Isabella Locatelli

Framingham risk score and alternatives for prediction of coronary heart disease in older adults

Background Guidelines for the prevention of coronary heart disease (CHD) recommend use of Framingham-based risk scores that were developed in white middle-aged populations. It remains unclear whether and how CHD risk prediction might be improved among older adults. We aimed to compare the prognostic performance of the Framingham risk score (FRS), directly and after recalibration, with refit functions derived from the present cohort, as well as to assess the utility of adding other routinely available risk parameters to FRS. Methods Among 2193 black and white older adults (mean age, 73.5 years) without pre-existing cardiovascular disease from the Health ABC cohort, we examined adjudicated CHD events, defined as incident myocardial infarction, CHD death, and hospitalization for angina or coronary revascularization. Results During 8-year follow-up, 351 participants experienced CHD events. The FRS poorly discriminated between persons who experienced CHD events vs. not (C-index: 0.577 in women; 0.583 in men) and underestimated absolute risk prediction by 51% in women and 8% in men. Recalibration of the FRS improved absolute risk prediction, particulary for women. For both genders, refitting these functions substantially improved absolute risk prediction, with similar discrimination to the FRS. Results did not differ between whites and blacks. The addition of lifestyle variables, waist circumference and creatinine did not improve risk prediction beyond risk factors of the FRS. Conclusions The FRS underestimates CHD risk in older adults, particularly in women, although traditional risk factors remain the best predictors of CHD. Re-estimated risk functions using these factors improve accurate estimation of absolute risk.

Participation in a population-based physical activity programme as an aid for smoking cessation: a randomised trial

Objectives Exercise combined with nicotine therapy may help smoking cessation and minimise weight gain after quitting. Low participation in vigorous-intensity physical activity programmes precludes their population-wide applicability. In a randomised controlled trial, we tested whether a population-based moderate-intensity physical activity programme increases quit rates among sedentary smokers receiving nicotine therapy. Methods Participants (n=481; 57% male; mean age, 42.2 years (SD 10.1); mean cigarette consumption, 27 (SD 10.2) per day) were offered a nine-week smoking cessation programme consisting of a weekly 15-minute counselling session and the prescription of nicotine replacement therapy. In addition, participants in the physical activity group (n=229) also took part in a programme of moderate-intensity physical activity implemented at the national level, and offering nine weekly 60-minute sessions of physical activity. To ensure equal contact conditions, participants in the control group (n=252) attended weekly 60-minute health behaviour education sessions unrelated to physical activity. The primary outcome was continuous CO-verified smoking abstinence rates at 1-year follow-up. Results Continuous smoking abstinence rates were high and similar in the physical activity group and the control group at the end of the intervention (47% versus 46%, p=0.81) and at 1-year follow-up (27% versus 29%, p=0.71). The mean weight gain after one year was 4.4 kg and 6.2 kg among sustained quitters of the physical activity and control groups, respectively (p=0.06). Conclusion Participation in a population-based moderate-intensity physical activity programme for 9 weeks in addition to a comprehensive smoking cessation programme did not significantly increase smoking cessation rates. A non-significant reduction in weight gain was observed among participants who quit smoking in the physical activity group. Trial registration ClinicalTrials.gov; US National Institutes for Health (available online at http://clinicaltrials.gov/; Clinical Trial Registration Number: NCT00521391)

Resting Heart Rate and the Risk of Heart Failure in Healthy Adults: The Rotterdam Study

Background—An elevated resting heart rate is associated with rehospitalization for heart failure and is a modifiable risk factor in heart failure patients. We aimed to examine the association between resting heart rate and incident heart failure in a population-based cohort study of healthy adults without pre-existing overt heart disease. Methods and Results—We studied 4768 men and women aged ≥55 years from the population-based Rotterdam Study. We excluded participants with prevalent heart failure, coronary heart disease, pacemaker, atrial fibrillation, atrioventricular block, and those using &bgr;-blockers or calcium channel blockers. We used extended Cox models allowing for time-dependent variation of resting heart rate along follow-up. During a median of 14.6 years of follow-up, 656 participants developed heart failure. The risk of heart failure was higher in men with higher resting heart rate. For each increment of 10 beats per minute, the multivariable adjusted hazard ratios in men were 1.16 (95% confidence interval, 1.05–1.28; P=0.005) in the time-fixed heart rate model and 1.13 (95% confidence interval, 1.02–1.25; P=0.017) in the time-dependent heart rate model. The association could not be demonstrated in women (P for interaction=0.004). Censoring participants for incident coronary heart disease or using time-dependent models to account for the use of &bgr;-blockers or calcium channel blockers during follow-up did not alter the results. Conclusions—Baseline or persistent higher resting heart rate is an independent risk factor for the development of heart failure in healthy older men in the general population.

Predictors of Weight Change in Sedentary Smokers Receiving a Standard Smoking Cessation Intervention

INTRODUCTION Quitting smoking is associated with weight gain, which may threaten motivation to engage or sustain a quit attempt. The pattern of weight gained by smokers treated according to smoking cessation guidelines has been poorly described. We aimed to determine the weight gained after smoking cessation and its predictors, by smokers receiving individual counseling and nicotine replacement therapies for smoking cessation. METHODS We performed an ancillary analysis of a randomized controlled trial assessing moderate physical activity as an aid for smoking cessation in addition to standard treatment in sedentary adult smokers. We used mixed longitudinal models to describe the evolution of weight over time, thus allowing us to take every participant into account. We also fitted a model to assess the effect of smoking status and reported use of nicotine replacement therapy at each time point. We adjusted for intervention group, sex, age, nicotine dependence, and education. RESULTS In the whole cohort, weight increased in the first 3 months, and stabilized afterwards. Mean 1-year weight gain was 3.3kg for women and 3.9kg for men (p = .002). Higher nicotine dependence and male sex were associated with more weight gained during abstinence. Age over median was associated with continuing weight gain during relapse. There was a nonsignificant trend toward slower weight gain with use of nicotine replacement therapies. CONCLUSION Sedentary smokers receiving a standard smoking cessation intervention experience a moderate weight gain, limited to the first 3 months. Older age, male sex, and higher nicotine dependence are predictors of weight gain.

Improved health of hospitality workers after a Swiss cantonal smoking ban

QUESTIONS UNDER STUDY Hospitality workers are a population particularly at risk from the noxious effects of environmental tobacco smoke (ETS). The Canton of Vaud, Switzerland banned smoking in public places in September 2009. This prospective study addresses the impact of the ban on the health of hospitality workers. METHODS ETS exposure was evaluated using a passive sampling device that measures airborne nicotine; lung function was assessed by spirometry; health-related quality of life, ETS exposure symptoms and satisfaction were measured by questionnaire. RESULTS 105 participants (smokers and non-smokers) were recruited initially and 66 were followed up after one year. ETS exposure was significantly lower after the ban. Hospitality workers had lower pre-ban forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) values than expected. FEV1 remained stable after the ban, with a near-significant increase in the subgroup of asthmatics only. FVC increased at one year follow-up from 90.42% to 93.05% (p = 0.02) in the entire cohort; women, non-smokers and older participants gained the greatest benefit. The health survey showed an increase in physical wellbeing after the ban, the greatest benefit being observed in non-smokers. ETS exposure symptoms were less frequent after the ban, especially red and irritated eyes and sneezing. The new law was judged useful and satisfactory by the vast majority of employees, including smokers. CONCLUSION The recent cantonal ban on smoking in public places brought about an improvement in lung function, physical well-being and ETS symptoms of hospitality workers, including smokers.

Robust accelerated failure time regression

Robust estimators for accelerated failure time models with asymmetric (or symmetric) error distribution and censored observations are proposed. It is assumed that the error model belongs to a log-location-scale family of distributions and that the mean response is the parameter of interest. Since scale is a main component of mean, scale is not treated as a nuisance parameter. A three steps procedure is proposed. In the first step, an initial high breakdown point S estimate is computed. In the second step, observations that are unlikely under the estimated model are rejected or down weighted. Finally, a weighted maximum likelihood estimate is computed. To define the estimates, functions of censored residuals are replaced by their estimated conditional expectation given that the response is larger than the observed censored value. The rejection rule in the second step is based on an adaptive cut-off that, asymptotically, does not reject any observation when the data are generated according to the model. Therefore, the final estimate attains full efficiency at the model, with respect to the maximum likelihood estimate, while maintaining the breakdown point of the initial estimator. Asymptotic results are provided. The new procedure is evaluated with the help of Monte Carlo simulations. Two examples with real data are discussed.

Adherence to Antiretroviral Treatment Decreases During Postpartum Compared to Pregnancy: A Longitudinal Electronic Monitoring Study

Dear Editor: As recently published in your Journal, the LILAC prospective cohort study showed a decrease in self-reported adherence between pregnancy and postpartum in South America.1 Interestingly, our smaller study with a longitudinal measure and analysis of adherence to antiretroviral treatment confirms these findings. Antiretroviral therapy (ART) during pregnancy and postpartum involves two issues: prophylaxis of perinatal transmission and treatment of maternal infection.2 Adherence, defined as “the process by which patients take their medications as prescribed,” is crucial to address these concerns.3,4 Pregnancy and the first months of motherhood cause important changes in a womens life, which might impact ART adherence. Most frequently cited barriers to adherence were competition with other issues including family obligation and hectic lifestyle. Conversely, the babys health was cited as a motivator for adherence.5 During postpartum, women tend to miss more medical visits, and adherence tends to be lower than during pregnancy.1,6–10 Between 10% and 50% of the women stopped their ART after childbirth, part of them on their own without physicians approval.7–10 Most of published studies are based on pill count or self-reported adherence. To our knowledge this is the first study assessing electronically the dynamics of adherence in a continuum from pregnancy to postpartum along with clinical data. This exploratory, retrospective study was approved by the Swiss Ethic Commission (Vaud) for clinical research. It aimed at comparing adherence to the entire ART—during pregnancy and postpartum—using continuous electronic drug monitoring data. The community Pharmacy of the Department of ambulatory care and community medicine in Lausanne has been running an adherence-enhancing program since 2004, which combines electronic drug monitoring and semistructured, repeated motivational interviews.4 All pregnant HIV-positive women having taken part in the program between 2004 and 2012 were retrieved. The maximal observation period extended from first adherence visit after last menstruation to 6 months after childbirth. Sociodemographic and clinical data were collected from the Swiss HIV Cohort Study database. Percent of attended visits were compared between pregnancy and postpartum using the McNemar test. Electronic data on medication adherence, extracted from the adherence-enhancing program database, were reconciled with pill count and interview notes in order to include reported pocket doses. For each woman, adherence was described with a binary variable (1=correct number of daily opening(s) of all electronic monitors; 0=less daily openings than prescribed). Data were analyzed via a piecewise logistic mixed effect model. Mixed effect models are methods of choice for analyzing data with repeated measures for each participant. They take into account the interindividual variability of the measures and can deal with unbalanced data due to missing values. In particular, a piecewise logistic mixed effect model allowed us to estimate the probability of taking ART as prescribed, for each day d of pregnancy and postpartum periods.11 Adherence at days 0–3 from childbirth has been replaced by missing values before entering the model, because of the bias due to hospitalization. Analysis of change in CD4 over time was performed using a piecewise polynomial mixed effect model. A qualitative inspection of viral RNA individual trajectories was made only graphically, as the large interindividual variability and the small number of data prevented the application of a mixed effect model. We used the Stata/IC software (v12.0, StataCorp, College Station, TX) for data description and the R system for computation and graphic of mixed effect models (v2.12.1, www.r-project.org/, library “nlme”). Among 400 patients referred to the adherence program, 29 pregnant women (7%) were screened and 25 (86%) were included. Three women who did not use electronic monitors were excluded, and one underwent an early pregnancy interruption. Median age was 29 (interquartile range [IQR]: 26.5, 32.0). Seventeen women (68%) were black and 11 (44%) were ART naive. ART included protease and nucleoside reverse transcriptase inhibitors (n=24; 96%). Six women (24%) stopped the program during pregnancy, 3 (12%) at childbirth and 4 (16%) during the postpartum period. Among these 13 women, 8 (62%) were kept on ART, 3 stopped ART after childbirth according to guidelines, and 2 stopped ART without physicians agreement. All these women were considered in the analysis. The percentage of unattended visits increased from 17% during pregnancy to 38% during postpartum (p=0.001). Probability of correct ART intake was continuously high during pregnancy (97% [95% CI: 0.94–0.98]), decreased to 93% (95% CI: 0.87–0.96) at childbirth (p of the difference=0.006), and increased again during postpartum (p of the slope coefficient=0.009) (Fig. 1A) to reach the same probability than during pregnancy after 164 days. A sensitivity analysis with the 10 women who were continuously monitored during pregnancy and postpartum confirmed the decrease in ART intake after childbirth. FIG. 1. Change in drug intake, viral load, and CD4 count over time. (A) Percentage of women with correct number of daily opening(s) of the electronic monitors over time. Curves in bold represent the prediction±95% confidence interval, (days 0–3 ... CD4 count increased during pregnancy, decreased around 40 days after childbirth then increased again (p of the linear, quadratic and cubic coefficient <0.005; Fig. 1B). Individual ARN curves decreased during pregnancy. Within the 13 continuing women after childbirth, 4 (31%) had at least one worsening viral load (range, 25–344 copies per milliliter; Fig. 1C). In summary, our data describe adherence during pregnancy and postpartum from a real-life medication adherence clinic. Our model predicts that 97 women of 100 take all doses of ART during pregnancy versus 93 women 3 days after childbirth. Our results also mean that missing doses increased from 1 per month (i.e., 3 per 100 days) during pregnancy to 2 per month (i.e., 7 per 100 days) at beginning of postpartum. We could show a lag time during postpartum before women were able to reach the same probability of adherence than during pregnancy. Strength of our analysis results from: (1) a day-by-day adherence monitoring to entire ART, (2) reconciliation of electronic data with pill count and interview to reflect actual drug intake, and (3) the use of advanced statistics. Our main limitation is due to the fact that 9 women stopped the program before or at childbirth. Fortunately, it did not impact the adherence level during pregnancy as confirmed by a sensitivity analysis. External validity is limited by the fact that women were included in an adherence-enhancing program. Drop in adherence during standard care might be more significant. Our data show that a major event such as childbirth impacts adherence transiently, which may result in viral rebound. Of note, 4 women of 13 had at least one worsening viral load. These preliminary results need to be confirmed by larger studies. Although much attention in clinical care is devoted to pregnant women, emphasis should be put on postpartum care as well.

Association of disclosure of HIV status with medication adherence

OBJECTIVE Disclosure may affect adherence to antiretroviral treatment. In a medication adherence program, this cross-sectional study describes disclosure, perceived reaction after disclosure, living situations, and the relationship of disclosure with antiretroviral adherence. METHODS A combination of a questionnaire to measure disclosure and longitudinal electronic monitoring of medication adherence was used. RESULTS A total of 103 out of 159 eligible patients gave informed consent. The characteristics differed between participants and nonparticipants (race, education, sexual orientation, medication adherence). Thirteen participants did not disclose their HIV status. Seventy-three (81%) participants judged the reaction after disclosure positive. Among the 62 participants cohabiting, 52% disclosed to all co-residents. Adherence was high (median 100%). HIV disclosure was negatively associated with adherence, when disclosing to the mother (OR=2.46, p-value=0.086) and to siblings (OR=2.89, p-value=0.029). Living alone was associated to a lower adherence than cohabitation (Rate Ratio=1.42, p-value=0.007). CONCLUSION HIV disclosure and adherence are sensitive issues, which may explain the reason for refusal. Nonparticipants may be those with the most difficulties disclosing. PRACTICE IMPLICATIONS An unbiased collection of sensitive information, as HIV disclosure, is a difficult task. A cohort design, with research data collected systematically by a trusted healthcare provider, may better describe the association between adherence and disclosure.

The Joint Influence of Gender and Amount of Smoking on Weight Gain One Year after Smoking Cessation

Weight gain is often associated with smoking cessation and may discourage smokers from quitting. This study estimated the weight gained one year after smoking cessation and examined the risk factors associated with weight gain in order to identify socio-demographic groups at higher risk of increased weight after quitting. We analyzed data from 750 adults in two randomized controlled studies that included smokers motivated to quit and found a gradient in weight gain according to the actual duration of abstinence during follow-up. Subjects who were abstinent for at least 40 weeks gained 4.6 kg (SD = 3.8) on average, compared to 1.2 kg (SD = 2.6) for those who were abstinent less than 20 weeks during the 1-year follow-up. Considering the duration of abstinence as an exposure variable, we found an age effect and a significant interaction between sex and the amount of smoking before quitting: younger subjects gained more weight than older subjects; among light smokers, men gained more weight on average than women one year after quitting, while the opposite was observed among heavy smokers. Young women smoking heavily at baseline had the highest risk of weight gain after quitting.

The Presence of Human Immunodeficiency Virus-Associated Neurocognitive Disorders Is Associated With a Lower Adherence to Combined Antiretroviral Treatment.

Abstract Background Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) are defined according to their diagnostic degrees as follows: asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia. Because high adherence to combined antiretroviral therapy (cART) is required to maintain viral suppression among HIV-infected patients, it is important to investigate the impact of HAND on medication adherence. Our study hypothesis was that patients with HAND had a lower medication adherence than patients who did not have HAND. Methods This was an observational, exploratory, 2-center pilot study of patients who had a state-of-the-art neurocognitive assessment performed between January 2011 and June 2015 while also being followed at their respective adherence clinics. Adherence was measured with electronic monitors. Patients’ sociodemographic characteristics, HIV viral load, and CD4 counts were retrieved from the Swiss HIV Cohort Study database. At each time t, adherence was computed as the proportion of patients taking medication as prescribed at that time. Results We included 59 patients, with a median (Q1, Q3) age of 53 years (47–58) and 39 (66%) were male participants. Twenty-two patients (35%) had no neurocognitive deficits, 16 (27%) patients had HAND, and 21 (35%) patients had non-HAND (mostly depression). Implementation over 3 years showed a significant decline (50%) in medication adherence among patients diagnosed with HAND in comparison with patients who had a normal neuropsychological status or a non-HIV-related cognitive deficit (implementation stayed 90% during follow-up). Conclusions Our findings support the hypothesis that HAND is associated with reduced cART adherence.