Use of injectable progestin contraception and risk of STI among South African women

Objective

This study was conducted to determine the association between the use of injectable progestin contraception (IPC) and the risk of infection with Neisseria gonorrhoeae (GC), Chlamydia trachomatis (CT), bacterial vaginosis (BV) and Trichomonas vaginalis (TV) among women in South Africa.

Methods

From August 1999 through May 2001, 643 HIV-1-negative women were recruited from family planning clinics in Orange Farm, South Africa. IPC [norethisterone enanthate (NET-EN) and depot medroxyprogesterone acetate (DMPA)] users and nonhormonal contraception users were recruited in approximately equal numbers. Eligible participants were seen at enrolment and on four follow-up visits over a 12-month period; 567 returned for at least one follow-up visit. Multivariable Poisson regression models with generalized estimating equations were used to compute the incidence rate ratios (IRRs) for infections with GC, CT, BV and TV by use of NET-EN or DMPA relative to nonuse during follow-up.

Results

In multivariable models, the use of DMPA slightly increased the risk of infection with CT [IRR=1.24; 95% confidence interval (95% CI)=0.80–1.94] and GC (IRR=1.30; 95% CI=0.58–2.98), although these associations were not statistically significant. In contrast, DMPA appeared to be protective for TV (IRR=0.35; 95% CI=0.12–1.01), although this estimate was very imprecise. The use of both DMPA and NET-EN was associated with a decreased risk of BV.

Conclusions

The use of DMPA among women in this study population was associated with an increased — but not statistically significant — risk of cervical infection with chlamydia and gonorrhea, and a decreased risk of TV and BV. Given the inconsistencies and limitations of the data describing an increased risk of CT and GC with IPC use, the potential risk of sexually transmitted infections (STIs) must be balanced against the risk of unintended pregnancy and its health consequences, especially in developing countries. Women opting to use IPC should be counseled to use condoms to protect against STIs and HIV.     

Prospective study of weight change in new adolescent users of DMPA, NET-EN, COCs, nonusers and discontinuers of hormonal contraception

Background

Weight gain is commonly reported as a side effect of hormonal contraception and can lead to method discontinuation or reluctance to initiate the method. The purpose of this study was to investigate weight change in adolescent (aged 15-19 years) users of depot-medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN), combined oral contraceptives (COCs) and discontinuers of these methods as compared to nonusers of hormonal contraception.

Study Design

This longitudinal study recruited initiators of DMPA (n=115), NET-EN (n=115), COCs (n=116) and nonusers of contraception (n=144). Participants were followed up for 4-5 years, and details of current contraceptive method, including switching, discontinuing and/or starting hormonal methods were documented at each 6-monthly visit. Women were classified according to their contraceptive histories on completion of the study, and injectable users were combined into one group for analysis. Height, weight and self-reported dieting were recorded at each visit.

Results

There was no difference in mean age or weight between the groups at baseline. Women using DMPA or NET-EN throughout, or switching between the two, had gained an average of 6.2 kg compared to average increases of 2.3 kg in the COC group, 2.8 kg in nonusers and 2.8 kg among discontinued users of any method (p=.02). There was no evidence of a difference in weight gain between women classified as nonobese or classified as overweight/obese in any of the four study groups at baseline.

Conclusion

There is fairly strong evidence that adolescent contraceptive hormonal injectable users appear to gain more weight than COC users, discontinuers and nonusers of contraception.     

Bone mineral density in young women aged 19-24 after 4-5 years of exclusive and mixed use of hormonal contraception

Background

Use of depot-medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN) and low-dose combined oral contraceptives (COCs) has been associated with loss of bone mineral density (BMD) in adolescents. However, the effect of using a combination of these methods over time in this age group is limited. The aim of this cross-sectional study was to investigate BMD in young women (aged 19-24 years) with a history of mixed hormonal contraceptive use.

Study Design

BMD was measured at the spine, hip and femoral neck using dual X-ray absorptiometry. Women were classified into three groups: (1) injectable users (DMPA, NET-EN or both) (n=40), (2) mixed COC and injectable users (n=13) and (3) non-user control (n=41).

Results

Women in the injectables-only user group were found to have lower BMDs compared to the non-user group at all three sites, and there was evidence of a difference in BMD between these two groups at the spine after adjusting for body mass index (p=.042), hip (p=.025) and femoral neck (p=.023). The mixed COC/injectable user group BMD values were lower than those for controls; however, there was no evidence of a significant difference between this group and the non-user group at any of the three sites.

Conclusion

This study suggests that BMD is lower in long-term injectable users but not when women have mixed injectable and COC use.     

When can a woman have repeat progestogen-only injectables-depot medroxyprogesterone acetate or norethisterone enantate?

Background

Currently, there is a generally accepted 2-week grace period for women returning early/late for reinjection of either depot medroxyprogesterone acetate (DMPA) or norethisterone enantate (NET-EN). This systematic review evaluates the evidence regarding return to fertility and ovulation after injection of a progestogen-only contraceptive.

Study Design

We searched the PubMed database to identify all relevant evidence published in peer-reviewed journals from database inception through November 2008 regarding timing of fertility and return to ovulation after the last injection of DMPA or NET-EN.

Results

We identified 20 articles, 10 on DMPA use, eight on NET-EN use and two examining both types of injectables. Six studies examining time to pregnancy after discontinuing DMPA or NET-EN reported that pregnancy rates during the currently recommended 2-week grace period were zero or very low. Studies of return to ovulation indicated a wide variation in time to ovulation post-injection with the majority ranging from 15-49 weeks from the last injection (for DMPA) and 4.9-24.3 weeks from the last injection (for NET-EN). Limitations of this body of evidence include small sample sizes, lack of data on the main outcome of interest (time to pregnancy) and inconsistency in measurement of ovulation, a surrogate measurement for pregnancy risk.

Conclusion

Studies evaluating time to pregnancy after last injection of DMPA or NET-EN reported extremely low pregnancy rates during the 2-week interval following the reinjection date; extremely low pregnancy rates for DMPA were also reported for 4 weeks following the reinjection date. Studies of return to ovulation after last injection of DMPA generally found that the earliest ovulation did not occur until several months after the last injection while studies of NET-EN reported ovulations around (or even before) the time for reinjection.     

Bone mineral density in a cohort of adolescents during use of norethisterone enanthate, depot-medroxyprogesterone acetate or combined oral contraceptives and after discontinuation of norethisterone enanthate

Background

Depot medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN) and combined oral contraceptives (COCs) have been shown to have a negative effect on bone mineral density (BMD) in adolescents. The aim of this study was to investigate BMD in 15- to 19-year-old new users of DMPA, NET-EN and COCs.

Study Design

This 5-year longitudinal study followed up new users of DMPA (n=115), NET-EN (n=115) and COCs (n=116) and 144 nonuser controls. BMD was measured at the distal radius using dual-energy X-ray absorptiometry.

Results

BMD increased in all groups (annual percent increase: nonusers, 1.49%; DMPA, 1.39%; NET-EN, 1.03%; COCs, 0.84%) during follow-up (p<.001). There was evidence for lower BMD increases per annum in NET-EN (p=.050) and COC (p=.010) users compared to nonusers but no difference between DMPA and nonusers (p=.76). In 14 NET-EN discontinuers, an overall reduction of 0.61% per year BMD was followed upon cessation by an increase of 0.69% per year (p=.066).

Conclusion

This study suggests that BMD increases in adolescents may be less in NET-EN and COC users; however, recovery of BMD in NET-EN users was found in the small sample of adolescents followed post-discontinuation.     

Injectable and oral contraception and the incidence and progression of cervical disease in HIV-infected women in South Africa

Background

Few data exist regarding the effect of hormonal contraception (HC) on incidence and progression of cervical disease (e.g., cervical dysplasia, squamous intraepithelial lesions, cervical intraepithelial neoplasia) in HIV-infected African women.

Study Design

We conducted an observational study of HIV-seropositive women in Johannesburg, South Africa. The effect of individual HC types on the incidence and progression of cervical disease was determined using Poisson regression to obtain adjusted incidence rate ratios.

Results

We evaluated 594 HIV-infected women, with median follow-up time of 445 days; 75 of these women were receiving some form of HC (largely DMPA, NET-EN, or COCs) at baseline. Risks of incidence and progression of cervical disease were similar comparing women not receiving HCs to women receiving DMPA, NET-EN, or COCs both individually by HC-type and considering all HC together.

Conclusions

There was no statistically significant effect of particular HC methods or of HC use in general on rates of incidence or progression of cervical disease in this study. These results should reassure us that use of HC is unlikely to substantially increase risks of cervical disease among HIV-positive women.     

Effect of long-acting progestagen-only injectable contraceptives on carbohydrate metabolism and its hormonal profile.

Two groups, each composed of 20 women, who used depomedroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) injectable contraceptives were investigated for changes in 75-g OGTT and in the fasting and two-hour post oral glucose load (2-hours) levels of serum insulin, growth hormone, glucagon, cortisol and blood pyruvate. Samples were taken before and 3, 6 and 12 months after use of injectables. DMPA and NET-EN caused significant changes in mean blood glucose and pyruvate and in mean serum insulin, growth hormone and glucagon, but not in mean fasting cortisol. Changes with NET-EN started after 3 months, became maximal after 6 months and reverted to normal after 12 months of use, due to more frequent administration during the first 6 months of use (every 60 +/- 5 days) and to more spacing of the injections (every 84 +/- 5 days) after that. Changes with DMPA started after 3 months, and increased with the duration of use to become maximal after 12 months. Maximal changes were similar with DMPA and NET-EN and consisted of: a significant increase in fasting blood glucose and pyruvate and serum insulin; a significant increase in 2-hour blood glucose and pyruvate, serum insulin, growth hormone and glucagon. Although significant changes in blood glucose levels occurred with both DMPA and NET-EN, yet they did not reach the lower cut-off levels for impaired glucose tolerance in any user. With the same spacing of injections, i.e. every 84 +/- 5 days for NET-EN and every 90 +/- 5 days for DMPA, the effects on various parameters studied were less with NET-EN.     

Detection of raised FSH levels among older women using depomedroxyprogesterone acetate and norethisterone enanthate

The objective of this study was to investigate whether follicle-stimulating hormone (FSH) levels can be used reliably to indicate approaching menopause in older (aged 40-49), long-term users of depomedroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN). One-hundred and seventeen women using DMPA, 60 NET-EN users and 161 nonusers of contraception were recruited. At recruitment, serum FSH levels were measured and questions were asked regarding menopausal symptoms, menstrual cycle and date of last injection. Results of the recruitment blood test showed that 32% of the nonusers had FSH levels in the menopausal range >25.8 mIU/mL compared to 28% of the DMPA users and 9% of the NET-EN group. After adjusting for age, there was no significant difference between the 3 groups (p = 0.13). An increase of 1 year in age increased the FSH level by 3 mIU/mL (p < 0.001). All the hormonal contraceptive users were between 1 day and 12 weeks of their injection interval. Many had been using the injectable contraceptive method for over 10 years and almost all were amenorrheic at the time of recruitment. The data show that a raised FSH level can be detected during use of DMPA and NET-EN and could be used as a menopausal indicator without interrupting method use in this group of contraceptive users.     

Preferences between injectable contraceptive methods among South African women

OBJECTIVE: To examine South African women's preferences between depot medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN), as well as the reasons for and correlates of these preferences. STUDY DESIGN: A cross-sectional study among women attending 26 primary health care clinics across the Western Cape Province. RESULTS: Of 893 women participating in the survey, 57% (n=511) and 45% (n=399) had ever used DMPA and NET-EN, respectively. Among women who knew of both injectables, 46% stated a preference for DMPA (n=365) and 37% stated a preference for NET-EN (n=297). Most women who preferred DMPA thought that it was more effective in preventing pregnancy, while women who preferred NET-EN stated that it was preferable for women who wanted children in the future. Preferences for NET-EN were independently associated with younger age, higher education and living in an urban area. CONCLUSION: These findings suggest that there are significant misperceptions among women regarding the differences between DMPA and NET-EN, which may have important resource implications for contraceptive services. It is likely that these misperceptions arise from popular discourse and individual user experiences, as well as poor communication with and counseling of women on the part of providers. Interventions aimed at both users and providers are required to dispel the myths and misinformation regarding progestogen-only injectable methods.     

Provision of DMPA by community health workers: what the evidence shows

Background

To reduce a large unmet need for family planning in many developing countries, governments are increasingly looking to community health workers (CHWs) as an effective service delivery option for health care and as a feasible option to increase access to family planning services. This article synthesizes evidence on the feasibility, safety and effectiveness of community-based delivery of the injectable contraceptive depot-medroxyprogesterone acetate (DMPA).

Study Design

Manual and electronic search and systematic review of published and unpublished documents on delivery of contraceptive injectables by CHWs.

Results

Of 600 identified documents, 19 had adequate information on injectables, almost exclusively intramuscular DMPA, provided by CHWs. The data showed that appropriately trained CHW demonstrate competency in screening clients, providing DMPA injections safely and counseling on side effects, although counseling appears equally suboptimal in both clinic and community settings. Clients and CHWs report high rates of satisfaction with community-based provision of DMPA. Provision of DMPA in community-based programs using CHWs expanded access to underserved clients and led to increased uptake of family planning services.

Conclusions

We conclude that DMPA can be provided safely by appropriately trained and supervised CHWs. The benefits of community-based provision of DMPA by CHWs outweigh any potential risks, and past experiences support increasing investments in and expansion of these programs.     

Dietary, self-reported oral health and socio-demographic predictors of general health status among older adults

Objective

Poor dietary habits and nutritional intake are associated with a range of chronic diseases. Oral health may be directly associated with general health status, as well as related to diet. The aims are to assess dietary, self-reported oral health and socio-demographic predictors of general health status among older adults.

Design

Cross-sectional mailed survey.

Participants

A random sample of adults in Adelaide, South Australia aged 60?C71 years in 2008.

Measurements

Health status was measured using the EuroQol (EQ-5D). Compliance with dietary guidelines was measured using a 16-item index of grocery purchasing. Oral health was measured by self-reported number of teeth, oro-facial pain and sore gums. Socio-demographics included age, sex, birth place and subjective social status.

Results

Responses were collected from n=444 persons (response rate = 68.8%). The average EQ-5D score was 0.80 (se=0.01). Unadjusted analyses showed (p<0.05) EQ-5D scores were lower in the bottom tertile of compliance with dietary guidelines, for those reporting oro-facial pain, sore gums and fewer teeth, and for the lower social status group. Multivariate analyses showed (p<0.05) lower compliance with dietary guidelines was associated with poorer general health (beta=?0.10), as was oro-facial pain (beta=?0.11), sore gums (beta=?0.17), and lower social status (beta=?0.28).

Conclusions

Socio-economic status, oral symptoms and compliance with dietary guidelines were associated with general health status.     

The age-dependent influence of self-reported health and job characteristics on retirement

Objectives

Social scientists and economists doubt the usefulness of self-reported health status as an indicator of overall health status. Self-reported health acts as a justification for retirement when this decision is in reality driven by other reasons. In this study, we looked at income, job satisfaction, and job status.

Methods

We introduce a survival model (Cox model) that simultaneously includes both health and job characteristics as independent variables. We also take the age-dependent character of these effects into account.

Results

An analysis of the European Community Household Panel data did not validate the justification bias with respect to these variables. The addition of job characteristics had no influence on the effect estimates of self-reported health.

Conclusions

We found significant effects for self-reported health as well as for objective health measures. The addition of job characteristics did not contribute to the explanation of the effect of self-reported health falsifying the justification bias hypothesis.     

Use of injectable progestin contraception and risk of STI among South African women

ObjectiveThis study was conducted to determine the association between the use of injectable progestin contraception (IPC) and the risk of infection with Neisseria gonorrhoeae (GC), Chlamydia trachomatis (CT), bacterial vaginosis (BV) and Trichomonas vaginalis (TV) among women in South Africa.MethodsFrom August 1999 through May 2001, 643 HIV-1-negative women were recruited from family planning clinics in Orange Farm, South Africa. IPC [norethisterone enanthate (NET-EN) and depot medroxyprogesterone acetate (DMPA)] users and nonhormonal contraception users were recruited in approximately equal numbers. Eligible participants were seen at enrolment and on four follow-up visits over a 12-month period; 567 returned for at least one follow-up visit. Multivariable Poisson regression models with generalized estimating equations were used to compute the incidence rate ratios (IRRs) for infections with GC, CT, BV and TV by use of NET-EN or DMPA relative to nonuse during follow-up.ResultsIn multivariable models, the use of DMPA slightly increased the risk of infection with CT [IRR=1.24; 95% confidence interval (95% CI)=0.80–1.94] and GC (IRR=1.30; 95% CI=0.58–2.98), although these associations were not statistically significant. In contrast, DMPA appeared to be protective for TV (IRR=0.35; 95% CI=0.12–1.01), although this estimate was very imprecise. The use of both DMPA and NET-EN was associated with a decreased risk of BV.ConclusionsThe use of DMPA among women in this study population was associated with an increased — but not statistically significant — risk of cervical infection with chlamydia and gonorrhea, and a decreased risk of TV and BV. Given the inconsistencies and limitations of the data describing an increased risk of CT and GC with IPC use, the potential risk of sexually transmitted infections (STIs) must be balanced against the risk of unintended pregnancy and its health consequences, especially in developing countries. Women opting to use IPC should be counseled to use condoms to protect against STIs and HIV.     

Walk on the sunny side of life — Epidemiology of hypovitaminosis D and mental health in elderly nursing home residents

Objectives

Old age is a well-known risk factor for both depression and hypovitaminosis D, and an association between both conditions has been postulated. We document the prevalence of vitamin D deficiency in nursing home residents, and we examine the link with self-reported depressive symptoms and pharmacotherapy for depression.

Design

Cross- sectional. Setting: nursing homes in Antwerp, Belgium.

Participants

Healthy elderly (n=589), with a mean age of 84 years.

Measurements

We detected depressive symptoms by means of SF-36, a validated quality of life assessment; we registered the use of antidepressants and anxiolytics, and we measured serum 25(OH)D concentrations in all participants.

Results

Almost our entire study population appeared to be vit D deficient. Comparison of the most severely and least deficient subgroups showed a consistent tendency towards more depressive symptoms and more use of antidepressants in the group with the lowest vit D level.

Conclusion

Nursing home residents are particularly vulnerable to preventable vit D deficiency. The relevance of the association with depressive symptoms and the possibilities for treatment are critically reviewed in the discussion.     

A qualitative exploration of travel-related risk behaviours of injection drug users from two Slovene regions

Background

This study aimed to explore issues that might impact on the acceptability and feasibility of offering smokers nicotine containing products either to quit nicotine use altogether by using as a short term means of quitting cigarettes or as a longer term substitute.

Method

Two small pilot studies, one in the UK (n = 34) involving face to face contact and direct provision of the product, the other in Australia (n = 31) conducted remotely with products sent in the mail.

Results

Nicotine lozenges were the most popular products, but significant minorities liked a smokeless product more. Use stimulated interest in quitting, and although many failed to use all the products provided, most were interested in future use, more often to help quit than as a planned long-term substitute.

Conclusions

These studies indicate an untapped interest in the use of substitutes to reduce the harmfulness of smoking. Studies of this sort do not inhibit interest in quitting nicotine altogether, and may facilitate it. The greater the range of products on offer, the more smokers are likely to try a product to quit.     

Dietary habits and ageing in a sample of Italian older people

Objectives

To analyse dietary habits and explore the role of socioeconomic status in a sample of elderly Italians.

Study design

Observational.

Participants and setting

306 elderly subjects aged 65 and over living in the Marche Region (Italy).

Measurements

Assessment of dietary habits and life-style characteristics using a ??Life-style questionnaire??. Nutritional data collected by means of a 53-item ??Frequency food questionnaire??.

Results

The study revealed differences in dietary patterns and food consumption. Age was negatively related to all food categories. Some socio-economic characteristics (level of education and economic status) were correlated with consumption of many foods, such ad Fish, Red Meat and Diary products. Between-the-sexes differences were also documented.

Conclusion

Our findings showed that the nutritional and dietary habits varied greatly within the sample investigated. The mapping of these dietary and nutritional patterns may be of value for future research in elderly populations, particularly those with low educational status and poor economic means. Conclusively, greater promotion of healthy dietary habits should be targeted towards elderly populations.     

Education and physical health trajectories in old age. Evidence from the Survey of Health, Ageing and Retirement in Europe (SHARE)

Objectives

The model of cumulative inequality predicts that health differences between educational levels increase with age. Using a variety of analytical approaches and measures of health, studies have, however, reported increasing as well as decreasing and constant patterns of educational health inequality. The aim of this study is use a standardized research design to compare different dimensions of health inequality trajectories across educational levels.

Methods

We used data from two waves (2004/2005 and 2006/2007) of SHARE. The sample consisted of respondents aged 50–80 (n = 14,818). Using OLS regression models, we analyzed trajectories of health inequality in self-reported measures (ADL, IADL, mobility, chronic diseases, and self-rated health) as well as non-invasive objective measures (grip strength) of physical health.

Results

Inequality between higher and lower educated individuals increased significantly in limitations of physical functioning and grip strength. In chronic diseases and self-rated health, the gap between these two groups remained constant.

Conclusion

Although our results mainly supported the model of cumulative inequality, they also showed that the trajectory of the education-health gradient is not uniform but varies across different dimensions of physical health.     

Operational assessments of Sayana® Press provision in Senegal and Uganda

Objective

Sayana® Press (SP) is a unique injectable contraceptive (depot medroxyprogesterone acetate, or DMPA) administered subcutaneously in the Uniject^TM injection system.¹ SP simplifies the injection process; it requires no assembly of components and is easily disposable. This new technology appears to be well suited for community-based delivery of injectable contraception. The study objective was to evaluate SP management and administration in low-resource settings, focusing on how the delivery logistics, administration time, storage and waste-management requirements compare to the traditional intramuscular DMPA injectable (DMPA IM).

Study design

We conducted 58 semistructured interviews with clinic providers and community health workers in Senegal and Uganda to identify the merits, challenges and appeal of SP relative to DMPA IM.

Results

Providers identified logistical challenges with the management and administration of DMPA IM, including stock outs, transportation, storage constraints, and, in a few instances, waste disposal. Most providers (between 63% and 88%, depending on the logistics issue) do not expect SP to either aggravate or solve those problems. Some envisioned that SP could facilitate supply management (5%), storage (11%) and waste disposal (22%). The all-in-one packaging of SP was perceived to reduce the incidence of mismatched supplies (syringes and vials), and its smaller size was expected to ease space constraints and reduce the frequency of safety box incineration.

Conclusion

Adding SP to the method mix is unlikely to have a profound impact on clinic operations but may lessen logistical problems related to supply, storage and waste management.

Implications

Community health workers and clinic providers who administer SP may see some modest improvements in service delivery logistics. Particularly in settings where service delivery logistical challenges are more pronounced, offering SP may facilitate injectable contraceptive delivery.     

The relative contribution of work exposure, leisure time exposure, and individual characteristics in the onset of arm–wrist–hand and neck–shoulder symptoms among office workers

Purpose

To identify the risk factors for the onset of arm–wrist–hand and neck–shoulder symptoms among office workers and to estimate the relative contribution of these risk factors by calculating Population Attributable Fractions (PAFs).

Methods

A prospective cohort study was conducted among 1951 office workers with a follow-up duration of 2?years. Data on self-reported risk factors were collected at baseline and after 1?year of follow-up. Every 3?months, the occurrence of upper extremity symptoms was assessed using questionnaires. PAFs for individual risk factors were estimated based on Rate ratios (RRs) obtained from Poisson regression using Generalized Estimation Equations.

Results

Previous disabling symptoms were identified as the most important risk factor for the onset of arm–wrist–hand and neck–shoulder symptoms. Modifiable risk factors for arm–wrist–hand symptoms with relatively large PAFs were: at least 4?h per day of self-reported computer use at work, high level of overcommitment, and low task variation and for neck-shoulder symptoms: supporting the arms during keyboard use and at least 4?h per day of self-reported mouse use at work. Compared to having 0 or 1 risk factor, the RR for arm–wrist–hand symptoms increased to 6.2 (95% CI 3.7–10.5) for having 5–7 potentially modifiable risk factors and for neck–shoulder symptoms to 3.0 (95% CI 2.1–4.4) for having 4 or 5 potentially modifiable risk factors.

Conclusion

Preventive interventions at the population level should be aimed at changing modifiable risk factors with large PAFs. At the individual level, preventive interventions should be aimed at changing multiple modifiable risk factors simultaneously.