Secure Delivery of HIV-Related and Tuberculosis Laboratory Results to Patient Cell Phones: A Pilot Comparative Study.

South Africa processes 5.1 million HIV CD4, viral load (VL), and tuberculosis (TB) tests annually. This pilot non-randomized trial in South Africa explored an intervention ("MatlaMobile") to deliver laboratory results via mobile phone. Adults completing CD4, VL, and/or TB laboratory tests were enrolled-either receiving results by returning to clinic (control, n = 174) or mobile phone (intervention, n = 226). Study staff instructed control participants to return within 6 days (standard-of-care). MatlaMobile instructed intervention participants with clinically actionable results requiring intervention or treatment change (i.e., < 200 CD4 cells per milliliter, ≥ 400 viral copies per milliliter, or TB positive) to return immediately. A greater proportion of intervention participants than controls saw their results within 7 days of enrollment (73% vs. 8.6%, p < 0.001). Among participants instructed to return, more intervention participants (20%, n = 14/70) returned than controls (8.6%, n = 15/174, p = 0.02). MatlaMobile demonstrated that patients can quickly receive and respond appropriately to digital delivery of health information.

Formative research for an mHealth program to improve the HIV care continuum in South Africa.

In South Africa, high attrition rates throughout the care continuum present major barriers to controlling the HIV epidemic. Mobile health (mHealth) interventions may provide innovative opportunities for efficient healthcare delivery and improving retention in care. In this formative research, we interviewed 11 patients and 28 healthcare providers in North West Province, South Africa, to identify perceived benefits, concerns and suggestions for a future mHealth program to deliver HIV Viral Load and CD4 Count test results directly to patients via mobile phone. Thematic analysis found that reduced workload for providers, reduced wait times for patients, potential expanded uses and patient empowerment were the main perceived benefits of an mHealth program. Perceived concerns included privacy, disseminating distressing results through text messages and patients' inability to interpret results. Participants felt that an mHealth program should complement face-to-face interactions and educational information to interpret results is needed. Providers identified logistical considerations and suggested protocols be developed. An mHealth program to deliver HIV test results directly to patients could mitigate multiple barriers to care but needs to be tested for efficacy. Concerns identified by patients and providers must be addressed in designing the program to successfully integrate with health facility workflow and ensure its sustainability.

COach2Quit: A Pilot Randomized Controlled Trial of a Personal Carbon Monoxide Monitor for Smoking Cessation.

INTRODUCTION: Mobile phone-based messaging support and biomarker feedback independently show evidence of increasing an individual's likelihood of quitting smoking. However, the combination of these two strategies to facilitate smoking cessation has not been adequately explored. METHODS: We conducted a randomized controlled trial in Baltimore, Maryland, to assess the efficacy of COach2Quit, a smartphone application that provides exhaled carbon monoxide readings with message support. The primary outcome was self-reported and biochemically verified smoking cessation at 30-day follow-up. Secondary outcomes were reduction in smoking, motivation to quit, and engagement and satisfaction with COach2Quit. An intention-to-treat analysis was conducted. RESULTS: Adult smokers were randomized 1:1 to receive brief advice and COach2Quit (intervention, n = 50) or brief advice only (control, n = 52). Thirteen participants were lost to follow-up. At 30-day follow-up, one participant in each arm quit smoking. Median change in carbon monoxide levels (in parts per million (ppm)) (intervention: -3.0 [interquartile range (IQR) -12.0, 2.0]; control: -2.5 [IQR -9.0, 2.0]) and median change in number of cigarettes smoked per day (intervention: -5.5 [IQR -14.0, -1.0]; control: -6.0 [IQR -10.0, -2.0]) was similar between study arms. There was no significant difference in mean percent change in the Reasons for Quitting scale score (intervention: 6.3 [95% confidence interval = -2.2% to 14.8%]; control: -3.6 [95% confidence interval = -9.2% to 2.1%]). A majority (n = 32, 91%) of participants liked having COach2Quit to help them quit smoking. CONCLUSIONS: There were no significant differences in smoking cessation, smoking reduction, and motivation to quit between study arms. However, high satisfaction with the COach2Quit application indicates its feasibility and acceptability as a smoking cessation tool. IMPLICATIONS: Smoking is the leading preventable cause of morbidity and mortality in the United States. Although counseling and pharmacotherapy are efficacious for smoking cessation, they are not easily accessible or desirable to all smokers, highlighting the need for identifying other interventions. There is evidence for the efficacy of mobile phone-based messaging support for smoking cessation. However, there is limited research on the efficacy of biomarker feedback, much less interventions that combine these two approaches. This research contributes to filling this gap and identifying novel interventions to facilitate smoking cessation.

Prevalence and Correlates of Snuff Use, and its Association With Tuberculosis, Among Women Living With HIV in South Africa.

INTRODUCTION: A higher proportion of people living with HIV (PLWH) smoke compared to the general population, but little information exists about the prevalence and correlates of smokeless tobacco use among PLWH. In South Africa, dry powdered tobacco is inhaled nasally as snuff. METHODS: A cross-sectional survey among PLWH attending three HIV clinics was conducted. Snuff use was assessed via self-report and urine cotinine. RESULTS: Given the low (3%) prevalence of snuff use among men, analysis was restricted to n = 606 nonsmoking women living with HIV. Half (n = 298, 49%) were snuff users, the majority of whom (n = 244, 84%) had a positive urine cotinine test. In adjusted analysis, snuff use was negatively associated with higher education (relative risk [RR] 0.55; 95% confidence interval [CI]: 0.39, 0.77) and mobile phone ownership (RR 0.83; 95% CI: 0.71, 0.98), and positively associated with ever having tuberculosis (TB) (RR 1.22; 95% CI: 1.03, 1.45). In adjusted analysis, with current TB as the outcome, snuff use was marginally statistically significantly associated with a twofold increase in odds of a current TB diagnosis (odds ratio [OR] 1.99; 95% CI: 0.98, 4.15). DISCUSSION: A high proportion of nonsmoking South African women living with HIV use snuff, which was a risk factor for TB. Additional research is needed to understand the relationship between snuff, TB, and other potential health risks. IMPLICATIONS: PLWH have a higher prevalence of smoking than their seronegative peers, but there is a paucity of research on smokeless tobacco use in this population, especially in low-resource settings. TB is the leading cause of death among PLWH, and with improvements to HIV treatment and care, PLWH are at greater risk of tobacco-related diseases. We report an extremely high prevalence of snuff use among women living with HIV in South Africa. Further, in this population snuff use is positively associated with ever having a TB diagnosis, as well as currently having TB.

The association of household fine particulate matter and kerosene with tuberculosis in women and children in Pune, India.

OBJECTIVES: Household air pollution (HAP) is a risk factor for respiratory disease, however has yet to be definitively associated with tuberculosis (TB). We aimed to assess the association between HAP and TB. METHODS: A matched case-control study was conducted among adult women and children patients with TB and healthy controls matched on geography, age and sex. HAP was assessed using questionnaires for pollution sources and 24-hour household concentrations of particulate matter <2.5 µm in diameter (PM2.5). RESULTS: In total, 192 individuals in 96 matched pairs were included. The median 24-hour time-weighted average PM2.5 was nearly seven times higher than the WHO's recommendation of 25 µg/m3, and did not vary between controls (179 µg/m3; IQR: 113-292) and cases (median 157 µg/m3; 95% CI 93 to 279; p=0.57). Reported use of wood fuel was not associated with TB (OR 2.32; 95% CI 0.65 to 24.20) and kerosene was significantly associated with TB (OR 5.49, 95% CI 1.24 to 24.20) in adjusted analysis. Household PM2.5 was not associated with TB in univariate or adjusted analysis. Controlling for PM2.5 concentration, kerosene was not significantly associated with TB, but effect sizes ranged from OR 4.30 (95% CI 0.78 to 30.86; p=0.09) to OR 5.49 (0.82 to 36.75; p=0.08). CONCLUSIONS: Use of kerosene cooking fuel is positively associated with TB in analysis using reported sources of exposure. Ubiquitously high levels of particulates limited detection of a difference in household PM2.5 between cases and controls.

Qualitative Exploration of a Smoking Cessation Trial for People Living With HIV in South Africa.

Introduction: In South Africa, people living with HIV have a high prevalence of smoking, which undermines the beneficial effects of antiretroviral therapy. However, little is known about barriers to smoking cessation and what interventions work for people living with HIV in this setting. Methods: A randomized trial comparing intensive anti-smoking counseling versus counseling and nicotine replacement therapy was recently concluded in Klerksdorp, South Africa. In a post-trial follow-up, 23 in-depth interviews with patients and one focus group discussion with counselors from the trial were conducted. A codebook was developed and codes were applied to the transcripts, which were analyzed using a thematic analysis. Results: Barriers at the economic, social/interpersonal, and individual levels induced stress, which hindered smoking cessation. Economic stressors included unemployment and poverty. Social or interpersonal stressors were lack of social support for quitting smoking and lack of social support due to having HIV. Individual stressors were traumatic life events. Alcohol was used to cope with stress and frequently co-occurred with smoking. Managing cravings was a barrier unrelated to stress. Participants proposed income and employment opportunities, group counseling, and more frequent counseling as solutions to address stressors at different levels. Nicotine replacement therapy was helpful to mitigate cravings. Conclusions: Future smoking cessation interventions need to target barriers at multiple levels. Increasing the supply and duration of nicotine replacement therapy may increase its effectiveness. Other behavioral approaches such as group counseling or peer counseling could hold promise in this setting but need to be tested for efficacy through randomized controlled trials. Implications: To our knowledge, this is the first qualitative study examining barriers to smoking cessation for people living with HIV in South Africa. Smoking is highly prevalent among people with HIV in South Africa and cessation interventions are urgently needed. A better understanding of barriers to smoking cessation that people with HIV face will lead to the development of contextually appropriate interventions. This study also provides feedback on interventions from a recently concluded smoking cessation randomized trial and will help guide the design of future smoking cessation trials.

Prevalence and Correlates of Smoking Among People Living With HIV in South Africa.

Introduction: Smoking likely exacerbates comorbidities which people living with HIV (PLWH) are predisposed. We assessed prevalence and correlates of smoking among PLWH in South Africa, which has 7 million PLWH but inadequate reporting of smoking. Methods: A cross-sectional survey was conducted among randomly selected adults with HIV infection in Klerksdorp, South Africa. Current smoking was assessed by questionnaire, exhaled carbon monoxide (eCO), and urine cotinine. Results: Of 1210 enrolled adults, 753 (62%) were women. In total, 409 (34%) self-reported ever smoking: 301 (74%) were current and 108 (26%) were former smokers. Using eCO and urine cotinine tests, 239 (52%) men and 100 (13%) women were defined as current smokers. Nearly all smokers (99%) were receiving ART, and had a median (IQR) CD4 count of 333 cells/µL (181-534), viral load of 31 IU/mL (25-4750), and BMI of 21 kg/m2 (19-24). Adjusted analysis among men showed higher odds of smoking with marijuana use (OR = 7.5, 95% CI = 4.1 to 14.6). Among women, 304 (43%) reported using snuff, compared to only 11 (3%) of men, and snuff use was inversely associated with smoking (OR = 0.1; 95% CI = 0.05 to 0.2). A subset of participants (n = 336) was asked about alcohol use, which was positively associated with smoking for men (OR = 8.1, 95% CI = 2.8 to 25.9) and women (OR = 8.5, 95% CI = 2.9 to 26.8). Conclusion: Smoking prevalence among PLWH in South Africa is alarmingly high. Prevention and cessation strategies that consider marijuana and alcohol use are needed. Implications: As long-term HIV care continues to improve, more people living with HIV (PLWH) will die of diseases, including tuberculosis, for which smoking plays an important causal role. The prevalence of smoking is markedly higher among PLWH in high-resource settings, but data for Africa and other low-resource settings that shoulder the brunt of the HIV epidemic has previously not been well documented. We report an alarmingly high prevalence of smoking among PLWH in South Africa, particularly among men, and a strong association between current smoking and use of other substances.

Unplanned cigarette purchases and tobacco point of sale advertising: a potential barrier to smoking cessation.

BACKGROUND: In the USA, tobacco marketing expenditure is increasingly concentrated at the point of sale (POS). Previous studies have demonstrated an association between exposure to tobacco POS advertising and increased smoking initiation, but limited evidence is available on adult smokers' decisions and behaviours. METHODS: An immediate post-cigarette purchase survey was administered to 301 cigarette purchasers outside of two grocery stores in Vermont to assess the prevalence of unplanned purchases and opinions about POS tobacco advertising and displays. RESULTS: In total, 11.3% of purchases were reported as unplanned. Certain groups were more likely to make unplanned purchases including: 18-24-year-olds (OR: 2.1, 95% CI 1.0 to 4.4), less than daily smokers (OR: 5.6, 95% CI 1.9 to 16.9), smokers who made 3+ quit attempts in the previous year (OR: 2.4, 95% CI 0.9 to 6.0), those who plan to quit in the next month (OR: 3.7, 95% CI 1.6 to 9.0), and those who agreed that tobacco POS advertising makes quitting smoking harder (OR: 2.3, 95% CI 1.1 to 4.8). Overall, 31.2% of participants agreed that tobacco POS advertising makes quitting smoking harder. Individuals who intended to quit within the next month, made 3+ quit attempts in the last year, or made an unplanned cigarette purchase were the most likely to agree. CONCLUSIONS: Young adults and individuals making multiple quit attempts or planning to quit in the next month are more likely to make unplanned cigarette purchases. Reducing unplanned purchases prompted by tobacco POS advertising could improve the likelihood of successful cessation among smokers.

Assessing secondhand smoke exposure with reported measures.

Non-smokers are exposed to tobacco smoke from the burning cigarette and the exhaled smoke from smokers. In spite of decades of development of approaches to assess secondhand smoke exposure (SHSe), there are still unresolved methodological issues. This manuscript summarises the scientific evidence on the use of SHSe reported measures and their methods, objectives, strengths and limitations; and discusses best practices for assessing behaviour leading to SHSe for lifetime and immediate or current SHSe. Recommendations for advancing measurement science of SHSe are provided. Behavioural measures of SHSe commonly rely on self-reports from children and adults. Most commonly, the methodology includes self, proxy and interview-based reporting styles using retrospective recall or diary-style reporting formats. The reporting method used will vary based upon the subject of interest, assessment objectives and cultural context. Appropriately implemented, reported measures of SHSe provide an accurate, timely and cost-effective method for assessing exposure time, location and quantity in a wide variety of populations.

A Cross-Sectional Analysis of the Nicotine Metabolite Ratio and Its Association with Sociodemographic and Smoking Characteristics among People with HIV Who Smoke in South Africa.

The nicotine metabolite ratio (NMR) is associated with race/ethnicity but has not been evaluated among smokers in the African region. We conducted a cross-sectional analysis of baseline data from a large randomized, controlled trial for smoking cessation among people with HIV (PWH) in South Africa. Urine samples were analyzed for the NMR and evaluated as a binary variable using a cutoff value of the fourth quartile to determine the fastest metabolizers. The median NMR was 0.31 (IQR: 0.31, 0.32; range: 0.29, 0.57); the cut-point for fast metabolizers was ≥0.3174 ng/mL. A high NMR was not associated with the number of cigarettes per day (OR = 1.10, 95% CI: 0.71, 1.70, p = 0.66) but was associated with 40% lower odds of a quit attempt in the past year (OR = 0.69; 95% CI: 0.44, 1.07, p = 0.09) and alcohol use (OR = 0.59, 95% CI: 0.32, 1.06, p = 0.07). No association was seen with marijuana or HIV clinical characteristics. As we found only minimal variability in the NMR and minimal associations with intensity of smoking, NMR may be of limited clinical value in this population, although it may inform which individuals are less likely to make a quit attempt.

A cross-sectional study of attitudes and behaviors of snuff use and cessation among people with and without HIV in South Africa.

Background: Despite a high (48%) prevalence of snuff use among women with HIV in South Africa, little is known of the attitudes and behaviors of use, strategies for cessation, and potential health risks. Methods: In a cross-sectional study, a questionnaire was administered to adults (≥18 years) with (HIV+) and without HIV (HIV-) who self-reported current snuff use to collect information on demographics, snuff use and cessation attempts, preferred strategies for cessation, other substance use, history of respiratory illness, and mental health. Results: 150 (74 HIV+, 76 HIV-) participants were enrolled; 115 (77%) were daily snuff users, 6 (4%) were current smokers, and 17 (11%) former smokers. Top reasons for current snuff use included improving health (n = 48, 32%), reducing stress (n = 26, 16%), and "being a habit" (n = 38, 25%). Participants believed snuff use to have mostly positive (n = 68, 46%) or no (n = 54, 36%) health impacts, and 57 (38%) participants believed snuff cures headaches. 103 (69%) participants reported a previous quit attempt, and 110 (73%) indicated high interest in quitting snuff. Although 105 (70%) participants indicated that advice from a healthcare provider would aid them in quitting snuff, only 30 (20%) reported ever receiving that advice. A majority of participants (n = 141, 94%) suffer from moderate to high levels of perceived stress, and overall few differences were seen by HIV status. Conclusions: Education on negative impacts of snuff, advice to quit from healthcare providers, and nicotine replacement therapy should be considered in the development of a snuff cessation program.

Prevalence and Correlates of Cardiovascular, Pulmonary, Cancer, and Mental Health Comorbidities Among Adults With HIV Who Smoke.

ABSTRACT: Using data from the D.C. Cohort Longitudinal HIV Study, we examined (a) diagnosed mental health and (b) cardiovascular, pulmonary, or cancer (CPC) comorbidity among adults with HIV who smoked. Among 8,581 adults, 4,273 (50%) smoked; 49% of smokers had mental health, and 13% of smokers had a CPC comorbidity. Among smokers, non-Hispanic Black participants had a lower risk for mental health (prevalence ratio [PR]: 0.69; 95% confidence interval [CI] [0.62-0.76]) but a higher risk for CPC (PR: 1.17; 95% CI [0.84-1.62]) comorbidity. Male participants had a lower risk for mental health (PR: 0.88; 95% CI [0.81-0.94]) and CPC (PR: 0.68; 95% CI [0.57-0.81]) comorbidity. All metrics of socioeconomic status were associated with a mental health comorbidity, but only housing status was associated with a CPC comorbidity. We did not find any association with substance use. Gender, socioeconomic factors, and race/ethnicity should inform clinical care and the development of smoking cessation strategies for this population.

A pilot randomized controlled trial of a tailored smoking cessation program for people living with HIV in the Washington, D.C. metropolitan area.

OBJECTIVE: Morbidity and mortality from smoking-related diseases among people living with HIV (PLWH) in the U.S. surpasses that due to HIV itself. Conventional smoking cessation treatments have not demonstrated strong efficacy among PLWH. We conducted a pilot randomized controlled trial (RCT) to evaluate a tailored smoking cessation intervention based on the minority stress model. We compared standard of care counseling (SOC) to a tailored intervention (TI) including one face-to-face counseling session incorporating cognitive behavioral therapy to build resilience, and 30 days of 2-way text messaging. RESULTS: The primary outcome was smoking cessation. Secondary outcomes included cigarettes per day (CPD), exhaled carbon monoxide (CO), and cessation self-efficacy. A total of 25 participants were enrolled (TI:11, SOC:14), and 2 were lost to follow-up. There were no significant differences in quit rates between study groups. However, there was a significantly greater decrease in CPD in the TI versus SOC (13.5 vs. 0.0, p-value:0.036). Additionally, self-efficacy increased in both groups (TI p-value:0.012, SOC p-value:0.049) and CO decreased in both groups (TI p-value: < 0.001, SOC p-value:0.049). This intervention shows promise to support smoking cessation among PLWH. A larger study is needed to fully evaluate the efficacy of this approach. CLINICAL TRIAL: Trial Registration: Retrospectively registered (10/20/2020) NCT04594109.

Sources of household air pollution and their association with fine particulate matter in low-income urban homes in India.

INTRODUCTION: Household air pollution (HAP) is poorly characterized in low-income urban Indian communities. MATERIALS AND METHODS: A questionnaire assessing sources of HAP and 24 h household concentrations of particulate matter less than 2.5 microns in diameter (PM2.5) were collected in a sample of low-income homes in Pune, India. RESULTS: In 166 homes, the median 24 h average concentration of PM2.5 was 167 µg/m3 (IQR: 106-294). Although kerosene and wood use were highly prevalent (22% and 25% of homes, respectively), primarily as secondary fuel sources, high PM2.5 concentrations were also found in 95 (57%) homes reporting LPG use alone (mean 141 µg/m3; IQR: 92-209). In adjusted linear regression, log PM2.5 concentration was positively associated with wood cooking fuel (GMR 1.5, 95% CI: 1.1-2.0), mosquito coils (GMR 1.5, 95% CI: 1.1-2.1), and winter season (GMR 1.7, 95% CI: 1.4-2.2). Households in the highest quartile of exposure were positively associated with wood cooking fuel (OR 1.3, 95% CI: 1.1-1.5), incense (OR 1.1, 95% CI: 1.0-1.3), mosquito coils (OR 1.3, 95% CI: 1.1-1.6), and winter season (OR 1.2, 95% CI: 1.1-1.4). DISCUSSION: We observed high concentrations of PM2.5 and identified associated determinants in urban Indian homes.

Secondhand Smoke Exposure and Validity of Self-Report in Low-Income Women and Children in India.

BACKGROUND: There is limited validation of self-reported measures for secondhand smoke (SHS) exposure in low- and middle-income countries. We evaluated the validity of standard self-reported measures among women and children in urban India. METHODS: Structured questionnaires were administered, and household air and hair samples were analyzed for nicotine concentration. RESULTS: In total, 141 households of 70 child and 71 adult participants were included. Air nicotine was detected in 72 (51%) homes, and 35 (75%) child and 12 (56%) adult participants had detectable hair nicotine. Correlation between air and hair nicotine was significant in children (r = 0.5; P = .0002) but not in adults (r = -0.1; P = .57). Poor correlation was found between self-reported measures of exposure and both air and hair nicotine. No questions were significantly correlated with hair nicotine, and the highest-magnitude correlation with air nicotine was for how often someone smoked inside for adults (r = 0.4; P = .10) and for home preparation of mishri (a smokeless tobacco product prepared for consumption by roasting) for children (r = 0.4; P = .39). The highest value for sensitivity by using air nicotine as the gold standard was for whether people smelled other families preparing mishri (47%; 95% confidence interval: 31-62) and prepared mishri in their own homes (50%; 95% confidence interval: 19-81). CONCLUSIONS: These results raise caution in using or evaluating self-reported SHS exposure in these communities. More appropriate questions for this population are needed, including mishri preparation as a source of SHS exposure.

Indoor air pollution from secondhand tobacco smoke, solid fuels, and kerosene in homes with active tuberculosis disease in South Africa.

OBJECTIVES: Secondhand tobacco smoke (SHS), use of solid fuels, and kerosene may play an important role in perpetuating the tuberculosis (TB) epidemic. The purpose of this study was to explore the prevalence of household air pollution (HAP) from these sources in homes of someone with TB in a high HIV-prevalence setting. A convenience sample of homes and household members participating in an ongoing active case-finding study in Matlosana district townships surrounding Klerksdorp, South Africa were included. RESULTS: We found a high prevalence of air pollution from SHS, solid fuels, and kerosene among individuals in homes with a case of prevalent active TB disease in Klerksdorp, South Africa. Adults in 40% of homes reported a daily smoker in the home, and 70% of homes had detectable air nicotine. In homes with a history of previous TB (prior to but not including the index case) as compared to those without previous TB, both SHS (83% vs. 65%, respectively) and solid/kerosene fuel use for more than 1 h/day (27% vs. 21%, respectively) were more prevalent. Larger studies are needed to estimate the risk of TB from these types of air pollution in HIV infected individuals and settings with high HIV prevalence.

Impact of tobacco control interventions on smoking initiation, cessation, and prevalence: a systematic review.

BACKGROUND: Policymakers need estimates of the impact of tobacco control (TC) policies to set priorities and targets for reducing tobacco use. We systematically reviewed the independent effects of TC policies on smoking behavior. METHODS: We searched MEDLINE (through January 2012) and EMBASE and other databases through February 2009, looking for studies published after 1989 in any language that assessed the effects of each TC intervention on smoking prevalence, initiation, cessation, or price participation elasticity. Paired reviewers extracted data from studies that isolated the impact of a single TC intervention. FINDINGS: We included 84 studies. The strength of evidence quantifying the independent effect on smoking prevalence was high for increasing tobacco prices and moderate for smoking bans in public places and antitobacco mass media campaigns. Limited direct evidence was available to quantify the effects of health warning labels and bans on advertising and sponsorship. Studies were too heterogeneous to pool effect estimates. INTERPRETATIONS: We found evidence of an independent effect for several TC policies on smoking prevalence. However, we could not derive precise estimates of the effects across different settings because of variability in the characteristics of the intervention, level of policy enforcement, and underlying tobacco control environment.

Nonobese diabetic mouse congenic analysis reveals chromosome 11 locus contributing to diabetes susceptibility, macrophage STAT5 dysfunction, and granulocyte-macrophage colony-stimulating factor overproduction.

Unstimulated monocytes of at-risk/type 1 diabetic humans and macrophages of the NOD mouse have markedly elevated autocrine GM-CSF production and persistent STAT5 phosphorylation. We analyzed the relationship between GM-CSF production and persistent STAT5 phosphorylation in NOD macrophages using reciprocal congenic mouse strains containing either diabetes-susceptible NOD (B6.NODC11), or diabetes-resistant C57L (NOD.LC11) loci on chromosome 11. These intervals contain the gene for GM-CSF (Csf2; 53.8 Mb) and those for STAT3, STAT5A, and STAT5B (Stat3, Stat5a, and Stat5b; 100.4-100.6 Mb). High GM-CSF production and persistent STAT5 phosphorylation in unactivated NOD macrophages can be linked to a region (44.9-55.7 Mb) containing the Csf2 gene, but not the Stat3/5a/5b genes. This locus, provisionally called Idd4.3, is upstream of the previously described Idd4.1 and Idd4.2 loci. Idd4.3 encodes an abundance of cytokine genes that use STAT5 in their macrophage activation signaling and contributes approximately 50% of the NOD.LC11 resistance to diabetes.