A wide range of preventive, treatment, and care programs for HIV/AIDS are currently available and some of them have been implemented in Thailand. Policy makers are now facing challenges on how the scarce resources for HIV/AIDS control can be spent more wisely. Although effectiveness and cost-effectiveness information is useful for guiding policy decisions, empirical evidence indicates the importance of other criteria, such as equity and the characteristics of the target population, also play important roles in priority setting. This study aims to experiment with the use of multi-criteria decision analysis (MCDA) to prioritise interventions in HIV/AIDS control in Thailand.We used MCDA to rank 40 HIV/AIDS interventions on the basis of the priority setting criteria put forward by three groups of stakeholders including policy makers, people living with HIV/AIDs (PLWHA), and village health volunteers (VHVs). MCDA incorporated an explicit component of deliberation to let stakeholders reflect on the rank ordering, and adapt where necessary.Upon deliberation, policy makers expressed a preference for programs that target high risk groups such as men who have sex with men, injecting drug users, and female sex workers. The VHVs preferred interventions that target the youth or the general population, and gave lower priority to programs that target high risk groups. PLWHA gave all interventions the same priority. The rank order correlation between the priorities as expressed before and after deliberation was 37% among the policy makers and 46% among the VHVs.This study documented the feasibility of MCDA to prioritize HIV/AIDS interventions in Thailand, and has shown the usefulness of a deliberative process as an integrated component of MCDA. MCDA holds potential to contribute to a more transparent and accountable priority setting process, and further application of this approach in the prioritisation of health interventions is warranted. Since HIV/AIDS has long been recognized as a leading cause of death and a high burden of disease in Thailand -3, a widA range of studies are available to guide Thai policy makers to prioritise HIV/AIDS interventions. International estimates are available on the effectiveness and cost-effectiveness of HIV/AIDS interventions -7, and aAlthough MCDA is used in only a few applications to guide the making of resource allocation decisions on health, it is routinely used in environmental, agricultural and marketing sciences to set intervention priorities . In thosThe primary aim of this study is to experiment with the use of MCDA, including the use of a deliberative process to prioritise interventions in HIV/AIDS control in Thailand. This research follows up on a recent study that employed discrete choice experiments (DCE) to identify and measure the relative importance of various quantifiable and non-quantifiable criteria for the priority setting of HIV/AIDS interventions in Thailand among various stakeholders .The MCDA in the present study includes three components. Firstly, we assessed the performance of interventions on the criteria as identified in the DCE (i.e. we constructed the performance matrix). Second, we ranked ordered interventions. Third, we engaged with the various stakeholders in a deliberative process to adapt the rank ordering where necessary. We also compared the rank order of interventions before and after the deliberative process. These components are discussed in turn.As a starting point, we identified a broad set of 40 HIV/AIDS interventions that are already implemented, or eligible for implementation, in Thailand. We then constructed the performance matrix, i.e. we scored each of the selected HIV/AIDS interventions as a function of their performance on a set of criteria as identified in a recent DCE study . This stSubsequently, we estimated the probability of selection of an intervention by using the logistic regression model derived from the DCE study :0 + β1-3 Target group + β4-5 Gender of target group + β6-7 Type of intervention + β8 Effectiveness + β9 Quality of evidence on effectiveness + εLogit(P) = ln [P/(1-P)] = β0 is the constant term, βi (i = 1-9) are the coefficients of the model indicating the probability of selection relative to the reference criterion level, and ε is the unobservable error term. The regression coefficients for all criteria were obtained from each of the three groups of stakeholders - policy makers, PLWHA, and community members - represented by VHVs during the DCE survey ; six members of the Thai network for PLWHA, representing PLWHA groups at the regional level in Thailand ('PLWHA'); and six community members who have been trained by public health providers to be the VHVs in Samutprakan province ('VHVs'). Participants were selected purposively from each group of stakeholders on the basis of their participation in the previous DCE study to ensure that they were familiar with the DCE and the priority setting process. Each group discussion began with a brief introduction of the purpose of the meeting. Next, participants were presented with the rank ordering of the interventions, and they were then asked whether they agreed with the rank and to provide their justifications. We then asked them to re-classify all interventions into three categories - based on the traffic-light analogy: 'good candidates for implementation' (green), 'not good candidates for implementation' (red), and 'in-between' (yellow). This re-classification was done through consensus or, when necessary, through voting. In all steps, participants were encouraged by the researcher (SY) to discuss, bring in additional criteria, and share their opinions with justifications regarding their preferences.We compared the rank ordering of interventions before and after the deliberative process to explore the impact of deliberation by estimating the Spearman's rank correlation coefficient.This study was approved by the Institute for the Development of Human Research Protections, Ministry of Public Health, Thailand. All participants provided their written informed consent.The rank ordering of the 40 HIV/AIDS interventions before and upon deliberation is presented in Table th of the post-exposure prophylaxis for healthcare workers before deliberation to 'good candidate for implementation' category, upon deliberation.Upon deliberation, the group of policy makers reinforced their preference for highly effective programs that target high risk groups. Community-based education and programs that target the youth or the general population (with the exception for those aimed at the improvement of STI treatment services) were not preferred. In the deliberative process, a number of additional criteria were put forward in addition to those identified in the DCE. The policy maker group proposed cost-effectiveness as an important additional criterion. This group also added the criteria of whether an intervention could be used for multiple purposes, and of safety. For example, a policy maker argued that introducing nucleic acid test screening for blood testing enables the Thai Red Cross Society to simultaneously investigate the existence of Hepatitis B and C with detecting HIV in the same specimen, thus creating added value. Also, a reliable blood donation system is very important to secure safety in Thailand in this respect. The other criterion mentioned was the importance of targeting health care workers at risk as a way of encouraging them to work with PLWHA in hospitals. This led to a change from the rank 10The group of PLWHA expressed a strong preference for the treatment or care for AIDS patients i.e. highly active antiretroviral therapy, and treatment for opportunistic infection and other palliative care, as elicited by the DCE study Table . HoweverPLWHA suggested the availability of alternatives as an additional criterion. For example, improving STI treatment services was not seen as a priority as alternative services were available in hospitals. PLWHA strongly disagreed with considering cost-effectiveness as a criterion - they argued that if an intervention is effective, it should be implemented, and that financial considerations should not be important. PLWHA also prioritized interventions that target the general population rather than high risk groups, because interventions for the general population cover a larger segment of the population, and reflect their notion that everyone has equal risk of HIV infection. One participant argued: "If these (interventions) are the national policy, they should be implemented to everyone not only the high risk groups. This is because everyone is at equal risk of HIV infection. We are all the same".The preferences of VHVs cohered largely with those of policy makers except for the target group of the interventions: VHVs preferred interventions that target the youth rather than high risk populations. Consequently, community-based education and improvement of STI treatment services for the youth were the highest priority Table . This prThere was a significant correlation between the rank ordering before and after deliberation for policy makers (correlation coefficient 37%) and VHVs (46%). The correlation coefficient presents the consistency of results between the DCE ranking and deliberation ranking. No such significant correlation was found for the PLWHA. In addition, from the group discussions, we found that both policy makers and VHVs were generally positive about the ease of interpreting DCE results and the MCDA process, whereas PLWHA were generally negative because of the difficulty of the DCE questionnaire, which might lead to a misunderstanding of the exercise among the respondents.This study has experimented with the use of MCDA to guide the priority setting of HIV/AIDS interventions in Thailand, on the basis of consultations with the relevant stakeholders through a deliberative process.This study revealed the importance of five criteria included in the DCE , and a number of additional criteria raised during the deliberative process availability of alternatives; number of beneficiaries; and inappropriate use or abuse of interventions). This reflects that stakeholders consider multiple criteria in prioritising interventions.The abovementioned results highlight that MCDA has good potential to be used for the making of explicit prioritisation decisions. Also, we observed that the group of policy makers and VHVs - although not PLWHA respondents - applauded the systematic approach for priority setting, including the development of relevant criteria, the presentation of the performance of interventions against these criteria, and the deliberative process. Although MCDA seems difficult for PLWHA as they may not be familiar or comfortable to make trade-off decisions, the considerable overlap of the rank ordering before and upon deliberation in the group of policy makers and VHVs indicates that the quantifiable criteria used in the DCE partly reflect the concerns that stakeholders have in their intervention priorities. We believe that, through its explicit approach, MCDA contributes to the transparency and accountability of the priority setting process. Moreover, the provision of the DCE ranking reduces the stream of information that stakeholders need to absorb when prioritising many interventions simultaneously. We therefore advocate that the identification and weighing of quantifiable criteria (whether through DCE or any other technique) should also be considered as an integrated MCDA component.generalized priority setting, can have far-reaching and constructive influences on policy formulation in the long term [The present application of MCDA seems especially useful for policy planning in the long run as it can set priorities among a large set of interventions without defining the allocation of resources in a precise fashion. This use, also labeled ong term . In contThis study has experimented with the inclusion of a process of deliberation in MCDA in a research environment. As of now, Thailand is stepping towards a routine application of MCDA to define its universal coverage benefit package. Observations of that process reveal that the inclusion of all relevant stakeholders right from the beginning of the MCDA process is imperative to its success .Yet, we also observed a number of shortcomings in the use of MCDA in this study. First, DCE are cognitive demanding and may not be appropriate for all stakeholders. Most notably, PLWHA had difficulties in completing the DCE survey and interpreting the DCE findings. Further research is needed on the use of less cognitive demanding techniques than DCE that serve the same goal . Second,Although the set of criteria for MCDA may vary by country and health system context, the approach is generalizable to other settings. Furthermore, the MCDA criteria may be different if priority setting is required across different health problems e.g. infectious diseases, cardiovascular conditions, and mental health problems. Therefore, further exploration is warranted.This study has documented the feasibility of MCDA for prioritising HIV/AIDS interventions in Thailand, and has shown the usefulness of a deliberative process as an integrated component of MCDA. MCDA holds potential to contribute to a more transparent and accountable priority setting process, and further application of this approach in the prioritisation of health interventions is warranted.The authors declare that they have no competing interests.SY, RB, and YT conceptualized the study. SY wrote the first draft of the manuscript. RB, ST, and YT made substantial contributions to the data interpretation and writing of the manuscript. All authors read and approved the final manuscript.Appendix 1. The performance matrix of HIV/AIDS interventions. Appendix 2. Discrete choice model results by perspective.Click here for file


Vaginitis is a common complaint in primary care. In uncomplicated candidal vaginitis, there are no differences in effectiveness between oral or vaginal treatment. Some studies describe that the preferred treatment is the oral one, but a Cochrane's review points out inconsistencies associated with the report of the preferred way that limit the use of such data. Risk factors associated with recurrent vulvovaginal candidiasis still remain controversial.This work describes a protocol of a multicentric prospective observational study with one year follow up, to describe the women's reasons and preferences to choose the way of administration  in the treatment of not complicated candidal vaginitis. The number of women required is 765, they are chosen by consecutive sampling. All of whom are aged 16 and over with vaginal discharge and/or vaginal pruritus, diagnosed with not complicated vulvovaginitis in Primary Care in Madrid.The main outcome variable is the preferences of the patients in treatment choice; secondary outcome variables are time to symptoms relief and adverse reactions and the frequency of recurrent vulvovaginitis and the risk factors. In the statistical analysis, for the main objective will be descriptive for each of the variables, bivariant analysis and multivariate analysis (logistic regression).. The dependent variable being the type of treatment chosen  and the independent, the variables that after bivariant analysis, have been associated to the treatment preference.Clinical decisions, recommendations, and practice guidelines must not only attend to the best available evidence, but also to the values and preferences of the informed patient. Vaginitis is the most frequent reason for gynecology consultation in primary health care services. It is estimated that 75% of women experience at least one episode of vulvovaginal candidiasis throughout her life and 40-50% of them have at least one recurrence .Gardnerella vaginalis (15-50%), Candida (C) (20-25%) and Trichomonas vaginalis (5-50%) species, with a frequency distribution that depends on the populations studied [Candida species. Candida albicans is responsible for 90% of vulvovaginal candidiasis; the remaining 10% corresponds to C. glabrata and C. tropicalis [The most frequent cause of vulvovaginal inflammation is infective, beeing the main organisms: dida (C) 0-25% andopicalis . No dataMicroscopic examination of vaginal discharge is the main tool for diagnosis. It allows the diagnosis in most of the cases. Fungal culture is useful when the mycroscopic examination of the swab is negative and patient refers suggestive symptoms of Candida infection or in cases of chronic recurrent vulvovaginitis. The culture is not useful in women who received an anti-fungal therapy during last week (90% will have a negative culture) . Common Vulvovaginal candidiasis is treated with a variety of anti-fungal drugs, administered oral or topically  -9. In siThe main purpose of Cochrane's review (2007), which included 17 clinical trials, was to assess the relative effectiveness of anti-fungals imidazol y triazol  for the treatment of uncomplicated vaginal candidiasis. Secondary endpoints evaluated the cost-effectiveness, safety and patient preference of oral versus intravaginal anti-fungals. According to this review no definitive conclusion can be made regarding the relative safety of oral and intravaginal anti-fungals for uncomplicated vaginal candidiasis because side effects data were poorly reported in different studies. It should be noted that in this review trials involving ketoconazol due to "its association with serious adverse reactions and to its limited license" were excluded .Intravaginal anti-fungals present a higher frequency of topical reactions  than the ones administered orally, although systemic effects (headache) are also reported. The oral administration is associated with a wide range of systemic effects including gastrointestinal side effects and headache. The rate of reported side effects per 100 patients was for each anti-fungal the follow: 21% for fluconazol, 22% for clotrimazol, 23% for itraconazol and 12% for econazol and miconazol .Ten clinical trials dealt with women's preference regarding the anti-fungals way of administration, but the presented data were not sufficient to answer this question -20. The We should bear in mind, however, that oral preparations are generally more expensive than intravaginal treatments and systemic side effects associated with oral therapy are likely to be more serious than the intravaginal one . As for C. glabrata was isolated in a 15% ratio, C. albicans is still the most common responsible organism [Candida mediated through IgE [According to american statistics between 5% -7% of women will have recurrent candidal vulvovaginitis (VVCR), defined as 4 or more microbiologically documented episodes in a year. In these cases, although organism . There aough IgE ,22. But ough IgE ,24. AlthClinical decisions, recommendations, and practice guidelines must not only attend to the best available evidence, but also to the values and preferences of the informed patient . IdentifIn the methodological manuals for the development of clinical practice guidelines, the incorporation of the patient's perspective is considered. In order to achive this, the following methodological options are proposed: a review of the literature on the subject from the patient's perspective; investigation focused on the perspective of patients; and the inclusion of patients in the process of development and discussion of the draft guide -30In order to develop researches that allow to incorporate patient's preferences in medical-decisions making, the different settings of decisions must be considered. The first field of decision is individual (micro level) and it should include decisions such as choice of doctor, how to provide information or choice of treatment. The second level (meso) is related to clinical decision guidelines for patient groups with similar characteristics and requires the combination of different preferences (groups of people with different preferences). The third level is called macro or social level. It deals essentially with elections of health programs and economic aspects and should always be taken into account .implications for research section [Our research proposal focuses on the micro level of decision making, studying preferences in individual decision making. The results can also be used at the meso level, through their inclusion into clinical practice guidelines. Our intention is to answer the pending questions that the Cochrane review authors highlight at the  section .The main aim of our study is to describe the preferences of women and the factors that let them to choose the type of administration  for the treatment of uncomplicated vulvovaginal candidiasis in primary health care. Secondary objectives are to determine: 1) the prevalence of different candida species, 2) the safety of administered treatments, calculated as the number of topical or systemic adverse reactions, 3) time of symptom relief and 4) the frequency of recurrent vulvovaginal candidiasis  as well as predisposing factors.Prospective observational study of one year follow up. Post-authorization study17 public health centers, Primary Care Health Service of Madrid (Spain).Women aged 16 years or over with symptoms of vaginitis .3. Treatment with topical or oral antifungals in the week prior to the consultation.4. Patients who are away from their homes and do not intend to reside in the district of the health service in the following year.5. Patients were the taking of the swab is not possible.6. Having had sex without use of barrier methods in the previous 24 hours.7. Intravaginal showers in the last 12 hours.8. Breastfeeding.9. Use of oral corticosteroids or immunosuppressants in the last week.10. HIV.11. Patients taking oral anticoagulants or anticonvulsants.11. Mental illnesses that prevent data collection.It was calculated to estimate a proportion, assuming an expected preference for oral treatment of 43% with an alpha risk of 0.05 and a precision 0.4. The sample size was overestimated, considering a 20% loss. The sample size required is 703.Assistant researchers included in the study all patients who meet the selection criteria during the year-long recruitment. Patients will be captured in a total of 17 Primary Health Care Centres of the National Health Service by 21 family physician.choice of treatment: type of drug, oral or intravaginal administration (pessary or cream), single or multiple doses and reasons for choosing it. The independent variables, will be: the demographics , data from the history , side effects , time to symptoms disappearance, and etiologic (Candida species).The variable result will be To study the factors associated with recurrent vulvovaginal candidiasis, the variables are: number of episodes of vaginitis per year , the use of hormonal contraceptives, hormone replacement therapy, allergic rhinitis, diabetes mellitus, antibiotic administration in the last week (specifying the type of antibiotic), use of spermicides, panty or pantyliners, intravaginal showers, history of childbirth, menstrual phase and sex.The information will be collected by the patient's own family physician through a personal interview. In patients who met the inclusion criteria, the physician will inform the patient of the study's characteristics and will ask informed consent. Women who do not agree to participate will be asked why.During first visit anamnesis and vulvar inspection will be carried out, with vaginal swab taking. A cotton swab transport medium will be used, that will be sent to the reference laboratory within 24 hours, as standard practice. In women with few symptoms the start of the treatment may be delayed until the microbiological confirmation.The doctor will inform the patient about treatment options  and a treatment will be initiated according to her preference. The proposed prescription options are the ones recommended in the literature ,6,9,21. The second visit will take place in a period between 5-8 days after initiating treatment. Microbiological diagnosis will be confirmed. Clinical cure (disappearance of symptoms) will be assessed as well as possible side effects.If no treatment was started at the first visit, information on treatments will be offered to woman and preferences will be asked. In these cases, information on side effects and symptoms disappearance after 7 days will be gathered by telephone.Patient will be informed for the necessity of contacting the doctor at the appearance of new episodes.The third visit will be arranged after the review of the clinical history, 12 months later. Whenever is possible, patient will be given an appointment in order to gather information; if it is not possible, the consultation will be carried out by telephone.For this study an electronic notebook for data collection was designed.Will be described for each of the objectives.Women's preferences on way of administration will be described, by calculating proportions with the corresponding confidence intervals. Thereafter, the association of each of the independent variables to the dependent ones will be studied, using as statistical tests to compare proportions Pearson's chi-square test or Fisher's exact test (when chi-square test conditions of application are not satisfactory) and to compare means Student's t-test or Mann Whitney U nonparametric test.Afterwards, multivariate analysis will be carried out, in order to build an explanatory model, where the dependent variable is the chosen way of administration, and the independent variables, the ones that in the bivariate analysis were associated with patient's preference or such an association is described in the literature.To describe the Candida species responsible of the clinicby proportions-calculator with their confidence intervals.To describe the adverse reactions observed by using the mean and standard deviation. To compare the adverse reactions for treatment regarding the way of administration, Student's t-test or Mann Whitney U non-parametric test will be used.To calculate the average number of days in the relief of symptoms for each way of administration. A survival analysis will be carried out applying Cox's regression model.To calculate the frequency of patients with VVCR criteria. There will be a multivariate analysis, applying logistic regression: the dependent variable will be recurrence (VVCR criteria) and the independent variables the ones that in the bivariate analysis were associated with the recurrence of infection or are described in the literature as risk factors.Patients will be included in the study by their own family physicians. The implication of a large number of professionals will increase diagnosis variability .The microbiological study will be carried out by 5 reference laboratories, therefore variability in the methods of sample analysis might also increase. But then, the results will reflect what is done usually in everyday-practice which gives the study feasibility and applicability.Doctor's style and his preferences can influence the way in which different treatment alternatives are offered to the patient, so bias might be introduced. This will be minimized by the choice card system of preferences in which all participant doctors will be trained in a 4 hours session.Although we have to contemplate losses in the follow up process, in primary health care service this is reduced due to the total accessibility to the public health system. In order to give answer to our main objectives, the follow up is of 7 days and it is unlikely that losses will be important. However, with the purpose of minimize them, women who do not attend the scheduled visit, will be located by telephone and try to recapture them. If she is unable to attend the consultation, the information on side effects will be gathered by telephone. The losses after a year may be higher but we will try to reduce them in the same way. Patients consent to be included in the study and the fact that her own family physician will make this offer, will limit losses as it is described in previous studies ,33. AlthThe study has been approved by the Clinical Research Ethics Committee of Area 9 of the Primary Care of Madrid. It has been registered with reference code ICG/TVC/2008/01 and it has also been authorized by the Department of Health of the Community of Madrid. The study will respect the 2008 Helsinki Declaration. Confidentiality and anonymity of data will be strictly maintained, according to 15/1999 data protection act, both in the implementation phase of the project and in the resulting presentations or publications. Any suspected adverse reaction to treatment will be reported to the Pharmacovigilance Centre of the Community of Madrid.Our study aims to provide information about the preferences of patients and the safety of treatments in order to help the family physician to take the decision to prescribe or recommend an oral or intavaginal antimycotic. To make this decision within the health system, beside efficacy and safety of treatment, costs and patient preferences, must be also taken into account. These preferences are mostly studied by the pharmaceutical industry on their own products, but in populations highly different from the Spanish one.The choice from various medical treatments is not a purely technical problem. As suggested by some authors, these elections call to resolve dilemmas that are emotive and subjective. Situations that are not usual during consultations but are normal when choosing a car or in different personal decision taking. Patients are not accustomed to these dilemmas in relation to health and illness and can not make these decisions intuitively. We need to make these kind of decisions in a structured way It is essential that treatments in clinical practice guidelines should incorporate the results of researches which main objective is to study the patient's preferences. In recent years, all agencies that develop guidelines are preparing methodological proposals in this regard ,29. Our The fact that the aim of the study was the safety of treatments had determined its characteristics. Initially we designed a prospective observational study that would reflect the preferences of patients, but adverse effects of treatments was a question still unanswered. By including such an aspect, our study became a post-authorization study with medication, although all treatments offered are licensed drugs, according the legislation of the Community of Madrid, with a longstanding experience.From the clinical point of view, the study incorporates some new aspects to measure therapeutic response. In most drug-efficacy studies, clinical cure is assessed after 7 days ,17,18,20On the other hand, risk factors associated with recurrent vulvovaginal candidiasis still remain controversial  and an aAs said before vaginitis is the most frequent gynecological cause of consultation in primary health care and many women throughout their life will consult their doctors for this reason. The different treatment options have all limited side effects, only exceptionally severe ones, and cost rates are affordable to the majority of the population.Probably all agree on the importance of incorporating preferences in dilemmas with a high emotional charge . But we can not ignore the fact that although family physicians in many cases have to inform the patient for serious health problems or for processes that limit their quality of life, there are many more everyday clinical decisions for minor health problems that are very important.It is important to raise research questions that can help us to make progress in the incorporation of patient preferences to the decision-making, so we can contribute to the change of the doctor-patient relationship. JL Pinto y cols  quote prThe authors declare that they have no competing interests.ICG conceived the study, participated in de design, coordinated, and reviewed the draft and the final manuscript. FGB coordinated the survey and reviewed the draft and the final manuscript. TSC participated in the design, coordinated the authorization, and reviewed the draft and the final manuscript. JMF, MAR, REF, CHA, LBA, RRB, ECW, CAR, YGD, APR, BGT, MSC, participated in the design of the study, and reviewed the manuscript. The another authors of PRESEVAC group review the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/11/63/prepub


We retrospectively estimated the incidence of culture-proven melioidosis in animals in Thailand during 2006–2010. The highest incidence was in goats , followed by incidence in pigs and cattle. The estimated incidence of melioidosis in humans in a given region paralleled that of melioidosis in goats. Burkholderia pseudomallei. It is the third most frequent cause of death from infectious diseases in northeastern Thailand (after HIV/AIDS and tuberculosis)  for B. pseudomallei from >1 clinical specimens; for 12 (20%) animals, cultures were negative but samples were IHA positive for melioidosis . Cases diagnosed by IHA, but culture negative, were excluded from further analysis because apparently healthy animals in melioidosis-endemic areas can have high bacterial titers  of these animals, diagnosis was based on a culture positive for  titers ,.–We mapped the geographic distribution of melioidosis in goats by province and compared the meloidosis distribution with the total number of goats in the country during the same period ; Figure.B. pseudomallei. This finding proved to be the case in northeastern Thailand, where the incidence of human melioidosis is high and where a small population of goats also had a high relative incidence. Such was not the case in the west, however, where the relative incidence of goat melioidosis was high, but human cases have not been reported in the literature. Possible explanations include a more active approach to determine causes of death in goats or failure to diagnose or report human disease in the west and, less plausibly, the presence of an animal-adapted B. pseudomallei strain that fails to infect humans. Contact with hospitals in western and eastern Thailand indicated that melioidosis was more common than the literature suggests. Further studies to determine an accurate incidence of human and animal melioidosis throughout Thailand are required. The ability to culture and detect B. pseudomallei in clinical microbiology laboratories countrywide also needs to be improved (,The cases of animal melioidosis in Thailand reported here probably underestimate actual cases because necropsies are performed on a small minority of animals that die of natural causes. Goats are a major domestic animal in Thailand, particularly in western and southern Thailand. We demonstrated that the estimated incidence of melioidosis in goats relative to other animals is high and might represent a substantial cause of economic loss for goat farmers. The high susceptibility of goats to melioidosis relative to that of pigs and cattle is consistent with a previous report from Australia (B. pseudomallei in milk. Our study was not designed to detect evidence for animal-to-human transmission in potentially at-risk populations, such as herdsmen, veterinarians, or abattoir workers. Such detection is a future objective in Thailand because presumptive zoonotic infection has been reported in Australia (Our findings support the recommendation for pasteurization of goat milk before consumption in Thailand, which is necessary to prevent human brucellosis and also will prevent ingestion of live


Available evidence in Ghana shows the implementation of tuberculosis (TB) control activities efforts since the beginning of the 1900s. In spite of that, TB continues to be one of the common diseases in the country. In 1994, local and international policy windows opened for renewed strategies for the control of TB. This paper explores some of the approaches which have been in place since 1994 and their implications for treatment outcomes.The study combines quantitative and qualitative data. The quantitative data consist of treatment outcome from 1997–2010 and the qualitative data are derived from in-depth interviews with some staff of the TB control programme. Poisson regression and inductive coding were applied to the quantitative and qualitative data respectively.Reported cure rates increased from 43.6% to 87.7% between 1997 and 2010. The data from the in-depth interviews (IDIs) suggested that improvements in diagnosis, community TB care, stigma reduction among community and health workers towards TB patients, the public-private partnership, and the enablers’ package contributed to the improved better treatment outcomes, particularly from 2008.Lessons learnt include the achievement of objectives with varying strategies and stakeholder interventions. Further studies would be needed to quantify the contributions of the various interventions to help determine those that are cost effective as well as efficient and effective for TB control. As part of the measures to reduce, if not eliminate, the adverse effects of TB, a number of interventions and strategies have been applied, from the individual, societal, national and international levels since the disease was first identified in the 1800s , p.11).The provision of sanatoria was also seen as one of the effective broad scale approaches to controlling TB infection and cure . Others The body of knowledge on factors contributing to the decline in the TB infections and death have been diverse and sometimes saddled with controversies, especially those, which deal with interventions prior to the development of chemotherapy. For instance, McKeown  has emphRecent approaches, often socio-medical in nature have also accounted for improved diagnosis and treatment of TB. For instance, the reduction in treatment duration from 18 months to six months  is consiIn Ghana, attempts to deal with TB dates back to the early 1900s. However, those attempts were sporadic and uncoordinated. Formalised institution for TB control came into being in 1959 with the establishment of the Ghana TB Services . HoweverFor instance, with the increasing burden of TB, partly fuelled by HIV/AIDS epidemic, the WHO, in 1993, declared TB a global emergency, calling for new efforts and commitments for control of the disease. Country health departments/ministries were called upon to formalise and establish national response programmes. In response to such calls, Ghana established a new TB control programme in 1994.Despite the fact that Ghana is not one of the high burden TB countries in Africa, it nevertheless considers TB as an important health challenge. Together with HIV, they account for about 7% of all deaths, the second after malaria . It is aThis paper tracks TB treatment outcomes in the country and explores possible social and biomedical interventions which are perceived to have contributed to the fight against the disease in Ghana. The aim is to identify the social and technical strategies which have been implemented since 1994, and their implications for TB diagnosis and treatment outcomes.This paper was extracted from a larger study which investigated policy environment for TB control in Ghana. Among the issues examined in the larger study were historical perspectives on the disease, public-private partnership, integration of TB and HIV control programmes, and obstacles and opportunities for TB control interventions.M. tuberculosis after four months of treatment. Treatment default is when treatment is interrupted for two or more consecutive months after initiation of treatment. Because the treatment outcome data were captured as count data, Poisson regression was used to analyse the treatment outcomes data. This was chosen because, first, the data did not contain any zeros to warrant the application of Zero-inflated and also, the data did not show evidence of dispersion to permit the use of Negative binomial regression. Simple linear regression will also not be applicable in this case because the data was not collected through random sampling. The results are presented in incident rate ratio (IRR).This study combined quantitative and qualitative methods, leading to a mixed method approach . The quaThe qualitative data was collected from national, regional, district and health facility TB coordinators and service providers. At the national level, three senior programme officers were interviewed, two of whom had been with the programme since 1994 and thus were able to provide detailed information about the programme. In addition to the national officers, four regional TB coordinators were selected based on the recorded TB case notifications in these regions. In each of the regions selected, the district with the highest notification rate of TB was chosen and the district coordinators (4) included in the study. In each district, three facilities (2 public and 1 private), and TB coordinators were interviewed. Finally, one respondent who works with a TB-related international NGO was also interviewed, resulting in overall sample size of 24 respondents. . Semi-structured interview guide used covered issues in TB control such as political commitment, public-private partnership, integration of TB and HIV services and sustainability current interventions. All the interviews were tape-recorded, transcribed and analysed manually. The qualitative data analysis plan followed an inductive approach as reported elsewhere . The UniResults of the study are reported in two sections: first is analysis of TB treatment outcomes based on the quantitative data and the second deals with perceived factors which may have contributed to the observed results using the qualitative data.Regardless of the number of reported TB cases in a setting, key treatment outcomes are expected to improve in line with WHO treatment outcomes benchmarks. Currently, international benchmark for assessing countries’ performance in respect of cure rates is 85%. Figure p < 0.001) while the least incident rate ratio of cure was reported at the Komfo-Anokye Teaching Hospital [KATH] . [The Western Region was used as the reference category because it reported one of the highest TB rates in the country]. Completed treatment was more likely in the Western compared to the others. TB deaths were more likely in the Eastern Region, approximately 55% compared to the Western Region. The rate of treatment failure was significantly lower in the Upper West Region.While there was increase in the cure rates, the proportion dying and experiencing treatment failure or default declined. The Poisson regression outputs confirming these are shown in Table Treatment outcomes varied by year of surveillance: the rate ratio of cure and treatment failure was lowest in 2009 and treatment completion was higher in 2010 than any of the earlier periods. The rate of TB death was significantly more likely in 1998, 2003, 2005 and 2006. Default in treatment was less likely in 2008. In respect of overall default, outstanding results are observed after 2006 (Table When decomposed by region and year (data not shown) and we found that in 2009, the likelihood of cure was significantly more likely in the Northern Region in 2009 (using 1997 as the base year) while the least cure rates were reported at the Korle-Bu Teaching Hospital for the years 2006, 2008 and 2009.The number of years of experience of the respondents varied from one level of service to another. Overall, the respondents had been in service for durations ranging from 2–15 years. The national officers and few regional personnel had been involved in TB control longer than the others, especially compared to those at the facilities. At the facility levels, there were indications of attrition due to regular postings. The conversation with the respondents revolved around factors contributing to the trend in the number of TB cases identified and the corresponding treatment outcomes. Depending on experience and the duration respondent had been involved in TB control; views on determinants of the treatment outcomes were diverse. The qualitative data collection was partly used to document perceptions on the management and outcomes of the various strategies which had been adopted since 1994. The following themes were extracted from the interviews: improvement in case management; improved diagnosis; the introduction of community TB care and enablers’ package, stigmatisation of TB patients, interest of health personnel in TB management, and the involvement of private sector in TB control.Respondents were of the view that improvement had occurred in case management and this was reflected in treatment outcomes, for example, cure and default rates. The respondents generally believed that more patients were now complying with treatment regimens than before. A low defaulter rate is beneficial to the individual patient as well as the larger health system as defaulting is associated with drug resistant bacteria . The folWhat I consider to be a major outcome of the new strategy is the reduction in defaulter rates. I learnt that defaulter rates in the region were around 20% in the past but presently; it has reduced to around 4-5% .The most prominent reason respondents gave for the decline in default rates was the introduction of a fixed dose combination therapy, which has reduced the treatment period to standardised six months, which hitherto, ranged from eight to 18 months. Fixed-dose combination (FDC) is a condensation of first-line drugs: ethanbutol, isoniazid, rifampicin and pyrazinamide into one dosage . FDC can… The result of the cutting down on treatment period from eight to six months for non-resistant TB has improved completion rate and subsequently, cure rates. Previously, the long duration for treatment led to more defaulters (Region 2 Coordinator).Improvements in technology which led to decline in the duration of administration of the drugs appears to have translated into adherence to drug regimens.Improvement in the diagnosis of suspected TB patients was also considered to be one of the important components of the TB control programme. To them, early and accurate diagnosis of suspected cases made it possible for treatment to start early. Because a single TB patient could transmit the disease to about 10 persons per annum, the identification of even one case at its early stage was important to reducing new infections. A respondent had this to say about improved diagnosis:We have ensured that the quality of sputum produced for diagnosis is appreciable because confirmation of cases is difficult or impossible without laboratory confirmation. In line with this, every patient is given two containers for sputum specimen – one for early morning specimen and other for on-the-spot specimen. We observed from this initiative that the quality of sputum improved … after implementing coaching of suspects, there were slight changes, about 2% in quality of sputum and we expect this to continue improving … quality sputum allows us to have proper bacilli formation through culturing .It has been reported that poor diagnosis was a major hindrance to TB control because imprecise diagnosis could result in false negative results. The provision of information on reasons for the collection of sputum, how to produce the sputum; information on characteristics of quality sputum have had impacts on the quality of sputum, leading to positive sputum microscopy analysis .One of the elements of the new approach to TB treatment is the participation of community members. The community treatment care concept recognises social capital and connectedness as instrumental to effective TB control. Under this intervention, individual TB patients are assigned a “significant other” to motivate and supervise patients to take his/her drugs. Health workers in collaboration with patients do the selection of treatment supporters. Some respondents were of the view that community involvement had played a very important role in improving treatment completion and helped to reduce defaulter rates. As noted by one of the respondents:Community involvement has helped to reduce defaulter rates because some selected individuals within patients’ immediate environment help to supervise treatment without necessarily travelling long distances for treatment (Region 2 Coordinator).To some of the respondents, the use of treatment supporters who could be family members, religious leaders, health workers or other gatekeepers who the patient trusts and feel comfortable dealing with might have contributed to the improved adherence to treatment.The available evidence suggests that stigma of infected people and the affected poses some amount of threat to effective TB control . Stigma Now even the cadres of health worker coming in are people who have opted to work with the TB control programme. Previously, it was considered a punishment to be posted to chest clinic. Personnel who were considered stubborn, indiscipline or rebels in the system were sent to DOTS centres – it was like Siberia. But that is changing. There is increasing commitment from health workers to be involved in TB control and this is helping a lot .Another respondent at the regional level also expressed satisfaction with the changing attitude of health workers towards TB control.It was a disease people did not want to get closer to; if you were in the chest clinic, even your colleagues were not willing to come close to you. But now, people feel comfortable working with TB patients. Although resources in TB may be a factor, the important thing is that some health workers have gone through training programmes to work with TB patients. Through these training programmes, we have been able to demystify people’s perception that TB is a dangerous .Funded disease control programmes such as TB, HIV/AIDS and Malaria tend to attract personnel, apparently, because of the financial resources associated with those programmes. Although the respondents were aware of the resources involved in TB control, their interests could not be attributed to the resources. Another reason respondents cited, as accounting for the changes in the attitude of health workers was the positive treatment outcomes being recorded – the perception that staff at the facilities are seeing results from their labours has given some of them further impetus to continue. As observed by one respondent:People see a clear vision for TB control, knowledge has improved, there is greater understanding, the disease has been demystified, logistics needed for control are available – workers don’t have to shout and shout for resources … health workers are beginning to see results, which translate into job satisfaction. If you treat somebody and notice the patient is getting healed, you become content .The claims by some of the senior management of the NTP at the national and regional levels were collaborated by personnel who were directly dealing with patients. Generally, the respondents at the health facilities confirmed the views expressed by the top management as many of them indicated that they willingly accepted postings to DOTS centres. Their argument was that it was professionally ethical for a health worker to accept to work on categories of patients without prejudice and discrimination.I accepted to come here because I have been trained to provide health care to all those who need it, regardless of their condition. There was no reason for me to refuse posting to the DOTS centre .An enablers’ package include a wide range of services such as travel vouchers, reimbursement, cash payments, toiletries, clothing, cell phone minutes, food during DOT visits, vouchers, periodic food packages; social welfare payments during treatment; income generation project; salary payments, legal services, housing or housing subsidies, personalised incentives or “bait for fishermen” (providing other payments to community or patients who bring suspects for treatment) . Cash paAmong the poorest of clients, they were given transportation, beverages and then home support visit … The enablers’ package was an encouragement factor; people came because their relations had told them to do so due to enablers’. This pushed people with chest/lung ailments to come on their own accord due to that small token.The enablers package also covered travel vouchers for health workers and this, according some respondents, it facilitated home verification, etc.Public-private partnership (PPP) for TB control is important of its effects on bridging access gaps . A sectiIt worked well in the few places where it was first started. We are able to manage many patients who could have been lost to follow-up, given that there are only five public hospitals in this metropolis providing DOTS services. At one point, we were recording no defaulters because almost every available private facility was involved in DOTS, even maternity homes .This paper has offered some insights about TB treatment outcomes in Ghana between 1997 and 2010. Coupled with that, attempts have been made to explore the views of key personnel involved in TB control about the possible patient and health system-based factors which have played important roles in achieving the current treatment outcomes. In spite of the modest contributions of this study to our understanding of TB treatment outcomes and the possible factors shaping these outcomes, we are limited to make attributions. However, the findings shed light on possible interventions and strategies which could be studied further to ascertain their measureable impacts on TB control in Ghana. The qualitative evidence is also not representative of the whole NTP establishment.Importantly, our results point to incremental improvements in five specific TB treatment outcomes: the rate of cure, completed treatment, treatment failure, default and death from TB. The timing (year) and places (region) where the best results were achieved on each of the treatment outcomes varied significantly. However, in 2009, impressive results were achieved on all outcome measures. Follow-up discussions at the headquarters of the NTP revealed that in 2009, there was high participation of TB related-NGOs in advocacy on the need for testing, early treatment seeking and other equally important components of TB management.Of comment, another relevant finding, is the high likelihood of TB deaths in the Eastern Region. The Eastern Region of Ghana has consistently recorded the highest burden of HIV . HIV infThe results further point to poor TB treatment outcomes at the two tertiary hospitals, particularly, the Korle-Bu Teaching Hospital. Whereas a number of factors may be contributing to the outcomes at the tertiary hospitals, few are hypothesised. First, as some respondents recounted, community treatment care and regular follow-ups on patients have been critical to treatment outcomes. However, because these hospitals are referral and also located in cosmopolitan areas, follow-up on patients may not be effective and efficient as it possibly happens at the lower levels of health delivery. Further studies that compare the quality of care at tertiary hospitals on the one hand and lower level hospitals/clinics on the other hand may help us get better understanding of these issues.Adherence to TB treatment is an important consideration in TB control programs because incomplete treatment can lead to prolonged infection, drug resistance, relapse, and death . The enaIt was also noticed that the increasing interest of health workers in TB control efforts is not arising from the amount of financial resources available to the TB programme, although an earlier study on barriers to the control of TB had revealed monetary incentives as one of the barriers . AccordiThe findings also suggest that a reverse causality between treatment outcomes and the interest of health workers in TB control. Some respondents perceived that with the rising positive outcomes in treatment, health workers are becoming more committed to TB management and this in turn served as the motivation to work harder. In their review of motivations of health workers, Dolea and Adams  found thIn keeping with earlier studies ,27,33,34Overall, the findings can be summarised into two broad areas: the perceived contributions of social and biomedical interventions. Social interventions included the enablers’ package, community participation in treatment and the public-private partnership. The contributions of biomedical interventions were linked to better case management through the use of FDC and improvement in diagnosis and confirmation of cases. It appears from the findings that an effective combination of social and biomedical interventions may be able to accelerate the global efforts towards significant improvements in TB control. While no attempts were made to match the specific interventions with any particular outcomes due to the exploratory nature of the study, it can be concluded that the interventions mentioned by the respondents  were perceived to have contributed to better treatment outcomes of TB in Ghana. The interventions noted and other novel ones should be pursued by the policy makers to help achieve the goals set for TB.The authors declare they have no competing interests.JAA wrote the first draft of the manuscript. KAA revised it critically and has given final approval of the version to be published. Both authors read and approved the final manuscript.JAA is completing PhD in Population and Health, University of Cape Coast with current interest on tuberculosis policies. KAA is a professor of Population Health, University of Cape Coast.


Background. Breast cancer is one of the most common types of cancer. However, only a few trials assess the effects of arts therapies. Material and Methods. We searched the Cochrane Central Register of Controlled Trials, PubMed, and Google Scholar from their start date to January 2012. We handsearched reference lists and contacted experts. All randomized controlled trials, quasi-randomized trials, and controlled clinical trials of art interventions in breast cancer patients were included. Data were extracted and risk of bias was assessed. Meta-analyses were performed using standardized mean differences. Results. Thirteen trials with a total of 606 patients were included. Arts therapies comprised music therapy interventions, various types of art therapy, and dance/movement therapies. The methodological quality ranged from poor to high quality with the majority scoring 3 of 4 points on the Jadad scale. Results suggest that arts therapies seem to positively affect patients' anxiety  but not depression or quality of life. No conclusion could be drawn regarding the effects of arts therapy on pain, functional assessment, coping, and mood states. Discussion. Our review indicates that arts interventions may have beneficial effects on anxiety in patients with breast cancer. Breast cancer is a condition whose diagnosis may result in extensive emotional, physical, and social suffering. It engenders stress and anxiety related to future prognosis and potential mortality. It may also cause uncertainty about changes in a woman's body image and treatment options. Patients may experience anxiety regarding surgical experience, coping with acute pain, treatment regimens, financial burdens of care, and disruptions of their personal and professional lives , 2.Cancer patients are increasingly turning to complementary and alternative medicine (CAM) therapies to reduce symptoms, improve quality of life, and boost their ability to cope with stress. Different types of arts interventions have been used to alleviate symptoms and treatment adverse effects in women suffering from breast cancer. Arts therapies are made use of especially by motivated patients who want to actively participate in their healing process. Amongst others, from a large New Zealand health survey which sampled 12.529 people, aged 15 years and older, it is known that CAM users are more likely to be middle aged, rich, well educated, of European descent, and female . They arArts as therapy have become increasingly popular in a number of medical and health fields and the application ranges from working with children suffering from psychiatric disorders to elderly dementia patients. As the importance of psychosocial aspects of dealing with a cancer diagnosis and treatment has been better recognized and understood, the interest in arts therapies for breast cancer patients has also increased. Art therapy is an umbrella term for therapies such as dance and movement therapy, music therapy, and art therapy working with visual arts materials. The use of the artistic media as a means for therapy offers patients a way to communicate experiences, feelings, and needs, which are hard to express verbally. This possibility for an alternative way of communication can be important in particular for patients who are dealing with emotional conflicts and spiritual or existential issues. In reflecting on the image, music, or dance as well as on the process of its production with the arts therapist, one's resources can be activated or new ways of coping with the situation can be developed. At the same time the artistic process can be a way for experiencing one's own capability or to relax in times of straining physical treatment. Arts therapies therefore are increasingly used in psychooncology with the goal of psychosocial stabilization and support in the process of coping with the disease –6.Mainly, studies have looked at symptomatic effects such as anxiety and depression, two of the most commonly coexisting accompanying illnesses of breast cancer, while there are only a few empirical trials assessing the effects of art therapy on coping and quality of life of the breast cancer patient, apart from a number of case studies.Wood et al. in 2011 carried out a systematic review of art therapy in adult cancer patients . They coTwo Cochrane reviews were also published the same year—one investigating the effects of dance/movement therapy and the other of music therapy for improving psychological and physical outcomes in cancer patients , 10. TheIt is the objective of this review to evaluate the current evidence and examine the effects of arts therapies (as defined above) on psychological outcomes in patients with breast cancer.PRISMA guidelines for systematic reviews and meta-analyses  and the We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Google Scholar. All databases were searched from their start date to January 2012. We handsearched reference lists and contacted experts. There were no language restrictions.Search terms used for Cochrane Central Register of Controlled Trials were as follows: (breast or mamma) and (carcinoma or cancer) for breast cancer search and  for arts therapies search which were combined. These search terms were slightly modified for other databases.We included all randomized controlled trials (RCTs), quasi-randomized trials, and controlled clinical trials of art interventions for improving psychological and physical outcomes in breast cancer patients. RCTs comparing the effect of art therapy with standard treatment or other treatments such as pharmacological medications in patients with breast cancer (aged >16 years) were eligible for inclusion. Trials that allowed other concomitant treatments were eligible, as long as they were given to both the art therapy and control groups. Participants undergoing biopsy and bone marrow transplantation were also included.Psychological outcome measures such as depression, anxiety, and quality of life as measured by validated instruments are the specific types of outcome measures that are closely being looked at in this review.Data were extracted and risk of bias was assessed. One reviewer (KB) reviewed all searched articles to evaluate suitability for inclusion. If there was uncertainty, it was resolved by discussion with the corresponding reviewers . After selection of studies, the aforementioned reviewer extracted data from the selected articles: author, year of publication, country of origin, study design, participants, outcome measures, arts therapy intervention, control intervention, main results, and adverse events. Data were extracted as intention-to-treat analyses; that is, all withdrawals and dropouts were assumed to be treatment failures, if trial reporting provided relevant information. Where possible, results were presented in meta-analyses using mean differences and standardized mean differences.To assess the methodological quality of the respective studies, the Jadad score was adopted, which refers to randomization (0 to 2 points), blinding of the assessor , and dropout reporting (0 or 1 point) as indicators of methodological quality of a study . Since dAllocation concealment was assessed in accordance with the Cochrane guidelines : (A) meaBased on the methodological quality and the confidence in the results, the quality of evidence for each outcome was assessed according to the GRADE recommendations as high quality, moderate quality, low quality, or very low quality .g using a standardized Excel spreadsheet. For crossover trials, the calculation was adapted for intercorrelations between groups. Where no correlation was reported, it was estimated as 0.7  (P = 0.05). This difference is not significant   see .The methodological quality of included studies ranged from poor to high quality in the assessment with the majority scoring 3 , 26, 28 This meta-analysis showed that arts therapies seem to positively affect the extent to which breast cancer patients score in anxiety and depression but not quality of life. It leads to the recommendation that in breast cancer patients the option of participation in arts therapies is being suggested and shown to be significantly effective for reduction of anxiety and depression over control.Apart from case reports, there are currently only a small number of empirical studies investigating the effect of art therapy on psychological parameters such as coping and quality of life accompanying the breast cancer diagnosis and treatment.Not all studies included the same outcomes. There were a small number of studies per outcome. Therefore, the effectiveness of medical interventions for anxiety and depression could not be compared with those of arts therapies interventions. Three of the studies report on the same study population only different outcome measures , 26, 28.n = 54 cancer patients who made use of art therapy during their outpatient experience whilst receiving chemotherapy was recently published [A qualitative study with ublished . Researcthe process in general perceived as relaxing or stimulating due to the creative activity;the therapeutic relationship allowing to communicate about oneself while feeling listened to;the patient-image-art triadic relationship supporting the expression of emotions (in this case) through the painting and its symbolic function.During the analysis of the interviews, three dimensions of effectiveness became clear:These findings correspond with the central categories describing processes of communication in art therapy as defined by Luzzatto: the direct communication between therapist and patient, a silent creative communication between patient and image, and the therapist trying to understand and elaborate the image together with the patient . In thisNevertheless, the appropriate intervention in the wide spectrum from offering relaxation to the trying process of reflecting one's present situation of a possibly life-threatening illness needs to be chosen carefully. The often rapid changes in patients' physical and emotional state, especially in the acute treatment, require a high level of flexibility of the arts therapist. In order to support the process of coping with the disease, while not undercutting patient's individual strategies for holding up her mental stability, the arts therapist often needs to intervene in very different ways with each patient as well as sometimes in each session.These coercively flexible strategies of intervention in combination with a broad range of concepts in arts therapies make it difficult to examine the effects of arts therapies. Accordingly, existing reviews and overviews of art therapy for cancer patients , 31 repoSince this review could not show a positive effect of art therapy on quality of life, what needs to follow is a comparative discussion of different intervention strategies according to phase of treatment in particular. In phases of great physical strain relaxation, oriented listening to music in receptive music therapy can result in fast effects, while those of a more confronting theme oriented intervention in visual art therapy possibly can be shown only in a longer interval.NCT01331629) [Currently, a French team of researchers is enrolling patients in a phase 2 and phase 3 studies of art therapy for supportive care labeled “Impact of art therapy on fatigue and quality of life of patients treated with adjuvant radiotherapy for breast cancer”  .Further studies investigate especially the influence of art therapy on symptoms of anxiety and depression. A significant improvement of their coping resources was found, for instance, in the RCT by Oster et al. for a group of breast cancer patients .Overall, the option of participation in arts therapies can be recommended and has shown to be significantly effective for the reduction of anxiety over control in breast cancer patients.


One of the key issues in our understanding of life is the study of the essential set of genes and proteins that make up a living cell and a living organism. Genome-wide studies have identified between 270 and 650 essential genes in bacteria and about 900 essential genes in yeast Comparative analyses of the essential gene sets of different bacteria have revealed a significant set of genes that is essential in all bacteria studied so far. These genes can be referred to as obligatory essential genes. In contrast, facultative essential genes are essential in one organism but may be non-essential or even absent in other organisms, related or unrelated. It is obvious that the obligatory essential genes encode proteins that fulfil the most important housekeeping functions, such as the processing of the genetic information. Indeed, many proteins involved in DNA replication, transcription and translation are conserved and essential in all bacteria.Escherichia coli. RNase E organizes a protein complex, the RNA degradosome, but none of the other degradosome components nor the corresponding scaffold region of RNase E are essential. The reason for the essentiality of this protein has remained enigmatic Bacillus subtilis, five RNases are essential. Two of them, RNase P and RNase Z, are required for the maturation of tRNA E. coli RNase E Several RNases are essential in many bacteria. Most prominently, RNase E, the paradigm of a key enzyme for bacterial RNA degradation, is essential in B. subtilis, whereas they are non-essential in other related Gram-positive bacteria such as Staphylococcus aureus and Streptococcus pyogenesB. subtilis cell. For RNase III, the existence of suppressor mutations allowing the deletion of the rnc gene was reported, suggesting that RNase III has a protective function PLOS Genetics, Durand et al. txpA and yonT. These toxin genes are parts of a cryptic prophage, the skin element, and of the prophage SPβ, respectively. Once the txpA and yonT toxin genes are expressed, they can harm their own cell since the two mRNAs have the strongest ribosomal binding sites found in B. subtilis, suggesting that they are very efficiently translated to toxin protein ratA and anti-yonT that form hybrids with the txpA and yonT toxin mRNAs, respectively. Biochemical experiments presented by Durand et al. Interestingly, RNases III and Y are essential in txpA, which has been studied down to the molecular details by Durand et al. ratA RNA as compared to the txpA mRNA. This strong excess ensures that the txpA mRNA is always bound by the ratA RNA and thus targeted for degradation. Indeed, the absence of the ratA RNA results in a substantial stabilization of the txpA mRNA. This accumulation of txpA mRNA can only be tolerated if the mRNA cannot be translated due to a mutation of the start codon. The double-stranded txpA mRNA–ratA RNA hybrid molecule is cleaved in vitro by RNase III at multiple sites, resulting in the inactivation of the txpA message  is directly coupled to the presence of toxin systems in the genomes where the RNases are essential. However, due to the experimental investigation of only few laboratory strains and the genomic variability of bacteria with non-essential RNases III and Y , no clear statement about such a correlation is possible at the moment. From an evolutionary point of view, a next interesting question would address the reason for the persistence of several prophages and sequences derived from prophage in the B. subtilis genome even though these sequences do not provide any obvious selective advantage to the cell.The current study by Durand et al.


AbstractBefore the discovery of Treponema pallidum as the etiologic agent, the origins of syphilis have been the subject of several debates. Diverse therapeutic agents were employed in an attempt to cure the disease. Examining the milestones in the history of syphilis, the present article reviews the existing theories that tried to explain the origins of the disease, the approach in art, the cultural and the evolution of the treatments from the empiric means to the discovery of penicillin. Of the aforementioned bacteria, syphilis is the sole sexually transmitted treponemal disease, as the other conditions are transmitted via direct contact with an infected individual [3]. Syphilis is a sexually transmitted disease caused by Treponema Pallidum, a bacterium classified under Spirochaets phylum, Spirochaetales order, Spirochaetaceae family, but there are at least three more known species causing human treponemal diseases such as Treponema pertenue that causes yaws, Treponema carateum causing pinta and Treponema pallidum endemicum-responsible for bejel or endemic syphilis. The four members of the bacterial family cannot be differentiated with morphological, chemical or immunological methods [4-6]. From the very beginning, syphilis has been a stigmatized, disgraceful disease; each country whose population was affected by the infection blamed the neighboring (and sometimes enemy) countries for the outbreak. So, the inhabitants of today’s Italy, Germany and United Kingdom named syphilis ‘the French disease’, the French named it ‘the Neapolitan disease’, the Russians assigned the name of ‘Polish disease’, the Polish called it ‘the German disease’, The Danish, the Portuguese and the inhabitants of Northern Africa named it ‘the Spanish/Castilian disease’ and the Turks coined the term ‘Christian disease’. Moreover, in Northern India, the Muslims blamed the Hindu for the outbreak of the affliction. However, the Hindu blamed the Muslims and in the end everyone blamed the Europeans [7]. Therefore, the term ‘syphilis’ was introduced by Girolamo Fracastoro, a poet and medical personality in Verona. His work “Syphilis sive Morbus Gallicus” (1530) encompasses three books and presents a character named Syphilus, who was a shepherd leading the flocks of King Alcihtous, a character from Greek mythology. In Fracastoro’s tale, Syphilus, mad at Apollo for parching the trees and consuming the springs that fed the shepherd’s flocks, vowed not worship Apollo, but his King. Apollo gets offended and curses people with a hydious disease named syphilis, after the shepherd’s name. The affliction spread to the whole population, including King Alcithous. The nymph Ammerice counseled the inhabitants to offer Apollo further sacrifices, one of which was Syphilus himself, and also to sacrifice to Juno and Tellus, the latter offering the people the tree of Guaiac , a very used therapeutic medicine in times of Fracastoro [6-8]. In the 16th century, Jean Fernelius, a Parisian teacher whose work and interests were channeled into the mercury treatment of the condition, coined the term ‘lues venera’  in his treaty dedicated to the affliction [ Hypotheses on the origin of syphilis3]. According to this hypothesis, pinta occurred in Afro-Asian zone by the year 15.000 BC, having an animal reservoir. Yaws appeared as a consequence of the mutations in pinta around 10.000 BC and spread allover the world, except for the American continent which was isolated. The endemic syphilis emerged from jaws by the selection of several treponemas, as a consequence of climate changes (the appearance of the arid climate) around 7000 BC. Around 3000 BC the sexually transmitted syphilis emerged from endemic syphilis in South-Western Asia, due to lower temperatures of the post-glacial era and spread to Europe and the rest of the world. Initially it manifested as a mild disease, eventually aggravated and grew in virulence, suffering from several mutations, at the end of the 15th century . The pre-columbian hypothesis. The advocates of this hypothesis claim that not only syphilis was widely spread in both Old and New World, but also the other treponemal diseases. In Europe, most of these conditions were mistaken for leprosy . In this respect, yaws had a starting point in Central and Western Africa, spreading towards the Iberian Peninsula along with the capturing and selling of Africans as slaves, fifty years before Columbus’ voyage. Yaws, endemic in Africa for that time being, would have remained unmodified in countries with similar climate conditions as those in the origin countries, but would have evolved into endemic syphilis in countries with colder and drier climate in which personal hygiene was overlooked and disregarded and into venereal syphilis in those areas where inhabitants exhibited a civilized society and paid more attention to personal hygiene. The advocates of this hypothesis consider as irrelevant the theory according to which the 44 members of Christopher Columbus crew and the 10 indigenes brought along to Europe could be blamed for syphilis spreading in the whole Europe in just a few years . The unitarian hypothesis. Considered by some authors as a variant of the pre-Columbian hypothesis, it advocates that the treponemal diseases had always had a global distribution. According to this theory, both syphilis and non-venereal treponemal diseases are variants of the same infections and the clinical differences happen only because of geographic and climate variations and to the degree of cultural development of populations within disparate areas. Briefly, pinta, yaws, endemic syphilis and venereal syphilis are considered as adaptative responses of T. Pallidum to changes in the environment, cultural differences and contact between various populations . This theory is supported by documents belonging to Fernandez de Oviedo and Ruy Diaz de Isla, two physicians with Spanish origins who were present at the moment when Christopher Columbus returned from America. The former, sent by King Ferdinand of Spain in the New World, confirms that the disease he had encountered for the first time in Europe was familiar at that time to the indigenes who had already developed elaborated treatment methods. As for Ruy Diaz de Isla, the physician acknowledges syphilis as an “unknown disease, so far not seen and never described”, that had onset in Barcelona in 1493 and originated in Española Island (Spanish: Isla Española), a part of the Galápagos Islands. Ruy Diaz de Isla is also the one that states in a manuscript that Pinzon de Palos, the pilot of Columbus, and also other members of the crew already suffered from syphilis on their return from the New World .The Columbian hypothesis. This very popular hypothesis states that the navigators in Columbus fleet would have brought the affliction on their return form the New World in 1493 [13]. Ever since, numerous opposites of the Columbian hypothesis tried to prove the pre-existence of syphilis in the Old World, by finding evidence consisting of specific lesions on skeletal remains dated before Columbus journey in America. Radiocarbon dating along with several other modern means of dating, as well as more careful examining of such remains proved that all skeletal parts with specific luetic lesions dated not before, but after 1492. On the other hand, not all skeletal parts evoked by the opposites of Columbian hypothesis were actually exhibiting syphilis lesions. However, in 16 bone fragments the syphilis diagnosis could be certified and modern dating methods showed pre-Columbian origin. Harper et al. explained in an article published in 2011 that all these skeletons were located in coast areas from Europe, in which sea food represented an important part of the inhabitants’ diet. The sea food contained older carbon from the bottom of the ocean that interferes with carbon dating, therefore, after corrections and adequate adjustments have been made, it could be proven that the skeletons actually could not be dated before Columbus return to Europe, as previously considered .Unlike Europe, the American continent was able to present clear evidences supporting the existence of syphilis in pre-Columbian period. In this respect, skeletal lesions characteristic for the diagnosis of syphilis which has been identified in various areas plead for syphilis existence in these areas before Columbus discovered America. In addition, radiocarbon dating of the bone fragments showed an age of several thousand years .In 1489, Pope Innocent VIII was in conflict with Ferdinand I of Naples because the Italian King refused to pay his debts to him. As such the Pope offered the kingdom of Naples to Charles VIII who was the Affable of France, and to a certain extent was entitled to reign over this territory by his paternal grandmother, Mary of Anjou. In 1494 Ferdinand I died and his successor, Alfonso II announced his pretences to the Duchy of Milan, which was controlled for a long time by Ludovic Sforza. Ludovic Sforza, in order to avert the threat represented by Alfonso II, encouraged Charles the VIII th to accept the proposal made by Pope Innocent VIII and to conquer the kingdom of Naples. At the end of 1494, one year after the return of Columbus from his first expedition to America, Charles VIII entered Italy with an army of 25.000 men, mainly Flammand, Garcon, Swiss, Spanish and even Italian mercenaries. Initially his army entered Rome, where, for one month, it led a life of limitless depravity. In February 1495 the army of Charles VIIIth entered Naples without encountering any resistance, as the Neapolitan army was made out of no more than 1.000 Italian, German and Spanish mercenaries. The French army was well received by the locals hoping for a better life under French occupation, but later on changed their opinion as they witnessed great flourish in thefts, depravity and mess. The increasing power of Charles VIII leads to an alliance made by the Italian princes, including Ludovic Sforza, who defeats Charles VIII in the battle of Fornovo in July 1495. It is during this battle that the Italian physicians described for the first time a disease they have seen on French soldiers’ bodies, manifested as a generalized eruption consisting of pustules, more terrifying than leprosy and elephantiasis and that could be lethal and was transmitted through sexual intercourse. The disease proved to be syphilis, and the French army was soon blamed for spreading the affliction throughout Italy . Laura M. Gough, specialist in history of medicine, notes that the war conditions represented a favorable field for the first outbreak of syphilis. It has occurred during Italian invasion by the French armies, in a period of time when all great powers of Europe  wanted to gain control over the Apennine Peninsula. As both French and Italian armies were made out of mercenaries brought from the entire Europe, and as the wars lasted for 30 years –a sufficient interval not only for marriages between mercenaries and local females, but also for rape and prostitution-the disease has spread rapidly across Europe as the mercenaries returned to their homeland [17]. An important aspect to consider is also that syphilis was, at the very beginning, a disease of great severity, a more rapid spreading and atypical in its evolution as compared to nowadays syphilis, the fatal cases were not rare. The supporters of the Columbian hypothesis advocate that the extreme severity if the condition was mainly due to its novelty, as the population had no time to gain any immunity against the ailment as the venereal syphilis became endemic in Europe, certain strains of T. pallidum have selected, and the disease gained a milder course . The spread of the syphilis across Europe was frequently associated with the invasion of Naples by the French army. However, ever since fewer popular theories have been developed. In 1492 Ferdinand de Aragon and Isabel of Castilla issued the Edict of Expulsion of the Jews, stating that all the individuals of Hebrew origins refusing to convert to Catholicism were to be expulsed from Spain and the rest of its territories. On this occasion, approximately 200.000 Jews have left the country for Northern Africa and Southern Europe. On their way, a part of them temporarily settled at the gates of Rome; they were not allowed in Rome, and in the new Diaspora an outbreak occurred, killing 30000 individuals. Despite all efforts, the disease later identified as syphilis entered the city of Rome. Therefore, some of the chroniclers of the time blamed the Jews for the spread of syphilis in Europe; according to them, the disease was already present on Italian territory before Naples invasion by the French in 1495 [Syphilis in artistic representations19]. The oldest artistic representation of syphilis is considered one on a Peruvian jug dating back to VIth century, depicting a mother suffering from syphilis holding a child in her arms; the mother shows a saddle nose and superior incisive teeth with notches on their free margins. The piece belongs to a collection of jugs also encompassing two jugs illustrating leprosy and leishmaniasis . Albrecht Dürer, a German artist, depicts in woodcuts, for the first time in Europe, in 1496, the image of a mercenary whose skin bears sores of multiple chancres ; the Holy Child throws light spears to punish or cure the sufferers of syphilis, represented as individuals with multiples ulcers and sores. In another part of the woodcut depiction, King Maximilian I and his Knights are ready to receive the crown as reward for the edict he issued in 1495, stating that the disease was a consequence of blasphemy and sins, punishing the suffers of syphilis for their immoral behavior .A work of Sebastian Brandt depicting Saint Mary with the Child dates from the same year, 1496 . On the barrel lays written “pur un plaisir, mil douleur” , a proverb very used in those years. Another verbatim translation of this proverb is “for a night with Venus, a life with Mercury” [23].Another significant painting belongs to Jacques Laniet, in the XVIIth century, an illustration of a man in a fumigation stove, a fashionable method of treatment at that time , as well as his portrait painted by Rembrandt in the XVIIth century highlight in a clear manner the congenital syphilis sequelae of the Dutch painter, amongst which, frontal bossing and saddle nose [25]. Eduard Munch (1863-1944), an expressionist Norwegian painter presents in “The inheritance” the image of a young mother in tears holding a child with syphilis stigmata in her arms. The painting was initially named “the syphilitic child. According to some critics, Munch was ridiculing in his painting the iconic image of Madonna and the child. Pablo Picasso (1881-1973) was also impressed by this disease. His work “The Wages of Sin” is an allegory of venereal diseases and presents a sailor among prostitutes and a medical student holding a skull, as the symbol of death. This work represents actually a sketch of Les Demoiselles d’Avignon (1907), in which the artist gives up the male characters of the painting and illustrates solely the women who are no longer feminine and beautiful, but unattractive. Some critics believe that this painting points out the artist’s fear of venereal disease [ Famous historical figures diagnosed with or strongly suspected of syphilis14]. However, the rapid spreading proved not to avoid any geographical, racial or social barriers, affecting also great personalities along the history.The transmittance of sexual diseases has always been associated with promiscuity and vulnerable population groups [26-28]. Even the philosophers, who were usually considered superior minds, insensitive to women charms, also have suffered for syphilis. The most famous of them were Friedrich Nietzsche (1844-1900) and Arthur Schopehnauer (1788-1860). The last has contracted the disease while still a student, and in time, developed a tendency to misogyny [26].The writers were among the most affected category which was more likely, due to the promiscuous and bohemian life, to have the disease. Alphonse Daudet, Thomas Chatterton, Keats, James Boswell, Baudelaire, Heinrich Heine, Dostoievski and Oscar Wild are only a few examples of writers suffering from syphilis. Romanian poet Mihai Eminescu was diagnosed with syphilis too. He died in a mental institution at the age of 39 years .Famous Casanova is widely and iconically known for his excellent techniques of seduction. However, most of his sexual partners were actually prostitutes, and this may be the reason why he had gonorrhea four times, cancroids for five times, syphilis and genital herpes [26].It is also presumed that famous painters as Eduard Manet, Paul Gauguin, Vincent van Gogh and Goya, as well as composers like Ludwig van Beethoven, Robert Schumann and Franz Schubert suffered for syphilis . King Henry III and Charles V of France, Henry VIII and George IV of England, Paul I of Russia and Maximilian I of Holy Roman Empire are other examples.Furthermore, the monarchy was not spared of the implacable disease. One example is Tsar Ivan IV Vasilievici (known in history as Ivan the Terrible), Prince of Moscow (1530-1584) who contacted syphilis after the death of his wife. Some authors blame syphilis for his brutal behavior .Al Capone, the famous gangster who led a crime syndicate in the times of Prohibition in the United States supposedly died of neurosyphilis, as a consequence of aggravation of its manifestation after his imprisonment in Alcatraz [ The history behind the establishment of the etiology of syphilis6].From the very beginning numerous theories on the origin of syphilis existed, most of which linking initially syphilis and leprosy together. According to several fables of the early XVI th century, syphilis was the result of a sexual relation between a Spanish prostitute and a leper. The prostitute also infected the soldiers of Charles VIII. Paracelsus (1493-1541) considered that syphilis was the result of a sexual intercourse between a prostitute suffering from gonorrhea and a French leper. In compliance to other theories of the time, the disease might have been the outcome of the relationship of a prostitute having a uterine abscess with a leper or the result of poisoning the wine with blood coming from a leper .Sexual transmitted diseases were seen as a single disease for many centuries. The differentiation between gonorrhea, cancroids and syphilis as distinct maladies was achieved no earlier than XIXth century. In the beginning of XVIIIth century there were several doctors who treated syphilis and gonorrhea as separate entities. However, in 1767 John Hunter a famous physician of venereal diseases at that time (1728-1793) conducted an experiment consisting of an inoculation of the urethral secretion of a gonorrhea patient in the prepuce of a healthy patient, the last developing syphilis shortly afterwards. Consequently, his experiment proved that syphilis resulted from gonorrhea. What Hunter has missed out was that the patient from whom the urethral secretion was taken had both syphilis and gonorrhea. However his experiment, widely acknowledged in his époque, delayed the differential diagnosis of the two diseases with a few decades [7]. In 1831 Ricord has designed a larger study on syphilis and gonorrhoea and succeeded to show that the last occurs only after contact with gonorrohea patients, whilst the former –only after contact with syphilis patients .It was not earlier than 1905 that Schaudinn (1871-1906) and Hoffman (1868 – 1959) have discovered the etiologic agent of syphilis, whom they have named Spirochaeta pallida, on various syhilis lesions, proving its existence in both fresh and Giemsa coloured specimens. It was them who changed the name of the bacterium subsequently to Treponema pallidum . Their discoveries had a very important role in detecting the disease in patients who were suspected of syphilis, as well as in other healthy individuals, and in monitoring syphilis response to treatment. In 1906 Landsteiner introduced the use of the dark-field microscopy method for the detection of the spirochete of syphilis. In 1910 the German bacteriologist August Wasserman (1866-1925) came with the first serologic test for syphilis and in 1949 Nelson and Mayer have conceived Treponema pallidum immobilization test (TPI), the first specific test for T. pallidum [Syphilis treatments along the history29]. Taking into consideration that the disease was associated with the discovery of the American continent, numerous treatments included plants brought from the New World, such as the guaiac tree , known also as sasafras or willow , which led to the widest recognition at the time . These plants acted as purgative agents, lead to sudoration, diarrhea and the increase in urinary debt and were believed to be “blood cleansers” [7]. One of the main supporters of the guaiac tree utilisation in the treatment of syphilis, and in the same time an ardupus opponent of mercury treatment, was Ulrich von Hutten (1488-1523), a former priest who described in a detail the manifestations of the disease as well the simptoms of mercury intoxication, based on his own experience as a sufferrer from the disease . From the guaiac tree a decoction was made, the resulted potion was boiled and the patient was assumed to consume the mixture daily for 30 days. Before drinking the potion, the patient was covered in blankets in order to induce perspiration, and a mild purgative was also administered [15].Initially, the treatment of syphilis included less efficient methods that were accompanied by pain and multiple adverse reactions . There were several methods of administering mercury. Thus, in a mixture with grease, mercury was administered topically, leading to ulcerations. Barbarossa pill, named after the Turk admiral who gave the pill to his soldiers and was affected by the malady, contained a mixture of mercury and perfume essence and fruit flavours [7]. Mercurous chloride  was a white salt able to be administered orally, topically or by injections. The metallic form of mercury was administered also under the form of therapeutic fumigation. Patients seemed to find the adverse reactions of the treatment acceptable, however, the treatment lead to systemic intoxication (hidrargirism) and pneumonia [33].Paracelus (1493-1541) was one of the first supporters of the mercury treatment. Mercury was used in Arabic medicine in the treatment of several dermatomes as well as leprosy, and succeeded to gain rapidly an important place in medical field at that time. Mercury is a potent diuretic that also leads to excessive salivation when administered in toxic doses. At the time, is was considered that the “virus” was eliminated from the body through sweat, salivation and diuresis [33].Bismuth salts were introduced in syphilis treatments in 1884. These compounds were less toxic than mercury, in the same time bearing a stronger bactericidal effect that the former, consequently, becoming the cardinal heavy metal employed in syphilis treatment . The safer novel drug that superseded the more toxic and less water-soluble salvarsan as a treatment for syphilis was Neosalvarsan, also an arsenic compound. Both Salvarsand and Neosalvarsan were replaced in the treatment of syphilis by Penicillin, after 1940.German scientist Paul Ehrlich (1854-1915) received Nobel Prize in Physiology and Medicine in 1908 for his discovery of arsphenamine . The scientist discovered the compound that acted like an antibiotic by accident, while working on finding a cure for Trypanosoma brucei. Ehrlich’s desire was to discover a “magical bullet”- a drug able to specifically bind to a bacterium and kill it, without affecting human cells. Salvarsan was also denominated as “Compound 606”, as it was discovered after 606 failed experiments  includes malaria in the treatment of syphilis. Malaria induced fever paroxysms able to be controlled, as quinine had already been discovered. Jauregg injected patients suffering from malaria with blood presenting Plasmodium vivax. The patients exhibited fever paroxysms lasting for approximately 6 hours and core temperature returning to normal values; quinine was injected after 3-4 cycles on a 2 day period, in order to treat malaria. In 1927 Jauregg received Nobel Prize for Physiology and Medicine for his discovery . Nowadays, worldwide, prevention and treatment programs control syphilis spreading.In 1928, Alexander Fleming (1881-1955) discovered penicilin and from 1943, it became the main treatment of syphilis [Treponema pallidum infection in men not only provoked a disease that represented a threat to humans for many centuries, but it also had a tumultuous history. From examining it, one could learn how easy was to place stigma not only on individuals affected by the disease, but on entire nations, as countries were blamed along the history for the spread of the disease. Throughout the centuries, syphilis has affected individuals of various origins, from monarchs, painters and philosophers to low income people, mainly due to promiscuity. Various treatments to cure the disease were tried along the centuries; nowadays, penicillin and prevention programs control the disease.