Staphylococcus aureus (MRSA) is difficult to assess, all the more so as they are often accompanied by a concomitant increase in the use of a specific antibiotic class.The impact of reductions in antibiotic use on the selection of antibiotic-resistant bacteria such as methicillin-resistant S. aureus transmission in a hospital ward and in the community, where methicillin-sensitive (MSSA), community-associated MRSA (CA-MRSA) and hospital-associated MRSA (HA-MRSA) strains co-circulate between these two settings. We assessed the impact of a 15-50% reduction in antibiotic use in community and hospitals, under several hypotheses regarding changes in the distribution of prescribed antibiotics.We developed a computerized model of S. aureus in both hospital and community settings. A similar reduction in hospitals had no impact on community dynamics.An overall reduction in antibiotic use in the community led to decreased frequency of MRSA but increased carriage of Antibiotic classes-specific changes over the time period of the reduction in global ambulatory antibiotic use had an important impact on MRSA selection in hospitals and in the community. For instance, in the hypothesis of a 15% antibiotic use reduction, the induced decrease in hospital MRSA frequency was 2.6 times less important if this was accompanied by a concomitant 30% increase in the use of quinolones.Antibiotic reduction policies may not prove sufficient to decrease antibiotic-resistance frequency. They should include a surveillance of changes in the consumption of each antibiotic class.None declared.


Existing incidence estimates of heroin use are usually based on one information source. This study aims to incorporate more sources to estimate heroin use incidence trends in Spain between 1971 and 2005.A multi-state model was constructed, whereby the initial state “heroin consumer” is followed by transition to either “admitted to first treatment” or to “left heroin use” (i.e. permanent cessation or death). Heroin use incidence and probabilities of entering first treatment ever were estimated following a back-calculation approach.The highest heroin use incidence rates in Spain, around 1.5 per 1,000 inhabitants aged 10–44, occurred between 1985 and 1990; subdividing by route of administration reveals higher incidences of injection between 1980 and 1985 (a mean of 0.62 per 1.000) and a peak for non-injectors in 1990 .A simple conceptual model for heroin users’ trajectories related to treatment admission, provided a broader view of the historical trend of heroin use incidence in Spain. Recently, there has been increasing interest in ascertaining illegal drug use incidence for planning and evaluating prevention strategies. In the The present study is an attempt to take the definition of problematic use incidence further by incorporating a proportion of individuals that used heroin who never show up in the main source under study . This proportion is based on other kinds of information, aggregated sources, estimates, or assumptions, such as mortality and cessation rates.The idea is to study the unobserved entry (or immigration) of people to the state of “consumer”, based on a later first entry to treatment. Since heroin users may exit the state of consuming heroin before entering treatment, whether due to death or permanent cessation of their consumption, a “left heroin use” state is added to the model. The situation is thus represented by a set of mutually related states, in a so-called multi-state model with immigration.This approach has parallels in studies in the HIV field, where a multi-state model was presented describing progression of HIV disease from infection to AIDS in several stages,11 or RoWe shall use a back-calculation type approach to estimating the incidence. This is similar in spirit to de Angelis et al.. HoweverTo our knowledge, previous approaches had to assume that treatment availability was stable over time,4-9. As In Spain, heroin use generated important health problems in the eighties and early nineties, thereafThe multi-state model approach may be successfully used to estimate heroin use incidence with the available Spanish heroin users’ treatment data. We use the same treatment database as the previous study to assess differences in the incidence estimates depending on the approach used.The objective of the present study was to estimate heroin use incidence in Spain through a multi-state model with immigration and assess differences with previous study’s estimates.We will describe a heroin user’s trajectory simply using the time of transition from state 1 (first heroin use) to one of two possible subsequent states: first treatment ever (state 2), or leaving heroin use before any treatment, either by permanent cessation or death (state 3)  at t. The number pt denotes the probability that a given heroin user initiates their first treatment ever at time t, given that they were in state 1 at the previous time. We assume this probability independent of the era when their heroin use began. The number qt denotes the probability of an individual leaving heroin use at time t, given that they were in state 1 at the previous time. The cause could be death or other permanent cessation of heroin use. We want to estimate the parameters ht, the expected number of new heroin users at time t. The probability qt is assumed known.We shall now formulate our back-calculation type model. We let  grounds. MoreoveNij be the observed number of individuals that start heroin use in year i and enter first treatment in year j. Let μij be the expected value of Nij . A short computation shows that:We now construct the likelihood function. This is a standard Poisson type likelihood, following the approaches in the basic back-calculation papers. Howeverμij is the product of the expected number of new heroin users in year i (hi), the probability that a given heroin user remains in state 1 from time i to time j-1 and the probability of a transition from state 1 to state 2 at time j. It also follows that each Nij is Poisson distributed. This gives us the following simple expression for the likelihood:We see that ht and pt.Maximizing this likelihood yields estimates for The Spanish Drug Observatory maintains a drug information system. Its indicator “treatment” is based on data from all treatment starts in public and publicly funded centres. The health coverage is universal and all kinds of treatment are considered. In the present study, we included 169,257 persons who entered first treatment for heroin use from 1991 to 2006 when aged 15 to 54 (mean 28 years), and who started their heroin use between 1971 and 2006 when aged 10 to 44 (mean 21 years). The database was split into two subsets: people who declared injection as the most frequent route for heroin use in the last 30 days before first treatment admission (29%) and people who declared using routes other than injection (68%). Route of administration was missing in 3% of persons.As in all applications of back-calculation where a detailed history of individuals is not observed, we havept, first treatment data was available for t between 1991 and 2006, thus restricting estimates to this period. For the preceding part of the study period (t in 1971–1990), we made an educated guess of pt based on general heroin use information in Spain. Based on the first appearances of admissions for heroin use in the emergency units in Spain in 1982[pt) as low as 0.01 between 1971 and 1981, as there were still no specific treatments available. Thereafter we assumed a linear increase to the value estimated for the parameter pt in 1991.In the estimation of  in 1982-19; we aMortality rates for heroin users were only available from two local cohort studies covering the period 1985 to 1999,21 in anDegenhardt et al. reported a pooled crude mortality rate of 2.09 per 100 person-years and that mortality risk was increased among out-of-treatment heroin users. In a seOwing to the impossibility of obtaining permanent cessation rates, we looked for lasting cessation rates from long-term cohort studies. As such studies are not available in Spain, we considered yearly cessation rates from a thorough review which reported a range of 0.02-0.04. Our anaht, t ranging from 1971 to 2006). As explained, the model also estimates the probability of entering first treatment . We considered the yearly cessation rate of 0.04 and the non-modified mortality rate derived from the local cohort studies. Note that the probability of leaving drug use without having ever been registered for first treatment (qt) is the sum of the cessation and mortality rates for each year from 1971 to 2006.For all heroin users and for injectors and non-injectors separately, we applied the aforementioned multi-state model with the Spanish treatment data and the assumed leaving rates to estimate the heroin use incidence .To assess the fit of the expected incidence values qt, that are reflected in four curves of estimated incidence rates. These combinations were: firstly and as a matter of choice, the available mortality rates and a yearly cessation rate of 0.04; secondly, the same mortality rates and a yearly cessation rate of 0.02; thirdly, the same mortality rates modified by adding 0.01 to the rate for each year and a yearly cessation rate of 0.04; and finally, the modified mortality rates and a yearly cessation rate of 0.02.As results can be dependent on assumptions, a sensitivity analysis was performed to evaluate the two chosen mortality and cessation rates obtaining four combinations of pt in the period from 1971 to 1990, and the cessation rate for all years were sampled from gamma distributions. The shape and scale parameters were derived from the mean and standard deviation, taking the mean as the “best-guess” value, and the standard deviation was established as 0.01.Statistical uncertainty was estimated using a bootstrap technique with 500 re-samples, where each re-sample was made up of two parts: 1) the treatment database was re-sampled with replacement and, 2) both our “best guesses” for The expected number of new heroin users per year was obtained, and converted into rates per 1,000 inhabitants, based on Spanish population yearly census data for people aged 10-44.Incidence estimates from the previous study were retrieved to compare with the present estimates. Both the period of years covered and the census figures were the same.The software used for the statistical analysis was R version 2.13.0. The stupt) which exhibited an overall increasing trend from 0.08 (95% CI 0.07-0.09) in 1991 to 0.29 (95% CI 0.23-0.49) in 2005. Incidence estimates of general heroin use and by route of administration with 95% confidence intervals are plotted in Figure Applying the multi-state model with immigration yielded estimated probabilities of entering treatment for the first time , we assessed that the fit was good . From 2001 differences increased progressively reaching a final value of 0.2 in 2005 between the lowest and highest combinations of cessation and mortality rates (probability of 0.22 versus 0.42).Confidence intervals for the various estimates overlap, except for the combination yielding the lowest estimates (results not shown).Incidence estimates from a previous study are showWe have established a conceptually simple multi-state model to obtain estimates for the incidence rates of heroin use and applied it over a long period in Spain. The highest incidences were observed from 1980 to 1985 corresponding to injectors and a peak in 1990 to non-injectors.In comparison with previous studies, our estimates are wider in scope since by including mortality and other permanent cessation into the multi-state model it is possible to account for almost all problematic heroin users after drug use onset.The conceptual model employed in this study focuses on the first phase of a heroin user’s “career”: from heroin use initiation to treatment. Other more complete models based on a theory of compartmental epidemic models over drug user “career” have also been described. Adding As a Spanish anthropologist described, in Spain heroin use had its first phase in the years 1977 and 1978, when the first users became visible, being endemic in the second phase between 1979 and 1982, and reaching its zenith between 1983 and 1986 leading to the institutionalization of the problem. Therefopt, the probability of entering first treatment, was independent of the era when a person's first heroin use began. Actually, this would be not entirely true if lag time between the drug use onset and first treatment followed a determined pattern, as previous studies assumed[Ni,j-i and for the expected values μi,j-i (j-i represents the lag time), for each year of heroin use onset from 1991 to 2004 all fitted well. So, to modify the equation 1 including the probability of entering first treatment conditional on the initiation of heroin use would be too complex and may not have great practical importance. Therefore, bias can be inherent in both the independence assumption and assuming a determined pattern of lag time, although the direction of such bias cannot be determined.We found a decreasing trend in the incidence estimates for the last years observed, which is probably related to the decreasing trend observed in all indicators towards the end of the period studied, as mentioned in the introduction. However, estimates for these last years from the previous study became stable overtaking the estimates from the present one Figure . This is assumed,6. HowevAs observed by de Angelis, resultsConcerning the assumptions made about the model parameters, such as 1) mortality rates, 2) permanent cessation, both before first treatment and 3) heroin users that started their first treatment before the observation period, we need to consider possible limitations:1) Mortality rates were extrapolated by applying to the whole country figures from the North-East of Spain where heroin use injection was more frequent than in the rest of the country. The ext2) Using lasting cessation rates from long-term cohort studies would overestimate incidence as they include persons with long cessation periods who finally may relapse. On the other hand, the fact that experimental users were not included in studies estimating cessation rates would produce underestimates. Nevertheless, these experimenters are only of anecdotic value for policy interventions.3) Although the exact dates and figures we have taken for first treatment probabilities prior to the observation period may not apply to the whole country, the values assumed seem plausible as we obtained an increasing sequence of probabilities from 1982 up to the first one estimated based on observed data in 1991, which happens to have a similar slope to that estimated in the observed period.Besides model building, it is important to consider other limitations related to treatment data, both to its overall availability and to its accuracy. Treatment register data covers public and publicly funded centres, missing people using private treatment centres. This entails a small proportion especially once public substitution treatment centres were widely implemented all over the country following legislation in 1990. In relaIncidence trends by route of administration do not necessarily reflect the route used at the time of onset, as the variable was collected referring to the 30 days prior to first treatment. However, in a previous study involving heroin users, both in and out of treatment, and a mean length of use of 10 years, more than 50% did not change their initial route of heroin administration. Thus thWith a simple conceptual model of heroin users’ trajectories related to treatment demand, it has been possible to obtain approximations of heroin use incidence trends. Moreover, different assumptions made do not systematically skew the conclusions. However, enhancing accuracy of drug users’ trajectories and an updating of new treatment admissions will further contribute to better incidence estimates.(HIV): Human immunodeficiency virus; (AIDS): Acquired immunodeficiency syndrome; (CI): Confidence interval.The authors declare that they have no competing interest.Albert Sánchez-Niubò participated in the study design, proceeded with data analysis and writing of the manuscript draft; Odd O. Aalen contributed to the design of the method and helped in the writing of the methodological part; Antònia Domingo-Salvany contributed to data acquisition, helped with the interpretation of the data and revised critically the draft for important intellectual content; Ellen J. Amundsen helped with the interpretation of the data and revised critically the manuscript for important intellectual content; Josep Fortiana helped in the analysis of the data and participated in the writing of the methodological part of the work; Kjetil Røysland designed the method implementation, supervised all the work and revised critically the manuscript. All authors approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2288/13/4/prepub


Mainstream research and the popular media often equate female-headship with household vulnerability, crisis, and disorganization. Epidemic levels of HIV/AIDS in some parts of sub-Saharan Africa compound this portrait of hopelessness. In South Africa, the impact of HIV/AIDS on households depends on race, class, and place. As female-headed households increase in number, we need to better understand how female-heads in poor rural areas contend with AIDS related challenges. We analyze qualitative interviews with 16 female heads and the members of their households in a rural community to examine the response to AIDS-related illness, death, or caring for orphaned children. Our analysis examines female-heads' financial and social resources and how these resources buffer against hardship in households affected by AIDS. We find considerable heterogeneity among rural female-headed households and their access to resources to combat AIDS-related hardship. Our findings have important policy implications both in terms of identifying individual and household vulnerabilities as well as leveraging the potential for resilience for female-heads in rural South African communities. Even thFeminist scholars, on the other hand, have deconstructed female-headed households bringing attention to variation and complexity . Three iIn South Africa women head nearly half of all households . The priUsing qualitative interviews with female-heads and household members in Agincourt, South Africa, we examine how inter- and intra-household relationships affect the management of AIDS-related disruptions brought on by the experience of recent AIDS-related death, the care of children orphaned by AIDS, or the care of a person living with AIDS. Our analysis gives primacy to the lived experience of female heads, highlights the dynamic nature of managing hardships related to HIV/AIDS, and provides insights for policy development.2Apartheid comprised of a range of policies and practices that created gendered, racial, and spatial segregation in South Africa. Apartheid policies included forcible relocation of African populations into rural areas  and severe restrictions on mobility . While AEven though apartheid was dismantled in 1990, the lack of rural development during apartheid continues to affect former homelands through endemic poverty, underdeveloped employment opportunities, and poor access to health and welfare services , resultiAccording to http://www.aidsinafrica.net/map.php), and within South Africa, HIV-prevalence varies greatly by province due in part to labor migration  in the country. In Agincourt, AIDS deaths increased rapidly starting in the 1990s. In 1992, just 1% of all adult deaths were attributable to AIDS but by 2003, that figure had risen to 22% , households affected by the AIDS-death of kin outside the household, and/or households providing care for fostered or orphaned children whose mother and/or father likely have/had AIDS.Our analysis includes households from the AIDS-death stratum, Most female-heads under the age of 60  became the head upon the death of a husband, who had been the head. Although the majority of older female-heads were widows, as would be expected , only three of these heads had recently experienced the death of her husband. More often, deaths in the households of older female-heads were of their son or daughter. These differences stem partly from the age structure of AIDS mortality, in which deaths occur primarily between the ages of 25 and 59. This results in younger female-heads being more likely to have been widowed recently due to AIDS, and in their overrepresentation in the AIDS-death stratum. The fact that households with older female-heads were more likely to be affected by AIDS in other ways brings generational differences to light. Older women are more likely to deal with the illness and death of adult children; younger women are more likely to be affected by the death of spouses.Older women are affected when their children, who might live outside their household and have young children, become infected with, need care for, or die from an AIDS-related illness; thus, older heads become the locus of care. These ill individuals might be the siblings of the younger heads with whom we spoke. It appears, however, that young heads are less likely than older heads to care for the sick person or for the children of others, and less likely to then take in orphans or contribute their care. Old-age pensions, and to a lesser degree, other social grants, probably play a role here. The stability of income in an older person's house might make it an attractive place to send children.4and external sources of household income, the head's management of household resources, the head's perception of her power and control in difficult circumstances, and her perceived ability to rely on and call on outside sources of support when needed. We use heads' social environment within and beyond households as a lens to examine emotional wellbeing and resources—monetary, physical, and emotional. We emphasize interview discussions related to respect and trustworthiness to highlight how heads interact with and are regarded by their children and grandchildren (their own reports and the reports of the other family member), as well as neighbors and extended family. Our understandings of emotional and physical wellbeing are shaped by the head's health, her feelings about household decision-making, and her ability to access resources in her community.Our analysis examines financial, emotional, and physical wellbeing of the heads and their households in the Agincourt community. Financial security of individuals and households usually is associated with more options to handle stressors. Analyses of financial wellbeing focus on internal We identify three points on a continuum of coping—strained/overburdened, essential lifelines/limited stability, and resourceful/stable. These points, assigned based on interview responses, highlight variations in household wellbeing and responses to hardship in this particular rural community. The weakest households include estranged heads, particularly young widows, who are disconnected from social ties and disaffected with their situation. The middle group manages precariously with a limited amount of emotional, physical, and financial support, usually due to one or two external lifelines. In the strongest group, households have a stalwart central figure, as well as strong intra- and inter-household ties. Each continuum point highlights the role of financial and social resources in how female-headed households manage stressors at a given moment. The passage of time and change in access to resources in the household's social environment or in the community at large could shift a household's place on the continuum.4.1We characterized five heads and households in our sample as estranged and disconnected. They handled substantial burdens without much support. They had fragile social environments with strained relationships within and beyond the household, precarious finances, and experienced loneliness and despondency. Young widows, whose husbands recently died of AIDS, headed three of these households and were likely HIV-positive themselves. These widows had strained relationships with the deceased husband's family regarding funeral decisions, proper mourning, and blame for the death. Unstable financial situations coupled with emotional and physical stress compounded the challenges that death brought to the household as shown in the case of Midah.Midah,Eunice, a 37 year-old widow, similarly was alienated from her three children and husband's kin. Officially, Eunice was the household decision-maker, but in practice her 20-year-old daughter Andiswa assumed responsibility; Andiswa expressed doubts about Eunice's competence. The household struggled financially; Eunice said, “The money we receive from the child grant is not enough to buy food, which will take us for the whole month. In the past the situation was better because my husband bought clothes and food properly.” Despite seeming responsible beyond her years, Andiswa expressed fears, “My father died at a young age and I am panicked for my mother, that she doesn't have a husband. And, I am panicked for my siblings and me. We have only one parent.” Andiswa's one remaining parent had low self-esteem, little social support, and may soon be ill, needing even more care and attention from Andiswa.Older women widowed long ago, who were caring for orphaned grandchildren at the time of the interviews, headed the remaining two households at this low point on the continuum. Both women were deeply concerned about their ability to carry out newly inherited responsibilities, and about the tone of relationships with their kin. For example, Mercy, age 75, lived with and used her pension to support her son and 20-year-old grandson. The main themes of her interview were unhappiness, ill health, and lack of respect. She worried aloud about her son's promiscuousness, and her grandson, Nhlamulo's failing out of school. Mercy and Nhlamulo both reported their household was poor compared to neighbors and the past. Mercy reported poor health and substantial medical expenses. She was dependent on a daughter, who lived elsewhere, for assistance with transport to obtain medical care, but complained about the lack of reliable help in old age. She expressed feeling disconnected from her son and others who “don't listen to me.” Her son, whose wife left him, had girlfriends coming to the house. Although employed, he was not contributing to the household, exacerbating Mercy's sense of disappointment and abandonment.Despite the many similarities, these households are not monolithic. For example, relationship strain for younger heads often revolved around young children and the deceased husband's family; for older women, such strain usually came from grown children and grandchildren who showed disrespect or do not contribute sufficiently to the household. However, these households were the most desolate on the continuum because of their overall poor financial, emotional, and physical state, as well as fragile social environments with few or no social connections on which to call in times of need. These female-heads, particularly the older women, saw little hope of change in the future. The younger widows contended that in time they might develop new relationships or find employment to improve their circumstances; however, the likelihood that many of the young widows were already HIV-positive might close even these doors.4.2A number of households managed with limited stability. These heads maintained respect and connectedness, but required external assistance. These households generally had sufficient means to feed their families, but most had some social, respect, health, or assistance challenges, issues not uncommon in this rural community. In most cases, just one or two lifelines kept the household from failing financially or emotionally. Additionally, in several cases the deceased's income had helped cover his or her medical expenses or the deceased's burial society covered funeral expenses, thus buffering the impact of AIDS.One such case is that of Esseny, age 53. Esseny's large household had 13 members and many social connections. Already a great-grandmother, Esseny's son in Johannesburg sent regular substantial remittances. Esseny shared household decision-making power with this son, but made day-to-day decisions in his absence. She worked several odd jobs, including stocking items at a nearby shop with one of her daughters. Of her large household, she said, “I am the mother of all those children, and I am also the grandmother to others. My responsibility is to look after them as a parent. I'm working for them to get food. I'm sewing clothes to sell, and I'm also selling fruit.” Four child grants supplemented the household income. Esseny reported that she took out a loan to start her sewing business and accessed credit at stores when she lacked money to buy necessities. She appeared to have good family and neighborly support, and drew on these in times of need. Rather than being discouraged by her large number of dependents, Esseny saw children and grandchildren as current and future support. “No, the household is not doing well financially,” she said. “Everyone wants money in this household, and everyone is using their own. My neighbors are my brothers. When I look at my situation, I can't compare with them, because I have children and grandchildren. Some of the families do not have children. That means that I've got more support, they do [not] progress because they don't have much support.” Although the household struggled financially, each member contributed labor and assistance to the household. Thus, Esseny viewed her broader social environment as benefitting her and her household as a whole. Her granddaughter mentioned, though Esseny did not, that in 2001 Esseny cared for an adult daughter with tuberculosis, possibly an early symptom of AIDS, suggesting that financial and emotional difficulties may loom in the future.The case of Octah's small household provides an interesting comparison. Octah was 65, and lived with just two fostered children; her sister was sick, so could not care for them. Octah helped the children and they reciprocated. AIDS affected her house through these fostered children, and a daughter-in-law who died after moving out. Her son and his family, and several other kin moved out over the past year, some still lived nearby. Octah seemed respected, but depressed, lonely and disconnected after her family moved out. She mentioned two recent positive events: “I am happy because I am staying with the children of my sister and they are helping me to fetch water.” And, “My grandson bought bricks and gave them to me and said that he would build a house if he gets more money.” This clear connection between social environment, proximity to kin, and physical place is an important one in this community. Perhaps her “small family” made household finances more manageable. She received a pension, remittances from a son, and help from a grandson, but other children no longer contributed because they were unemployed or had their own households. She had enough extra money this year to buy a cell phone, and generally seemed to make ends meet. However, she reported not doing well compared to neighbors, largely because she felt less connected to kin.Some female-heads in the middle of the continuum had good support from family and neighbors, as well as pensions and/or a large number of child grants or remittances. Other households struggled financially, but had strong social environments stabilized through family relationships and outside support. Even so, these households did not see themselves as secure but rather as teetering on the edge.4.3A few heads and their households seemed to manage fairly well despite the hardships their households faced. They had some complaints and problems, but used resources and coped with crises in ways that separated them from the rest. These households were more likely to be headed by older women, but their similarities were otherwise difficult to classify. Each household appeared to have a strong woman who took care of the family, though not necessarily the head. One household exemplifies the complex nature of this theme; this household was managing well, but the head herself was essentially a figurehead.Dumazile, aged 69, lived with seven people, including two orphaned grandchildren from a daughter who died in 2000. Judith, Dumazile's 35-year-old daughter, revealed that one of Dumazile's sons, who was living in the household, was HIV-positive. Judith, a teacher, assisted with her brother's medical needs, and helped keep his status secret from Dumazile, possibly to protect her. Judith eloquently explained how AIDS was affecting her and their household, “It affected my life because I am always worried that I don't know how must I live with an HIV-person. I don't know how I can tell my children about this. And if I tell them, how will they react toward my brother because they are responsible for washing and cooking for him.” About financial burdens, she said, “I spend a lot of money paying doctors for [my brother] in order to get better treatment. I even consulted without money. When I receive money I then pay the doctor. We made an arrangement that I must come with him even if I don't have the money, and I will pay him back. The problem was with the transport. I have to pay when I go to the doctor because he was unable to walk. Every time I have to pay R150.00 for transport.” Access to health services remains a major obstacle to health care in this rural community. And regarding the emotional costs, she reported, “The difficult part was when giving him a bath because he is a man. My mother used to roll him with clothes on his chest, then wash his back and legs and leave him to finish where she had rolled him. If he was a lady, it would be easy to wash him.”Although Dumazile was the official head of the household, her daughter was the primary decision-maker. The household depended on Judith's salary, plus four child grants and Dumazile's private pension from her work as a cleaner at a public health clinic. The household was not wealthy, but Judith claimed that they were doing better than in the past and better than neighbors because of multiple income sources and always having food. Still, the son's illness was producing high medical expenses, and Dumazile needed care for high blood pressure and arthritis resulting in visits to various local and more distant doctors, clinics, hospitals, and pharmacies. Despite the costs, this household prioritized seeking health care. To reduce costs, they requested help with transport and expenses from Judith's colleagues and their neighbors when necessary. Although this household appeared to manage well through hardships, the future is uncertain. Rising medical costs for Dumazile's son and related burdens likely will increase financial and emotional adversity. These changes could shift this household downward on the continuum. If Judith was to lose her job or leave the household, the situation could shift even further toward despair.Dumazile relied heavily on her daughter's support, but in another household, the emotional rock of the family was the older female-head, Thandi, age 66. Thandi lived with three of her sons, three grandchildren, and four great-grandchildren. Her granddaughter Pretty held her in great esteem, “[After my mother died] I felt alone in a strange place. I felt that heaven was over me, I thank God because my grandmother always stayed with me, [so I could] share my ideas with her. Everything I do, I tell her. I can't do anything without her. She is my friend. She is all to us.” This attitude is a reflection of Thandi's respected place in her social environment and offers a partial explanation of why some households fare better than others against the challenges of AIDS in their households.5Our interviews reveal substantial heterogeneity in the coping abilities of female heads and their households in terms of access to financial, emotional, and physical support. Social and geographic isolation created by apartheid have made inter-household social connections particularly important to household survival in rural South Africa. Struggling households have weak social connections and more difficulty coping with AIDS-related disruptions. Female-heads' financial and social wellbeing is particularly important, regardless of age. Interpersonal relationships, social support, social grants, and formal labor opportunities bolster female-heads' wellbeing, which in turn mediates the impact of AIDS-related stressors on their households. Those that are disconnected or lack support from important relatives, such as in-laws or children, are challenged more by AIDS-related disruptions. Such households, lacking familial support, rely heavily on government sponsored social support such as child grants and pensions, something not available in most AIDS endemic areas. Although social grants provide important income for many female-headed households, they are often insufficient to cover even the basic needs, especially for younger heads who cannot access pensions. For younger heads, employment is crucial for household wellbeing, yet is limited in this rural area.Clear differences exist in the ways AIDS illness and death impact households headed by younger and older heads. Differences often relate to the head's relationship to the deceased (spouse or child), and the place and timing of the illness and death (inside/outside the household and very recent/more distant past). Among households with older female-heads, only one seemed particularly estranged or disaffected, whereas the majority stayed afloat; a few seemed to manage relatively well compared to all the other households/heads in the sample. Our interviews with younger heads and other household members suggest that deaths of husbands not only reduced the number of income-earners, but also created tension with in-laws. Lack of support from a husband's family fractured a young female-heads' social environment, further diminishing her ability to absorb the financial shock of an AIDS-related death. Being younger, these women may not have had the time to build up the social connections beyond husbands' kin, which may be key to absorbing AIDS-related shocks.Keeping the unique features of the rural environment in mind, policy makers should attend to these generational differences. In our sample, a greater proportion of younger household heads struggled to cope with a recent AIDS-related death, particularly of a spouse, which appears to be a greater burden than other types of AIDS-related impacts. These younger widows appear to have fewer resources for coping with current and future AIDS-related disruptions. Hence, they are more vulnerable and in need of additional assistance. Although many of these households receive social support through child grants, younger heads often struggle to find money for basic household needs. Many undertook informal work to supplement household income, but most seemed overwhelmed by household demands. Such households would benefit from additional grants to younger widows, namely programs that help replace social networks lost to stigma, and employment opportunities for women. These interventions need not continue indefinitely. Time-limited programs may alleviate many immediate stresses related to an AIDS-death. Although income lost to death is permanent, many death-related costs, such as health care debts, funeral, and burial costs, are incurred only once.AIDS-widows, here shown to be primarily younger female-heads, may be HIV-positive themselves, which may lead to additional problems for their households in the longer term. It is important to note that antiretroviral therapy (ART) rollout in the area may mediate these impacts if individuals are tested and receive treatment. Future research should focus on the likelihood of testing and treatment after the death of a spouse, the wellbeing of children in these households, and the long-term costs and consequences of AIDS. Households headed by older women may also see a shift in the need for resources and social connections with ART rollout in terms of more prolonged costs related to managing illness, but possibly a decrease in young orphaned children in the household. However distance to health care services may continue to be an obstacle. Greater public transportation infrastructure would benefit both young female heads seeking testing, treatment for HIV and AIDS-related illnesses, and older female heads dealing with other chronic age-related health problems.A limitation of this study is the portrayal of each household at one point in time. The data suggest ways that the proximity of a death both in time and place, as well as the head's age might influence social environments and coping. However, social connections, as well as coping strategies and capacity are dynamic, so the experiences of these households and female-heads are likely to change as events and relationships evolve. Future studies would benefit from tracking households' social connections, coping capacity, and strategies over time in relation to the timing and magnitude of disruptions, such as AIDS-related illnesses, deaths, and caregiving for orphaned children. Tracing rural/urban social and financial connections is an essential extension of this. While similar to the rest of South or Southern Africa, the rural experience in Agincourt may not be comparable to other African rural contexts. For example, connections made through labor migration offer a resource for women, which may not be found in other contexts. Therefore, similar studies should be undertaken in other rural contexts in Africa that are facing HIV/AIDS-related challenges.


Background - Bacterial resistance has reached an alarming level worldwide. There is a worrying gap between the current worldwide spread of multiresistant bacteria and the lack of new antimicrobial drugs. Urgent measures are then needed in order to preserve the efficacy of antibiotics.Our aim was then to raise awareness and call for action to save antibiotics.Objectives and results - We created in 2011 an international network, named the World Alliance Against Antibiotic resistance (WAAR). It gathers health professionals, veterinarians, environment specialists, economists, politicians and delegates of the public. This association is supported by 51 professional societies (40 in France and 11 non-French societies) and counts 470 members, from 45 different countries. We have met with government delegates, have communicated on the topic in the media  and in the scientific literature. We have contacted the APUA (Alliance for the Prudent Use of Antibiotics), the BSAC , React (Action on Antibiotic Resistance) and GARP  in order to participate in a common international call for action . Our next step in the coming months is to suggest to government delegates to conduct a strong initiative showing that antibiotics are a very special class of drugs. Namely, we will suggest that doctors, including those in the outpatient setting, prescribe antibiotics on a dedicated form, mentioning the clinical indication and the duration of therapy. Moreover, a systematic reassessment of therapy around day 3 is of critical importance. We are planning to evaluate these strategies in randomized controlled trials, assessing total antibiotic use as the main outcome. Adding the antibiotics to the UNESCO World Heritage list would also be very useful.Conclusion - We believe that such global initiatives are urgently needed worldwide if antibiotics are to be saved. Those precious drugs must be considered as "special" drugs, and actively protected.J. Carlet Consultant for Astellas, Other Basilea, C. Pulcini: None declared.


Impulsivity refers to a wide spectrum of actions characterized by quick and nonplanned reactions to external and internal stimuli, without taking into account the possible negative consequences for the individual or others, and decision-making is one of the biologically dissociated impulsive behaviors. Changes in impulsivity may be associated with norepinephrine. Various populations of drug addicts all performed impulsive decision making, which is a key risk factor in drug dependence and relapse. The present study investigated the effects of clonidine, which decreased norepinephrine release through presynaptic alpha-2 receptor activation, on the impaired decision-making performance in abstinent heroin addicts.Decision-making performance was assessed using the original version of Iowa Gambling Task (IGT). Both heroin addicts and normal controls were randomly assigned to three groups receiving clonidine, 0, 75 µg or 150 µg orally under double blind conditions. Psychiatric symptoms, including anxiety, depression and impulsivity, were rated on standardized scales. Heroin addicts reported higher scores on the Barratt Impulsiveness Scale and exhibited impaired decision-making on the IGT. A single high-dose of clonidine improved the decision-making performance in heroin addicts.Our results suggest clonidine may have a potential therapeutic role in heroin addicts by improving the impaired impulsive decision-making. The current findings have important implications for behavioral and pharmacological interventions targeting decision-making in heroin addiction. The high propensity to relapse is a hallmark feature of drug addiction and a main challenge for treatment strategies. Impulsivity, which refers to behavior performed with little or inadequate forethought, is a key vulnerability factor in drug addiction and risk factor in relapse Impulsivity is a multifactorial construct that can be measured by tasks such as decision-making, response inhibition, and reflective impulsivity Prefrontal cortical (PFC) network plays an important role in gating impulsive actions in a variety of behavior tasks Thus, our hypothesis was that, at doses that decreased behavioral arousal or activation, clonidine would improve decision-making performance in abstinent heroin addicts. Since 150 µg clonidine can suppress blood pressure F = 16.38, p<0.05). The analysis revealed that each subgroup of heroin addicts scored higher on depression compared with controls (p<0.05). No significant differences in age, education and anxiety score were found in the three subgroups of heroin addicts and normal controls. No significant differences were found in drug use characteristics (duration of heroin use and average dose abused) across heroin groups.Fifty-three heroin addicts and 56 normal controls were enrolled and completed the study. The demographic, substance abuse characteristics, as well as BDI and HAMA scores of the participants were summarized in F = 54.288, p<0.05) on self-report ratings of the BIS-II total score, which meant that heroin addicts reported higher scores than normal controls. Significant differences were also found on the subscales motor impulsiveness  = 17.789, p<0.05), attention impulsiveness  = 24.77, p<0.05), and nonplanning impulsiveness  = 47.254, p<0.05). No significant differences were found between the three subgroups of heroin addicts and normal controls in total scores and subscale scores of self-reported impulsivity on the BIS-II (p>0.05).[(C+D)−(A+B)] in heroin addicts and normal controls. The analysis revealed that the heroin group tended to select more disadvantageous cards in the IGT at baseline compared with the control group  = 6.09, p<0.05). No difference was found across the three subgroups in both the control group and heroin group (p>0.05). The analysis revealed a significant effect of Time  = 4.495, p<0.05), a Time×Group interaction  = 4.687, p<0.05), and a Time×Dose interaction  = 2.24, p<0.05). In the heroin addict groups, two-way ANOVA revealed a significant effect of Time  = 8.17, p<0.05) and a Time×Dose interaction  = 2.68, p<0.05). In within-group comparisons, 150 µg clonidine, but not 75 µg clonidine or placebo, improved decision-making performance (p<0.05). In all three subgroups of normal controls, no significant difference was found between pretreatment and post-treatment (p>0.05).p>0.05). Both doses of clonidine decreased SBP of heroin addicts and control subjects  = 40.01, p<0.05; Time×Dose interaction:  = 7.17, p<0.05)  = 42.07, p<0.05), Time×Group interaction  = 5.09, p<0.05), Time×Dose interaction  = 8.77, p<0.05)) ( p<0.05) , but not p>0.05; . 150 µg p<0.05)) .The present placebo-controlled, double-blind study demonstrated that 150 µg clonidine improved the impaired decision-making performance in abstinent heroin addicts, which was assessed with the original card version of the IGT. The impulsive decision-making in heroin addicts were consistent with previous studies in opiate dependents using IGT, Game of Dice Task The lower dose of 75 µg clonidine did not show the significant effect on the decision-making ability in heroin abusers. But the pharmacokinetics study has found the cumulative concentration of chronic dosing with 75 µg clonidine, which suggested this lower dose of clonidine could be effective to enhance the decision-making ability.Studies using neuroimaging and brain lesion technologies have implicated that prefrontal cortex (PFC), medial frontal cortex and basal ganglia in controlling impulsive decision making It has been suggested that stimulation of the alpha-2 adrenoceptor improved PFC function in animals Second, our present results did not show the low dose of clonidine significantly improved the decision-making ability, which may attribute to the small sample size. The further research work should enlarge the number of subjects. The third potential limitation is that the noradrenergic effects of clonidine were not measured directly in this preliminary study. However, both the 75 µg and 150 µg clonidine decreased blood pressure significantly. It has been shown that clonidine decreased the norepinephrine metabolites and altered working memory performance Some limitations of our present study should be noted. First, retest of IGT may produce a practice effect. However, the decision-making capacity of drug addicts is similar to that of patients with ventromedial prefrontal cortex (vmPFC) damage In conclusion, we found that abstinent heroin addicts perform more impulsively, and clonidine may play a potential therapeutic role in improving the impaired decision-making performance. These findings have important implications for behavioral and pharmacological interventions targeting impulsivity in heroin addiction.The study was approved by the Peking University Research Ethics Board. All participants provided written informed consent and received monetary compensation for taking part in the study.Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) Eighty-six male abstinent heroin addicts were recruited from the Yichang Compulsory Rehabilitation Center, Hubei province, China. Sixty-one normal subjects were recruited through advertisements followed by telephone screening. All subjects were 20 to 40 years old. The study's procedures and risks were explained and discussed thoroughly, and written informed consent was obtained from subjects before study participation. Prior to enrollment, the addicts were screened using the Structured Clinical Interview for the Demographic characteristics of the subjects were collected upon arrival, including gender, age, education years, heroin use time and dose, time of last drug use, and smoking status.The 14-item Hamilton Anxiety Scale (HAMA) questionnaire was used to measure anxiety. Items 1–6 and 14 were about psychological anxiety, and items 7–13 were about somatic anxiety Depressive symptoms were measured using the 13-item Beck Depression Inventory (BDI). Each of the 13 items measured the presence and severity of depressive symptoms by requiring a self-rating from 0 to 3 The Barratt Impulsiveness Scale (BIS-11) is a validated questionnaire that measures different dimensions of impulsivity [(C+D)−(A+B)].We used the original card version of the IGT to evaluate decision-making performance. The task was administered according to the procedure described by the Iowa group Systolic and diastolic blood pressure was measured with a 9062D monitor . A pulse sensor was attached to the subject's finger and connected to an SD-700 monitor to provide a continuous measure of pulse Following recruitment, both the normal participants and heroin addicts were randomly assigned to three groups: placebo, 75 µg and 150 µg clonidine  group. The participants and the experimenters were blind to the study treatment. Each participant attended a testing session at the clinical laboratory at 8:00 am. Upon arrival, the experimental procedure was explained to each participant . Followivs. control group) and Dose  and the within-subjects factor of Time (pretreatment vs. post-treatment). In the heroin addict groups, IGT scores were analyzed by two-way ANOVA with the between-subjects factor of Dose  and the within-subjects factor of Time (pretreatment vs. post-treatment). Repeated-measures ANOVA with the between-subjects factors of Group (heroin group vs. control group) and Dose  and the within-subjects factor of Time  were used to analyze systolic blood pressure, diastolic blood pressure and heart rate. Post hoc pairwise comparisons were conducted with Fisher's Least Significant Difference (LSD) test. Values of p<0.05 were considered statistically significant. Means are given with standard deviations.All data were analyzed with SPSS v. 13.0 . Demographic characteristics  and psychiatric symptoms, including anxiety, depression, and impulsivity among groups were compared using one-way analysis of variance (ANOVA). Iowa Gambling Task scores were analyzed by three-way ANOVA with the between-subjects factors of Group (heroin group


Pseudomonas aeruginosa has a high resistance to external environmental conditions, with a remarkable ability to adapt and numerous virulence factors, being involved in the etiology of nosocomial infections and severe infections in immunodeficient patients. The strains isolated in hospitals need supervision due to the risk of transmission and antibiotic resistance.Pseudomonas strains isolated from pathological products collected from hospitalized patients in non-ICU departments of the hospital.We pursued the epidemiological context to elaborate therapeutic recommendations on first-line antibioterapy adapted to the evolution of antibiotic resistance of P aeruginosa hospitalized in the “Victor Babeş” Hospital Craiova in the period 01 January 2006 – 31 December 2012. We evaluated the studied cases based on the following parameters: the risk of infection with antibiotic-resistant germs (Carmeli score), infection localization and antibiotic resistance profile of the isolated strains of P aeruginosa, achieved by the classical diffusimetric system.The retrospective study included 192 patients diagnosed with infections caused by The annual evolution of cases showed an upward trend since 2009, the age groups most affected were infants (8.3% of cases), small children (11.1%) and the elderly over 65 years (26.5%). According to the Carmeli score, patients were divided into 3 categories: 4 patients (2.1%) with community infections, 112 patients (58.4%) with community apparent infections and 76 patients (39.5%) with probable nosocomial infections. The location of infection was: respiratory (49.6%), ear (16.1%), urinary (12.8%), digestive (10.1%), overinfected wounds (2.7%), sepsis (1.6%), other sites  1%.P aeruginosa to be carbapenem-resistant showed respiratory and urinary localization and wound infections. Colistin was the safest alternative treatment for P aeruginosa strains resistant to meropenem, becoming the most effective antibiotic in the absence of its use for a long time.Antibiotic sensitivity was: colistin 99.1%, quinolone 88.7%, cefoperazone-sulbactam 88%, aminoglycosides 87.7%, meropenem 84.4%, aztreonam 83.9%, piperacillin-tazobactam 82.14% ticarcillin-clavulanate 77.3%, ceftazidime 73.8%, cefpirome 72.7%, ceftriaxone 71.6%, cefepime 60.9%, amoxicillin-clavulanate 16.1%. The comparative analysis of antibiotic sensitivity according to the Carmeli score indicates caution in the use of cephalosporins and quinolones for patients with Carmeli score 3, since these patients probably have infections with antibiotic resistant strains. The risk for strains of P aeruginosa was determined by antibiotic selection pressure, the chemosensitivity data are useful in developing therapeutic recommendations tailored to the local situation.The antibiotic resistance of


It is known that the level of HIV/AIDS-related knowledge and the degree of condom use varies by socioeconomic status (SES). However, there is limited research on the effect of mass media use on HIV/AIDS-related cognitive and behavioral outcomes in low-income countries and how it might influence the association between SES and HIV-related outcomes. We investigated the moderating effect of media use on the relationship between SES and HIV/AIDS-related knowledge and condom use in sub-Saharan Africa in terms of communication inequalities. Cross-sectional data from the Demographic Health Surveys from 13 sub-Saharan countries (2004–10) were pooled. Gender-stratified multivariable poisson regression of 151,209 women and 68,890 men were used to calculate adjusted relative ratios and 95% confidence intervals for the associations between SES, media use, HIV-related outcomes, and condom use. We found significant disparities in mass media use among people from different SES groups as well as among countries. Education and wealth are strongly and positively associated with awareness of HIV/AIDS and knowledge about transmission and prevention of HIV/AIDS and are significantly associated with condom use. These associations are attenuated when the use of various types of mass media is added to the models, with newspapers showing the strongest effect. The findings of this study suggest that media use has the potential to blunt the impact of socioeconomic status though not completely eliminate it. Thus, we need to pay attention to reducing communication inequalities among social groups and countries to moderate the effect of wealth and SES on HIV/AIDS. Two-thirds of all people infected with HIV live in sub-Saharan Africa, although this region contains little more than 12 percent of the world’s population The importance of mass media in health promotion and disease prevention is well documented, since both routine exposure to and strategic use of mass media play a significant role in promoting awareness, increasing knowledge and changing health behaviors While the contribution of media use to disease prevention and to the promotion of healthy behavior is widely acknowledged Sub-Saharan Africa has lagged behind in mass media use and telecommunications during the last 50 years, since gaining independence from Western colonial rule. However, the use of media has spread rapidly since the start of the twenty-first century As limited research on health communication inequalities has been conducted in sub-Saharan Africa, the purpose of this study is to use nationally representative surveys of men and women from thirteen African countries to investigate the effect of media use on HIV/AIDS-related knowledge and behavior. Our hypothesis is that communication inequalities, differential media use among social classes, may be one plausible mechanism through which social inequalities in wealth and education lead to knowledge disparities of HIV/AIDS in sub-Saharan Africa.Approval for the study was granted by the Harvard School of Public Health Institutional Review Board . All participants gave written informed consent to participate. The Ethics Committees of the Demographic Health Survey approved this consent procedure. During the data collection process, any information that could distinguish individual respondents was not collected.All of the data used in this study were collected by Demographic and Health Surveys (DHS) conducted in various sub-Saharan African countries from 2004 to 2010. The DHS are nationally representative cross-sectional household surveys that use a standardized questionnaire to facilitate comparisons among countries, particularly for low-income settings The measurement indicators of the DHS were developed by the United States Agency for International Development Four binary variables were created using a methodology developed by the Joint United Nations Program on HIV/AIDS to measure knowledge and behavior about HIV/AIDS: awareness, prevention knowledge, transmission knowledge, and condom use Media use: Individuals reported how often they used three mass media sources–radio, television, and newspaper–with possible answers being “almost every day” (4), “at least once a week” (3), “less than once a week” (2), and “not at all” (1).Socioeconomic status: Wealth was defined using an established methodology developed for the sub-Saharan Africa context in which each individual was assigned a wealth score created by weighting responses to 33 questions regarding household possessions and characteristics such as quality of housing, ownership of land, and possession of an automobile with a factor analysis procedure and dividing the results into quintiles Sociodemographic confounders were selected based on a theoretically Y has a Poisson distribution, and it assumes the logarithm of its expected value can be modeled by a linear combination of unknown parameters. Survey weights were applied to each model to account for multiple adjustments in the sampling procedure to ensure that sample was representative of each sub-Saharan African country. Features of complex sampling design were taken into account using Stata’s svy suite of commands.Each binary HIV/AIDS-related outcome was modeled with a modified Poisson regression by gender using STATA version 10.0  for providing an accurate relative risk and 95% confidence interval while simultaneously accounting for clustering within neighborhoods n = 48,871), and the smallest was from Swaziland . On average, over 90% of the respondents were aware of what HIV/AIDS is , but a smaller proportion had knowledge about HIV/AIDS transmission  and prevention . Practice of condom use  was much lower than the level of HIV/AIDS knowledge. Only 1–2 people out of ten had used a condom during their last sexual intercourse. Regarding the practice of condom use, the scores for men were two times higher than those of women, which is in line with the literature As detailed in The descriptive characteristics of the sample from Appendix S1 in File S1), and they were consistently associated with HIV/AIDS knowledge and condom use (See Appendix S2 in File S1). Based on these associations, we modeled the multivariate Poisson regression.Both socioeconomic status and media use indicators were positively associated with each other  and having 13 or more years of education  were most likely to have heard of HIV/AIDS compared to those in the lowest wealth quintile and those with no education, respectively. These relationships were attenuated  after adjusting for mass media use Table 3.HIV/AIDS Transmission Knowledge: HIV/AIDS transmission knowledge was also strongly associated with wealth and education among women, as shown in Model 1 of HIV/AIDS Prevention Knowledge: As shown in Condom Use: The pattern of the influence of SES and the attenuation of its role with media exposure continued for condom use. We found wealth- and education-based gradients on condom use, and these gradients were attenuated once we accounted for mass media use Table 3.After standardizing the average characteristics of the pooled population of all countries as the reference (1.00), the associations between media use and HIV/AIDS-related knowledge and condom use which were shown in Appendix S1 and S2 in File S1). This observation is consistent with the notion that individuals of higher SES tend to gain more benefits from information resources than their counterparts of lower SES in LICs Communication behaviors are often linked to an individual’s socioeconomic background and his or her knowledge and behavior relating to a specific issue. Our results indicated that the relationship between SES and HIV/AIDS-related knowledge and safe-sex behavior are moderated by the effect of media use. We found that social inequalities are associated with communication inequalities in sub-Saharan Africa. First, while there is substantial HIV/AIDS awareness among individuals at every socioeconomic level, increasing wealth and education are consistently associated with HIV/AIDS awareness, prevention and transmission knowledge, and condom use among both men and women. Education is particularly strongly associated with both forms of knowledge and behavior. This result is consistent with the results of other HIV/AIDS studies in sub-Saharan Africa, which have found a social gradient in the relationship between SES and HIV/AIDS Several limitations of this study should be noted. The observational nature of the cross-sectional data prevents us from making causal inferences regarding the associations among socioeconomic variables, media use, and HIV/AIDS-related knowledge. However, the outcomes of interest in this study–the aspects of media use–are unlikely to precede the exposures under investigation, education and income, thereby reducing the possibility that the results would reflect reverse causation. In addition, previous studies demonstrating that media use leads to increased knowledge and healthy behavior support our assumptions regarding the ordering of the constructs The findings of this study clearly point to an opportunity for mass media to promote HIV/AIDS knowledge and condom use to reduce the invidious impact of socioeconomic status on health. The caveat, however, is that inequalities in communication, specifically unequal use and exposure to different communication channels between higher and lower SES groups, has the potential to obstruct the promise of mass media. This calls for public health communication strategies that take into account these inequalities in order to overcome barriers across social classes. Thus, we need to apply media-based approaches to improve HIV/AIDS-related knowledge and condom use in sub-Saharan Africa while considering the differences in media use and exposure according to wealth and education. At the same time, we should pay attention to reducing communication inequalities among social groups and countries so as to achieve health equity on HIV/AIDS.File S1Appendix S1, Correlations among independent variables. P<0.01, a figure in bold caps. Appendix S2, Correlations among independent and dependent variables. P<0.01, a figure in bold caps.(DOCX)Click here for additional data file.


No significant association between the presence of a Met allele and violence was found for women or when outcome was restricted to homicide. We conclude that male schizophrenia patients who carry the low activity Met allele in the COMT gene are at a modestly elevated risk of violence. This finding has potential implications for the pharmacogenetics of violent behavior in schizophrenia.We conducted a meta-analysis of studies examining the association between the Val158Met COMT polymorphism and violence against others in schizophrenia. A systematic search current to November 1, 2011 was conducted using MEDLINE, EMBASE, CINAHL, PsycINFO, ProQuest, and the National Criminal Justice Reference Service and identified 15 studies comprising 2,370 individuals with schizophrenia for inclusion. Bivariate analyses of study sensitivities and specificities were conducted. This methodology allowed for the calculation of pooled diagnostic odds ratios (DOR). Evidence of a significant association between the presence of a Met allele and violence was found such that men's violence risk increased by approximately 50% for those with at least one Met allele compared with homozygous Val individuals (DOR = 1.45; 95% CI = 1.05–2.00;  Schizophrenia elevates the risk of violent behavior Violence is a complicated phenomenon that results from the interaction between many biological and social factors. Although serotonin is the principal neurotransmitter in the regulation of violence, dopamine and noradrenaline are also involved O-methyltransferase (COMT) is one of the enzymes responsible for the catabolism of dopamine and noradrenaline in the brain. A common biallelic single nucleotide polymorphism, involving a Val  to Met (methionine) substitution at codon 158 of the COMT gene (rs4680) has been identified and localized to chromosome 22q11.1-q11.2 Catechol-Male heterozygous COMT knockout mice have been shown to exhibit increased aggressive behavior Thus, consistent with the enhancing effects of catecholamines on aggression, low expression of the COMT is associated with increased aggression in animal models. Based on the findings discussed above, it would seem appropriate to hypothesize that, in general, the COMT polymorphism would exert an effect in humans such that the Met allele would be associated with increased violent behavior. This would also be expected in schizophrenia patients. However, the original reason for COMT genotyping in these patients was to study association between this genotype and the diagnosis of schizophrenia rather than violence. Serendipitously, it was noted that the Met allele was associated with dangerousness Subsequent studies of violence and the COMT polymorphism in schizophrenia were conducted to replicate and expand these findings. The studies were heterogeneous in diagnoses and outcome variables. The samples included patients with schizophrenia, schizoaffective disorder, delusional disorder, and other diagnoses. The outcome variables combined physical violence against others with self-harm, violence against objects, verbal aggression, and threats. These differences make the findings of available studies difficult to compare directly, and may be responsible for their conflicting results. We present a meta-analysis of these studies focused on one diagnosis (schizophrenia) and one outcome .The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Statement Val158Met, Val(158)Met, 158 Val/Met, and rs4680. Additional articles were located through reference lists, annotated bibliographies, and discussion with experts. Studies in all languages and those not published in academic journals were considered. Studies were included if their titles, abstracts, or methods sections demonstrated testing of the association between the Met allele of the Val158Met polymorphism of the COMT gene and physical violence against others in schizophrenia.A systematic search current to November 1, 2011 was conducted using MEDLINE, EMBASE, CINAHL, PsycINFO, ProQuest, and National Criminal Justice Reference Service Abstracts with the following keywords: The initial search identified a total of 2,018 records . The numInclusion in the meta-analysis required that the number of participants with Val/Val, Val/Met, and Met/Met genotypes be available, as well as the number of individuals within each genotype that engaged in physical violence against others. Such tabular data were either available in the manuscript or obtained directly from authors for 15 (88.2%) of the 17 eligible studies, 14 (93.3%) of which also contributed specific information on homicide as an outcome, and 13 (86.7%) of which contributed outcome data separately for men and women. As this data concerned only those participants diagnosed with schizophrenia and the published data often included persons with other schizophrenia-spectrum disorders, the sample sizes, number of participants with each genotype, and base rates of violence used in the present review often differ from those published in the original manuscripts. The two studies for which tabular data were unobtainable JS extracted 39 demographic and descriptive characteristics from each of the included studies. As a measure of quality control, five (33.3%) of the studies were randomly selected and coded by a second investigator (PC). A high level of inter-rater agreement was established (κ = 0.93), and disagreements were settled by consensus Genotypic comparisons) 2I index Following current Cochrane Collaboration guidance a priori, was based on an analogous meta-analysis of COMT polymorphism and suicide The hypothesis that the presence of a single Met allele would result in elevated violence risk was meta-analytically investigated. Individuals with Val/Met or Met/Met genotypes were combined and compared with individuals with the Val/Val genotype. This approach, adopted a priori to explore the effect of the Met allele in subsets of participants: First, heterozygous Val/Met individuals were compared to homozygous Met/Met individuals to examine whether a dose-response effect existed. Second, individuals with the Val/Val genotype were compared to individuals with the Met/Met genotype to examine whether the Met allele increased violence risk, in the absence of the potential effects of genetic heterozygosity Two alternative genotypic comparisons were planned a priori to conduct metaregression analyses regardless of heterogeneity levels, as current expert opinion dictates that sources of heterogeneity should be investigated regardless of between-study variability levels Random effects metaregression analyses were conducted to investigate whether sample or study characteristics were associated with variation in DORs Publication bias is assessed routinely using statistical analogues of funnel plots A significance level of α = 0.05 was adopted for all analyses.Information was collected on 2,370 individuals with schizophrenia from 15 retrospective investigations of the association between the Val158Met polymorphism of the COMT gene and physical violence against others. One article Over a mean time at risk of 136.7 (SD  = 184.4) months, 951 (40.1%) of the 2 370 participants were violent, with 460 (20.7%) committing homicide. Six (40.0%) investigations used community offending as their outcome, whereas one (6.7%) used institutional offending, and eight (53.3%) used offending in either setting. Four (26.7%) studies relied upon institutional records to ascertain whether participants had been violent, 1 (6.7%) relied upon criminal records, and the remaining 10 (66.7%) used a combination of institutional and criminal records along with self- and collateral-report. Whether violent individuals were on antipsychotic medication at the time of their offense was only ascertainable from three studies z  =  2.37, p  = 0.02; z  = 0.24, p  = 0.81), suggesting the Met allele may be associated with less serious physical violence. No significant association between the presence of a Met allele and violence was found for women or when men and women were combined .When homozygous individuals were compared, high rates of specificity (range  = 0.72–0.86) were found. While the association with violence in the pairwise comparison between the Met homozygous and Val homozygous groups did not reach our threshold of statistical significance, a clear trend was identified in the anticipated direction . No statistically significant moderators were identified using data from the alternative genotypic comparisons.Low to moderate levels of between-study heterogeneity were found, with the upper-limits of all p>0.05 in all cases).No significant evidence of publication bias was found in any of the genotypic comparison datasets  eligible retrospective investigations that assessed the association between the Val158Met polymorphism of the COMT gene and physical violence against others.Our principal finding is that the presence of one or more Met alleles in the COMT genotype elevates interpersonal violence risk in male schizophrenia patients. The Met allele codes for the low activity form of the enzyme, and thus this finding is consistent with the report of elevated aggressivity in male COMT knockout mice The role of many other biological factors in violence in schizophrenia is well documented Some of these factors may be related to the COMT polymorphism. Met/Met homozygotes have been found to be at significantly increased risk of behavioral and emotional disturbances such as impulsiveness and conduct problems at the ages of 7 and 11 years, relative to either heterozygous or homozygous Val carriers of the Val158Met polymorphism, but only when they were exposed to maternal stress in utero Impulsivity and violence are related to suicide risk in male schizophrenia patients We were able to obtain limited information regarding patients' antipsychotic treatment at the time of their violent incidents. Less than one-third were reported to be receiving such treatment at the time of their violence, and this may be an over-estimate, given the fact that at least 40% of schizophrenia patients are non-adherent to treatment There was a marginal trend for higher violence risk in individuals with the Met allele in samples with higher rates of lifetime drug  abuse. Substance abuse elevates the risk of violence in schizophrenia No significant association between the presence of the Met allele and violence was found when outcome was restricted to homicide. With a subset of 460 homicide cases in our sample, if the Met allele were strongly associated with homicide in the population, one would expect that such an effect would have been detectable in a subset of this size. Although we cannot exclude the possibility of a Type II error, it is possible that the genetic underpinning of homicide is not identical with that of less severe forms of violence. Specifically, a functional single nucleotide polymorphism (Ala72Ser) in the COMT gene has been shown to differentiate schizophrenia patients who commit homicide The present study has several limitations in addition to the lack of information on comorbid substance abuse. First, while no evidence of a significant association between the presence of a Met allele and violence against others was found in women, this is based on eight (53.3%) predominantly male samples. Future studies may wish to further investigate the effect of the Met allele in women only. A second limitation was that, as detailed previously, two studies that met inclusion criteria had to be excluded, as the reports commingled physical violence against others with other antisocial behaviors. One of these excluded studies, using 37 patients, reported an association between the Met allele and generally “aggressive and antisocial behavior” The principal strength of our meta-analysis is its narrow focus. We have limited the diagnosis to schizophrenia, and the behavior of interest to physical violence against others. Self-harm, violence against objects, verbal aggression, as well as threats and other antisocial behaviors were excluded. These behaviors have often been commingled with physical violence in previous studies. One of the reasons for variability in the findings of past studies of this type may have been between-study heterogeneity in diagnostic criteria and the operationalization of violence.Our findings may have several implications for treatment. Clozapine is currently the most effective treatment of violent behavior in schizophrenia patients Although we have narrowed our violent phenotype as much as possible given the retrospective nature of our study, future prospective research is warranted to examine the association between the Met allele and violence in men with psychosis. Violence against others in schizophrenia has several subtypes that differ in their pathogenesis, treatment, and prognosis We conclude that male schizophrenia patients who carry the low activity Met allele in the COMT gene are at a modestly elevated risk of violence. This finding has potential implications for the pharmacogenetics of violent behavior in schizophrenia.


Antibiotic consumption is associated with adverse drug events (ADE) and increasing antibiotic resistance. Detailed information of antibiotic prescribing in different age categories is scarce, but necessary to develop strategies for prudent antibiotic use. The aim of this study was to determine the antibiotic prescriptions of different antibiotic classes in general practice in relation to age.Retrospective study of 22 rural and urban general practices from the Dutch Registration Network Family Practices (RNH). Antibiotic prescribing data were extracted from the RNH database from 2000–2009. Trends over time in antibiotic prescriptions were assessed with multivariate logistic regression including interaction terms with age. Registered ADEs as a result of antibiotic prescriptions were also analyzed.P<0.001). Elderly patients had more ADEs with antibiotics and co-medication was identified as the only independent determinant for ADEs.In total 658,940 patients years were analyzed. In 11.5%  of the patient years at least one antibiotic was prescribed. Antibiotic prescriptions increased for all age categories during 2000–2009, but the increase in elderly patients (>80 years) was most prominent. In 2000 9% of the patients >80 years was prescribed at least one antibiotic to 22% in 2009 (The rate of antibiotic prescribing for patients who made a visit to the GP is increasing in the Netherlands with the most evident increase in the elderly patients. This may lead to more ADEs, which might lead to higher consumption of health care and more antibiotic resistance. The majority of antibiotics (80%) in the Netherlands are prescribed in primary care Antibiotic use is slowly, but steadily increasing in the Netherlands since 2005 To determine trends in antibiotic prescribing in elderly, we have assessed antibiotic prescription rates by age categories in general practices over a ten year period in a large general practice database. Additionally, we have analyzed the incidence of registered ADEs due to antibiotics.The data for this study are obtained retrospectively from the Dutch Registratie Netwerk Huisartsen . The study group is described and regrouped into four different age categories: 18–44 years, 45–64 years, 65–79 years and ≥80 years. In these age categories, we have compared rates and trends over time in antibiotic prescriptions. Individual prescriptions per patient in a year were used as measure of prescriptions. For each prescription (at the moment of the specific consultation) information on ADE (until 4 weeks after prescription) and co-medication (at and during the prescription) were used. Data were then aggregated over a specific patient and calendar year to obtain a meaningful measure (% per patient-year).The RNH is a continuous, computerized and anonymous database from 22 rural and urban general practices in the south of the Netherlands, Limburg, The GP is responsible for the inclusion of patients. When a patient is included a unique RNH number is attributed to the patient. The GP records patient characteristics, i.e. birthdates, sex, educational level, insurance, type of household, marital status, place of residence, date of entry, last update and end of registration. The GP records all relevant health problems, only permanent, chronic and recurrent (>3 recurrences within a period of 6 months) are recorded, or when they had lasting consequences for the functional status or prognosis of the patient. Medication prescriptions  are included in the RNH database Registration. This includes type of medication, start and end date, and dose. Diagnoses are coded in a standardized fashion, according to the International Classification of Primary Care, using the criteria of the International Classification of Health in Primary Care and the current guidelines of the Dutch College of GPs A number of instruments are available in order to improve the quality and to reduce the inter-doctor variation: all GPs participating in the RNH are instructed and trained, RNH help program exists with all guidelines and criteria described, regional consensus group meeting take place at least 4 times a year to discus their registration difficulties, special software for data control in the health information system used by the GP and, special software for data control in the central database, several quality control experiments have been performed to gain insight into the quality of the database and several measures of agreement were done Chronic diseases are selected from the classification from chronic diseases of Knottnerus Unit of analyses are patient years, where a patient contributed one patient-year when he or she had attended a GP in that calendar year. Outcome measures included in the analyses are: antibiotic prescriptions (yes/no in a year), the number of antibiotic prescriptions (cumulated within a patient over a year) and ADEs (yes/no in a year). For antibiotic prescriptions, a multivariate model was build including age, time, gender, education level and rural versus and urban general practice, and chronic disease. In analyses with ADE as outcome restricted the study population to patient-years with antibiotic prescription and the multivariate model included age, time, gender, education level and rural versus and urban general practice, chronic disease and co-medication. The variables on age and time were presented, as these were our main focus, while controlling for the other variables. Interaction terms between age and time were explored. Statistical analysis is done with SPSS 16.0. A p-value <0.05 is considered statistically significant.All patients included in the RNH database have been informed about the potential anonymous use of their health information. If a patient does not agree, the inclusion of this patient in the RNH database is stopped. All data in this study were analyzed anonymously, only medications and clinical data were used. The Medical Ethics Committee of the Maastricht University Medical Center approved this study (METC 12-4-053).A total of 658,940 patient years were analyzed from 2000–2009: 43%  of the patients years were aged between 18–44 years, 36%  between 45–64 years, 16%  between 65–79 years and 5.0%  ≥80 years. Forty eight percent  of the patient years were comprised by male and 52%  were comprised by female, see In total 11.5%  of the patient years at least one antibiotic per year was prescribed. Antibiotics were more often prescribed in elderly patients (p<0.001), as shown in Of all patients who received an antibiotic prescription, the minority  reported an ADE in the four weeks time window. In a random sample of 4 week periods from the same patients, compared to any 4 week period, excluding antibiotic prescriptions during this period, rates found were 0.06%  without antibiotics. No time trend in ADE reporting was observed. ADEs were not reported more frequently in the later years (2008/2009) compared to the earlier years (2000/2001). ADEs increased per age category per calendar year from 1.8% in 18–44 years, 1.9% in 45–64 years and 2.3% in 65–79 years to 2.8% in ≥80 years. However, co-medication also increased per age category from 23%  in 18–44 years, 49%  in 45–64 years and 70%  in 65–79 years to 78%  in ≥80 years. As expected, underlying chronic diseases increased by age. Of all patient years analyzed 18%  were diagnosed with at least one chronic disease, 40%  in the 45–64, 72%  in 65–79 and 85%  in >80 years age category. In the univariate analysis older age, having one or more chronic disease and co-medication were associated with occurrence of ADE. In the multivariate analysis use of co-medication remained associated with ADE (p<0.001) Figure 3This large primary cohort shows that the rate of antibiotic prescribing for patients who made a visit to the GP has increased in Dutch general practice from 2000 to 2009 in all adult age categories. We have observed the highest increase in the rate of antibiotic prescriptions in elderly patients; from 9% of patients receiving at least one antibiotic in 2000 to 22% in 2009. Additionally, elderly patients more often receive two or more antibiotic prescriptions per patient than younger patients. We have shown increasing trends for all antibiotic subgroups. This is particularly striking for the fluoroquinolones, as these are not indicated as first choice in any Dutch general practice guideline. In the United States nonapproved fluoroquinolone prescribing has already been described in 2005 Our finding that the antibiotic prescription is increasing since 2005 in the Netherlands is comparable with the increase in Europe as shown in the European Surveillance of Antimicrobial Consumption data To our knowledge only three previous studies, one in England/Wales, one in New Zealand and one in Italy, have shown higher antibiotic consumption in elderly patients (>75 years) The highest risk group to develop ADEs is aged over 80 years with multiple co-morbidity and co-medication The main strengths of this study are the long study period and the large representative study group. Since 1996 this RNH database is keeping records of all medications (including antibiotics) via a computerized medical registration program. Data accuracy can be guaranteed as data extraction takes place from electronic medical records of practices and regular training of the GPs and quality controls of the data take place However, this study has several limitations. Firstly, antibiotic prescriptions could not be given in daily defined dosages (DDDs) like some international data Based on our findings, future strategies to decrease the antibiotic consumption and antibiotic resistance in the Netherlands should be addressed to all adult age categories. The elderly could be a specific target group and more in-depth study into the reasons for increasing antibiotic prescribing is necessary.