Sexually Transmitted diseases (STD) syndrome management has been one cornerstone of STD treatment. Persons with STD symptoms in many countries, especially those with limited resources, often initially seek care in pharmacies. The objective of the study was to develop and evaluate an integrated network of physicians, midwives and pharmacy workers trained in STD syndromic management (The PREVEN Network) as part of a national urban community-randomized trial of sexually transmitted infection prevention in Peru.After a comprehensive census of physicians, midwives, and pharmacies in ten intervention and ten control cities, we introduced seminars and workshops for pharmacy workers, and continuing education for physicians and midwives in intervention cities and invited graduates to join the PREVEN Network. “Prevention Salespersons” visited pharmacies, boticas and clinicians regularly for educational support and collection of information on numbers of cases of STD syndromes seen at pharmacies and by clinicians in intervention cities. Simulated patients evaluated outcomes of training of pharmacy workers with respect to adequate STD syndrome management, recommendations for condom use and for treatment of partners. In intervention cities we trained, certified, and incorporated into the PREVEN Network the workers at 623 (80.6%) of 773 pharmacies and 701 (69.6%) of 1007 physicians and midwives in private practice. Extremely high clinician and pharmacy worker turnover, 13.4% and 44% respectively in the first year, dictated continued training of new pharmacy workers and clinicians. By the end of the intervention the Network included 792 pharmacies and 597 clinicians. Pharmacies reported more cases of STDs than did clinicians. Evaluations by simulated patients showed significant and substantial improvements in the management of STD syndromes at pharmacies in intervention cities but not in control cities.Training pharmacy workers linked to a referral network of clinicians proved feasible and acceptable. High turn-over was challenging but over come. Sexually transmitted diseases (STD) syndrome management has been one cornerstone of STD treatment.Thus public health strategies for STI control cannot ignore the role of pharmacies. One approach, motivated in part by concerns about over-use of antimicrobials and emerging antimicrobial resistance, involves enforcement of regulations proscribing antimicrobial dispensing by pharmacies without prescription. Efforts to enforce such regulation significantly decreased antimicrobial consumption in Chile,In Peru we have evaluated incremental enhancements of training programs for pharmacy workers linked to training of clinicians, designed to strengthen management of four STD syndromes: urethral discharge (UD), vaginal discharge (VD), genital ulcer disease (GUD), and pelvic inflammatory disease (PID). Initially, we assessed the impact of short didactic training on management of these four syndromes, using simulated patients to evaluate impact.To formally test the impact of such a program on the population-level prevalence of the STIs associated with these four syndromes, as part of a multicomponent urban community-randomized trial of STI prevention in PeruInstitutional Review Boards at the University of Washington (Seattle USA), Universidad Peruana Cayetano Heredia (UPCH), and US-NMRCD  approved the protocol and instruments. All IRBs exempted pharmacy workers and clinicians from informed consent.Twenty cities with populations between 50,000 and 300,000 located on the coast, the Andean region or the jungle of Peru were randomized in pairwise fashion into intervention and control arms. The ten intervention cities received a multicomponent intervention. One of the four intervention modalities involved training of clinicians and pharmacy workers in improved recognition and management of STD syndromes, including STI/HIV prevention counseling, resulting in formation of the PREVEN Network. The intervention began in July 2003 and continued through December 2006.Potential Network members were pharmacy workers, physicians, and midwives working in private practice and at public health settings. Leaders representing each group in intervention cities, including physicians, midwives, pharmacists, and pharmacy workers were recruited to help develop the strategy for improving STD syndromic management. These leaders helped form discussion panels involving representatives of regional governments, Network leaders, and other civil society members, to discuss management of STD syndromes and creating sustainable strategies for prevention and control of STIs including HIV infection in the city.A comprehensive map-based, street-by-street census of pharmacies and boticas , and of physicians and midwives www.proyectopreven.org.Pharmacy seminars and workshops included four 90-minute training sessions with small groups of eight to ten pharmacy workers who met over lunch with two training specialists (a pharmacist and a midwife). Interactive workshops included case-oriented discussions, role-playing, and self-evaluation, with certification upon successful completion. Training emphasized recognition of STD syndromes, syndromic management guidelines, and referral of clients with GUD or PID to the PREVEN Network of certified clinicians. The final session provided training in client-centered counseling by pharmacy workers using motivational interviewing “Prevention salespersons” were pharmacists and midwives who received 50 hours of specialized training on STDs, health education, and counseling and communication skills, and were responsible not only for conducting the prevention seminars, but also for providing follow-up structural support to certified Network members, making monthly visits to each pharmacy and clinician in the Network, distributing educational materials for pharmacy workers and for pharmacy clients, and answering questions and discussing concerns. Pharmacy workers themselves suggested the “Prevention Salesperson” approach–analogous to that of pharmaceutical salespersons–as an innovation to provide ongoing peer-mediated diffusion of information.Because of frequent pharmacy and botica worker turnover, the “Prevention Salesperson” provided continued on-site training for new pharmacy workers, with the participation of any initially trained and certified pharmacy workers who remained on site.Continuing education (CE) is not mandatory in Peru for physicians or any health professional. We decided to introduce a CE program for physicians and midwifes in private practice -about half of whom also worked in the public sector- based on a training curriculum which took into account the adult learning process, Also, we developed a 2003–05 health communication campaign targeting young adults to enable them to recognize STD symptoms, and to promote early health care-seeking for such symptoms, utilizing the PREVEN Network. We implemented this health communication campaign locally in each intervention city using pamphlets, posters, local media, radios and local TV.Process and output measures included percentages of pharmacies, pharmacy workers, physicians, and midwives completing training and continuing in follow up; numbers of activities undertaken and promotional materials distributed by “Prevention Salespersons”; and monthly reports of STD syndromes seen by Network pharmacies and clinicians in intervention cities.“Prevention Salespersons” paid monthly visits in intervention cities to each pharmacy, physician, and midwife in the PREVEN Network, asking them to estimate numbers of clients with UD, VD, GUD, or PID seen during the last week. These numbers were extrapolated to four weeks to estimate numbers seen per month. Results are presented as STD cases reported by Network members.We employed and trained simulated patients to present clinical vignettes (scripted scenarios), to evaluate certified pharmacy workers management of UD, VD, and GUD, and their recommendations for condom use and for partner treatment. For each evaluation, we randomly chose 30 pharmacies in each of the ten intervention and control cities, and compared management of the three syndromes through visits by different simulated patients for each syndrome. No simulated patient visited any pharmacy more than once. For UD, management was considered adequate if the patient was offered treatments for gonorrhoea and chlamydial infection that conformed to national guidelines  or was referred to a PREVEN Network clinician. We allowed simulated patients to buy medications for up to $10 US when necessary to avoid the “artificiality” of the interaction between the simulated patient and the pharmacy worker and so as not to curtail recommendations from pharmacy workers for partner treatment or condom use. For abnormal VD, management was considered adequate if the patient was offered treatment with 2 g single oral dose of metronidazole or was referred to a PREVEN Network clinician. For symptoms of GUD, management was considered adequate only if the patient was referred to a PREVEN Network clinician. Evaluations by simulated patients were done at baseline and at three, six, and 18 months post-training, for each of the three syndromes, using previously described methodology. We also performed sentinel surveillance of STD cases seen at pharmacies from control and intervention cities at three, nine, and 18 months post-initiation of the intervention. These results are reported separately.All information was collected in standardized formats, by local teams in each city. Data were reviewed for consistency and entered into a data base for analysis. For the simulated patient analysis we compared intervention and control cities with unconditional logistic regression by using cities as clusters using generalized estimating equations (GEE) to control for intracluster correlation. Statistical analyses were performed using STATA 8·0 for Windows .In the initial 2003 census of the ten intervention cities we identified 773 pharmacies and boticas, 2,292 pharmacy workers, 629 physicians, and 378 midwives. All were invited to participate in the program. Pharmacy workers were organized in groups according to their past training and role at the pharmacy: 23·6% were pharmacists (with university degree), 36·7% were pharmacy technicians , 11% were nurse technicians, 18·7% were pharmacy owners with no specific training in pharmacy, and 10% were relatives of owners or others with no specific training. Most (62%) were women; median age was 34·6 years for men (range 13 to 86) and 31·8 years for women (range 15 to 75). Those 18 years or older were invited to participate in training. Characteristics of private physician and midwife populations have been described elsewhere.After training, pharmacy workers averaged 18 of 20, and physicians and midwives 19 of 20, in correct responses to questions on STD syndromic management, with improvement in correct responses from pre-training to post-training tests of 54·8% for pharmacy workers and 40% for physicians and midwives. Most pharmacy workers and most physicians and midwives in private practice in each city were trained, certified and recruited to the PREVEN Network .During the trial, as Network participants left their jobs or moved to other cities, new pharmacy workers, physicians, and midwives were trained, certified, and added to the Network. Of the pharmacies initially enrolled, 119 (19%) closed during the first year and 183 (29·3%) closed during the three year trial period, including 39 (19·6%) of the true pharmacies and 144 (34%) of the boticas, while 352 new pharmacies opened including 74 true pharmacies and 278 boticas. The rate of turnover of pharmacy workers was exceptionally high. During the first year alone, 920 (44%) of the pharmacy workers left their jobs, and during the three years of the trial 1,677 (80·8%) of our initial trainees left, including 457 (76·2%) leaving a true pharmacy and 1,220 (82·8%) leaving boticas. However, we managed to train and certify 1,928 new pharmacy workers during this period. We also experienced substantial loss of physicians and midwives from the Network, including 94 (13·4%) in the first year and 286 (41%) during the three year period, while 182 new clinicians joined the Network during this period . Rates oMore than 250,000 educational pamphlets regarding STIs and condoms were distributed to clients of pharmacy workers and clinicians. Additionally more than 50,000 posters, calendars, stickers, manuals, and other pieces of merchandising related to the PREVEN Network were distributed during the intervention.In the ten intervention cities, the number of cases of STD syndromes reported to the “Prevention salesperson” from Network pharmacies was substantially higher than the numbers reported by Network physicians and midwives for 2004, 2005 and 2006, especially for urethral discharge, less so for suspected PID . NumbersA total of 7,280 simulated patient visits were made to the 30 pharmacies randomly chosen in each of the ten intervention and ten control cities during the trial. At baseline, intervention and control cities showed no significant differences in syndromic therapeutic management or referral, or in recommendations for use of condoms or partner treatment, but subsequent evaluations at three, six and 18 months showed significantly better performance for all measures of management in intervention cities. Substantial improvement in practice was sustained for 18 months following completion of initial training .Training pharmacy workers in STD syndrome management and creating a linked referral network of trained and certified clinicians proved feasible and acceptable at the community level. We emphasized referral of GUD and suspected PID to a clinician, because of the need for serologic testing for syphilis, and the complexity of the treatment including injection of benzathine penicillin in GUD management, and the need for physical examination and potentially for laboratory testing in women with symptoms of PID. In a recent paper, Khan Efforts to implement similar programs may similarly require continuous training to deal with high worker and facility turn-over. Turnover of boticas was far more frequent than for pharmacies, both for closing and for opening of new boticas. Regulations for boticas are less rigorous, but they provide a very large percent of the market for dispensing pharmaceuticals in Peru, representing almost 70% of the baseline census of pharmacies and boticas and 80% at the end of the intervention. Workers in actual pharmacies themselves represented a heterogeneous population with only 60% having received formal pharmacy training. Attention at the policy level to academic and occupational professionalism seems important to reduce the turn-over of pharmacy and botica workers. The rate of turn-over of physicians and midwives was approximately half that of pharmacy workers. Follow up of all physicians and midwives lost to the Network, suggested most if not all actually left the intervention cities. Migration of health professionals within the country and especially emigration to other countries is well known but not well documented in Peru. The National Institute of Statistics and Informatics Evaluations by simulated patients strongly supports the effectiveness of STD syndromic management training of pharmacy workers. Simulated patients were blinded to the intervention and we changed the teams for each evaluation. We cannot rule out an influence of the presence of posters and STD merchandising information on the evaluations in intervention cities, but our systematic post-evaluation interviews of simulated patients provided no evidence of such bias. Improvement in pharmacy workers performance over time is perhaps attributable to reinforcement by the visits of “Prevention Salespersons” and to more “practice” and confidence acquired by the workers.Although the number of physicians and midwives certified (728) in 2003 exceeded the number of pharmacies certified (642), substantially more cases of UD and VD in particular were seen by pharmacies than by the clinicians in the Network. One limitation is that we do not have a way of validating the number of clients with UD, VD, GUD or PID reported seen at pharmacies.Strengths of this study include the lessons learned from previous extensive studies with pharmacies and clinicians in Lima that guided design of this intervention modality for the multicomponent intervention trial. The baseline census of pharmacies and clinicians prior to the intervention enabled us to plan activities and define intervention targets.We believe that the simultaneous training of pharmacy workers and clinicians and linking trained pharmacies workers to the trained physicians and midwives in a Network, not only encouraged cross-referrals including referral of genital ulcer disease and suspected PID from pharmacies to clinicians, but enhanced the acceptability of the Network to pharmacy, physicians’, and midwives’ sectors. The creation of the “Prevention salesperson” support mechanism was also useful and could be used for other social and public health benefits. The impact of the multicomponent intervention at the population level is reported separately.We conclude that opportunities exist to train and empower pharmacy workers, physicians, and midwives in the management of STD syndromes, creating a network that provides better quality in the management of STIs. Training was feasible, well accepted at the community level and appears effective in terms of process and outcome indicators.


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Novel low-cost approaches for conducting rapid health assessments and health promotion interventions among underserved worker groups are needed. Recruitment and participation of construction workers is particularly challenging due to their often transient periods of work at any one construction site, and their limited time during work to participate in such studies. In the present methodology report, we discuss the experience, advantages and disadvantages of using touch screen handheld devices for the collection of field data from a largely underserved worker population.® devices. Language sensitive (English and Spanish) recruitment scripts, verbal consent forms, and survey questions were all preloaded onto the handheld devices. The experience  of the handheld administration method was recorded and compared to approaches available in the extant literature.In March 2010, a workplace-centered pilot study to examine the feasibility of using a handheld personal device for the rapid health assessment of construction workers in two South Florida Construction sites was undertaken. A 45-item survey instrument, including health-related questions on tobacco exposure, workplace safety practices, musculoskeletal disorders and health symptoms, was programmed onto Apple iPod TouchConstruction workers were very receptive to the recruitment, interview and assessment processes conducted through the handheld devices. Some workers even welcomed the opportunity to complete the questionnaire themselves using the touch screen handheld device. A list of advantages and disadvantages emerged from this experience that may be useful in the rapid health assessment of underserved populations working in a variety of environmental and occupational health settings.Handheld devices, which are relatively inexpensive, minimize survey response error, and allow for easy storage of data. These technological research modalities are useful in the collection and assessment of environmental and occupational research data. The construction industry is one of the largest industries in the United States, employing over eleven million persons representing 8% of the total labor force -3. Each Tailored health promotion interventions and workplace health assessments are powerful tools that increase the relevance and salience of health information by making it workplace and personally relevant . UnfortuTechnical devices, such as handheld computers and text messaging, have been suggested as convenient methods for survey data collection and participant engagement due to the fact that they allow for rapid assessment and information sharing at a relatively low cost ,10. For In the present methodology report, we describe and discuss the experience, advantages and disadvantages of using touch screen handheld devices for the collection of field data from an underserved transient worker population.® devices using Touch Metric's Surveyor® software , was programmed onto Apple iPod Touche Figure  12,13].,13.® devLanguage sensitive (English or Spanish) recruitment scripts, verbal consent forms, and survey questions were all preloaded onto the handheld devices. These forms and survey instruments were also made available on-site in paper format in the event a handheld device failed and for researchers who preferred to use paper. In collaboration and conjunction with visitation by a local lunch truck service, the research team recruited participants at two construction sites in South Florida either in the morning during the construction workers 15-minute breakfast break, or at noon during their designated 45-minute lunch break. Bilingual student interviewers approached construction workers congregating around the lunch truck armed only with their handheld devices to provide the construction worker a description of the study, an invitation to participate, verbal consent, and interview administration Figure . The samAcross the two construction sites, we approached a total of 57 construction workers that walked to the lunch trunk; 54 enrolled and completed the workplace health assessment pilot study of which 91% self-reported being Hispanic (n = 49). Among the completed assessments, 32 were completed by handheld device, and 22 by traditional paper method. Eleven assessments were administered in English (7 on handhelds and 4 by paper) and 43 in Spanish (25 on handhelds and 18 by paper). For workplace assessments conducted using the handheld devices, it took an average of 9 minutes and 37 seconds to complete the questionnaire; 11 minutes and 8 seconds for the Spanish version, and 9 minutes and 4 seconds for the English version. We did not collect the amount of time needed to administer the paper questionnaires. In terms of data validation, there were no missing or incorrectly entered questionnaire items among all handheld device user entries, while on average 2 items were not intelligibly circled or clearly printed on the paper version of the questionnaire.Overall, construction workers were very receptive to the recruitment, interview and assessment processes conducted through the handheld devices. Some workers even welcomed the opportunity to complete the questionnaire themselves using the touch screen handheld device, although ultimately all interviews conducted with handhelds were completed solely by trained study personnel. A list of advantages and disadvantages emerged from this experience that may be useful in the rapid health assessment of underserved populations working in a variety of field settings is displayed in Table ® software) of using handheld devices may be one strategy for expanding capacity building within the context of community-based participatory research partnerships [Some disadvantages should be noted. Senior study interviewers were reluctant to embrace use of the handheld device, citing difficulties with seeing the screens outside in bright light and in pressing the screen question options. In addition, while the devices have very long battery life (~30 hours) between charges, quality checks for battery life were necessary to ensure workability and function in the field. Although the initial start up cost may appear high for each device (~$200), data entry costs were eliminated, making use of handheld devices particularly attractive for researchers conducting multiple, ongoing field assessments. Finally, the relative ease of use combined with the low long-term cost  during the construction workers breakfast and lunch breaks at the lunch truck may reduce commonly encountered barriers to real-time workplace assessments. Future research in the application of these devices among time-constrained worker groups could improve engagement and retention in workplace health promotion programs for occupational groups that do not have a formal workplace setting. Furthermore, the interest and acceptance of these devices expressed by the workers in this study might lead to the use of self-administered questionnaires on handheld personal devices in future studies.From our field experience, we concluded that the use of a handheld personal device designed for time-pressed and hard to reach workers is a cost-effective and flexible modality for data collection that can assist with the rapid engagement of a traditionally difficult-to-reach vulnerable worker population. This methodology report adds to the extant literature on the advantages and disadvantages of using handheld devices in among hard to reach worker populations. Public health practitioners are encouraged to embrace informatics tools that enhance public health practice.US: United States; NHIS: National Health Interview SurveyThe authors declare that they have no competing interests.AJCM was responsible for conception, acquisition of funding, and general supervision of the research group. AJCM, TCC, EPD, LEF, and DJL made substantial contributions to data collection and study design. AJCM, TCC, EPD, LEF, and DJL contributed to analysis and interpretation of data; AJCM, TCC, EPD, LEF, and DJL were involved in drafting the manuscript or revising it critically for intellectual content. All authors read and approved the final manuscript.The study authors have obtained and keep on file photographic consent for Figure


Chinese American patients with Major Depressive Disorder (MDD) tend to underutilize mental health services and are more likely to seek help in primary care settings than from mental health specialists. Our team has reported that Culturally Sensitive Collaborative Treatment (CSCT) is effective in improving recognition and treatment engagement of depressed Chinese Americans in primary care. The current study builds on this prior research by incorporating telemedicine technology into the CSCT model.telepsychiatry-based culturally sensitive collaborative treatment (T-CSCT) intervention targeted toward Chinese Americans. Patients meeting the study's eligibility criteria will receive either treatment as usual or the intervention under investigation. The six-month intervention involves: 1) an initial psychiatric interview using a culturally sensitive protocol via videoconference; 2) eight scheduled phone visits with a care manager assigned to the patient, who will monitor the patient's progress, as well as medication side effects and dosage if applicable; and 3) collaboration between the patient's PCP, psychiatrist, and care manager. Outcome measures include depressive symptom severity as well as patient and PCP satisfaction with the telepsychiatry-based care management service.We propose a randomized controlled trial to evaluate the acceptability and effectiveness of a The study investigates the T-CSCT model, which we believe will increase the feasibility and practicality of the CSCT model by adopting telemedicine technology. We anticipate that this model will expand access to culturally competent psychiatrists fluent in patients' native languages to improve treatment of depressed minority patients in primary care settings.NCT00854542 Chinese Americans with depression tend to underutilize specialty mental health services and seek help in primary care settings instead . In an eRecognizing and treating symptoms of depression in ethnic minorities can be particularly challenging in populations in which depression is highly stigmatized . ResearcOne reason that Chinese Americans tend to underutilize mental healthcare services may be a lack of culturally sensitive options for mental health treatment, including treatment that can be administered in their native language . AlthougThese significant barriers to effective psychiatric treatment in primary care settings could be overcome by protocols including collaborative care management. Collaborative treatment, in which mental health professionals work closely with primary care doctors in delivering mental health treatment to patients, may be a valuable option for patients who are reluctant to seek treatment outside of primary care.Since language barriers can also lead to misdiagnosis and misunderstandings between patients and their caregivers, there is increasing interest in finding potential solutions for the dearth of Chinese-speaking clinicians to serve the needs of the growing Chinese American population in the United States. The current study will evaluate the viability of one such approach, telepsychiatry-based Culturally Sensitive Collaborative Treatment, or T-CSCT.Many Chinese Americans, as well as other non-English speaking immigrants to the United States, lack access to mental health professionals who are proficient in their native language. For these populations, telepsychiatry-based collaborative management could be both a convenient and beneficial option for comprehensive healthcare.The research team responsible for the current study has developed a model of Culturally Sensitive Collaborative Treatment (CSCT)  based onThe CSCT model in the current study consists of the following five components:PCPs are educated on the available options for treatment of patients with depression and how to improve patient adherence to treatment, one of the most significant challenges to treating depression . ResearcThe CB-PHQ-9, which was validated in a study by Yeung and colleagues , is a brThe EIP is an interview guideline of how to communicate with patients about their depression and negotiate treatment in a way that is compatible with patients' cultural beliefs, as detailed in a study by Yeung and colleagues . The EIPWhen PCPs and mental health professionals deliver patient care in a collaborative way, patients with MDD are more likely to adhere to their medication regimen and also express more satisfaction with the quality of care they receive . There iCare management has been found to be very effective in improving treatment adherence and general outcomes of depression; patients also tend to report higher satisfaction with their depression treatment when they are receiving collaborative care management . CollaboResearchers found that implementing the CSCT model in a primary care setting greatly increased the number of Chinese American patients who were diagnosed with depression and subsequently engaged in treatment, with 6.5% of depressed Chinese Americans receiving psychiatric treatment before and 43% after. In addition, patients in both care management and treatment as usual groups demonstrated a good response to treatment, although no significant differences were found between the treatment outcomes of the patients in the two groups . FurtherPast studies have indicated that videoconferencing is both a reliable and cost-effective method of administering mental health assessments and delivering patient care . When coTelepsychiatry is advantageous in situations where patients lack access to clinicians who would be able to treat their mental health most effectively. It would be particularly useful for patients living in isolated or rural areas with a shortage of psychiatrists or other mental health professionals, as well as in situations where a clinician fluent in the patient's native language is unavailable.The dual aims of this study are 1) to determine whether telepsychiatry-based CSCT is acceptable to both depressed Chinese American patients and their PCPs and 2) to gain insight into the model's efficacy in improving the treatment outcomes of depressed Chinese Americans in primary care clinics.Chinese Americans who screen positive for depression in participating primary care clinics will be called by research assistants. Eligible and interested patients will then be randomized into one of two groups. Those in the T-CSCT group will receive telepsychiatry-based Culturally Sensitive Collaborative Treatment (T-CSCT) from a multidisciplinary team, while patients in the Usual Care (UC) group will continue to receive treatment as usual from their PCPs alone. The proposed sample size is 60 patients in each group. However, anticipating a dropout rate of 20%, we aim to have at least 48 patients in each group complete all study procedures through the final week of the study.The T-CSCT intervention involves two major components:T-CSCT assessment: Patients in the T-CSCT group will undergo a telepsychiatry-based culturally sensitive psychiatry assessment by a bilingual psychiatrist using the Engagement Interview Protocol (EIP), described above. Patients in the UC arm will also undergo the initial telepsychiatry-based assessment with a psychiatrist, but this assessment will not utilize the EIP.1)Care management: The goal of care management is to monitor patients' psychiatric treatment as well as to consolidate and streamline the treatment efforts of the patient's PCP and psychiatrist. Via regularly scheduled phone visits with patients, bilingual care managers will monitor the following: patients' depressive symptoms, adherence to the MDD treatment protocol that their doctor(s) recommended, adverse events (for patients taking antidepressant medications), and patients' self-management of their depression. Care managers are accessible to patients through telephone contact or videoconferencing for questions on depression and medication, and they also can provide culturally sensitive interpretations of patients' symptoms and their treatment for depression. They serve as a link between the patient, PCP, and the consulting psychiatrist.2) The first care management interview is a face-to-face meeting with a bilingual care manager to establish rapport and to explain the roles of care manager and blind assessor (see below for details on the blind assessments), as well as to review the patient's course of illness and provide an explanation of MDD and how it can be treated.Subsequent visits will take place via telephone at seven scheduled points throughout the study .Patients will be included if they 1) are monolingual Chinese Americans, meaning that they require or prefer to be interviewed in Chinese (Cantonese or Mandarin), 2) are 18 years of age or older, 3) are competent to consent to study participation, 4) meet criteria for MDD as diagnosed by the Mini International Neuropsychiatric Interview (MINI) , 5) recePatients will be excluded if they 1) present with serious suicidal risk, 2) have an unstable medical illness requiring imminent hospitalization, 3) have comorbid severe mental disorders , or 4) have been treated by a psychiatrist within the past four months.The study will be conducted in collaboration with PCPs at the South Cove Community Health Center (hereafter South Cove), one of the largest community health centers for Chinese Americans in the Boston area. Although we expect that most patients who enroll in the study will have PCPs at South Cove, patients who do not have South Cove PCPs will still be allowed to enroll.Both the patients who screen positive as well as their PCPs will be informed about their screening outcomes. The PCPs of enrolled patients in both groups will be provided information about the study and must assent to treating their depressed patients who are enrolled in the study in the context of T-CSCT.At the beginning of the study, PCPs at South Cove will attend education sessions where study staff will explain study procedures, discuss depression treatment based on the Agency for Health Care Policy and Research (AHCPR) guidelines , and ansIn contrast to the protocol for the original CSCT study  on whichPCPs will be advised to schedule follow-up visits with the study patients at weeks 1, 3, 6, 10, 16, and 22 of the study. For patients in the T-CSCT group, the care manager will remind and assist patients in setting up these appointments; patients in the control group will set up their own appointments.All patients in the intervention and control arms will be recruited from patients in primary care using the PHQ-9; patients with scores of 10 or greater will be considered to have screened positive for depression.Subjects will be recruited primarily through depression screening at the three primary care clinics of South Cove, and through advertisements. Advertisements for the research study will be placed in community primary care clinics as well as in high-traffic areas in the Chinese community, in local Chinese newspapers, and on the Internet. Participants will also be recruited through referrals from primary care doctors. Research staff will distribute copies of the CB-PHQ-9 to patients in primary care clinics. Patients who score at or above a 10 on this assessment will be encouraged to call a research assistant or give the form to a nurse, who will send it to a research assistant; the RA will then contact the patient directly.not receive protocol-driven collaborative care management; however, they may seek psychotherapy and/or psychopharmacological consultation, including a telepsychiatry-based consultation from the study psychiatrist.PCPs of the patients who are randomized to UC will be informed that their patient is participating in the study and that the patient has depression. Patients will All study procedures have been approved by the Institutional Review Board (IRB) of the Partners HealthCare System.The CB-PHQ-9 will be used as the initial screening tool for patients interested in participating in the study. The CB-PHQ-9 has demonstrated promising validity, with 81% sensitivity and 98% specificity . The EngIn addition to the CB-PHQ-9, other instruments administered at the screening/baseline visit will include the Hamilton Rating Scale for Depression (HAM-D 17-item), the Clinical Global Impressions-Severity (CGI-S) and Improvement (CGI-I), the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), the 16-item, Quick Inventory of Depressive Symptomatology (QIDS-SR) and the Explanatory Model of Interview Catalogue. The MINI, and the EIP (for patients in the T-CSCT arm)  will be After the screening visit, the care manager will provide seven additional scheduled phone visits to patients in the T-CSCT group  and random effects logistic regressions (for binary outcomes measured repeatedly) will be performed to detect associations between interventions and outcomes, controlling for relevant covariates. Random effects models for repeated measures will be used, since multiple assessments will take place throughout the study. Binary outcomes that are not measured repeatedly, like treatment initiation or trial completion, will be analyzed using multivariate logistic regressions. Relevant covariates that will be controlled for in all random and fixed effect regressions include the HAM-D-17 score at the baseline visit, the use of alternative treatments for depression, study site, and gender.One of the major goals of the study is to test the null hypothesis that the proportion of responders in the T-CSCT group is equal to the proportion of responders in the usual care group. Assuming a sample size of 48 , an alpha of 0.05, and a two-sided alternative hypothesis, the study will have power of 0.80 to detect a statistically significant difference between the proportions of responders in the two treatment arms. This computation assumes that the difference in proportions of treatment response is 0.30 (at least 70% of patients receiving T-CSCT will meet criteria for treatment response and up to 40% of patients in the control group will meet criteria for treatment response).If found to be acceptable and effective, the telepsychiatry consultation paired with collaborative care management may be an effective model in treating the mental health not only of Chinese American patients, but also of an ever diversifying American population with limited access to clinicians fluent in their culture and language.Consultation via videoconferencing may help to widen the accessibility of culturally and linguistically competent mental health practitioners. Discussing their mental health with a clinician familiar with their culture and fluent in their native language may help patients feel more comfortable disclosing stigmatized symptoms.This intervention may significantly increase the accessibility of mental health services to immigrant populations. The collaborative care management model may help these populations navigate the healthcare system more fluidly, thereby facilitating their adjustment to life in a new country. The current study could help clarify whether care management can or cannot improve treatment outcomes in depressed Chinese Americans, which had been questioned by a prior study .If successful, the T-CSCT model has the potential to become the prototype for telemedicine-based multilingual mental health resource centers across the country, providing services to other underserved minority populations and ultimately reducing disparities in mental health treatment.The current study proposes a model that seeks to improve the mental health care of Chinese Americans at several different levels. This multifaceted model involves: 1)screening patients for depression in primary care settings, 2) having PCPs deliver effective preliminary psychiatric care before a patient can be seen by a mental health practitioner, 3) interviewing patients via telepsychiatry using a culturally sensitive psychiatric interview protocol, 4) appointing a care manager to check in with patients by phone at regular intervals, and 5) constructing a collaborative group of practitioners involved with patients' mental healthcare about how best to treat the patient.Although this model may appear complex, we anticipate that over time, the benefits of such a model will outweigh its implementation costs, just as collaborative care models for depressed English-speaking patients in primary care have proven cost-effective . This stExcept for Dr. Fava and Dr. Chang, whose financial competing interests are listed below, all other contributors report they have no competing interests.Trina Chang, MD, MPHDr. Chang has received research funding from AstraZeneca, CeNeRx, Euthymics, Forest, GlaxoSmithKline, Johnson & Johnson, and Pfizer.Maurizio Fava, MD® LLC; Photothera; Roche; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst LaboratoriesAbbott Laboratories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; Cephalon, Inc.; CeNeRx BioPharma; Clinical Trials Solutions, LLC; Clintara, LLC; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Icon Clinical Research; i3 Innovus; Johnson & Johnson Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; NCCAM; NIDA; NIMH; Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmavitefinancial remuneration is $0 unless otherwise noted2010-5500.); Eli Lilly and Company; ePharmaSolutions; EPIX Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; GenOmind, LLC; GlaxoSmithKline; Grunenthal GmbH; i3 Innovus; Janssen Pharmaceutica; Jazz Pharmaceuticals, Inc.; Johnson & Johnson Pharmaceutical Research & Development, LLC ; Knoll Pharmaceuticals Corp.; Labopharm Inc.; Lorex Pharmaceuticals; Lundbeck Inc.; MedAvante, Inc.; Merck & Co., Inc.; MSI Methylation Sciences, Inc.; Naurex, Inc.; Neuronetics, Inc.; Novartis AG; Nutrition 21; Orexigen Therapeutics, Inc.; Organon Pharmaceuticals; Otsuka Pharmaceuticals; PamLab, LLC.; Pfizer Inc.(2011-$3500.); PharmaStar; Pharmavite® LLC.; PharmoRx Therapeutics; Precision Human Biolaboratory; Prexa Pharmaceuticals, Inc.; Puretech Ventures; PsychoGenics; Psylin Neurosciences, Inc.; Rexahn Pharmaceuticals, Inc.; Ridge Diagnostics, Inc.; Roche; RCT Logic, LLC; Sanofi-Aventis US LLC.; Sepracor Inc.; Servier Laboratories; Schering-Plough Corporation; Solvay Pharmaceuticals, Inc.; Somaxon Pharmaceuticals, Inc.; Somerset Pharmaceuticals, Inc.; Sunovion Pharmaceuticals; Synthelabo; Takeda Pharmaceutical Company Limited; Tetragenex Pharmaceuticals, Inc.; TransForm Pharmaceuticals, Inc.; Transcept Pharmaceuticals, Inc.; Vanda Pharmaceuticals, Inc.Abbott Laboratories; Affectis Pharmaceuticals AG; Alkermes, Inc.; Amarin Pharma Inc.; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management, Inc.; BioMarin Pharmaceuticals, Inc.; Biovail Corporation; BrainCells Inc; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon, Inc.; Clinical Trials Solutions, LLC; CNS Response, Inc.; Compellis Pharmaceuticals; Cypress Pharmaceutical, Inc.; DiagnoSearch Life Sciences (P) Ltd.; Dinippon Sumitomo Pharma Co. Inc.; Dov Pharmaceuticals, Inc.; Edgemont Pharmaceuticals, Inc.; Eisai Inc.; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Cephalon, Inc.; CME Institute/Physicians Postgraduate Press, Inc. for editing supplements & CME web activity  ; Eli Lilly and Company; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; Imedex, LLC; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier for speaking at symposium ;MGH Psychiatry Academy for speaking at symposium 3/26/11 (2011-$2500.) Novartis AG; Organon Pharmaceuticals; Pfizer Inc.; PharmaStar; United BioSource, Corp.; Wyeth-Ayerst LaboratoriesAdamed, Co; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; AstraZeneca; Belvoir Media Group for editing a newsletter (CompellisHandbook of Psychiatric Drug Therapy (2010-$835.) Royalty from Wolters Kluwer Health Inc., ) World Scientific Publishing Co. Pte. Ltd. (2011: $544. for 2010)Patent for SPCD and patent application for a combination of azapirones and bupropion in MDD, copyright royalties for the MGH CPFQ, SFI, ATRQ, DESS, and SAFER. Patent for research and licensing of SPCD with RCT Logic. Royalty from Lippincott, Williams & Wilkins for AY originated and supervised the study, completed the analyses, and led the writing of the article. KH, TC, and NT assisted with the study and the writing of the article. MF assisted with the origination and supervision of the study and the writing of the article. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-244X/11/154/prepub


Systematic evaluation of cumulative health risks from the combined effects of multiple environmental stressors is becoming a vital component of risk-based decisions aimed at protecting human populations and communities. This article briefly examines the historical development of cumulative risk assessment as an analytical tool, and discusses current approaches for evaluating cumulative health effects from exposure to both chemical mixtures and combinations of chemical and nonchemical stressors. A comparison of stressor-based and effects-based assessment methods is presented, and the potential value of focusing on viable risk management options to limit the scope of cumulative evaluations is discussed. The ultimate goal of cumulative risk assessment is to provide answers to decision-relevant questions based on organized scientific analysis; even if the answers, at least for the time being, are inexact and uncertain.  When formal methods to estimate human health risk from exposure to environmental agents were first employed by the U.S. Environmental Protection Agency (EPA) and the U.S. Food and Drug Administration (FDA) in the 1970s, the emphasis was on determining the carcinogenic potency of individual manufactured chemicals. Early risk assessments consequently focused on evaluating adverse health outcomes from anthropogenic carcinogens in air, water, and food. The risk assessment processes and procedures that subsequently evolved were strongly influenced by the regulatory attitude prevailing in that epoch, which stressed implementation of national command-and-control strategies and technology-based legal statutes to control pollution on a chemical-by-chemical basis ,3,4. OveThe potential for interactions among mixture constituents to produce synergistic effects is well known , and EPA has conducted risk assessments for a few chemical mixtures with sufficient epidemiologic evidence  ,6,7. TheEfforts are currently underway to develop and apply innovative methods that assess cumulative health risk, where “cumulative risk” refers to the combined threats from exposures via all relevant routes to multiple environmental stressors, including biological, chemical, physical, and psychosocial entities ,4. “CumuScientists and risk assessors are well aware that toxicity can be modified by exposure to multiple environmental agents . There iHistorically, most risk assessments described as “cumulative” have focused primarily on reasonably simple chemical mixtures ,22,23,24In 1986, EPA published risk assessment guidelines . AccordiThe National Research Council (NRC) published a report in 1993 , which rIn 1999, the International Life Sciences Institute issued a report  proposinIn 2004, the Agency for Toxic Substances and Disease Registry (ATSDR) released its guidance manual  for riskPhthalates and Cumulative Risk Assessment 3], the Ni.e., differential biological susceptibility and exposure, as well as differential preparedness to withstand stressor effects and ability to recover from stressor effects) into the assessment explicitly – rather than treating it implicitly as is done in most conventional assessments; it focuses on population-based or location-based assessments of real-world cumulative exposures experienced by actual people – most conventional assessments entail source-based assessments of hypothetical people and theoretical exposures; it recognizes that the details  and history  of exposure to multiple stressors may be important for predicting risk – conventional assessments typically assume adverse effects are related solely to a combination of duration and intensity; it takes account of background exposures , which may contribute to the cumulative risk under consideration – not normally evaluated as part of conventional risk assessments; and it provides for the possibility, depending on the circumstances, of a semi-quantitative or qualitative analysis/result – in contrast to most previous assessments, which are quantitative [Assessment of cumulative risk differs from conventional assessments in several important ways : it invotitative .In point of fact, relatively few cumulative risk assessments have been conducted, and requisite conceptual models, theoretical frameworks, and analytical procedures are still being developed. The incorporation of nonchemical stressors, like discrimination and poverty, has been especially problematic; so much so that, to date, EPA has not included psychosocial stressors as part of any formal risk assessments . The sit


With the inverse relationship between fiber content and energy digestibility being well described for several feed ingredients, it is only logical that development of processing techniques or enzymes that degrade fiber, and thereby improve energy digestibility or voluntary feed intake, will be both metabolically and economically beneficial to pork production.Application of feed processing methods and use of exogenous feed additives in an effort to improve nutrient digestibility of plant-based feed ingredients for swine has been studied for decades. The following review will discuss several of these topics, including: fiber characterization, impact of dietary fiber on gastrointestinal physiology, energy, and nutrient digestibility, mechanical processing of feed on fiber and energy digestibility, and the use of exogenous enzymes in diets fed to growing pigs. Taken together, the diversity and concentration of chemical characteristics that exists among plant-based feed ingredients, as well as interactions among constituents within feed ingredients and diets, suggests that improvements in nutrient digestibility and pig performance from mechanical processing or adding exogenous enzymes to diets fed to swine depends on a better understanding of these characteristics, but also relating enzyme activity to targeted substrates. It may be that an enzyme must not only match a target substrate(s), but there may also need to be a  It . It 7]. abundant . As showVFA) such as acetate, propionate, and butyrate. These VFA are rapidly absorbed and have been shown to supply between 5 and 28% of the maintenance energy requirement of pigs . Ho. Ho82]. ectively , which aSince most of the starch in corn has been converted to ethanol, DDGS contains approximately 35% insoluble and 6% soluble dietary fiber  Table 88. LikewiThe apparent total tract digestibility of dietary fiber in DDGS averages 43.7%, but ranges from 23% to 55%. This variation in fiber digestibility is believed to influence digestibility of energy in DDGS. Apparent ileal digestibility and total tract digestibility of dietary fiber in DDGS is higher than in corn, and are presumed to be improved as a result of the processing and fermentation processes used in ethanol plants . HoweverConsequently, when evaluating the effectiveness of exogenous enzymes, the composition of ″fiber″ must be considered in order for energy and nutrient digestibility to potentially be improved. This is clearly demonstrated by Li et al.,  who evalIt is clear that there needs to be an improved characterization of fibrous components in all feedstuffs . Likewis′cocktail′ of enzymes to effectively breakdown the complex matrixes of fibrous carbohydrate structures, and there must be some negative role that these substrates have on nutrient digestibility or voluntary feed intake. With the inverse relationship between fiber content and energy digestibility being well described for several feed ingredients, it is only logical that development of enzymes that degrade fiber, and thereby improve energy digestibility or voluntary feed intake will have a greater likelihood to be beneficial to improve fiber utilization in swine, both metabolically and economically. The results of an unpublished study by the authors suggests that although some of the enzyme/additive products evaluated had variable, but small effects on nutrient digestibility, none of these products were effective in improving starter and finishing pig growth performance when fed nutritionally adequate corn-soy diets containing 30% DDGS.Application of enzymes in an effort to improve nutrient digestibility of plant-based feed ingredients for swine and poultry has been studied for decades. However, with a large diversity and concentration of chemical characteristics existing among plant-based feed ingredients, as well as interactions among constituents within feed ingredients and diets, improvements in nutrient digestibility and pig performance from adding exogenous enzymes to growing pig diets depends on understanding these characteristics in relation to enzyme activity. Essentially, the enzyme must match the target substrate(s), there may need to be a ADF: Acid detergent fiber; ADG: Average daily gain; ADFI: Average daily feed intake; AID: Apparent ileal digestibility; ATTD: Apparent total tract digestibility; C: Carbon; CP: Crude protein; DE: Digestible energy; DDGS: Dried distillers grains with soluble; DM: Dry matter; EE: Ether extract; GE: Gross energy; GF: Gain to feed ratio; ME: Metabolizable energy; N: Nitrogen; NDF: Neutral detergent fiber; NSP: Nonstarch polysaccharides; P: Phosphorus; S: Sulfur; TDF: Total dietary fiber; TTD: Total-tract digestibility; VFA: Volatile fatty acids.The authors declared that they have no competing interests.BJK and GCS co-wrote this review and any internal research reported was jointly designed and interpreted. Both authors have read and approved the manuscript.Brian J. Kerr, Ph.D., is a Lead Scientist/Animal Scientist for the USDA Agricultural Research Service, with expertise in digestibility, nutrient utilization, and evaluation of alternative feed ingredients. Gerald C. Shurson, Ph.D., is a Professor of Animal Science at the University of Minnesota with expertise in nutrition and the use of alternative feed ingredients in swine production.Mention of a trade name, proprietary product, or specific equipment does not constitute a guarantee or warranty by the USDA or the University of Minnesota and does not imply approval to the exclusion of other products that may be suitable. The USDA is an equal opportunity provider and employer.


Population ageing, changes to the profiles of life-limiting illnesses and evolving societal attitudes prompt a critical evaluation of models of palliative care. We set out to identify evidence-based models of palliative care to inform policy reform in Australia.A rapid review of electronic databases and the grey literature was undertaken over an eight week period in April-June 2012. We included policy documents and comparative studies from countries within the Organisation for Economic Co-operation and Development (OECD) published in English since 2001. Meta-analysis was planned where >1 study met criteria; otherwise, synthesis was narrative using methods described by Popay et al. (2006).Of 1,959 peer-reviewed articles, 23 reported systematic reviews, 9 additional RCTs and 34 non-randomised comparative studies. Variation in the content of models, contexts in which these were implemented and lack of detailed reporting meant that elements of models constituted a more meaningful unit of analysis than models themselves. Case management was the element most consistently reported in models for which comparative studies provided evidence for effectiveness. Essential attributes of population-based palliative care models identified by policy and addressed by more than one element were communication and coordination between providers (including primary care), skill enhancement, and capacity to respond rapidly to individuals’ changing needs and preferences over time.Models of palliative care should integrate specialist expertise with primary and community care services and enable transitions across settings, including residential aged care. The increasing complexity of care needs, services, interventions and contextual drivers warrants future research aimed at elucidating the interactions between different components and the roles played by patient, provider and health system factors. The findings of this review are limited by its rapid methodology and focus on model elements relevant to Australia’s health system. Access to appropriate care and support at the end of life is recognised by many as a basic human right . HoweverAdvances in detection and treatment mean that diseases such as cancer and HIV that previously killed people quickly are now chronic conditions that confer an increasing burden of symptoms and functional decline over many years ,5. MedicThe current study set out to inform Australian palliative care policy reform by identifying and synthesising:1) recommendations for population based palliative care from international policy, and2) the evidence for improvements on patient, family and health system outcomes available for different population-based models of palliative care from studies of any design comparing one model with another or models to usual care.A rapid review of the palliative care literature was undertaken over an eight week period in April 2012. Rapid review methodology utilises similar processes to a full systematic review but generates a more timely synthesis of the evidence by limiting scope (e.g. search terms and inclusion criteria ) and various aspects of synthesis (e.g. data extraction and bias assessment) . In deciTwo kinds of document were deemed informative. First, we were interested to identify how various models of palliative care had been defined in the literature and which of these have been supported by evidence. We also sought international policy documents/reports with most applicability to Australia’s universal health care system and federal/state structure of funding. To be included, documents of both kinds needed to come from an Organisation for Economic Co-operation and Development (OECD) country and have been made publically available in English since 2001. We limited to more recent publications to maximise relevance to contemporary populations and healthcare contexts. Documents had to be concerned with facilitating the delivery of palliative care to people with progressive life-limiting illness in any setting.Inclusion criteria relating to palliative care were based on the World Health Organisation (WHO) definition on the basis of being the most widely used internationally . Models Studies were considered eligible for inclusion if they provided data on effectiveness and/or cost-effectiveness based on comparison either between two alternative models of palliative care or between a model of palliative care and usual care. Usual care was assumed to include routine community and hospital services other than SPC models (including private). Comparisons could be concurrent or historical. Studies providing level 1 and 2 evidence  were prioritised, with studies using other, less rigorous designs (e.g. multiple time series) being treated as secondary sources of information .We were also interested to see which models of palliative care had been recommended by current international policy. Policy document were defined as any publically available statement of position, standards or recommendations officially put forward by a government. Eligible document types included reports by health services and peak bodies as well as peer-reviewed journal articles and books/book sections.http://www.caresearch.com.au/caresearch/tabid/501/Default.aspx) were also reviewed for inclusion.We searched Medline, AMED, CINAHL, the Cochrane Database of Systematic Reviews, Health Technology Assessment Database and CENTRAL from their earliest records. We also searched the grey literature via internet search engines (Google and Google Scholar), the online Australian palliative care knowledge network, CareSearch, and other relevant online clearinghouses (e.g. Americans for Better Care of the Dying). Deep web searching using Mednar was considered useful for the targeting of scientific material unavailable to search engines like Google . DocumenThe reference lists of all included reviews were searched manually for further relevant articles.Searches for literature reporting on palliative care were conducted simultaneously with those aimed at meeting secondary aims of identifying service planning tools and research on the palliative care needs of Australians (not reported in this paper). Database searches used Medical Subject Headings (MeSH) terms or equivalent as well as keywords relating to palliative and end of life care + service models (see Table Articles returned from searches of electronic databases were imported into Endnote (version X4) and coded by a single researcher against inclusion criteria for evaluative studies using a standardised proforma.Given the rapid nature of our review, we extracted detailed data only from those original studies not contributing to the findings of an included systematic review and data extraction was undertaken by one researcher only. Data on each model of palliative care were extracted using an electronic proforma according to a recently published disease management taxonomy which considered: patient population, intervention recipient; intervention content, delivery personnel, method of communication, intensity and complexity, environment and clinical outcomes . VariablSystematic reviews were quality rated by a single reviewer using the AMSTAR checklist . Any RCTModels of care were classified according to definitions provided by a range of sources identified by Medline and Google searches; wherever possible, definitions were taken from Australian sources to ensure relevance to the Australian healthcare system -33. ClasTable A total of 1,959 articles returned from electronic databases were screened for inclusion as evaluative studies, of which 23 reported systematic reviews, 9 RCTs and 34 non-randomised comparative studies. Systematic reviews included an average of 18 studies range 2–43) and varied as to whether they defined their focus by setting  devformance ; and iiiscomfort . Systemascomfort ,59.Models of care are faced with special challenges during transitions between care settings  where support is needed to avoid patients ‘falling through the cracks’  and/or wThis review identified a number of dynamic elements that have been integrated into palliative care models in a range of care settings to enable access to appropriate services, improve communication and coordination between providers, enhance palliative care skills of non-specialist and informal carers, and inrease capacity to respond rapidly to individual patient needs and preferences as these change over time.Case management is a recurring feature of many successful models ,62,64-69Whilst defintions of shared care have varied Table , it has A model of care that incorporates case management and shared care and has been recommended by policy in Australia in the absence of evaluation data is the ‘pop up’ model. This model was originally developed to extend palliative care to rural/remote adult services and has since been recommended for paediatric palliative care . The modInternationally, specialist outreach services have been widely adopted to improve care outcomes for underserved populations through the establishment of: i) specialist clinics in urban primary care practices; ii) specialist clinics in rural hospitals where no specialist services exist; and iii) sub-specialist clinics in regional centres . A CochrAcross the globe, clinical networks have been integrated into many healthcare systems as part of a wider reform agenda to ensure that underserved populations and those with poorer outcomes have better access to quality, clinically-effective health services ,116. CliNumerous studies identified the crucial role of integrated care -56. InteIntegrated care is especially important when supporting adults or children in the community, the enablement of which is increasingly prioritised by policy in many countries ,119. WhiUse of volunteers may have potential where informal caregivers are lacking; however, appropriate governance models are needed. Volunteer models have been used across a range of palliative care settings but evidence of implementation and evaluation is limited -132.Most studies that have examined cost-effectiveness of palliative care services versus usual care have found either no significant difference or palliative care to compare favourably ,51,53,56per se.Like previous systematic reviews in palliative care , we founOur review also identified the role required of political drivers in leveraging health system reform. Case management demands care across jurisdictions and care settings, which is not easy to achieve in a state/federal funding structure of the kind seen in Australia. The influence of local drivers also means that some models of care have been based on geo-political boundaries that may not be readily transferrable to other regions ,134-136.Two new systematic reviews published since our search was conducted have provided important data on cost-effectiveness of palliative care. The value of home based palliative care has been demonstrated in a recent meta-analysis which found that receiving home palliative care doubles the odds of dying at home and reduces symptom burden, especially for patients with cancer, without having an adverse impact on caregiver grief . A systeThe rapid nature of the current review is associated with a number of methodological limitations ,13. LimiAs mentioned, the current review was also limited by variations in reporting of service models that precluded comparison and accumulation of evidence for any given model. The term ‘model of care’ was itself used inconsistently and relatively infrequently in the literature; a Medline search using terms for ‘palliative care’ combined with ‘model(s) of care’ returned only 1% of articles returned by searching for palliative care alone. Inconsistency and incompleteness in reporting impairs not only synthesis of research but also replication of successful models in future evaluations and implementation into practice. Researchers are encouraged to follow guidance on key variables to report that would enable greater comparability and support replication and refinement of models in research and practice .The literature’s focus on elements rather than models raises important questions about how these elements might interact to the betterment or detriment of care quality and outcomes. The pop up model is one example of a model of care that has been recommended by policy without evidence for its effectiveness as a whole but rather an assumption that effective elements can be combined to optimise benefit . Future Finally, our review was limited by the problem we encountered in mapping between evidence at the outcome levels of patient (e.g. symptoms), caregiver (e.g. satisfaction), provider  and service . A recent systematic review identified 15 patient-level domains alone, including quality of life, quality of care, symptoms and problems, performance status, psychological symptoms, decision-making and communication, place of death, stage of disease, mortality and survival, distress and wish to die, spirituality and personality, disease-specific outcomes, clinical features, meaning in life and needs . The pleHeterogeneity in definitions and reporting mechanisms limit the focus of conclusions from this rapid review to attributes and elements of successful palliative care services rather than whole models. Best practice palliative care should be accessible to all who need it, tailored to individual patient and family’s palliative care needs in a timely manner, and extend beyond organisational and disciplinary boundaries as required via strategies that support communication and coordination. Population-based models of palliative care should therefore include elements that support case management via integration of SPC with primary and community care services, and enable transitions across settings, including residential aged care.While palliative care models may have once been relatively homogenous, dynamic models are increasingly required to accommodate rapidly changing population demands and health system structure and drivers. Access to specialist services for rural and regional patients and carers has been identified as especially in need of targeted intervention. The current focus on medical and nursing service delivery should also be broadened to incorporate services addressing social and environmental determinants of health as required.Increasing complexity in service configuration warrants consideration by future research of the roles played by contextual factors such as funding and policy in order to inform planning at the population level. Research should ideally test the impact of changes over time both within and between regions using standard measures of process and outcomes.GP: General practitioner; SPC: Specialist palliative care.The authors declare that they have no competing interests.All authors contributed to design and conduct of the review, synthesis and interpretation of results and reporting. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/14/136/prepub


Association of dystrophic calcifications and lipodystrophy are mostly described in patients with juvenile dermatomyositis (JDM), only occasionaly as part of some other clinical entities. To our knowledge, these conditions are rarely reported as main reasons for first refferal to pediatric rheumatologist.Our goal is to demonstrate the benefit of basic and multidisciplinary diagnostic work up  required for definitive diagnosis as in this case as well as therapy decision.We describe a 13,5 y old girl presented (april 2011) with extensive calcinosis and lipodystrophy, which were lasting for 10 years, without any treatment. General, musculoskeletal, pulmological and orthodontist evaluations were undertaken. Investigations included multiple radiographs of the calcified regions and chest X-ray, computed-tomography of the lungs, MRI of pelvis, coxofemoral and sacroiliacal joints.Patient did not have typical clinical and laboratory signs required for definite JDM diagnosis, as is usually seen at disease onset, but history data confirmed that they existed 10 years ago. At the time of first referral to pediatric rheumatologist, she had extensive calcinosis (mixed forms), radiological signs of interstitial lung disease, mild pulmonary hypertension, osteopenia, multiple osteofits and lateroghenia.Distinction between muscle and skin inflammation and residual state can be difficult expecially in case of probably monocyclic course of muscle disease. Multidisciplinary diagnostic work up is ultimate in process of therapy decision in case of 10 years non-treated juvenile dermatomyositis.


The overwhelming need to improve preclinical models in oncology has stimulated research efforts to refine and validate robust orthotopic models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Sophisticated technologies including bioluminescence, contrast enhanced ultrasound imaging, positron emission tomography, computed tomography and magnetic resonance imaging have been added to existing serum- and histology-based biomarkers to assist with patient selection and the design of clinical trials. The rationale for the use of human hepatocellular carcinoma (HCC) cell lines, implementation of xenograft and orthotopic animal models and utilization of available biomarkers have been discussed, providing guidelines to facilitate preclinical research for the development of treatments for HCC patients. Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and its incidence in the United States and other countries has been steadily increasing over the past 25 years ,2. Given®, Adria Laboratories), showed rather low efficacy; however, with a response rate of 10-15%, doxorubicin remains the most effective single agent currently available [®, Bayer), significantly prolonged the time to tumor progression, increased overall survival in a placebo-controlled phase III study in HCC patients [®, Pfizer Inc.) was also tested in phase II clinical trials in HCC patients showing that HCC could be susceptible to treatment with anti-angiogenic compounds [Advanced HCC is highly refractive to currently available chemotherapies, and patients suffering from HCC often develop drug resistance during treatment. Several chemotherapeutic agents have been tested in patients with advanced HCC; however, the results were disappointing and life-threatening side effects frequently limit prolonged treatment . One of patients ,7 and sipatients . Becauseompounds ,10.Preclinical experimentation allows for simultaneous longitudinal implementation of various technologies and biomarkers to monitor the tumor take rate, growth and response to treatment as well as to confirm and correlate histological and histochemical results at various time points with serum or imaging biomarkers, which cannot be determined in HCC patients. Different animal models and biomarkers, such as serum alpha-fetoprotein (AFP), bioluminescence imaging (BLI), contrast enhanced ultrasound imaging (CEUS), positron emission tomography (PET), computed tomography (CT) and immunohistochemistry (IHC), can be utilized to build confidence in the efficacy and safety of tested compounds during preclinical research and help to develop biomarker strategies and design clinical trials.in vitro testing of human HCC cell lines is usually an early step in the process of anticancer drug discovery that involves evaluating viability, cell proliferation, clonogenicity and apoptosis. In vitro results from our studies in four commonly used human HCC cell lines: Huh7.5, HepG2, Hep3B and SK-Hep1, showed that sunitinib alone moderately inhibits proliferation in all four HCC cell lines with IC50s in the low micromolar or high nanomolar range. Doxorubicin used as a monotherapy was also effective; the IC50 was in the low nanomolar range in all four HCC cell lines deployed. Combining doxorubicin and sunitinib resulted in additive inhibitory effects on cell proliferation in all cell lines used in the study; however, none of the cell lines were very sensitive or resistant to imposed treatments [in vitro therapeutic efficacy with the drug combination was mainly due to the induction of apoptosis and inhibition of proliferation.Similar to other cancers, eatments . Mechaniin vitro systems lack the power to recapitulate the complex relationship between the tumor and its microenvironment, including local blood supply and angiogenesis, interactions between tumor cells and the organ where the tumor resides, and the influence of hormones, growth factors and cytokines on tumor growth and survival. Scientists usually start in vivo oncology work with subcutaneous (SC) xenograft models because these are relatively easy to perform; tumors are externally placed and simple caliper measurement of tumor size provides insight regarding compound efficacy measured as inhibition of tumor growth (TGI) [While results obtained using cell cultures provide important information regarding drug efficacy and mechanisms of action, th (TGI) A and 1Aath (TGI) ,13,14,15in vivo study, testing combination therapy using two or three drugs adds to the complexity of the study design and study execution. For example, if the study design calls for the use of only one imaging method and one biomarker, then each methodology must be deployed in the same model/study in all study groups treated with sole therapy as well as in study group(s) treated with two or three drugs used in combination. The practicality of study conduct end execution becomes even more complex if the study design requires testing a combination of two drugs in several HCC cell lines. Such a study will require 16 different study groups and with a minimum of eight animals per group to achieve statistical significance, anticipated study conduct will become very challenging for any lab even if a simple subcutaneous xenograft model is deployed. Because the number of available tumor cell lines is constantly increasing, testing novel compounds in all available cell lines becomes increasingly difficult, in particular since the research community in general lacks firm criteria to guide the decision on which HCC cell line has relevance for a particular patient population. In addition, tumor cells grown in culture are susceptible to undergoing genetic alterations not found in the original tumor, such that xenografts created by these cells may differ from those of naturally occurring tumors [Selecting the cell line(s) for an animal study is often challenging because the scientist must decide which cell line, from all cell lines available for a particular tumor type, best represents a particular human cancer, and selecting only one cell line that responds to exact treatment could be very misleading when it comes to clinical outcome . Even ifg tumors . in vivo data, we propose the use of cell cocktails composed of several HCC cell lines to create xenograft or orthotopic models as the next step in screening cascades aimed at building confidence in compound efficacy in in vivo studies in single-cell xenografts have confirmed therapeutic effect. Also, the deployment of cell cocktails allows for the assessment of eventual resistance to treatment of individual cell line(s) used to make the cocktail, pending same exposure to drug(s) and treatment duration. Finally, the use of tumor cell cocktails if and when possible will reduce the amount of drug needed for testing, lessen the time and resources needed for preclinical studies without compromising data quality and integrity as well as support the 3Rs animal welfare paradigm  [in vivo study to assess which cell line(s) used in the cell cocktail did not respond to treatment. To improve the robustness and predictive value of  Reduce) . When usAlternatively, human biopsies instead of tumor cell lines can be used to create xenograft or orthotopic models, but caveats to this approach are the high cost of procedures and transfer of biopsies along with safety issues due to a high rate of hepatitis C (HCV) and hepatitis B (HBV) infections in HCC patients ,20,21,22The local vasculature of the liver is extremely complex and is composed of nutritional and functional blood supplies that in addition to neo-vasculature created by tumor itself, collectively support tumor growth within the liver. In brief, total liver blood flow represents approximately 25% of the cardiac output, with roughly 100-130 mL of blood circulating through 100 g of liver tissue per minute, and this number is fairly constant across all mammalian species. The hepatic artery accounts for about 65% of the oxygen supply to the liver ,24,25. TOne of the most clinically effective ways to deliver drugs to the liver is through the hepatic artery because it allows continuous infusion directly into the arterial bed from which the tumor derives nearly all of its blood supply ,33. InjeClinical diagnosis and monitoring of HCC in patients consists of a blood test for elevated AFP concentrations followed by structural imaging utilizing one of several imaging modalities that are currently available. The most frequently used imaging methods are CEUS, contrast CT and MRI. Also, PET imaging with FDG and/or FLT is increasingly being used both preclinically and in clinical practice ,40,41,42AFP is the primary serum biomarker for HCC and is elevated in up to 40% of patients with early-stage HCC, with expression increasing in advanced disease ,46. AlthUS technology using microbubbles as a contrast agent is known to be an extremely useful tool for non-invasive assessment of liver vascular structure . CEUS isBLI is based on the detection of light emitted by living cells expressing a luciferase gene ,44. StabThe use of PET and MRI imaging is increasing as these technologies are becoming more affordable. However, due to the high cost, associated radiation, high level of skills required for data acquisition and interpretation as well as need for other labor-intensive procedures, PET and MRI imaging should be reserved only for advanced projects with a specific question in mind that cannot be answered using other imaging modalities. in vivo research and ensure translation of results to the clinical situation. A thorough preclinical approach to HCC research should build confidence in compound efficacy as well as safety and lead to the discovery of novel compounds or more efficacious drug combinations for treating HCC.There are multiple and independent biomarkers, including serum AFP, CEUS, PET and MRI imaging and tissue IHC, available for use in preclinical animal studies investigating novel compounds and therapeutic combination paradigms for HCC. The use of the cell cocktail approach, orthotopic models and careful study design as well as selection of biomarkers can maximize the value of