomic groups are a cost-effective use of healthcare resources. Intensive Care was the most cost-effective strategy both for men and women. TRIAL REGISTRATION NUMBER: NCT00948129; Results.

Understanding the link between contingency management and smoking cessation: The roles of sex and self-efficacy.

INTRODUCTION: Little is known about the mechanisms linking contingency management (CM) treatment with smoking cessation, and recent research suggests that the CM approach is associated with better smoking cessation outcomes among females than males. The current study investigated self-efficacy as a potential mechanism through which CM treatment influences smoking cessation, and explored whether these relationships differed by sex. METHODS: Participants (N = 139) were primarily Black (63.3%) and female (57.6%) adults enrolled in a safety-net hospital smoking cessation program. Participants received usual care (UC), which included pharmacotherapy and counseling sessions (n = 66) or a CM intervention (UC + 4 weeks of small, abstinence contingent financial incentives; n = 73). Self-efficacy for quitting was measured on the day after quitting with the Self-Efficacy Scale/Confidence (SESC) questionnaire. Mediation analyses were conducted to evaluate the indirect effects of treatment group on biochemically-verified abstinence (4-weeks post-quit) via self-efficacy, and moderated mediation analyses were conducted to evaluate the moderating role of sex. RESULTS: Self-efficacy was not found to mediate the relations between CM treatment and smoking cessation in the overall sample. However, analyses indicated a significant moderating effect of sex on the indirect effect of treatment group on smoking cessation through self-efficacy (each of the 3 SESC subscales). Specifically, there was a stronger association between CM and greater self-efficacy among females than males. CONCLUSION: Findings suggest that CM treatment had a differing impact on self-efficacy among males and females, which in turn influenced the likelihood of smoking cessation.

Enhancing Smoking Risk Communications: The Influence of Health Literacy and Message Content.

Background: Efforts are needed to ensure that smokers with lower health literacy are provided with understandable and impactful information about the health consequences of smoking and benefits of quitting. Purpose: To test the influence of health literacy on smokers' responses to health risk messages manipulated on framing (gain vs. loss) and emotionality (factual vs. emotional). Methods: Participants (N = 402) were randomized to evaluate one of four sets of smoking risk messages (factual gain-framed, factual loss-framed, emotional gain-framed, or emotional loss-framed). Multiple linear regressions examined main effects of health literacy, message emotionality, and message framing on: (a) risk perceptions, (b) behavioral expectations (i.e. cut down, limit, quit), and (c) risk knowledge. Two-way interactions of health literacy with emotionality and framing were examined for these outcomes. Analyses were based on theory-driven, a priori hypotheses. Results: As hypothesized, main effects emerged such that smokers with higher health literacy reported stronger risk perceptions and knowledge retention regardless of message type. Additionally, emotional (vs. factual) and gain- (vs. loss-) framed messages were associated with certain lower risk perceptions regardless of health literacy level. Consistent with hypotheses, two-way crossover interactions emerged between health literacy and emotionality. Among smokers with higher health literacy, factual messages produced higher perceived risk and stronger expectations for quitting. Among smokers with lower health literacy, emotional messages produced higher perceived risk and stronger expectations for quitting. Conclusions: Health literacy plays an important role in influencing how smokers respond to different risk messages. One's health literacy should be considered when determining whether risk communications emphasize factual or emotional content.

An ecological momentary intervention for smoking cessation: The associations of just-in-time, tailored messages with lapse risk factors.

BACKGROUND: Smartphone apps can provide real-time, tailored interventions for smoking cessation. The current study examines the effectiveness of a smartphone-based smoking cessation application that assessed risk for imminent smoking lapse multiple times per day and provided messages tailored to current smoking lapse risk and specific lapse triggers. METHODS: Participants (N=59) recruited from a safety-net hospital smoking cessation clinic completed phone-based ecological momentary assessments (EMAs) 5 times/day for 3 consecutive weeks (1week pre-quit, 2weeks post-quit). Risk for smoking lapse was estimated in real-time using a novel weighted lapse risk estimator. With each EMA, participants received messages tailored to current level of risk for imminent smoking lapse and self-reported presence of smoking urge, stress, cigarette availability, and motivation to quit. Generalized linear mixed model analyses determined whether messages tailored to specific lapse risk factors were associated with greater reductions in these triggers than messages not tailored to specific triggers. RESULTS: Overall, messages tailored to smoking urge, cigarette availability, or stress corresponded with greater reductions in those triggers than messages that were not tailored to specific triggers (p's=0.02 to <0.001). Although messages tailored to stress were associated with greater reductions in stress than messages not tailored to stress, the association was non-significant (p=0.892) when only moments of high stress were included in the analysis. CONCLUSIONS: Mobile technology can be used to conduct real-time smoking lapse risk assessment and provide tailored treatment content. Findings provide initial evidence that tailored content may impact users' urge to smoke, stress, and cigarette availability.

HIV Care Initiation: A Teachable Moment for Smoking Cessation?

Introduction: Tobacco use among persons living with HIV represents an important risk factor for poor treatment outcomes, morbidity, and mortality. Thus, efforts designed to inform the development of appropriate smoking cessation programs for this population remains a public health priority. To address this need, a study was conducted to longitudinally assess the relationship between intention to quit smoking and cessation over the 12-month period following initiation of HIV care. Methods: Patients initiating HIV care at a large inner city safety net clinic were enrolled (n = 378) in a 12-month prospective study. Audio computer-assisted self-interviews were conducted at baseline, and at 3, 6, 9, and 12 months post-enrollment, and HIV-related clinical data were collected from participants' electronic medical records. Variables of interest included intention to quit smoking, 7-day point prevalence smoking abstinence (biochemically verified), and stage of HIV. Data were collected in Houston, Texas from 2009 to 2015. Results: The sample was 75% male and 62% Black. Findings indicated that intention to quit smoking increased between baseline and 3 months, and subsequently trended downward from 3 to 12 months. Results from linear and generalized linear mixed models indicated that participants with advanced HIV disease (vs. not advanced) reported significantly (p < .05) higher intention to quit smoking at 3, 6, and 12 months post-study enrollment. A similar though nonsignificant pattern was observed in the smoking abstinence outcome. Conclusions: HIV treatment initiation appears to be associated with increases in intention to quit smoking thus serves as a potential teachable moment for smoking cessation intervention. Implications: This study documents significant increases in intention to quit smoking in the 3-month period following HIV care initiation. Moreover, quit intention trended downward following the 3-month follow-up until the 12-month follow-up. In addition, a marked effect for HIV disease stage was observed, whereby participants with advanced HIV disease (vs. those without) experienced a greater increase in intention to quit. HIV treatment initiation appears to be associated with increases in intention to quit smoking, thus serves as a crucial teachable moment for smoking cessation intervention for people living with HIV.

Financial strain indirectly influences smoking cessation through withdrawal symptom severity.

BACKGROUND: Financial strain has an adverse impact on smoking cessation. However, the mechanisms through which financial strain influences cessation remain unclear. The purpose of the current study was to determine whether financial strain indirectly influenced smoking cessation through withdrawal symptom severity. METHODS: Participants (N=139) were primarily Black (63.3%) and female (57.6%) adults enrolled in a smoking cessation program at a safety-net hospital. A self-report financial strain questionnaire was completed one week prior to the scheduled quit date, and the Wisconsin Smoking Withdrawal Scale (WSWS) was completed on the day after the scheduled quit date. Biochemically-verified 7-day point prevalence abstinence was assessed four weeks after the scheduled quit date. Adjusted mediation analyses were conducted using the PROCESS macro for SPSS to evaluate the indirect effects of financial strain on smoking cessation via post-quit withdrawal symptom severity. RESULTS: Analyses indicated a significant indirect effect of financial strain on smoking cessation through total withdrawal symptom severity, B=0.027; 95% CI (0.003, 0.066); and specifically anger, B=0.035; 95% CI (0.008, 0.074), anxiety, B=0.021; 95% CI (0.001, 0.051), and sleep symptoms, B=0.015; 95% CI (0.005, 0.043). Greater pre-quit financial strain was associated with greater post-quit withdrawal symptom severity, which increased the likelihood of non-abstinence 4 weeks after the scheduled quit attempt. The direct effect of financial strain on smoking cessation was not significant in any of the mediation models. CONCLUSIONS: Findings: suggest that withdrawal severity is an underlying mechanism through which financial strain influences smoking cessation.

Have combustible cigarettes met their match? The nicotine delivery profiles and harmful constituent exposures of second-generation and third-generation electronic cigarette users.

INTRODUCTION: Electronic cigarettes' (e-cigarettes) viability as a public health strategy to end smoking will likely be determined by their ability to mimic the pharmacokinetic profile of a cigarette while also exposing users to significantly lower levels of harmful/potentially harmful constituents (HPHCs). The present study examined the nicotine delivery profile of third- (G3) versus second-generation (G2) e-cigarette devices and their users' exposure to nicotine and select HPHCs compared with cigarette smokers. METHODS: 30 participants (10 smokers, 9 G2 and 11 G3 users) completed baseline questionnaires and provided exhaled carbon monoxide (eCO), saliva and urine samples. Following a 12-hour nicotine abstinence, G2 and G3 users completed a 2-hour vaping session (ie, 5 min, 10-puff bout followed by ad libitum puffing for 115 min). Blood samples, subjective effects, device characteristics and e-liquid consumption were assessed. RESULTS: Smokers, G2 and G3 users had similar baseline levels of cotinine, but smokers had 4 and 7 times higher levels of eCO (p<0.0001) and total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (i.e., NNAL, p<0.01), respectively, than G2 or G3 users. Compared with G2s, G3 devices delivered significantly higher power to the atomiser, but G3 users vaped e-cigarette liquids with significantly lower nicotine concentrations. During the vaping session, G3 users achieved significantly higher plasma nicotine concentrations than G2 users following the first 10 puffs (17.5 vs 7.3 ng/mL, respectively) and at 25 and 40 min of ad libitum use. G3 users consumed significantly more e-liquid than G2 users. Vaping urges/withdrawal were reduced following 10 puffs, with no significant differences between device groups. DISCUSSION: Under normal use conditions, both G2 and G3 devices deliver cigarette-like amounts of nicotine, but G3 devices matched the amount and speed of nicotine delivery of a conventional cigarette. Compared with cigarettes, G2 and G3 e-cigarettes resulted in significantly lower levels of exposure to a potent lung carcinogen and cardiovascular toxicant. These findings have significant implications for understanding the addiction potential of these devices and their viability/suitability as aids to smoking cessation.

Evaluation of a Shelter-Based Diet and Physical Activity Intervention for Homeless Adults.

BACKGROUND: The current study evaluated the feasibility and effectiveness of a diet and physical activity intervention for homeless adults. METHODS: Shelter residents (N = 32) were randomly assigned to a 4-week diet and physical activity intervention (n = 17) or an assessment-only control group (n = 15). Intervention participants received tailored educational newsletters, pedometers with step goals, and twice daily fruit/vegetable snacks. Key measures included 24-hour dietary recall interviews and accelerometer-measured moderate-to-vigorous intensity physical activity (MVPA). RESULTS: At baseline, 68.8% of participants were overweight or obese, 93.8% reported food insecurity, and 43.8% reported activity levels below physical activity guidelines. Baseline dietary recall interviews indicated low fruit/vegetable consumption, and elevated intake of added sugar, saturated fat, and sodium relative to current dietary recommendations. During the 4-week study period, intervention participants engaged in significantly greater accelerometer-measured daily MVPA (P < .001) than controls (median = 60 daily minutes p vs. 41 daily minutes). Between groups differences in fruit/vegetable consumption at the end of treatment did not reach statistical significance. Most participants reported that the intervention was helpful for increasing fruit/vegetable intake and physical activity. CONCLUSIONS: Findings highlight the potential to improve dietary quality and increase physical activity among sheltered homeless adults.

An Ecological Momentary Intervention for Smoking Cessation: Evaluation of Feasibility and Effectiveness.

BACKGROUND: Despite substantial public health progress in reducing the prevalence of smoking in the United States overall, smoking among socioeconomically disadvantaged adults remains high. OBJECTIVE: To determine the feasibility and preliminary effectiveness of a novel smartphone-based smoking cessation app designed for socioeconomically disadvantaged smokers. METHODS: Participants were recruited from a safety-net hospital smoking cessation clinic in Dallas, Texas, and were followed for 13 weeks. All participants received standard smoking cessation clinic care (ie, group counseling and cessation pharmacotherapy) and a smartphone with a novel smoking cessation app (ie, Smart-T). The Smart-T app prompted 5 daily ecological momentary assessments (EMAs) for 3 weeks (ie, 1 week before cessation and 2 weeks after cessation). During the precessation period, EMAs were followed by messages that focused on planning and preparing for the quit attempt. During the postcessation period, participant responses to EMAs drove an algorithm that tailored messages to the current level of smoking lapse risk and currently present lapse triggers (eg, urge to smoke, stress). Smart-T offered additional intervention features on demand (eg, one-click access to the tobacco cessation quitline; "Quit Tips" on coping with urges to smoke, mood, and stress). RESULTS: Participants (N=59) were 52.0 (SD 7.0) years old, 54% (32/59) female, and 53% (31/59) African American, and 70% (40/57) had annual household income less than US $16,000. Participants smoked 20.3 (SD 11.6) cigarettes per day and had been smoking for 31.6 (SD 10.9) years. Twelve weeks after the scheduled quit date, 20% (12/59) of all participants were biochemically confirmed abstinent. Participants responded to 87% of all prompted EMAs and received approximately 102 treatment messages over the 3-week EMA period. Most participants (83%, 49/59) used the on-demand app features. Individuals with greater nicotine dependence and minority race used the Quit Tips feature more than their counterparts. Greater use of the Quit Tips feature was linked to nonabstinence at the 2 (P=.02), 4 (P<.01), and 12 (P=.03) week follow-up visits. Most participants reported that they actually used or implemented the tailored app-generated messages and suggestions (83%, 49/59); the app-generated messages were helpful (97%, 57/59); they would like to use the app in the future if they were to lapse (97%, 57/59); and they would like to refer friends who smoke to use the Smart-T app (85%, 50/59). A minority of participants (15%, 9/59) reported that the number of daily assessments (ie, 5) was "too high." CONCLUSIONS: This novel just-in-time adaptive intervention delivered an intensive intervention (ie, 102 messages over a 3-week period), was well-liked, and was perceived as helpful and useful by socioeconomically disadvantaged adults who were seeking smoking cessation treatment. Smartphone apps may be used to increase treatment exposure and may ultimately reduce tobacco-related health disparities among socioeconomically disadvantaged adults.

Using Intensive Longitudinal Data Collected via Mobile Phone to Detect Imminent Lapse in Smokers Undergoing a Scheduled Quit Attempt.

BACKGROUND: Mobile phone‒based real-time ecological momentary assessments (EMAs) have been used to record health risk behaviors, and antecedents to those behaviors, as they occur in near real time. OBJECTIVE: The objective of this study was to determine if intensive longitudinal data, collected via mobile phone, could be used to identify imminent risk for smoking lapse among socioeconomically disadvantaged smokers seeking smoking cessation treatment. METHODS: Participants were recruited into a randomized controlled smoking cessation trial at an urban safety-net hospital tobacco cessation clinic. All participants completed in-person EMAs on mobile phones provided by the study. The presence of six commonly cited lapse risk variables (ie, urge to smoke, stress, recent alcohol consumption, interaction with someone smoking, cessation motivation, and cigarette availability) collected during 2152 prompted or self-initiated postcessation EMAs was examined to determine whether the number of lapse risk factors was greater when lapse was imminent (ie, within 4 hours) than when lapse was not imminent. Various strategies were used to weight variables in efforts to improve the predictive utility of the lapse risk estimator. RESULTS: Participants (N=92) were mostly female (52/92, 57%), minority (65/92, 71%), 51.9 (SD 7.4) years old, and smoked 18.0 (SD 8.5) cigarettes per day. EMA data indicated significantly higher urges (P=.01), stress (P=.002), alcohol consumption (P<.001), interaction with someone smoking (P<.001), and lower cessation motivation (P=.03) within 4 hours of the first lapse compared with EMAs collected when lapse was not imminent. Further, the total number of lapse risk factors present within 4 hours of lapse (mean 2.43, SD 1.37) was significantly higher than the number of lapse risk factors present during periods when lapse was not imminent (mean 1.35, SD 1.04), P<.001. Overall, 62% (32/52) of all participants who lapsed completed at least one EMA wherein they reported ≥3 lapse risk factors within 4 hours of their first lapse. Differentially weighting lapse risk variables resulted in an improved risk estimator (weighted area=0.76 vs unweighted area=0.72, P<.004). Specifically, 80% (42/52) of all participants who lapsed had at least one EMA with a lapse risk score above the cut-off within 4 hours of their first lapse. CONCLUSIONS: Real-time estimation of smoking lapse risk is feasible and may pave the way for development of mobile phone‒based smoking cessation treatments that automatically tailor treatment content in real time based on presence of specific lapse triggers. Interventions that identify risk for lapse and automatically deliver tailored messages or other treatment components in real time could offer effective, low cost, and highly disseminable treatments to individuals who do not have access to other more standard cessation treatments.

Polymorphisms in the Hsp70 gene locus are genetically associated with systemic lupus erythematosus.

BACKGROUND: Heat shock proteins (Hsps) play a role in the delivery and presentation of antigenic peptides and are thought to be involved in the pathogenesis of multifactorial diseases. OBJECTIVE: To investigate genes encoding cytosolic Hsp70 proteins for associations of allelic variants with systemic lupus erythematosus (SLE). METHODS: Case-control studies of two independent Caucasian SLE cohorts were performed. In a haplotype-tagging single-nucleotide polymorphism approach, common variants of HspA1L, HspA1A and HspA1B were genotyped and principal component analyses were performed for the cohort from the Oklahoma Medical Research Foundation (OMRF). Relative quantification of mRNA was carried out for each Hsp70 gene in healthy controls. Conditional regression analysis was performed to determine if allelic variants in Hsp70 act independently of HLA-DR3. RESULTS: On analysis of common genetic variants of HspA1L, HspA1A and HspA1B, a haplotype significantly associated with SLE in the Erlangen-SLE cohort was identified, which was confirmed in the OMRF cohort. Depending on the cohorts, OR ranging from 1.43 to 1.88 and 2.64 to 3.16 was observed for individuals heterozygous and homozygous for the associated haplotype, respectively. Patients carrying the risk haplotype or the risk allele more often displayed autoantibodies to Ro and La in both cohorts. In healthy controls bearing this haplotype, the amount of HspA1A mRNA was significantly increased, whereas total Hsp70 protein concentration was not altered. CONCLUSIONS: Allelic variants of the Hsp70 genes are significantly associated with SLE in Caucasians, independently of HLA-DR3, and correlate with the presence of autoantibodies to Ro and La. Hence, the Hsp70 gene locus appears to be involved in SLE pathogenesis.

Adjuvant chemotherapy for the "oldest old" ovarian cancer patients: can we anticipate toxicity-related treatment failure in a vulnerable population?

BACKGROUND: Patients aged > or = 80 years who are diagnosed with advanced ovarian cancer (OC) have been reported to have a poor prognosis. In the current study, chemotherapy-related toxicity data were evaluated between patients aged > or = 80 years and those aged < 80 years. METHODS: Patients with OC who underwent cytoreductive surgery with chemotherapy were included. Self-reported toxicity data were obtained from National Cancer Institute Common Toxicity Criteria (CTC) forms. Objective indicators of status including albumin level, weight, and creatinine clearance were abstracted both before and after therapy. Data were compared between patients by decade of age. RESULTS: A total of 246 patients were included. A presenting Karnofsky performance status >2 was recorded in 17% of patients aged > or = 80 years versus 0% to 4% of patients aged < 80 years (P = .002). Platinum-based chemotherapy was used in all patients. For patients aged < 80 years, combination chemotherapy was used in > 90% versus 69% in those aged > or = 80 years (P < .0001). Standard-dose combination therapy was used in 72% to 86% of patients aged <80 years versus 28% of patients aged > or =80 years (P < .0001). Patients aged > or =80 years completed > or =6 cycles of therapy approximately 57% of the time versus 84% to 97% of the time for those aged < 80 years (P = .0001). CTC forms identified no self-reported toxicities to be more common among patients aged > or =80 years. Multivariate logistic regression identified creatinine clearance < 65 mL/minute (odds ratio [OR] of 4.6), 5% weight loss (OR of 2.5), prechemotherapy albumin level of < 2 g/dL (OR of 3.65), and initiation of therapy with a single agent (OR of 3.9) as independent predictors of failure to complete chemotherapy. CONCLUSIONS: Despite initial treatment modifications as well as toxicity assessment, only 57% of patients aged > or =80 years completed planned chemotherapy. It was confirmed that further studies into the pharmacokinetics of chemotherapy in the elderly and more sensitive assessment of therapy-related toxicity are required.

Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci.

Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) < P(overall) < 1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.

Genetic variation in the CRP promoter: association with systemic lupus erythematosus.

The pentraxin C-reactive protein (CRP), an innate immune system opsonin which binds nuclear debris and apoptotic bodies, may protect against autoimmunity. A relative deficiency of CRP levels in patients with systemic lupus erythematosus (SLE) might contribute to altered handling of self-antigens. We report that the proximal 5' promoter region of CRP contains several polymorphisms that exhibit association with SLE in multiple populations. Strongest association was observed at the proximal promoter single nucleotide polymorphism (SNP) rs3093061 (CRP-707) (P = 6.41 x 10(-7) and P = 2.13 x 10(-6) in African-American and Caucasian case-control samples respectively). This association remains after adjustment for admixture. Linkage disequilibrium exists between SNPs in the proximal promoter and association of functional haplotypes containing rs3091244/rs3093062 (CRP-409/-390) appear to be driven by the rs3093061 (CRP-707) association. These data demonstrate that rs3093061 at the -707 site within the CRP gene is an SLE susceptibility locus.

Evaluation of the genetic association of the PTPN22 R620W polymorphism in familial and sporadic systemic lupus erythematosus.

OBJECTIVE: The R620W (1858C-->T) polymorphism in PTPN22 has been implicated in type 1 diabetes mellitus, rheumatoid arthritis, Graves' disease, Hashimoto thyroiditis, autoimmune thyroid disease, and systemic lupus erythematosus (SLE). The aim of this study was to evaluate this polymorphism in patients with familial SLE and in those with sporadic SLE. METHODS: A total of 4,981 DNA samples were genotyped (from 1,680 SLE patients, 1,834 family members, and 1,467 controls). Both population-based case-control and family-based association designs were used for the analyses. RESULTS: In the European American familial SLE cohort, the minor 1858T allele was more common in randomly selected patients compared with controls (chi2= 5.61, P = 0.018, odds ratio [OR] 1.46, 95% confidence interval [95% CI] 1.07-1.99). The heterozygous C/T genotype was also more common in these European American patients compared with controls (OR 1.63, 95% CI 1.15-2.30). Family-based association tests showed preferential transmission of the 1858T allele to affected offspring (chi2 = 5.87, P = 0.015). In contrast, the frequency of the 1858T minor allele was not significantly increased in the European American patients with sporadic SLE compared with controls, nor did these patients have preferential transmission of the 1858T allele. Indeed, the difference in the 1858T allele frequency between patients with familial SLE and those with sporadic SLE was measurable (allelic chi2= 4.22, P = 0.04, OR 1.51, 95% CI 1.02-2.24). Our data also showed that among patients with SLE, the 1858T allele was separately associated with type 1 diabetes mellitus and with autoimmune thyroid disease, confirming the findings of other investigators. CONCLUSION: The 1858T allele of PTPN22 is associated with familial SLE but not with sporadic SLE in European Americans, thereby potentially explaining previous contradictory reports.