Information about the feasibility, barriers and facilitators of antimicrobial stewardship (AMS) in residential aged care facilities (RACFs) has been scant. Exploring the prevailing perceptions and attitudes of key healthcare providers towards antibiotic prescribing behaviour, antibiotic resistance and AMS in the RACF setting is imperative to guide AMS interventions.Semi-structured interviews and focus groups were conducted with key RACF healthcare providers until saturation of themes occurred. Participants were recruited using purposive and snowball sampling. The framework approach was applied for data analysis.A total of 40 nurses, 15 general practitioners (GPs) and 6 pharmacists from 12 RACFs were recruited. Five major themes emerged; perceptions of current antibiotic prescribing behaviour, perceptions of antibiotic resistance, attitude towards and understanding of AMS, perceived barriers to and facilitators of AMS implementation, and feasible AMS interventions. A higher proportion of GPs and pharmacists compared with nurses felt there was over-prescribing of antibiotics in the RACF setting. Antibiotic resistance was generally perceived as an issue for infection control rather than impacting clinical decisions. All key stakeholders were supportive of AMS implementation in RACFs; however, they recognized barriers related to workload and logistical issues. A range of practical AMS interventions were identified, with nursing-based education, aged-care specific antibiotic guidelines and regular antibiotic surveillance deemed most useful and feasible.Areas of antibiotic over-prescribing have been identified from different healthcare providers’ perspectives. However, concern about the clinical impact of antibiotic resistance was generally lacking. Importantly, information gathered about feasibility, barriers and facilitators of various AMS interventions will provide important insights to guide development of AMS programs in the RACF setting.The online version of this article (doi:10.1186/1471-2334-14-410) contains supplementary material, which is available to authorized users. There is increasing evidence that the elderly population in residential aged care facilities (RACFs) serves as an important reservoir for multidrug-resistant (MDR) organisms , 2, withEssentially, the need for AMS and the potential areas for AMS interventions are reliant upon existing antibiotic use and resistance patterns. For example, a study in Australian RACFs has shown less frequent use of broad-spectrum antibiotics such as fluoroquinolones  comparedInternational guidelines for infection control and prevention have strongly recommended initiation of AMS programs in the RACF setting ; howeverThis is part of a larger study exploring key healthcare providers’ views about improving antibiotic use in the RACF setting. The study targeted primarily high-level care RACFs (i.e. nursing homes) affiliated with four major public healthcare service networks within metropolitan and regional Victoria, Australia. These residential care facilities deliver 24-hour nursing care to elderly residents requiring significant assistance in their activities of daily living. There was no institutional policy for antibiotic prescribing in any of the RACFs; however, intravenous antibiotic therapy when required is normally delivered via specialized support from hospitals.Three major groups of healthcare providers servicing the participating RACFs were invited to participate, namely general practitioners (GPs), nurses and pharmacists. At these RACFs, the medical care is provided by off-site GPs  from different practices, who visit residents periodically or upon request. There are significant roles for nursing staff in daily care of residents, including ringing GPs to request medical assessment. Prescription medicines, including antibiotics, require an order from the GPs and are supplied by external community pharmacies. Medication review for individual residents [known as Residential Medication Management Review (RMMR)] is normally performed on an annual basis by consultant pharmacists, however this does not involve audit of short-term antibiotic use.Institutional ethics approvals from the human research ethics committees of all participating healthcare service networks and Monash University were obtained prior to participant recruitment. A combination of purposive and snowball sampling strategies were used for recruitment of different healthcare providers . The afoNursing staff in different clinical positions  were involved in either one-on-one interviews or focus groups. All NUMs and RNs were involved in daily care of residents, whilst the executive nursing staff were responsible at the policy-making level for quality improvement of resident care. Face-to-face or phone interviews were conducted with the GPs and pharmacists, depending on their preference. We used several triangulation strategies; we sought information from different stakeholders’ perspectives (i.e. data triangulation), performed onsite observation on the organizational workflow and documentations related to antibiotic prescribing , and explored views of participants from RACFs in different locations .All interviews were conducted using a semi-structured interview guide, which was tailored to different healthcare providers , and 21 registered nurses (RNs)], 15 GPs and six pharmacists consented to participate in the study. The majority of participants were interviewed individually, with 15 RNs participating in three focus groups (range 4–6 RNs per focus group). All except four interviews were conducted face-to-face with participants. The demographic characteristics of the participants are described in Table There were mixed views about existing antibiotic prescribing behavior Table . SeveralThere were also mixed perceptions about antibiotic resistance Table . SeveralThe majority of participating nursing staff were unaware of the concept of AMS. In comparison, more GPs and pharmacists were aware of AMS, although they generally felt that AMS was relatively new in the RACF setting. AMS refers to integrated activities that help to optimize antibiotic therapy, ensuring the best clinical outcomes whilst minimizing the risk for the emergence of antimicrobial resistance. When this concept of AMS was explained, in general, all key stakeholders were supportive of AMS programs in RACFs. Amongst GPs, the main value of AMS was thought to be in promoting evidence-based practices for antibiotic prescribing in this setting Table , Q1. AllA number of perceived barriers and facilitators in relation to implementation of AMS interventions were raised. From the GPs’ perspective, several raised concerns about the potential for doctor autonomy to hinder acceptance of institutional policies and guidelines. Heterogeneity in prescribing practices amongst GPs from different practices pose another barrier, thus having fewer GPs with greater patient loads working in each facility would promote more consistent prescribing practices Table , Q7-Q8. Three major areas of AMS interventions emerged as potentially useful and practical in the RACF setting Table . The mosTo our knowledge, this is the first study exploring the perceptions and attitudes of a range of healthcare providers towards antibiotic prescribing behaviour, antibiotic resistance, and AMS implementation in the RACF setting. A greater proportion of GPs and pharmacists than nursing staff felt that there was over-prescribing of antibiotics, suggesting a lack of awareness amongst nurses about potential antibiotic misuse among this population. Antibiotic resistance and the emergence of MDR organisms were perceived as more of a concern from the infection control perspective as opposed to impacting empiric antibiotic selections. Additionally, this study has highlighted the prevailing attitudes amongst key healthcare providers that AMS interventions were needed and deemed useful in the RACF setting. A number of perceived barriers to AMS programs were identified, in particular, nursing staff workload and the logistical issues of off-site GPs and pharmacists. A range of potential AMS interventions have been suggested to provide insights into feasible AMS model for the RACF setting.et al. has explored the views of the physicians and nurses about antibiotic prescribing in Canadian RACFs but it focused specifically on treatment for asymptomatic bacteriuria, reporting that education about asymptomatic bacteriuria was viewed as an important priority by both physicians and nurses [Published data describing the key stakeholders’ views of antibiotic prescribing and antibiotic resistance have mainly focused on the general practice setting, with limited information from the RACF setting , 19. A sd nurses . In addid nurses , 8.Previous studies have reported that increasing the awareness about antibiotic resistance would potentially influence GPs’ decisions in selecting antibiotics, underlining the importance of knowledge about MDR organisms in assisting clinical decisions , 21, 22.AMS interventions in the RACF setting have been few despite mounting evidence of inappropriate antibiotic prescribing among this elderly population , 24. ExiThis study has predominantly involved high-level care hospital-affiliated RACFs. There may be differences in antibiotic prescribing behaviour in comparison to low-level care or private RACFs, and thus this study could be replicated more widely to other RACF setting for further exploration. Given the differences in long-term healthcare delivery models between different countries , the finIn summary, AMS interventions have been deemed applicable and useful by the key stakeholder groups involved in the provision of healthcare in RACFs. Potential barriers and facilitators for AMS interventions have been highlighted, providing important information to guide allocation of future AMS resources. More importantly, the major areas of AMS deemed most needed and practical in the RACF setting have been identified to guide the development of a feasible AMS model.Caroline Marshall and David CM Kong are senior authors.Additional file 1: Semi-structured interview guide for general practitioners.(PDF 216 KB)Additional file 2: Semi-structured interview guide for nursing staff.(PDF 209 KB)Additional file 3: Semi-structured interview guide for pharmacists.(PDF 155 KB)


The causes of severe morbidity in health facilities implementing Antiretroviral Treatment (ART) programmes are poorly documented in sub-Saharan Africa. We aimed to describe severe morbidity among HIV-infected patients after ART initiation, based on data from an active surveillance system established within a network of specialized care facilities in West African cities.Within the International epidemiological Database to Evaluate AIDS (IeDEA) - West Africa collaboration, we conducted a prospective, multicenter data collection that involved two facilities in Abidjan, Côte d’Ivoire and one in Cotonou, Benin. Among HIV-infected adults receiving ART, events were recorded using a standardized form. A simple case-definition of severe morbidity  was used at any patient contact point. Then a physician confirmed and classified the event as WHO stage 3 or 4 according to the WHO clinical classification or as degree 3 or 4 of the ANRS scale.From December 2009 to December 2011, 978 adults  presented with 1449 severe events. The main diagnoses were: non-AIDS-defining infections (33%), AIDS-defining illnesses (33%), suspected adverse drug reactions (7%), other illnesses (4%) and syndromic diagnoses (16%). The most common specific diagnoses were: malaria (25%), pneumonia (13%) and tuberculosis (8%). The diagnoses were reported as syndromic in one out of five events recorded during this study.This study highlights the ongoing importance of conventional infectious diseases among severe morbid events occurring in patients on ART in ambulatory HIV care facilities in West Africa. Meanwhile, additional studies are needed due to the undiagnosed aspect of severe morbidity in substantial proportion.The online version of this article (doi:10.1186/s12879-015-0910-3) contains supplementary material, which is available to authorized users. In December 2010, an estimated 5,640,000 Human Immunodeficiency Virus (HIV)-infected people were receiving Antiretroviral Treatment (ART) in Sub-Saharan Africa (SSA), which represented a 20% increase in ART coverage compared to a year earlier ,4. This According to the available literature, severe morbidity is common during the first months after ART initiation and remains high thereafter. Specifically, this severe morbidity is characterized by a high incidence of invasive bacterial diseases and tuberculosis ,7. AmongAvailable data on morbidity mainly come from research settings with advanced diagnostic capacities ,4,7. In To fill this lack of data, the International epidemiological Database to Evaluate AIDS (IeDEA) was implemented in the West African region. It was launched to collect and harmonize data from multiple HIV⁄AIDS cohorts from industrialized and resource-limited countries. The IeDEA collaboration aims to address research questions in the field of HIV⁄AIDS care and treatment, especially in low-income countries, where most ART scale-up take place. The IeDEA West Africa is a prospective and observational multi-cohort collaboration established in 2006. It includes data from 8 countries with 15 centers for adult-patients infected with HIV on ART in Benin, Burkina Faso, Côte d’Ivoire, Guinea-Bissau, Mali, Nigeria, Senegal and Togo ,19.This collaboration could help address questions that have been poorly documented in this context, such as morbidity. Because of rapid changes in therapeutic strategies, a minimal morbidity surveillance in HIV care facilities of SSA is required -22.The objective of our study was, to describe severe morbidity occurring among HIV-infected adult patients, receiving ART based on surveillance data collected prospectively under routine circumstances in HIV/AIDS care facilities in SSA.The current study was conducted between December 2009 and December 2011, within the IeDEA network in West Africa ,18  or Karnofsky index < 70% in any patient on ART. Any patient with at least one of these signs was included in this study. The centers involved in this study were exclusively outpatient clinics. Therefore, deaths were reported by the patients’ siblings during telephone reminders made by the social workers. A standardized data collection form was used to record these events..Physicians and other Health care workers (HCWs)  from participating centers were trained to identify severe morbidity based on the four signs included in the definition. HCWs other than physicians, initiate a form by filling in the survey form with the sign(s) of severe morbidity experienced by the patients and their identification numbers. Physicians were responsible for completing the forms with clinical examination results. In case the physician noticed signs of severe morbidity by himself, he could initiate and fill the entire record. Each diagnosis was classified by the physician according to the World Health Organization (WHO) clinical stage classification  (Table The main diagnoses reported among these 1449 severe events were: non-AIDS-defining infection 32.6%), AIDS-defining illness (33.2%) with 23.3% in WHO stage 3 and 9.5% in WHO stage 4, suspected adverse drug reactions (7.1%), and finally non-infectious diseases and non-AIDS-defining illnesses (4.8%). In 16% of the cases, the diagnosis remained syndromic  the definition of reported signs of severe morbidity adapted to all staff and all care facilities and (ii) the definition and use of a simple data form. This organization involving all staff  and all services  had the advantage of being reproducible and affordable due to its integration within the existing system.Regarding the WHO clinical stage 3 or 4 events, our results are consistent with those of previous studies . DespiteThe World Health Organization recently recommended to supply centers with rapid diagnostic tests for malaria . This de. This result was also mentioned in previous studies in SSA [We also found that pneumonia as well as tuberculosis were the most common frequent AIDS-defining event while on ARTs in SSA ,33, confs in SSA ,35.. Among the challenges health care services deal with in Africa, underdeveloped infrastructures and weak healthcare systems are the most predominant [Improvements have been made in the health care system in Africa more particularly in SSA. However, progress remains to be madedominant . As regadominant -39. One dominant ,41. Freedominant ,43 will The main strengths of this study are its prospective and multicenter design. First, a prospective study because for each patient’s symptom, all the information were documented according to a standardized procedure that minimized the risk of information bias. Then, a multicenter study, as it involved a large and unselected population of HIV-infected patients in care in the West African region. The use of a standardized data collection form contributed to ensure accuracy in data collection and limitation of variations within and among facilities. The involvement of almost all health care professionals at all levels and from all services was also instrumental in collecting the maximum number of events occurring during the study period.Our study also had some limitations. The severity of a morbid event can be a reason for treatment discontinuation in HIV care centers. Thus, the methodology of our study, which consisted in capturing information about patients with severe morbidities at the three study facilities, is a limitation. Some patients suffering from severe events with restricted mobility and those with severe events lacking financial resources to travel to the facilities may have been excluded from this study, therefore leading to a selection bias. Another limitation is that specific signs of interest were identified a priori before taking the event into account. Some events may have been severe but without any of these predefined signs, thus leading to their inappropriate exclusion. In addition, due to the lack of resources, some patients might have restricted access to definitive diagnoses. Besides, some hospitalizations might have not been reported to us. All these biases may have contributed to an underestimation of severe morbidity.In order to carry out an efficient intervention and deliver a more adequate service in a context of general weak health systems, further studies with access to diagnostic tests are needed to confirm the patterns observed in terms of syndromic diagnoses. Such studies could contribute to promote funding and the routine use of general laboratory tests to diagnose morbid events in resource-limited settings.Standardized and routine collection of severe morbidity data is possible in HIV/AIDS care facilities under routine circumstances. This study highlights the ongoing importance of common infectious diseases among severe morbid events occurring in patients on ART in national HIV care facilities in West Africa. Meanwhile, additional studies are needed due to the undiagnosed aspect of severe morbidity in substantial proportion.


A part of the ocular adnexal EMZLs were accompanied with IgG4-positive cells. Significantly, most IgG4-positive ocular adnexal EMZLs occurred in the lacrimal gland, and can be related with a more frequent treatment failure.This study aims to analyze clinical and pathologicalcharacteristics of ocular adnexal extranodal marginal zone B-celllymphoma (EMZL) accompanying IgG4-positive cells. Fifty patients with a diagnosis of primary non-conjunctival ocular adnexal EMZL were enrolled in this study. The number of IgG4-positive cells and the ratio of IgG/IgG4 were evaluated by immunohistochemistry in the biopsy specimens. The patients were divided into two groups based on the absolute number and the ratio of IgG4-positive cells (IgG4-posivite vs IgG4-negative groups). The demographic data, clinical staging at diagnosis, histopathological characteristics, and response to initial treatment were comparatively analyzed between the 2 groups. Five (10%) of 50 patients were defined as IgG4-positive group, and all the cases showed characteristic histological features such as extensive plasma cell infiltration and dense fibrosis. Most of these patients (4 of 5 patients) had lymphoma of the lacrimal gland. The patients from the IgG4-positive group showed a lower response rate to initial treatment (87.5 vs 33%,  Recognition of IgG4-related sclerosing disease is clinically important because it can be mistaken for malignancy owing to its tumefactive nature. Essentially, it is non-neoplastic disease that is histologically characterized by dense sclerosis and by the presence of abundant IgG4-positive plasma cells –3. IndivSeveral studies have investigated a potential relationship between IgG4-related disease and extranodal marginal zone B-cell lymphoma (EMZL) –10. CheuTherefore, the present study was designed to establish clinical and pathological characteristics of ocular adnexal EMZL accompanying IgG4-positive cells.We surveyed our database for patients with a diagnosis of ocular adnexal EMZL, confirmed by a surgical biopsy at the Department of Ophthalmology of Seoul National University, Seoul National University Boramae Hospital, and Seoul National University Bundang Hospital between 2000 and 2010. Patients with solely conjunctival lymphoma or secondary lymphoma were excluded from the study. Clinical data were obtained from medical records, and pretreatment biopsy specimens were collected from all patients. The written informed consent was waived due to the study’s retrospective nature. This study followed the tenets of Helsinki Declaration, and the data were analyzed anonymously. The protocol for this study was approved by the institutional review board of Seoul National University Boramae Hospital (16-2013-19).11 Each 4-μm tissue section was incubated with anti-IgG  and anti-IgG4 , using a BenchMark automatic immunostaining device  with standard heat-induced antigen retrieval.Serial 4-μm-thick sections were sliced from formalin-fixed and paraffin-embedded tissue blocks, and subjected to haematoxylin and eosin (H&E) staining and immunohistochemistry. Three haematopathologists  reviewed all H&E and immunohistochemistry slides and achieve a consensus. PCR-based gene rearrangement study for immunoglobulin heavy chain was performed for a few selected cases. Immunohistochemical staining of paraffin-embedded tissue sections was performed as previously described.2. Images were taken by a DP72 digital camera mounted on a BX51 microscope . The patients with IgG4/IgG cell ratio > 40% and IgG4-positive plasma cell density ≥ 50/HPF were classified as IgG4-positive ocular adnexal EMZL patients (IgG4-positive group). The patients who did not meet the requirements were considered as IgG4-negative ocular adnexal EMZL (IgG4-negative group) [The extent of IgG4-positive plasma cell infiltration was evaluated either by the absolute number of IgG4-positive cells or by the ratio of IgG4 to IgG-positive cells per high-power field (HPF), defined as a region with the highest density of immunostained cells, covering an area of 0.14 mmChlamydia psittaci was tested in 32 samples of ocular adnexal EMZL via touchdown enzyme time-release PCR (TETR-PCR) as previously described [Cp were 5'-CCC AAG GTG AGG CTG ATG AC-3' (forward) and 5'-CAA ACC GTC CTA AGA CAG TTA-3' (reverse). Ta-CLONED Cp DNA was used as a positive control. The annealing temperature was 54°C. The amplified DNA fragments were electrophoresed on 2% agarose gels and were visualized after staining with ethidium bromide.Presence of escribed . GenomicDisease stage was defined according to the American Joint Committee on Cancer (AJCC) classification . The resp < 0.05 was considered to be statistically significant. All the statistical analyses were performed using the SPSS software .Progression-free survival was calculated from the date of first-line treatment to the date of disease progression, death, or the last follow-up visit. The Fisher’s exact test was used to compare possible associations between the categorical variables. For the continuous variables, the Mann-Whitney U test was used. For all the tests, Data from 143 patients with ocular adnexal EMZL were retrieved from medical records by computerized search. Among them, 88 patients with conjunctival lymphoma and 5 patients without available tissue-blocks were excluded, and finally 50 patients were enrolled in this study. Ten of fifty patients were overlapped with previous research conducted at Seoul National University Hospital [p = 0.02). In the IgG4-positive group, most of the patients (4 of 5 patients) had lacrimal gland lymphoma (T2b), whereas most of the patients in the IgG4-negative group (25 of 41 patients) showed lymphoma occupying the posterior orbit (T2c). Although no patient showed lymph node metastasis, 3 patients in the IgG4-negative group presented distant metastasis at diagnosis. Cp DNA was observed in 16 (50%) of 32 patients with available samples. Cp-positivity was 75.0% (3 of 4) in IgG4-positive group and 46% (13 of 28) in IgG4-negative group. However, there was no statistically significant difference between two groups (p = 0.59).The demographic data including age, gender, and clinical stage at diagnosis were collected and compared between the IgG4-positive and IgG4-negative groups . Age, gep = 0.03). The IgG4-negative group showed prolonged progression-free survival compared with the IgG4-positive group, although the results did not reach statistical significance .Forty-three patients (3 patients in the IgG4-positive group and 40 patients in the IgG4-negative group) were followed up for more than 6 months and were therefore eligible for the treatment outcome analysis . Front-lIgG4-related disease is a recently proposed entity with several unique clinicopathological features, such as enlargement of affected organs, elevated serum IgG4 level, and infiltration with IgG4-positive plasma cells ,3,15. IgRecently, Kubota et al analyzed 114 biopsy samples of ocular adnexal EMZLs, and reported IgG4-positive plasma cell infiltration in 9% of cases, similar to the results of the present study (10%) . HoweverIgG4-positive group showed lacrimal gland preponderance either unilaterally or bilaterally , whereas the IgG4-negative group revealed an even distribution of the primary site throughout the orbital tissues . Our resA link between ocular adnexal IgG4-related disease and EMZL has been proposed ,18. EMZLCp has also been reported [Cp was known to have geographical difference, and some studies from Korea reported relatively high prevalence over 70% [Cp in this study, showing similar incidence reported by other Korean researchers. Although Cp-positivity was slightly higher (75%) in IgG4-positive group, than IgG4-negative group (46%), the difference was not fully significant because of the small number of IgG4-positive cases. One possible suggestion is that Cp infection is just prevalent in longstanding inflammatory lesions of ocular area in our country, not directly associated with recruitment of IgG4+ cells. Further investigations will be needed to clarify this issue.Regarding pathogenesis of ocular adnexal EMZL, several genetic abnormalities including chromosomal aneuploidy and gene translocations affecting activation of NF-Kb pathway have been reported . Unlike reported ,25. The over 70% ,26,27. WThere are no established prognostic indicators for the treatment of ocular adnexal EMZL, although CD5+, trisomy 18, and high Ki-67 have been shown to correlate with a poor outcome in some patients –30. ReceBecause of its retrospective nature, there is no data about serum IgG4/IgG, which is one of the main limitations of this study. Although serum IgG4 level elevation is helpful in diagnosing IgG4-related disease, it is not a specific diagnostic marker. Rather than serum IgG4 concentration, histopathological findings, such as dense lymphoplasmacytic infiltration and storiform fibrosis, are more essential for diagnosis ,33. ReceIn conclusion, some nonconjunctival ocular adnexal EMZLs were associated with IgG4-positive sclerosing disease. The patients in the IgG4-positive group showed masses predominantly in the lacrimal gland and had a poor response to initial therapy. Although the results from this study were limited to be generalized because of the small number of cases, our data suggest that ocular adnexal EMZL accompanying IgG4-positive cells has unique clinical features discriminated with those without IgG4-positive cells. Further large-scaled studies will be needed to confirm these findings.


Antibiotics are an essential tool to treat bacterial infections, but inappropriate use of these drugs has promoted antibiotic resistance and compromised their effectiveness. Health-care providers prescribed an estimated 258 million courses of antibiotics to outpatients in the United States in 2010 (In acute care hospitals, each year approximately half of all patients admitted receive an antibiotic, and nearly 50% of antimicrobial use in hospitals is unnecessary or inappropriate . Drug-rehttp://www.cdc.gov/getsmart.November 18–24, 2013, is Get Smart About Antibiotics Week, an annual observance to coordinate the work of CDC’s Get Smart: Know When Antibiotics Work and Get Smart for Healthcare programs, state-based appropriate antibiotic use campaigns, nonprofit partners, and for-profit partners during a week-long observance on antibiotic resistance and the importance of appropriate antibiotic use. Information on scheduled activities and how to participate during the observance week is available at


Dosing of antibiotics in critically ill patients is a significant challenge. The increasing number of patients undergoing extracorporeal membrane oxygenation further complicates the issue due to inflammatory activation and to drug sequestration in the circuit. Since patients receiving extracorporeal membrane oxygenation commonly face severe infections, appropriate antibiotic selection and correct dosing is of paramount importance to improve survival. Therapeutic drug monitoring (whenever available) or population pharmacokinetics, based on readily available clinical and laboratory data, should help tailor antibiotic dosing to the individual patient. Critical Care, on behalf of the Antibiotic, Sedative and Analgesic Pharmacokinetics during Extracorporeal Membrane Oxygenation study investigators, Shekar and colleagues assessed meropenem pharmacokinetics (PK) in patients receiving extracorporeal membrane oxygenation (ECMO), with or without continuous renal replacement therapy (CRRT) [In a recent edition of y (CRRT) .Patients on ECMO commonly have infections, reaching rates of more than 15 per 1,000 ECMO days according to data pooled from the Extracorporeal Life Support Organization Registry , and theHigh antibiotic doses are usually needed to achieve therapeutic concentrations early in the infection course. This has been shown for β-lactams , vancomyAntibiotics are usually prescribed in a traditional pattern, taking into account only the existence of renal or liver dysfunction and considering the susceptibility pattern of the microorganism. Moreover, the antibiotic dose is usually maintained throughout the treatment course, although significant PK changes occur from the resuscitation phase to the recovery phase .Ideally, individualized dosing strategies should account for the altered PK and pathogen susceptibility in each patient. In order to achieve this goal it is necessary to understand the full impact of therapeutic interventions and patient characteristics on antibiotic PK.Drug dosing in critically ill patients is especially challenging due to the frequent and hard to predict changes in PK, especially the increased volume of distribution and clearance variation , secondaECMO is among the most rapidly increasing support techniques in intensive care , and itsIn their study, Shekar and colleagues showed that the volume of distribution of meropenem is increased in patients undergoing ECMO (with or without CRRT) and consequently high initial antibiotic doses were commonly needed . On the Therapeutic drug monitoring has been shown to facilitate the achievement of adequate antibiotic concentration . UnfortuThe study by Shekar and colleagues is part of a larger multicentric effort aimed at the determination of PK of multiple drugs, namely sedatives, opioids, antibiotics and antifungals, in ECMO patients . This stIn conclusion, we can clearly no longer rely on the ‘one size fits all’ paradigm when choosing the antibiotic dose. Knowledge of antibiotic PK, patient status and immune function, bacteria virulence, susceptibility and inoculum, as well as the PK impact of different therapies, should all contribute to dose selection.


Objective To determine whether the incidence of pneumonia, peritonsillar abscess, mastoiditis, empyema, meningitis, intracranial abscess, and Lemierre’s syndrome is higher in general practices that prescribe fewer antibiotics for self limiting respiratory tract infections (RTIs).Design Cohort study.Setting 610 UK general practices from the UK Clinical Practice Research Datalink.Participants Registered patients with 45.5 million person years of follow-up from 2005 to 2014.Exposures Standardised proportion of RTI consultations with antibiotics prescribed for each general practice, and rate of antibiotic prescriptions for RTIs per 1000 registered patients.Main outcome measures Incidence of pneumonia, peritonsillar abscess, mastoiditis, empyema, meningitis, intracranial abscess, and Lemierre’s syndrome, adjusting for age group, sex, region, deprivation fifth, RTI consultation rate, and general practice.Results From 2005 to 2014 the proportion of RTI consultations with antibiotics prescribed decreased from 53.9% to 50.5% in men and from 54.5% to 51.5% in women. From 2005 to 2014, new episodes of meningitis, mastoiditis, and peritonsillar abscess decreased annually by 5.3%, 4.6%, and 1.0%, respectively, whereas new episodes of pneumonia increased by 0.4%. Age and sex standardised incidences for pneumonia and peritonsillar abscess were higher for practices in the lowest fourth of antibiotic prescribing compared with the highest fourth. The adjusted relative risk increases for a 10% reduction in antibiotic prescribing were 12.8%  for pneumonia and 9.9%  for peritonsillar abscess. If a general practice with an average list size of 7000 patients reduces the proportion of RTI consultations with antibiotics prescribed by 10%, then it might observe 1.1  more cases of pneumonia each year and 0.9 (0.5 to 1.3) more cases of peritonsillar abscess each decade. Mastoiditis, empyema, meningitis, intracranial abscess, and Lemierre’s syndrome were similar in frequency at low prescribing and high prescribing practices.Conclusions General practices that adopt a policy to reduce antibiotic prescribing for RTIs might expect a slight increase in the incidence of treatable pneumonia and peritonsillar abscess. No increase is likely in mastoiditis, empyema, bacterial meningitis, intracranial abscess, or Lemierre’s syndrome. Even a substantial reduction in antibiotic prescribing was predicted to be associated with only a small increase in numbers of cases observed overall, but caution might be required in subgroups at higher risk of pneumonia. Concern is growing that the widespread and sometimes unnecessary use of antibiotics is leading to the development of antimicrobial drug resistance and potentially to infections caused by resistant organisms that are difficult to treat.Fusobacterium necrophorum infection, is a rare complication of sore throat,F necrophorum might be frequently detectable in patients with symptoms of sore throat.Clinical concern that reducing antibiotic use might increase the risk of complications following RTIs might be realistic. Evidence from clinical trials suggests that antibiotics may reduce the risk of suppurative complications of RTIs,These observations raise important questions for a policy to reduce antibiotic prescribing for RTIs in primary care: Is there a safe level of antibiotic prescribing for RTIs? What target can general practices safely adopt in reducing the proportion of consultations for RTIs with antibiotics prescribed? Is there a threshold for antibiotic prescribing below which complications may increase? We evaluated the safety of a policy to reduce antibiotic prescribing for RTIs in primary care and the incidence of pneumonia, peritonsillar abscess, mastoiditis, empyema, meningitis, intracranial abscess, and Lemierre’s syndrome. We determined whether these complications were more common in general practices that prescribe fewer antibiotics for self limiting RTIs than higher prescribing practices. We aimed to use this information to quantify the potential clinical and public health impact of changes in antibiotic prescribing practice.The data source for the study was the UK Clinical Practice Research Datalink (CPRD).We evaluated the number of first episodes of infective complications in the entire registered population of CPRD from 2005 to 2014. Such complications were defined using Read medical codes recorded in participants’ electronic health records. The Read code classification represents a terminology used to code primary care electronic health records in the UK.We estimated age standardised measures for RTI consultations and antibiotic prescribing as reported previously.In the final stage of the analysis, we estimated the numbers of infective complications with person years at risk, in relation to general practice specific rates of RTI consultations and antibiotic prescribing. Mixed effects Poisson models were fitted using the hglm packageTo present the clinical implications of these findings, we calculated the number of events expected in a general practice with 7000 patients  during 10 years of follow-up. To estimate the expected number of consultations for RTIs we used the median (95% range) for the RTI consultation rate. To estimate expected numbers of complications and antibiotic prescriptions we used the disease incidence and distribution of antibiotic prescribing proportion for the highest prescribing fourth. We used the relative risk increase for a 10% change in antibiotic prescribing from the Poisson model to estimate the expected change in number of infective complications.No patients were involved in setting the research question or the outcome measures, nor were they involved in developing plans for design or implementation of the study. No patients were asked to advise on interpretation or writing up of results. Results will be disseminated to relevant patient communities through news media.Data were analysed for 610 UK Clinical Practice Research Datalink (CPRD) general practices, with 45 465 201 registered person years of observation from 2005 to 2014. Figure 1Figure 2General practices were divided into fourths according to the proportion of RTI consultations with antibiotics prescribed  for RTIs over 10 years  in primary care. The results show that general practices prescribing fewer antibiotics for RTIs may expect to have a slightly higher incidence of pneumonia and peritonsillar abscess than higher prescribing general practices. If a general practice with an average list size of 7000 patients reduced the proportion of RTI consultations with antibiotics prescribed by 10%, it might encounter about one additional case of pneumonia each year and one additional case of peritonsillar abscess each decade. Changes will be proportionately greater for larger reductions in antibiotic prescribing. These estimates represent averages across general practice populations, but complications might be fewer than expected if general practitioners are able effectively to stratify antibiotic prescribing according to level of risk. There was no evidence that diagnoses of mastoiditis, empyema, bacterial meningitis, or intracranial abscess might increase. Lemierre’s syndrome was rare, with about one case per two million person years, but there was no evidence that this was more common at low prescribing practices. This is reassuring in view of recent suggestions that Reducing the proportion of RTI consultations with antibiotics prescribed by 10% is expected to be accompanied by some 2000 fewer antibiotic prescriptions for each practice over 10 years. Benefits to individual patients from avoiding antibiotics include reductions in common adverse reactions to antibiotics, such as rashes, vomiting, and diarrhoea, which may affect 10% of patients,Previous studies have consistently shown high levels of unnecessary prescribing of antibiotics for RTIs in primary care.The present results represent averages across general practice populations. Diversity among the population of patients at risk of RTIs is considerable. Current management guidelines for RTIs recommend that specific groups of patients should be considered to have positive indications for antibiotic treatment. An immediate antibiotic prescription is recommended if patients have clinical features suggestive of serious illness or complications,39This study included more than 600 general practices, with a registered population of more than four million patients and 45 million person years of observation. Consequently, the study provided precise estimates for the more common outcomes evaluated. We acknowledge that there was lower power to evaluate potential changes in less common outcomes. We can conclude that the absolute risks of mastoiditis, empyema, intracranial abscess, and Lemierre’s syndrome remain small, even in practices with low rates of antibiotic prescribing. This study adopted a population perspective, aiming to quantify the outcomes of either high prescribing or low prescribing strategies in the management of RTIs. Consequently, we evaluated changes in infective complications at the level of the general practice population. The research did not deal with variation in prescribing at the level of the individual doctor. The research did not show whether individual patients who experienced complications received antibiotics. Conclusions might differ if individual level analyses showed that complications arise in patients who were treated with antibiotics. We did not evaluate the outcomes of individual patients identified as having complications in this study. Further research is required to evaluate the severity of complications, such as pneumonia, and their outcomes, including mortality. Future studies might also make use of linked hospital episode data, which in recent years have become available for selected CPRD practices in England to evaluate patients in more detail who have been admitted to hospital. The risk of complications associated with different classes of antibiotics also merits study. We acknowledge that there may be other complications, such as a proportion of all cases of septicaemia diagnosed in primary care, which might follow from an RTI. We acknowledge several sources of misclassification: we used a sample of the UK Clinical Practice Research Datalink (CPRD) to estimate consultation and prescribing rates; there is variation among general practices in the use of diagnostic categoriesThis study provides evidence that general practices prescribing antibiotics less often at consultations for RTIs may experience a slight increase in the incidence of pneumonia and peritonsillar abscess, both of which would be expected to respond to treatment while bacterial pathogens remain sensitive to antibiotics. No increase is likely in mastoiditis, empyema, meningitis, intracranial abscess, or Lemierre’s syndrome. Even a large reduction in antibiotic prescribing was predicted to be associated with only a small increase in numbers of cases observed over a 10 year period, and this would be expected to reduce the risks of antibiotic resistance, the side effects of antibiotics, and the medicalisation of largely self limiting illnesses. The safety outcomes of no antibiotic prescribing strategies for RTIs are an important aspect for communication to patients and the public in the context of wider communication strategies to support antimicrobial stewardship.42Further research is needed to quantify associations based on individual patient characteristics and consultation patterns in primary care, particularly in children and older adults, as we used age standardised prescribing measures. However, associations might vary in different age groups. We also recommend that future randomised studies should be sufficiently large to evaluate safety outcomes of strategies to reduce antibiotic prescribing.Widespread unnecessary utilisation of antibiotics is leading to an increase in antimicrobial drug resistanceMany respiratory tract infections (RTIs) are largely self limiting, but antibiotics continue to be prescribed for about 50% of consultations for RTIs in primary careRTIs are infrequently associated with complications, including pneumonia, peritonsillar abscess, mastoiditis, meningitis, intracranial abscess, and Lemierre’s syndrome, but it is not known whether these are more common in general practices that prescribe antibiotics less oftenGeneral practices prescribing antibiotics less often for RTIs had slightly higher rates of pneumonia and peritonsillar abscess than higher prescribing practicesThere was no evidence that mastoiditis, empyema, meningitis, intracranial abscess, or Lemierre’s syndrome were more frequent at low prescribing practicesEven a substantial reduction in antibiotic prescribing was predicted to be associated with only a small increase in numbers of cases observed, and this would be expected to reduce the risks of antibiotic resistance, the side effects of antibiotics, and the medicalisation of largely self limiting illnesses


Scientometric data on the citation success of different publication types and publication genres in psychology publications are presented. Data refer to references that are cited in these scientific publications and that are documented in PSYNDEX, the exhaustive database of psychology publications from the German-speaking countries either published in German or in English language. Firstly, data analyses refer to the references that are cited in publications of 2009 versus 2010 versus 2011. With reference to all cited references, the portion of journal articles ranges from 57 to 61 %, of books from 22 to 24 %, and of book chapters from 14 to 15 %, with a rather high stability across the three publication years analysed. Secondly, data analyses refer to the numbers of cited references from the German-speaking countries, which are also documented in PSYNDEX. These compose about 11 % of all cited references indicating that nearly 90 % of the references cited are of international and/or interdisciplinary publications not stemming from the German-speaking countries. The subsample shows the proportion of journal articles, books, and chapters, and these are very similar to the percentages identified for all references that are cited. Thirdly, analyses refer to document type, scientific genre, and psychological sub-discipline of the most frequently cited references in the psychology publications. The frequency of top-cited references of books and book chapters is almost equal to that of journal articles; two-thirds of the top-cited references are non-empirical publications, only one-third are empirical publications. Top-cited references stem particularly from clinical psychology, experimental psychology, as well as tests, testing and psychometrics. In summary, the results point to the fact that citation analyses, which are limited to journal papers, tend to neglect very high portions of references that are cited in scientific publications. Limitations of the databases that are used in citation analyses hinder and complicate evaluations of the citation success of different scientific publication types  and publication genres . This can result in serious unfairness in scientometric evaluations of individual scientists, research teams, departments, institutions, and nations as well, because some of their scientific and scholarly work is underrepresented or—even worse—neglected.This problem applies—for example—to textbooks and teaching materials published in book chapters, because these publications appertain to the scholarly performance of scientists, which report and integrate primary research results and theory building in (more or less) creative and—more important—didactically clear, structured form, which is motivating for students in education and further training. At least in medicine and psychology, this applies also to test manuals, therapy and prevention manuals as well as diagnostic and therapeutic guidelines, because of their outstanding significance not only for education and training, but also for applied diagnostic and therapeutic work in medical and psychotherapeutic treatments. Thus, these scientific publication types and publication genres must be considered in evaluations of scientists and science as well as primary research reports. Besides other criteria and indicator variables of scientific productivity and performance , this belongs to the criteria of scientific and scholarly publication output which constitute multiple bibliometric indicators and—if cited—scientometric indicators of productivity and its impact in the sciences  that are used in citation analyses hinders evaluations of the citation success of different scientific publication types  and publication genres , and this is a situation which can result in serious unfairness in scientometric evaluations. For example, the Web of Science (WoS) and Scopus, surely the most frequently used citation databases, pushes journal articles  including all and perhaps nothing, because the references identified refer not only to citations in scientific publications, but to these at homepages of individuals, institutions, and organizations, in excerpts, homework of high school and college students, examination schedules and exam papers, self-presentations, advertising and advertisements, etc. without any type of quality control. Therefore, citation success according to Google Scholar can be manipulated very easily and, therefore, can be considered poor and not very useful for scientometrics .Since the publication year 2009, PSYNDEX, the database of psychology publications from Austria, Germany, Liechtenstein, and the German-speaking regions of Luxemburg and Switzerland published either in German or in English language, includes the complete reference lists of publications documented. Thus, PSYNDEX is a local disciplinary database for psychology and its neighbouring disciplines. Access to PSYNDEX is provided, e.g., by the platforms Ovid and Ebsco as well as WoS  the frequencies of different publication types  to which reference is given by citations in the publications of the years 2009, 2010, and 2011. The second research question refers to (2) the replication of the first analysis; however, data refer only to the cited references in publications from the German-speaking countries that are also documented in PSYNDEX  and whose PSYNDEX documentation contains meta-data about the publication genre and on the psychological sub-discipline to which they belong. The third research question refers to (3) the characteristics of the most frequently cited references in the psychology publications from the German speaking countries published in 2009, 2010, and 2011. These top-cited references are analysed with the help of PSYNDEX meta-data for the relative frequencies of (3a) different document types, i.e., journal articles, books, chapters, (3b) different scientific publication genres, i.e., empirical and non-empirical publications, and (3c) different psychological sub-disciplines following the classification codes (CC) of the Thesaurus of Psychological Index Terms of the American Psychological Association , we conduct a case study with the local disciplinary databases PSYNDEX. The For the scientometric analysis, we use the raw frequencies of the documents included in PSYNDEX published in 2009, 2010, and 2011. PSYNDEX includes 7358 documents with reference lists published in 2009, 8484 documents published in 2010, and 8059 documents published in 2011. For the citation analysis, we use the reference lists of these documents, which sum up to 402,830 references cited in 2009, 426,014 references cited in 2010, and 475,935 references cited in 2011. PSYNDEX and PubPsych documents include various meta-data  are reported in the upper part of Table The subsets of references cited from the German-speaking countries, which are also documented in PSYNDEX, are presented in the lower part of Table Specifically, the proportions of journal articles (around 60 %), books (around 20 %), and book chapters around 17 %) in these subsets are very similar to the percentages identified for all references that are cited  not to be very selective, we think the f > 14 criterion is justifiable in an exploratory approximation.We use the frequency The frequency distributions across the publication years of the most frequently cited references in psychology publications from the German-speaking countries in 2009, 2010, and 2011 are graphically presented in Fig. Most top-cited references in the 2009 publications stem from a rather narrow time frame of only 4 years  of books and book chapters on the one side and journal articles on the other side are represented very similarly  of all experimental psychology publications documented in PSYNDEX is pe = 10.4 %, their observed proportion (po) in the top-cited references is mean po = 18.0 % . Thus, in comparison to the publication output of experimental psychology, of research on tests and psychometrics as well as of psychology publications on statistics and mathematics, these sub-disciplines are visibly overrepresented in the top-cited references.At first glance this result seems to be rather trivial. However, it must be noted that the proportions of experimental psychology publications as well as publications on tests, testing, psychometrics, and test development in the top-cited references are higher than is expected with reference to the complete relative publication output of these sub-disciplines: For example, the expected proportion , educational psychology , industrial and organizational psychology , personality psychology  as well as on social processes and social issues . Thus, in comparison to their publication output, publications on these psychological sub-disciplines are markedly underrepresented in the top-cited reference lists. For completion, it is reported that the relations between expected relative frequencies and the observed relative frequencies in the top-cited reference lists are balanced for publications on research methods and experimental design, physiological psychology and neuroscience, developmental psychology as well as social psychology ; nevertheless, this is less than is expected according to their proportions of the complete publication output (pe = 63 %). The basic psychological sub-disciplines are ranked second (mean po = 34 %) and publications on methodology are ranked third (mean po = 23 %) in the top-cited references. Thereby, it must be considered that psychology publications dealing with the applied sub-disciplines and at least some of the basic sub-disciplines  are of special relevance in the education and training of many other professionals . Thus, the publication output is rather high , but these publications are less cited in psychology publications because they address other target groups.Last, but not the least, it should be noted that—summed up—the applied psychological sub-disciplines possess the highest proportions at the top-cited references (Web of Science or Scopus), neglect at least about 40 % of the scientific and scholarly publications and result in extremely biased scientometric results that are unfair for individual scientists, scientific teams, departments, institutions, and nations.The results of the present case study confirm serious deficits in citation analyses, which refer exclusively to selective databases including only journal articles, only publications of certain publishers or publishing groups or—at the other extreme—everything that can be detected on the World Wide Web. Our data refer to all the references cited in the scientific and scholarly psychology publications that are documented in PSYNDEX, the local disciplinary database of psychology publications from Austria, Germany, Liechtenstein, and the German-speaking regions of Luxemburg and Switzerland, in either the German or English language. With reference to all of the more than 1,303,000 cited references, the proportion of cited journal articles ranges from 57 to 61 %, of cited books from 22 to 24 %, and of cited book chapters from 14 to 15 %, with a rather high stability across the three different publication years analysed. Thus, evaluations of scientists and sciences, which rely solely or primarily journal articles including citation databases  or other countries. Thus, psychology in the D–A–CH–L–L states is a very strongly international oriented working and publishing research community. This scientometric result conforms to these on an increasing international collaboration ; only one-third are empirical publications . This result on the publication success of different publication genres in psychology differs from that presented by Johnston et al.  for the An a posteriori hypothesis for our results on the lower citation success of empirical publications in psychology may be the interpretation that empirical studies (in psychology) try to contribute to the solving of empirical problems or—at best—solve such a problem but nevertheless frequently conclude that “further research is needed”. This original empirical study will be cited in some (but rather few) subsequent empirical studies on the same research question, which—at best—advance the research and replace the earlier study, thus remaining only one link in a longer chain of empirical studies , and in the reference lists of the following publications . On the contrary, non-empirical publications  describe, structure, integrate, and evaluate research in a broader problem domain where, at best, such publications identify significant topics for research, describe research deficits, and motivate (more or less) innovative research in a wider problem domain. This actually results in higher citation success, because many later publications can have direct access to the conclusions made in these non-empirical publications.The results show that the top-cited references stem particularly from clinical psychology, experimental psychology, as well as from research on tests, testing and psychometrics. This covaries only partially with the size of the sub-disciplines’ scientific community in terms of personnel and research funding resources as well as publication media. Contrasts of the expected relative frequencies, which are computed with reference to the complete publication output of a sub-discipline and its proportion of indexed documents recorded in PSYNDEX with the observed relative frequencies in the top-cited reference lists, show that publications on clinical psychology, educational psychology, personality psychology, and research on social processes and social issues appear less frequently in the top-cited references than would be expected. This is contrary for the relative frequency of references given to publications on experimental psychology, on research on tests and psychometrics as well as on psychology publications on statistics and mathematics.In summary, the results points to the fact that citation analyses, which are limited to journal papers, neglect very high proportions of references that are cited in scientific and scholarly publications. The same is valid for databases that concentrate on books and chapters—at least in psychology publications from the German-speaking countries. Professional—and perhaps special databases for scientific disciplines—databases with high quality control and high coverage of the publications and their complete reference lists are required for serious and reliable citation analyses, which result in fair evaluations of the citation success of scientists, research teams, institutions and nations. Such scientometric results will be accepted with a higher probability in the scientific community.WoS or Scopus as databases for citation analysis in psychology not only misses a large part of publication output but the most important one: While books and book chapters account for 30 % percentage of the publication output in psychology, 52 % of the highly cited documents are books or book chapters. Hence, books and book chapters are still an important document type that must not be neglected. If evaluation focuses only on journal articles, most of the highly cited, i.e., important, works are not taken into account.The focus on journals when using


This review presents the role of strigolactone transport in regulating plant root and shoot architecture, plant-fungal symbiosis and the crosstalk with several phytohormone pathways. The authors, based on their data and recently published results, suggest that long-distance, as well local strigolactone transport might occur in a cell-to-cell manner rather than via the xylem stream.Petunia axillaris (PDR1) and, in less detail, its close homologue from Nicotiana tabacum PLEIOTROPIC DRUG RESISTANCE 6 (PDR6). PDR1 is a plasma membrane-localized SL cellular exporter, expressed in root cortex and shoot axils. Its expression level is regulated by its own substrate, but also by the phytohormone auxin, soil nutrient conditions (mainly phosphate availability) and mycorrhization levels. Hence, PDR1 integrates information from nutrient availability and hormonal signaling, thus synchronizing plant growth with nutrient uptake. In this review we discuss the effects of PDR1 de-regulation on plant development and mycorrhization, the possible cross-talk between SLs and other phytohormone transporters and finally the need for SL transporters in different plant species.Strigolactones (SLs) are recently characterized carotenoid-derived phytohormones. They play multiple roles in plant architecture and, once exuded from roots to soil, in plant-rhizosphere interactions. Above ground SLs regulate plant developmental processes, such as lateral bud outgrowth, internode elongation and stem secondary growth. Below ground, SLs are involved in lateral root initiation, main root elongation and the establishment of the plant-fungal symbiosis known as mycorrhiza. Much has been discovered on players and patterns of SL biosynthesis and signaling and shown to be largely conserved among different plant species, however little is known about SL distribution in plants and its transport from the root to the soil. At present, the only characterized SL transporters are the ABCG protein PLEIOTROPIC DRUG RESISTANCE 1 from  Strigolactones (SLs) are carotenoid derived phytohormones involved in several plant developmental processes. Initially discovered as germination stimulants for parasitic weeds    and BRASSINAZOLE 1 (BZR1) . D14 hydrolyzes the SL molecule at the enol-ether bond, between the SL tricyclic lactone (ABC ring) and the butenolide moiety (D ring). SL signal transduction is then carried on by the D14-D ring complex, which promotes the ubiquitination and subsequent proteolysis of DWARF53 (D53), suggesting that D53 is a repressor of SL signaling. D53 interacts in vitro with TOPLESS (TPL) and TPL-related co-repressors . This receptor is capable of detecting karrikins (KARs), bioactive components from smoke that are stimulants for germination  transporter   protein PDR1 from petunia , thus suggesting that PDR1 is the main player in SL root exudation. Furthermore, Arabidopsis plants overexpressing PDR1 became tolerant against high SL concentrations in the growth medium, suggesting that their capacity to excrete SLs was strongly increased.A first indirect indication that SLs are exported from the root to the soil was provided by the observation that SLs induce the germination of parasitic weeds  are non-suberized cells located in the hypodermis that serve as entry points for the mycorrhizal fungus: their distribution along the root affects mycorrhization success  in the root tip and show alterations in root tip homeostasis, such as cell division. Furthermore, the strong down-regulation of CDD8/DAD1 observed in pdr1 root tips indicates that SL biosynthesis is feedback regulated by its own substrate. Such negative feedback might be also useful to avoid SL accumulation in the root tip that could be detrimental by inducing hyphal branching of mycorrhizal fungi towards the wrong root side: root tips have no suberized hypodermis and potentially SL could diffuse out of the root tip in the rhizosphere, thus inducing hyphal branching and penetration in the dividing root meristem. Additionally, PDR1 protein levels are increased by exogenous GR24 treatments: such observation is in line with the need for the root tip to remove SLs accumulating close to the root meristem. Interestingly, GR24 not only increases PDR1 protein amounts but also expands PDR1 protein pattern to deeper cortical layers  is furthermore active in cortical cells along the vasculature, but excluded from the stele. In this differentiated region of the root, HPCs are present. Analysis of its sub-cellular localization revealed PDR1 to be confined to the outer-lateral plasma membrane of HPCs, consistent with its role in exuding SLs towards the rhizosphere to facilitate mycorrhization  responsible for cellular uptake of SL in order to understand the entire cell-to-cell flux of SL. An active cell-to-cell transport hypothesis is supported by recent work using fluorescent-tagged SL  in Arabidopsis, showed that PDR1 can transport and exude radiolabeled GR24 even in a plant species that is not related to petunia. However, we did not observe PDR1 OE effects on Arabidopsis plant architecture  could indicate that carlactone or methyl carlactone are transported by multiple and redundant ABC transporters or by other transporters not related to ABC transporters, making the reverse genetic approach less effective. For abscisic acid it has been shown that, besides ABCG transporters, NITRATE TRANSPORTERS (NRTs) and MULTI MICROBIAL EXTRUSION PROTEINS (MATEs) can catalyze the transfer through membranes  mutants not only showed that SLs and/or SL precursors are transported from the root to the shoot but also demonstrated that shoot-synthesized SLs are sufficient to support above ground SL functions, when no SL is translocated shoot-wards  plants showed that wild type root stocks can suppress the branching phenotype of mutant scions, indicating that also SL precursors like methyl carlactone can be transported from roots to shoots  and CCD8/RAMOSUS1 (RMS1) are upregulated by auxin  is the closest homolog to PDR1. PDR4, however, is not strongly expressed in roots and not induced by GR24 (Fig. Oryza sativa, Sorghum bicolor and Zea mays (Fig. Lotus japonicus, where only a single PDR1 homolog is present, making this plant attractive for studies on SL transport. However, the lotus genome is at present only 67 % sequenced and hence further homologs may be present in the yet unsequenced part.When carrying out PDR1 phylogeny analyses on mono- and di-cotyledons to identify SL transporters in other plant families, possible duplication events for PDR1 homologues in ted Fig. . In PetuR24 Fig. h, and heays Fig. . TherefoSolanum lycopersicum, Oryza sativa, Nicotiana tabacum, Sorghum bicolor and Arabidopsis thaliana (Xie et al. The recent investigations on PDR1 showed that not only biosynthesis and signal reception, but also transport of the phytohormone SL plays a main role in regulation of plant development and plant-fungal symbiosis. Although no PDR1 ortholog was characterized out of Solanaceae yet, the need for a SL transporter is probably widespread among different plant species. It was recently shown that no SLs were detected in the xylem sap of LB, GL and EM conceived and designed research. LB, AE and TK conducted experiments. LB, GL and EM wrote the manuscript. All authors read and approved the manuscript.


A form based on the MSDH was used to collect sociodemographic dataaddressing individual, proximal, intermediate determinants and the influence ofsocial networks together with an instrument used to assess the QoL of people withHIV/AIDS. The project was approved by the Institutional Review Board (Protocol No.040.06.12).  according to MSDH, most men with AIDS were between 30 and 49 years old (68.1%),mixed race (59.4%), heterosexual (46.4%), single (64.5%), Catholic (68.8%), had abachelor's degree (39.2%), had no children (61.6%), and had a formal job (71.0%).The perception of QoL in the physical, level of independence, environment, andspirituality domains was intermediate, while QoL was perceived to be superior inthe domains of psychological and social relationship. A perception of lower QoLwas presented by homosexual (p=0.037) and married men (p=0.077), and those withincome below one times the minimum wage (p=0.042). A perception of greater QoL waspresented by those without a religion (p=0.005), living with a partner (p=0.049),and those who had a formal job (p=0.045).  social determinants influence the QoL of men with AIDS. The epidemic is currently stable in Brazil and concentrated in vulnerablepopulation groups, but male adults are still the most frequently affected(-).The Human Immunodeficiency Virus (HIV) infection is currently a health problem due toits pandemic nature and severity. A total of 686,478 cases of AIDS were reported to theNotifiable Diseases Information System (SINAN) from 1980 to December 2013; 445,197 ofwhich refer to men and 241,223 to women.The availability of antiretroviral treatment (ART) in Brazil since 1996 has enabled areduction in both morbidity and mortality caused by HIV. Brazil was the first developingcountry to adopt a public policy for patients to have access to ART and is recognizedworldwide for providing a program that has achieved good response against the HIV/AIDSepidemic..Even though there is a national program and very well-organized to combat sexuallytransmitted diseases (STD) and AIDS, one should consider that economic and politicalaspects have an essential meaning to each population in which AIDS has beendisseminated. Most cases of AIDS are located in poor countries, suggesting the need toanalyze the social determinants of health in these populations.Because ART has enabled increased survival rates of people with HIV/AIDS, characterizingit as a chronic disease, the health care provided to these individuals gains greaterimportance for these individuals who require unique care procedures to maintain theirquality of life (QoL) that has been already validated in Brazil. QoL is a perception of individuals in regard to their position in life inthe context of the culture and value system in which they live and in relation to theirobjectives, expectations, standards and concerns. Studies show that the QoL of people with HIV/AIDS is compromised due todiscrimination and the unfavorable socioeconomic conditions in which they live, whichmay determine increased rates of mortality(-).The World Health Organization (WHO) developed, within a multi-center collaborativestudy, an instrument to assess QoL from an international and cross-cultural perspective.This instrument is called the World Health Organization Quality of Life WHOQOL-100),which originated a specific instrument for people living with HIV/AIDS,WHOQOL-HIV that han Brazil. QoL isconcerns. Studieortality-10.0,which Given the previous discussion and with the intent to contribute to the quality ofhealthcare provided to people living with HIV/AIDS, considering that most individualsaffected by HIV infection are male and that social determinants impacting this process,we proposed this study to analyze the QoL of men with AIDS using the WHOQOL-HIV bref,with the Model of Social Determinants of Health (MSDH) as theoretical framework..The social determinants of health are the social conditions in which people live andthat affect people's health. There are different models of social determinants of healthbut the National Commission on the Social Determinants of Health chose Dahlgren andWhitehead's model to be used in Brazil due to its simplicity and clear graphicrepresentation of social determinants., the social determinants of health are displayed in concentric layers,where individuals are in the center of the model: layer 1 ; layer 2 ; layer 3 ; layer 4 ; layer 5 .In this model, the soThis cross-sectional study with quantitative approach was conducted in an infectiousdisease outpatient clinic in a Brazilian university hospital that provides care toadults with HIV/AIDS. This hospital has an outpatient service, inpatient wards and anintensive care unit and also provides laboratorial and radiological exams, ART andcondoms., with a 95% confidence level that the estimation error would not surpass3%, considering that the mean of these scores, according to prior studies(-), is about 13.7, with a standard error of 3.8, and also that there were 235male patients receiving care from the outpatient clinic up to the end of 2001. For that,the following expression was used:Data were collected over the course of one year. In order to meet the study'sobjectives, the sample size was determined to estimate the mean of the scores obtainedin the domains assessing the QoL of people living with HIV/AIDS, the WHOQOL-HIVbref, with a studies-14, iGC is equal to the z-statistic (1.96), standard deviation(SD), X̅ and ε correspond to mean and acceptable error (0.03), respectively. Hence, asample of 138 patients was computed.In this formula, zInclusion criteria were: being a man and having AIDS; being older than 28 years of age;being in outpatient follow-up; using ART; and signing a free and informed consent form.Exclusion criteria were having access to ART at the hospital but with follow-upperformed in a private facility; suffering from mental disease or any other conditionthat would impede the individual from answering the study's forms. The participants wereinvited to participate in the study when they attended the outpatient consultations. Twoforms were applied through interviews in a private room. (12) to address thesociodemographic characterization of people with HIV/AIDS and was arranged into fourlayers 1- identification, age, race; 2 - category of exposure, marital status, religion,schooling; 3 - number of children, number of household members, and whether theindividual lives with a partner; 4 - occupation and per capita income(times minimum wage). The form was based on the MSDH layers 1, 2, 3 and 4, while layer 5was used in the discussion of findings because it refers to the distal ormacro-determinants involving economic, cultural, and environmental conditions ofsociety, current policies, supranational determinants and globalization and does notdirectly refer to the personal characteristics of the study's participants. The form wasvalidated after being applied to 20 male individuals with AIDS, who did not compose partof the sample.A form was developed in accordance with MSDH. The full version includes 120 questions (WHOQOL-HIV), so the brief version(WHOQOL-HIV bref) was used instead. It assesses the generic QoL of people with HIV/AIDS.WHOQOL-HIV bref has 31 items measuring QoL distributed into six domains: I. Physical; II. Psychological ; III. Level ofIndependence ; IV. Social Relationships ; V. Environment ; VI.Spirituality/religion/personal beliefs . The questions are scored on a 5-point Likert scale containing 1 , 2 (a little), 3 (a moderate amount), 4 (very much) and 5 (an extreme amount),such that 1 indicates negative perceptions and 5 indicates positive perceptions. Thescores obtained in each domain are scaled in a positive direction, where higher scoresindicate better QoL. For the items pain, discomfort, negative feelings, dependence onmedication, death and dying, scores are not scaled in a positive direction and higherscores do not represent better QoL and need to be inverted. Scores range from 4 to 20points, which reflect worst and best QoL, respectively.The other form was an instrument used to assess the QoL of people with HIV/AIDS, theWorld Health Organization Quality of Life instrument - HIV/AIDS module (WHOQOL-HIV), thePortuguese version of which has already been validated in Brazil. The fuectively.(-).The classification of previous studies addressing people living with HIV/AIDS was usedto characterize the level of perception of QoL in each domain in which the scorestranslated, as follows: between 4 and 9.9 indicate a perception of low QoL, from 10 to14.9 indicate a perception of intermediate QoL, and scores from 15 to 20 represent aperception of superior QoL-14.(r) and processed by theStatistical Package for Social Sciences (SPSS) version 18(r). Absolute andrelative frequencies, mean, standard deviation, median, minimum and maximum values wereused in the descriptive statistics. Analysis of variance (ANOVA) was used to compare themeans of the WHOQOL-HIV bref's domains with the variables of interest and Tukey's testand the T test were also applied for the intragroup analyses. Level of significance wasestablished at 5% and considered statistically significant when p <0.05.Data were organized in Microsoft Excel 2007The study project was approved by the Institutional Review Board on July 30, 2012 inaccordance with Resolution No. 196/96, National Council of Health (Protocol No.040.06.12). The participants signed free and informed consent forms and anonymity wasensured; the study's data were used only for scientific purposes.per capita monthly income more than two times the minimumwage.Most men had no children (61.6%) and only 11.6% reported more than six children, withnine being the highest number of children reported. Most lived together with three tofive people (47.1%), had a formal job at the time of the study (71.0%), and 58.0%reported a The analysis of association between the scores of the WHOQOL-HIV bref's scores and theMSDH's layers 1 and 2 presented statistical significance in some situations. The meanscores of homosexual participants for the domain VI were lower than that of heterosexualmen, showing a perception of lower QoL concerning spirituality (p=0.037). Married menobtained lower scores in domain V (environment) in comparison to single men (p=0.077).Those who did not report a religion scored higher than the Catholic participants in thefollowing domains: I (p=0.005), II (p=0.017) and III (p=0.038) .per capita income below one times the minimum wage (p=0.003)and between one and two times the minimum wage (p=0.042) scored lower on average in thedomain when compared to individuals with per capita income greater thanthree times the minimum wage . Men with a formal job scored higheron average on domains II (p=0.045) and III (p=0.023) than those without formal jobs.Those with mum wage ..The social determinants of health are important because they predict the proportion ofvariation in one's health condition, sanitary inequity, and health-related behaviors.The social determination of health is rooted in an ethical foundation that is equity,defined as the absence of unfair differences among population groups so that inequitiesin health are socially-produced differences.. In regard to race, the results were similar to those found by a studyconducted in Maranhão, Brazil in which mixed race was prevalent. Note that individual determinants are, in general, considered to benon-modifiable determinants.According to MSDH's layer 1, which depicts individual determinants, the age of mostindividuals was between 30 and 49 years old, revealing national dynamics in which mostmen infected with AIDS between 2000 and 2011 were in this age rangerevalent. Note t. This finding involves the issue of vulnerability in regard to HIV/AIDS,which is linked to a set of individual and behavioral aspects that facilitate onebecoming infected, in addition to sociopolitical aspects, which are represented by thecommitment displayed by authorities, inter-sector actions and funding.The analysis of layer 2 showed that the category of exposure heterosexual waspredominant, which also represents the national context. This f funding.. In regard to education, most had a bachelor's degree and percapita income greater than two times the minimum wage, differing from thefindings of other studies, where most men with AIDS had low educational levels andincome, and performed occasional jobs without formal contracts. Most men had no children, which may be explained by the considerablenumber of homosexual (39.9%) and bisexual (13.7%) individuals.Most men with AIDS were single and Catholic, which also was observed in anotherstudy. In regtracts,,17. M(-). Note that the lowest scores are for domain III, which represents level ofindependence. Hence, the individuals face changes in their mobility, activities of dailyliving, depend on medication and treatment, in addition to experiencing interference intheir capacity to work. These results are related to changes in lifestyle after thediagnosis of HIV infection, starting ART, and also as a consequence ofstigmatization.The average scores obtained for the WHOQOL-HIV bref domains were similar to those foundin other studies addressing people living with AIDS, highlighting an intermediateperception of QoL-14. Non-,,-14.(-).In the context of MSDH, homosexual men obtained low average scores in regard tospirituality (p=0.037), the domain that refers to forgiveness and blame, concerns overthe future, death and dying. This finding reflects the early days of HIV/AIDS, duringwhich the infection was attributed to risk groups, especially homosexual individuals, inaddition to the fact that infection meant death, a situation which was later changed dueto the advent of ART, which led to increased survival rates for people withAIDS-11.per capita income of those living in thesame household.Married men scored lower than single men, on average, in regard to domain V (p=0.077),which refers to physical safety, housing, finance, access to health and social care, theability to acquire information and learn new skills, leisure, environment and transport.This result may be explained by the fact that married men have to provide for theirfamilies, which decreases the ousehold.(-).Those who did not profess a religion scored higher than Catholics in domains I(p=0.005), II (p=0.017) and III (p=0.038). This finding contrasts with relatedliterature, which shows positive correlation between health and spirituality as having areligion supports and strengthens the individual in the face of the adversities imposedby pathological conditions. Additionally, AIDS represents, in the social sphere, aseries of disparaging metaphors such as associations with punishment, which would amountto being convicted for socially disapproved behaviors-19..Living with a partner also increased the perception of QoL in regard to domain V(p=0.049). This aspect may be related to social support, which indicates the influenceof social interactions with the well-being and health of people. Due to stigma, however,a seropositive status for HIV may hinder social support specifically related to thedisease.per capita income greater than three times theminimum wage increased the average values of scores in regard to domain V when comparedto people's per capita income of below one times the minimum wage(p=0.003) and between one and two times the minimum wage (p=0.042).Having a formal job increased the average scores obtained for domains II (p=0.045) andIII (p=0.023), while .Given the previous discussion, the social inclusion of people with HIV in the workenvironment has a considerable positive impact on QoL. What is observed, however, isdiscrimination both on the part of employers and co-workers. This fact culminates indenying to these people the most elementary right, the right to work. Since the 1990s inBrazil, an inter-ministerial decree prohibits, in the sphere of federal public service,the requirement of HIV tests in pre-hiring exams and in periodic health exams, becausebeing HIV-positive does not cause loss of working capacity and social and/orprofessional contact with these individuals does not constitute a risk ofinfection.. This layer was not included in the data collection, which may be seen as alimitation of this study. The lack of inclusion was because the study's participants donot recognize the more general macro-determinants or aspects of the society to whichthey belong, including understanding of health policies directed to the prevention,control, and treatment of HIV/AIDS infection.As for layer 5, we have the distal or macro-determinants, represented by society'seconomic, cultural, and environmental conditions. This l.In this context, initially, due to a lack of a public policy structured by the Stateaiming to fight HIV/AIDS, a large number of Non-Governmental Organizations (ONGs)emerged in the country to fight the disease. This coping policy gained momentum byreaching various social groups, when civil society mobilized and ensured its priority,political pressure to accomplish it and funding for it. Currently, Brazil has one of themost progressive policies to cope with HIV/AIDS and is a point of reference for theworld..The current policy concerning the prevention, treatment and control of HIV/AIDS is aresult of the epidemic's social and historical construction. The first discussionsconcerning its control were directed to the identification of risk factors, a conceptthat is no longer used because it resulted in the stigmatization of certain groups, suchas homosexuals. Later, it was replaced by the concept of risk behavior, which blamed thepopulation for failures in preventing HIV/AIDS. Hence, these approaches were inefficientand did not favor coping with the epidemic, for they did not consider social, culturaland contextual determinants.. This means that, in addition to groups initially affected by HIV/AIDS,such as homosexuals, sex workers, intravenous drug users and hemophiliacs, people instable relationships with a risk behavior and who do not use condoms, adolescents,elderly individuals, those with a low level of education, low income, and living in theinterior of the country are also taken into account.The epidemic in Brazil is currently stable and the concept of vulnerability began to beconsidered in the context of HIV/AIDS, since the epidemic is centered in vulnerablepopulation subgroups,18. Tount,,-23.The use of MSDH and the application of the WHOQOL-HIV bref enabled identifying theperceptions of QoL held by men with AIDS, who for the most part considered their QoL tobe intermediate. This finding shows that despite the existence of policies concerningaccess to ART and to healthcare provided in the public health network, other aspectssuch as social determinants of health should be considered for the populations intowhich HIV has been disseminated.Studies of this nature are important to understanding the context in which individualswith HIV/AIDS are inserted because the lives of these individuals can be seen from amultidimensional perspective and interventions can thereby be more efficient.Statistical associations concerning category of exposure, marital status, religion, jobcontract, and income were observed, confirming the importance of social determinants ofhealth in impacting the way men experience the process of health and disease.We stress the importance of this study for understanding the context of those livingwith AIDS, since it can contribute to the delivery of care. Note that further studiesare needed to contribute to the QoL of these individuals and reduce morbidity andmortality. Hence, even through there is no cure, HIV infection and AIDS can effectivelybe considered chronic conditions.


World AIDS Day draws attention to the current status of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic worldwide. The theme for this year’s December 1 observance is “Shared Responsibility: Strengthening Results for an AIDS-Free Generation.”MMWR. Since then, an estimated 36 million persons worldwide have died from HIV/AIDS; an estimated 35.3 million persons continue to live with HIV infection , provided antiretroviral therapy to approximately 9.7 million persons in low-income and middle-income countries in 2012, an increase of 1.6 million persons from 2011 .