A severe healthcare worker shortage in sub-Saharan Africa is inhibiting the expansion of HIV treatment. Task shifting, the transfer of antiretroviral therapy (ART) management and initiation from doctors to nurses and other non-physician clinicians, has been proposed to address this problem. However, many health officials remain wary about implementing task shifting policies due to concerns that non-physicians will provide care inferior to physicians. To determine if non-physician-provided HIV care does result in equivalent outcomes to physician-provided care, a meta-analysis was performed.Online databases were searched using a predefined strategy. The results for four primary outcomes were combined using a random effects model with sub-groups of non-physician-managed ART and -initiated ART. TB diagnosis rates, adherence, weight gain and patient satisfaction were summarized qualitatively.N=59,666) had similar outcomes for non-physicians and physicians, with a hazard ratio of 1.05 (CI: 0.88–1.26). The increase in CD4 levels at one year, as a difference in means of 2.3 , and viral failure at one year, as a risk ratio of 0.89 , were similar for physicians and non-physicians. Interestingly, loss to follow-up (LTFU)  was reduced for non-physicians with a hazard ratio of 0.72 (CI: 0.56–0.94). TB diagnosis rates, adherence and weight gain were similar for non-physicians and physicians. Patient satisfaction appeared higher for non-physicians in qualitative components of studies and was attributed to non-physicians spending more time with patients as well as providing more holistic care.Mortality (Non-physician-provided HIV care results in equivalent outcomes to care provided by physicians and may result in decreased LTFU rates. In response to the HIV epidemic, countries in sub-Saharan Africa and other low-income regions are attempting to increase access to antiretroviral therapy (ART). The HPTN052 treatment as prevention trial, which demonstrated the ability of ART to prevent HIV transmission, has provided further impetus for nations to provide universal ART access . HoweverThere is a large body of research evaluating the effects of task shifting policies with regard to access, outcomes and cost. Many field reports have described using task shifting policies, particularly nurse-initiated ART, as critical to increasing access to HIV treatment . HoweverConsidering that task shifting policies appear to be able to increase access to HIV treatment with a reduced cost, it would be reasonable to think that there would be widespread implementation of task shifting in low-income countries. However, formal implementation of nurse-managed and -initiated HIV treatment remains limited. While Rwanda and South Africa, among other countries, have begun to phase in nurse-initiated ART, many countries in sub-Saharan Africa limit prescription of ARVs to physicians . There rIn order for policy makers to provide evidence-based guidelines for task shifting policies, the highly heterogeneous literature must be evaluated and pooled. Although recent systematic reviews have qualitatively evaluated the impact task shifting policies have on access to ART  and summThis systematic review was performed using the meta-analysis of observational studies in pidemiology (MOOSE) statement as a guideline. This systematic review was also registered with the International Prospective Register of Systematic Reviews (ID: CRD42012001956) prior to its initiation, with the search strategy described there.Task shifting was defined for this review as non-physician managed and initiated ART. Non-physician clinicians were considered to be nurses, clinical nurses, registered nurses, nurse practitioners, nurse specialists as well as specialized non-physician clinicians such as clinical officers. Trainees and community health workers were excluded. Four separate types of studies were eligible for inclusion in the meta-analysis: randomized controlled trials, non-randomized controlled trials, cohort studies and case-control studies. Cross-sectional studies were eligible for narrative review but not included in the meta-analysis. Studies which measured either non-physician-initiated or -managed ART were eligible. Non-physician-initiated ART refers to non-physicians both initiating and managing ART, while non-physician-managed ART refers to non-physicians refilling prescriptions and managing treatment after diagnosis and initial prescription by a physician. Studies which measured either adults or children (0–18 years) were also eligible for inclusion. No language or age restrictions were applied.The following databases were searched until August 2012: PubMed, EMBASE, CINAHL, Social Science Citation Index, Arts and Humanities Index, Cochrane Controlled Trials Registry as well as the abstract databases from the International AIDS Society Conferences, the Conferences on Retroviruses and Opportunistic Infections and the conferences of the International Society of Sexually Transmitted Diseases Research. Bibliographies of relevant studies were manually searched. A grey literature search was also conducted.Supplementary File 3. A variety of synonyms were used for each theme and both keywords and MeSH headings were used. No keywords were used for outcomes or quality of care, as relevant studies may not have contained these keywords. Instead, papers were reviewed manually.The search strategy combined three themes: HIV/AIDS, ART and task shifting. The detailed strategy is described in Two reviewers (CE and NC) performed the search independently, screening studies by title and abstract. Those studies identified as being possibly relevant to ART task shifting were assessed using the full text by two reviewers (CE and NC). Once the full-text screen was performed, differences between the eligible studies were resolved by consensus. Excluded studies with the reasons for exclusions were recorded and provided. Information was extracted independently and in duplicate using a pre-created form. The primary outcomes were death, loss to follow-up (LTFU), CD4 increase at one year and virological failure at one year. Secondary outcomes were patients requiring change of ART prescription, change in weight, documented medical or prescription failures, prevalence of opportunistic infections, adherence and patient satisfaction. Performance indicators, including the ability to properly stage HIV infection, prescribe ART and document treatment, were also evaluated.Quality of individual studies was assessed using a series of predefined measures. Randomized controlled trials and controlled before and after studies were assessed using eight measures: calculation of power, description of eligibility, baseline assessment, incomplete outcome data, selective outcome reporting, clear description of roles of nurses, measurement of implementation of intervention and discussion of confounding factors. Cohort studies were assessed through the same measures with the removal of calculation of power. No case-control studies were eligible for inclusion, however, if one had been identified, it would have been assessed through the same seven measures as a cohort study. Cross-sectional studies were assessed with the same measures with the additional removal of baseline assessment. Studies which described and reported each measure were marked as having fulfilled that assessment. If the study did not report the measure, it was marked as not having fulfilled the quality assessment. For selective outcome reporting, protocols published prior to the trial being performed were used to determine if select outcomes had been excluded. As a result, studies which did not have previously published protocols were assessed as being unclear for selective outcome reporting.I2 was calculated for each sub-group as a measure of between-study heterogeneity. For all outcomes, the generic inverse variance method was used to report pooled summary statistics. For outcomes reported as hazard ratios , Parmar's methods were used to extract hazard ratios and standard errors from reported confidence intervals and were also used to estimate hazard ratios for studies which reported total mortality at discrete time points [The software RevMan 5.0, provided by the Cochrane collaboration, was used for all statistical calculations. A meta-analysis was applied for each sub-group of non-physician-managed ART and -initiated ART using a DerSimonian–Laird random effects model, which was chosen over a fixed effects model as there was heterogeneity between studies. e points . An incrSupplementary File 3. In summary, 29 did not measure outcomes, 21 lacked a control group, 7 were irrelevant to the task shifting of HIV care to non-physician clinicians, 4 had results reported in another study and 1 was irrelevant to low-resource settings. Three studies were located by reviewing the bibliography of relevant studies. Of the remaining 12 studies, 9 studies were eligible for the meta-analysis while 3 studies were only eligible for the qualitative review.Of the 2021 studies screened by title and abstract, 71 were screened using the full text . Of thosNine studies were included in the meta-analysis . Of thosThree cross-sectional studies were included in the narrative review. One was conducted in Botswana, measuring nurse-initiated ART , one in Supplementary File 1). Only two of the nine studies in the meta-analysis were randomized controlled trials with a third study being a non-randomized controlled trial. All controlled trials had at least six of the eight quality factors. The remaining five cohort studies were of lower methodological quality, with two cohort studies having only three of the seven factors. The remaining four had at least four of the factors. The most common error among all studies was a lack of an evaluation of the degree to which nurse-managed and -initiated care was actually being implemented within the clinic. The STRETCH randomized controlled trial was one of the few studies which monitored the implementation of nurse-initiated ART [The methodological quality of the studies varied significantly . While there were too few studies to apply a quantitative test for bias, visual inspection of the plot did not indicate significant bias. There was significant heterogeneity between studies with I2=76% (p<0.0001) for mortality and I2=87% (p<0.00001) for LTFU. Consequently, a random effects model was used for analysis. Meta-analysis of mortality  found no significant difference between non-physicians and physicians with a hazard ratio of 1.04  (p=0.30) or -initiated ART (p=0.31). However, non-physicians had reduced LTFU , with a hazard ratio of 0.72  (p<0.00001) and combined sub-groups  remains.Funnel plots were produced for mortality and LTFU to determine if there was publication bias ( p=0.72) . In a su p=0.01) . This efN=17,142) found no evidence of a significant difference between physicians and non-physicians, with a mean difference of −2.32 favouring non-physicians  , defined as having >400 units/mL of blood, was also found not to be significant between non-physicians and physicians   . Neither p=0.47) . SignifiEight studies reported secondary outcomes . In two Satisfaction rates were generally found to be better for non-physicians than physicians. Two qualitative components of cohort studies found that patients expressed a preference for nurses over physicians, who were seen as friendlier, more supportive and providing more holistic care , 15. TheA cross-sectional study in Cameroon evaluated which factors were associated with non-adherence and treatment interruptions to ART . AttendiTwo cross-sectional studies compared non-physicians to physicians on performance indicators. A study in Botswana compared the ability of nurses and physicians to properly document eight variables including WHO staging and dosing of therapy for paediatric HIV patients . Nurses Our meta-analysis and systematic review found that non-physician-provided care resulted in equivalent outcomes to physician-provided treatment. This is consistent with the two randomized controlled trials included in this meta-analysis , 14, as Many of the strengths of this review can also be considered weaknesses. No restrictions were put on publication status and both peer-reviewed papers as well as conference abstracts were accepted for inclusion. This was done to reduce the risk of publication bias and include as many studies as possible. Two abstracts , 12 wereA second potential pitfall with this meta-analysis relates to the use of Parmar's methods for extracting hazard ratios from summary statistics . While tA strength of our meta-analysis is the inclusion of both randomized trials and observational studies. Randomized trials typically have higher internal validity than observational studies. However, they may lack applicability to the health systems typically found in sub-Saharan Africa . This caa priori, varied significantly. The two included randomized controlled trials were of higher quality than the included cohort studies, although they did not differ significantly in their findings. The most troubling factor among most studies was a lack of an assessment to a degree to which nurses actually initiated and managed ART. In the STRETCH trial, only 26% of initial prescriptions of ARVs in the nurse-led cohort were actually prescribed by nurses [The quality of the included studies, analyzed through a set of assessments defined y nurses . This raThis meta-analysis supports the general trend in sub-Saharan Africa towards the provision of ART by nurses and other non-physicians. Many countries, including South Africa, Lesotho and Malawi have implemented national policies allowing the prescription of ARVs by nurses . HoweverThese barriers suggest areas for future research. First, research should be conducted into the ability of various combinations of task shifting to non-physicians and lower level cadres to increase access to HIV treatment. Second, the cost effectiveness of task shifting to non-physicians should be examined. A recent cohort study, conducted in South Africa, concluded that down-referral to a nurse-managed clinic was 11% less expensive than physician provided care due to nurses ordering more expensive drugs. However, if down-referral was implemented throughout the South African healthcare system, even its relatively moderate reduction in cost could provide for millions of dollars in savings at an aggregate level . ComprehThis meta-analysis of the result of a combined 59,666 subjects found that non-physician-provided HIV treatment results in the same outcomes as traditional physician-provided treatment and may result in reduced LTFU rates. Patients were more likely to be satisfied by care provided by non-physicians, which was attributed to the perception that nurses provided more holistic care and that nurse-led clinics were closer to patients’ homes. These results support the current expansion of task shifting policies in sub-Saharan Africa and suggest that countries that have not implemented such policies may be unnecessarily rationing their care. Future research should be conducted into evaluating training programmes for non-physicians as well as identifying barriers that are inhibiting the expansion of task shifting policies.


Background and Purpose. Several studies have evaluated the role of fluorine-18-fluorodeoxyglucose positron emission tomography and positron emission tomography/computed tomography (FDG-PET and PET/CT) in diagnosing and assessing disease activity in patients with retroperitoneal fibrosis (RF). The aim of our paper is to perform a literature review on this topic. Methods. Scientific articles that evaluated the usefulness of FDG-PET and PET/CT in patients with RF were searched and discussed. Results. Eleven studies were found, and the main findings of these articles were described. Conclusion. FDG-PET and PET/CT are useful functional imaging methods for assessing patients with RF both in the diagnosis and in the treatment response evaluation. Moreover, further studies are needed to substantiate the role of FDG-PET and PET/CT in patients with RF. Retroperitoneal fibrosis (RF) is a chronic inflammatory disease, characterized by the presence of retroperitoneal inflammatory tissue, typically surrounding abdominal aorta and/or iliac arteries, and often leading to the involvement of adjacent structures, more frequently the ureters and inferior vena cava –7.RF is a complex clinical entity still incompletely defined and with unclear etiology. Idiopathic RF (even reported as Ormond's disease) represents two thirds of all cases of RF. A true idiopathic form is present in any cases of RF in which no potential etiologic condition may be identified. The pathogenesis of the idiopathic RF appears today to be related to IgG4 autoimmune mechanisms “hyper-IgG4 disease”. Otherwise, RF in the presence of aortic atheromatous inflammation (atheromatous aortitis) has been included, more than twenty years ago, among the secondary forms, since this condition appears to be elicited by antigen-acting oxidized-LDL and/or ceroid, that are present within the atheromatous plaque. Etiology of other secondary RF refers to medications (drug-induced RF), infections, traumas, surgery, radiation therapy, and malignancies –7.Clinical presentation of RF is usually characterized by constitutional symptoms and back or abdominal pain. Because of the presence of increased serum inflammatory markers levels and positive autoantibodies, and the frequent association with autoimmune diseases , some authors suspected that RF may result from autoimmune mechanisms  or, evenA frequent complication of RF is unilateral or bilateral ureteral obstruction, secondary to fibrosis and stenosis of the ureters , 4, 5. OThe treatment of RF can be medical and/or surgical although a consensus has not been currently reached. The medical therapy is usually based on corticosteroids and immunosuppressive agents (such as tamoxifen) at different doses and various combinations on the base of disease activity and often leads to a substantial reduction of size of the retroperitoneal mass. The surgical procedure is required when severe obstructive complications are present , 13–15.However, determining the presence of active inflammation, and thus the potential for response to medical therapy, is crucial for the management of patients with RF and can be quite difficult, especially on the basis of only clinical parameters.Most commonly used imaging methods in this pathologic entity are computed tomography (CT) and magnetic resonance imaging (MRI), despite their difficulty in discriminating between active and fibrotic lesions and in differentiating between RF and other retroperitoneal diseases such as tumors , 17.Fluorine-18-fluorodeoxyglucose positron emission tomography and positron emission tomography/computed tomography (FDG-PET and PET/CT) are noninvasive functional imaging techniques which have become established tools in oncology –23. In fSeveral studies have evaluated the role of FDG-PET and PET/CT in diagnosing, assessing disease activity, and monitoring RF. The aim of our paper is to review relevant published articles on this topic.A comprehensive computer literature search of PubMed/MEDLINE was conducted in order to find relevant published articles on the role of FDG-PET and PET/CT in patients with RF. We used a search algorithm based on a combination of the following terms: (a) “retroperitoneal fibrosis” or “Ormond” and (b) “positron emission tomography” or “PET.” No beginning date limit was used; the search was updated until July 31st 2012. Studies investigating the role of FDG-PET and PET/CT in patients with RF were eligible for inclusion. Review articles or editorials, articles not in the field of interest of this paper, case reports, and preclinical studies were excluded.Eleven relevant articles about the role of FDG-PET and PET/CT in patients with RF were found and discussed .In 2005, Salvarani et al.  evaluateIn the same year, Vaglio et al.  used FDGIn 2007, Nakajo et al.  reviewedIn 2008, Young et al.  reportedP = 0.02) and a larger mass size at CT scan (P = 0.01) compared with patients with a negative FDG-PET scan. FDG uptake decreased following treatment, in agreement with inflammatory markers reduction (P < 0.001), but not with CT-documented mass regression. These findings confirmed that FDG-PET may be useful to evaluate the severity and the extent of RF. Furthermore, these authors demonstrated that FDG-PET may be a valuable tool in assessing disease activity during or after treatment in patients with normal inflammatory marker levels and stable residual mass on repeated CT scans. Nevertheless, short-term FDG-PET followup did not accurately predict success of tamoxifen treatment [In 2010, Jansen et al.  evaluatereatment .In the same year, Piccoli et al.  supporteRecently, Pipitone et al.  presenteHa et al.  recentlyBertagna et al.  assessedGuignard et al.  evaluateP < 0.01) was found among FDG uptake, and serum levels of inflammatory markers and among FDG uptake and analysis of contrast enhancement at CT images in the retroperitoneal mass. The authors concluded that FDG PET/CT may be considered an alternative imaging method for the assessment of different stages of RF [Lastly, Moroni et al.  in theires of RF .The diagnosis of RF is based on clinical and radiological findings, and there are no established PET criteria for the diagnosis of this pathological entity. Many authors used a visual analysis of PET images for the evaluation of metabolic activity of RF. The visual analysis was usually performed using a four-point graded scale, based on the vessel-to-liver FDG uptake ratio ; a visual score above 1 was usually considered a positive criteria for active RF.However, standardization of FDG-PET studies by using semiquantitative analysis in order to achieve interchangeability in multicenter trials was recently recommended . Six outThe added value of the hybrid technique PET/CT versus PET alone for RF diagnosis needs to be confirmed by further studies. In fact, only four articles evaluated the usefulness of FDG-PET/CT in patients with RF , 32–34. Overall, FDG-PET and PET/CT seem to be useful methods both in evaluating disease extent and severity at the time of diagnosis and in assessing disease activity during or after treatment, mainly in patients with normal inflammatory marker levels and stable residual mass on repeated CT scans. Further prospective and multicentric studies with a larger patient population and cost-effectiveness studies are needed to correctly define the role of FDG-PET and PET/CT in patients with RF.From this overview on the role of FDG-PET and PET/CT in patients with RF, we are led to conclude that these functional imaging techniques seem to be useful both in the diagnosis and in evaluating the treatment response. Further studies are needed to substantiate the role of FDG-PET and PET/CT in this setting.


Objective. To compare center of mass (COM) compensation in the frontal and sagittal plane during gait in patients with large diameter head total hip arthroplasty (LDH-THA) and hip resurfacing (HR). Design. Observational study. Setting. Outpatient biomechanical laboratory. Participants. Two groups of 12 patients with LDH-THA and HR recruited from a larger randomized study and 11 healthy controls. Interventions. Not applicable. Main Outcome Measures. To compare the distance between the hip prosthetic joint center (HPJC) and the COM. The ratio (RHPJC-COM) and the variability (CVHPJC-COM) were compared between groups. Hip flexor, abductor, and adductor muscle strength was also correlated between groups while radiographic measurements were correlated with the outcome measures. Results. In the frontal plane, HR shows less variability than healthy controls at push-off and toe-off and RHPJC-COM is correlated with the muscle strength ratios (FRABD) at heel contact, maximal weight acceptance, and mid stance. In the sagittal plane, LDH-THA has a higher RHPJC-COM than healthy controls at push-off, and CVHPJC-COM is significantly correlated with FRFLEX. Conclusions. One year after surgery, both groups of patients, LDH-THA and HR, demonstrate minor compensations at some specific instant of the gait cycle, in both frontal and sagittal planes. However, their locomotion pattern is similar to the healthy controls. Hip arthroplasty has become a standard procedure –3 to impThe techniques available to treat the young patients with advanced OA, include, among others, total hip arthroplasty (THA) and hip resurfacing (HR). During THA procedure, a stem is inserted in the femoral canal while the femoral head and neck are resected and replaced by a femoral head of 28 mm diameter, articulating with a cup inserted in the acetabulum cavity . Over thAfter THA, pain is usually relieved and the range of motion improved, but normal activities may still be compromised in some patients . An asymEven if patients recover mostly within the first three to six months after THA , completPatients with advanced hip joint degeneration were screened at the orthopaedic clinic of Maisonneuve-Rosemont Hospital, they were candidates for either LDH-THA or HR. Among volunteers recruited from a larger randomized study , patientAll hip replacements were performed by three surgeons from the same hospital, and the posterior approach  was usedCOR) and vertical (VCOR) center of rotation of the prosthetic hip joint, the femoral offset (FOFFSET), and leg length (LL) inequality were measured for the replaced and contralateral hip  and analysed using Imagika software . The horizontal  Subjects were asked to walk at their normal speed on a 10-meter walkway with two embedded force platforms  recording at 120 Hz. Three gait cycles were collected for each subject, 12 months postoperatively. Trials were included when both feet made full contact on each of the two force platforms. A sufficient resting period was given between trials to avoid fatigue. Subjects were tested barefoot, wearing shorts, and t-shirt. Twenty-nine 14 mm diameter reflective markers were positioned on bony landmarks to define body segments using Vicon Plug- in-Gait model . SpatiotHPJC-COM) was determined as the distance between HPJC-COM/inter-ASIS distance (HPJC-COM) of the distance between HPJC and COM was also calculated [HPJC-COM was The COM position was calculated from marker positions and anthropometric tables  while thdistance  for bothlculated . The metσ is the standard deviation and μ the mean of the HPJC-COM distance. Data were calculated at five specific instants of the gait cycle, extracted from vertical ground reaction forces: (1) heel contact, (2) maximum weight acceptance, (3) midstance, (4) push-off, and (5) toe-off . Hip abductor, adductor, and flexor muscle strength of both sides was tested. For the hip flexor muscle, the patient was seated  while foHPJC-COM and CVHPJC-COM were analyzed using a one-way ANOVA. The results were then further analyzed if necessary, with Tukey post hoc test. For non-normality distributed data, as required, results were analyzed with a Kruskal-Wallis test. In the frontal plane, Pearson correlations were calculated between the parameters evaluated RHPJC-COM and CVHPJC-COM and the FOFFSET, HCOR, FRABD, and FRADD, while in the sagittal plane, correlations were made between RHPJC-COM and CVHPJC-COM and VCOR, LL, and FRFLEX. Correlations included both groups, LDH-THA and HR. Significant difference was set at P < 0.05.All statistical analyses were performed using SPSS 17.0 . The sociodemographic  and spatiotemporal data were analysed using one-way analysis of variance (ANOVA). Chi-square test was used for gender. The RNo difference was observed between the three groups for the sociodemographic data .P = 0.00) and HR (P = 0.04) group. Healthy controls also showed a reduced walking speed compared to LDH-THA (P = 0.02) group.Statistical difference was found for the spatiotemporal data . The heaHPJC-COM between the three groups  and toe-off (P = 0.02). Patients undergoing HR tended to show less variability than healthy controls . LDH-THA patients seem to increase their HPJC-COM moment lever arm by bending their trunk forward . On the other hand, correlations were found between the RHPJC-COM and the FRABD at heel contact (P = 0.04), maximum weight acceptance (P = 0.04) and mid stance (P = 0.02). No correlation was found for the CVHPJC-COM  and the force ratio (FRFLEX). However, a correlation was found for the CVHPJC-COM and the FRFLEX at MWA (P = 0.00)  .Lavigne et al. , using dUsing a selected subgroup of patients from this study, the aim of the present study was to determine if the presence of a femoral stem combined to the loss of bone in LDH-THA have an impact on COM position, with respect to HJC, during gait at 12 months after surgery compared to HR. Data from LDH-THA and HR patients were also compared to a healthy controls group. The statistical analysis showed no difference in sociodemographic data while a statistical difference was found in some spatiotemporal parameters. Particularly, LDH-THA and HR patients of this study showed a higher cadence compared to healthy controls while LDH-THA patients walked with a greater velocity when compared to healthy controls. In previous studies, patients undergoing THA were walking slower than healthy controls , 22, 35.In order to maintain pelvic equilibrium, agonist and antagonist muscles must generate an equal net moment . One wayHPJC-COM in the frontal plane. However, HR patients maintain a smaller RHPJC-COM than LDH-THA and healthy controls on almost all the gait cycle. This suggests that LDH-THA and HR patients performed as well as healthy controls but used different strategies. In fact, patients undergoing LDH-THA did not decrease their HPJC-COM moment arm length by shifting body weight toward the affected limb in order to reduce constraints on their prosthetic hip joint and minimize the effort of hip abductor muscles [During walking, the proper function of hip muscles is mandatory to maintain stability of the head-arm-trunk (HAT) segment. In the frontal plane, this role is achieved by the abductor muscles . Althoug muscles . Patient muscles  found th muscles  hip powe muscles  LDH-THA  muscles –46. Furt muscles  suggesteIt has already been established that identical movement patterns cannot be generated by successive attempts . In otheHPJC-COM between HR and healthy controls at the end of the stance phase (push-off and toe-off) but HR and LDH-THA are less variable than healthy controls for all the gait cycle. These results might be explained by the surgical intervention. Normally, hip joint stability is partly provided by the strong ligaments and powerful muscles [In our study, a statistical difference was found for the CV muscles  surroundHPJC-COM at push-off between LDH-THA and healthy controls. Specifically, LDH-THA patients showed an increased RHPJC-COM distance, which increased the moment lever arm at PO. This can be done by bending the trunk forward which creates a mechanical advantage and improves the extensor moment at the hip. Previous studies [In the sagittal plane, the effects of surgery may also have an impact on the patient's gait strategies mainly on the HAT segment that is under the control of the hip flexor and extensor muscles . In the  studies , 41 have studies  conclude studies . In the HPJC-COM and the FRABD from heel contact to mid stance. These results suggest that stronger they are, patients undergoing hip arthroplasty can more easily position their COM closer to their HJC while patients who are weaker cannot reduce their moment lever arm.During gait, contribution from the hip abductor muscles is more important from heel contact to mid stance because they help in supporting the body weight. To reduce the muscular demand on hip muscles patients must bring their COM closer to the HJC. In the present study, a negative moderate  correlatHPJC-COM and the FRFLEX at maximum weight acceptance (P = 0.04). These results propose that when patients undergoing hip arthroplasty are stronger, they can afford to be more variable because they will be able to manage excursion of their COM more easily at that instant.In the sagittal plane, muscle involvement is also essential in order to maintain pelvis stability. The results showed a moderate positive correlation between the CVIn the present study, the predictive method  was usedOne year after surgery, patients undergoing LDH-THA or HR still have gait impairments, at some instants during the gait cycle, related to the positioning and variability of their COM with respect to their hip joint center in both the frontal and sagittal planes compared to healthy controls. The use of a large diameter head in THA seems to reduce the anatomical difference with HR and no major differences were found during locomotion between these two types of prostheses and they walked like healthy controls. However, walking is a simple task compared to physical activities such as sports. The integration of a specific rehabilitation program would be necessary to promote their participation in sports and prepare them for higher demanding activities.


Once-daily compared with twice-daily antiretroviral therapy regimens increased adherence; however, the difference was modest and not associated with a difference in virological suppression. In addition, higher pill burden was associated with lower rates of virological suppression, whether once- or twice-daily regimens. Background. Contemporary antiretroviral treatment regimens are simpler than in the past, with lower pill burden and once-daily dosing frequency common. We performed a meta-analysis of randomized controlled trials (RCTs) to investigate the impact of pill burden and once-daily vs twice-daily dosing on ART adherence and virological outcomes.Methods. A literature search of 4 electronic databases through 31 March 2013 was used. RCTs comparing once-daily vs twice-daily ART regimens that also reported on adherence and virological suppression were included. Study design, study population characteristics, intervention, outcome measures, and study quality were extracted. Study quality was rated using the Cochrane risk-of-bias tool.Results. Nineteen studies met our inclusion criteria (N = 6312 adult patients). Higher pill burden was associated with both lower adherence rates (P = .004) and worse virological suppression (P < .0001) in both once-daily and twice-daily subgroups, although the association with adherence in the once-daily subgroup was not statistically significant. The average adherence was modestly higher in once-daily regimens than twice-daily regimens . Patients on once-daily regimens did not achieve virological suppression more frequently than patients on twice-daily regimens . Both adherence and viral load suppression decreased over time, but adherence decreased less with once-daily dosing than with twice-daily dosing.Conclusions. Lower pill burden was associated with both better adherence and virological suppression. Adherence, but not virological suppression, was slightly better with once- vs twice-daily regimens. Among human immunodeficiency virus (HIV)–infected patients, adherence to antiretroviral therapy (ART) is a primary determinant of virological suppression, disease progression, and death –3. ART rLittle is known about the impact of once- vs twice-daily ART and pill burden on adherence and virological outcomes. Indeed, in some patients with suboptimal adherence and/or virological failure, reducing the pill burden may be more important than switching from a twice-daily regimen to a once-daily regimen. Furthermore, governments, third-party payers, and HIV programs may prefer the use of non-coformulated ART generics because they are less expensive than brand name STRs. Therefore, as more generics become available, there is the potential for a paradoxical “desimplification,” with movement away from STR regimens , 11.A 2009 meta-analysis by Parienti and colleagues of 11 randomized trials reported that ART adherence rates were significantly better with once-daily than with twice-daily regimens , with a Thus, we conducted an updated meta-analysis to evaluate the impact of pill burden and once- vs twice-daily ART on adherence as well as virological outcomes in both ART-naive and -experienced HIV-infected adults.The study background, rationale, and methods were specified in advance and documented in a protocol that was published in the PROSPERO register (CRD42012002515).We included only randomized controlled trials (RCTs) that compared once-daily vs twice-daily regimens in either ART-naive or -experienced patients with objective measures of adherence and measures of virological outcomes.We systematically searched the following databases from their inception until 31 March 2013 : Cochrane CENTRAL, PubMed, Google scholar, and Web of Science. Our search terms included the following: “HIV,” “treatment simplification,” “co-formulation,” “fixed-dose combination,” “QD,” “twice-daily,” “once-daily,” “adherence,” “HAART,” “ART,” “cART,” and “patient preference.” We also searched abstracts from major HIV/AIDS and infectious diseases conferences (from 2008 onward) including Conference on Retrovirus and Opportunistic Infections, International AIDS Conference, International AIDS Society Conference on HIV Treatment, Pathogenesis and Prevention, International Conference on Antimicrobial Agents and Chemotherapy, and Infectious Diseases Society of America Conference. In addition, the bibliographies of relevant review articles, metaanalyses, and selected articles were examined for pertinent studies.We evaluated each identified study using the following predetermined selection criteria: open-label RCTs of HIV-infected subjects either ART naive or ART experienced that compared once-daily ART regimens with any twice-daily antiretroviral regimens and assessed both adherence  and viral suppression . Placebo-controlled, blinded trials were excluded because the regimen frequency was identical for the comparator arms (to maintain blinding) and, therefore, the impact of the placebo on adherence could not be measured. We chose to exclude trials that used self-reported adherence as the patients are more likely to overestimate adherence due to social desirability and typically these trials do not reflect true variability in adherence due to a ceiling effect –30.We used the Cochrane Collaboration's tool for assessing the risk of bias for quality assessment of the included studies . The stuThree reviewers  independently evaluated the eligibility and methodological quality of studies obtained from the literature search. These same reviewers also independently extracted and compared the data. For each identified study that met the selection criteria, details on study design, study population characteristics, intervention, outcome measures, and study quality were extracted. Discrepancies were resolved by consensus through discussion.P value; and imputation of the SD reported in similar studies.The primary measures of treatment effects were weighted mean difference (WMD) with 95% confidence interval (CI) for adherence to treatment and relative risk (RR) with 95% CI for virological suppression. We used the following methods to compute effect sizes, when incompletely reported: contact with the corresponding author; estimation of the standard deviation (SD) on the basis of the sample size, median, and range as suggested by Hozo and colleagues  or on thThe Spearman rank correlation coefficient (rho) was used to examine the associations between regimen pill burden (daily number of tablets), length of follow-up period, adherence rates, and virological response.2I statistic, which reports the percentage of total variation across studies due to heterogeneity rather than chance [We used DerSimonian and Laird  random en chance , 35. Basn chance , subgrouWe examined the reliability and conclusiveness of the available evidence using a trial sequential analysis (TSA) –39 and thttp://ims.cochrane.org/revman) were used for meta-analysis; Trial Sequential Analysis Software, version 0.9 beta (www.ctu.dk/tsa), was used for the trial sequential analyses.This review was performed according to the PRISMA recommendations for meta-analyses of RCTs . Stata 1Supplementary Table 1 shows the characteristics of studies that were excluded from the meta-analysis, and Supplementary Table 2 shows the assessment of bias risk among the included studies.The literature search yielded 428 articles Figure . After rA) between adherence and pill burden  for both once-daily and twice-daily regimens. However, when the analysis was stratified by the regimens, the association between adherence and pill burden was significant in the twice-daily regimens  but not in the once-daily regimens . There was also a statistically significant negative association  between pill burden and virological suppression , which was significant in both the once-daily  and twice-daily subgroups .There was a negative and statistically significant association Figure A betweenP = .0002; Figure Supplementary Figure 1). In prespecified subgroup analyses, the greater average adherence with once-daily vs twice-daily dosing was more pronounced in treatment-naive patients . There was no significant difference in virological suppression among patients following once-daily vs twice-daily regimens . Furthermore, there was no significant difference between once- and twice-daily regimens in virological suppression in the treatment-naive or -experienced subgroups . When the analysis was stratified by dosing regimens, twice-daily remained statistically significant , whereas the once-daily was not . Similarly, there was a significant negative association  between virological suppression and duration of follow-up , such that virological suppression declined with longer follow-up. The associations were similar to the overall for both twice-daily  and once-daily  regimens.Adherence declined significantly over time .This meta-analysis of 19 RCTs which included 6312 patients found that higher pill burden was associated with both lower adherence and worse virological suppression in both twice-daily and once-daily subgroups. In addition, adherence was higher with once-daily ART regimens than with twice-daily regimens when adherence was measured objectively using pill counts and/or MEMS caps. However, this difference was minimal and did not translate into better treatment outcomes. Furthermore, the greater adherence with once-daily dosing was only statistically significant in treatment-naive individuals and in those who switched from twice- to once-daily dosing with virological failure. Adherence did not increase among treatment-experienced patients who switched from twice- to once-daily dosing while virologically suppressed; adherence was likely high in these patients prior to the switch. Both adherence and virological suppression decreased with longer follow-up, but the adherence decrease was less pronounced with once-daily dosing than with twice-daily dosing.Interestingly, none of the included randomized trials directly evaluated the effect of an STR, which we consider an unanswered question for further research. However, in our study, there was a significant negative association between pill burden and virological suppression, suggesting that regimen simplification with STRs may be helpful in select situations. One small observational study conducted among marginally housed individuals and 2 large observational studies conducted found better adherence with STRs  , 56, 57,There are several possible explanations for the apparent lack of impact of once- vs twice-daily dosing on virological outcomes. First, the impact of once-daily dosing on adherence was relatively small (2.5% absolute increase in adherence); this was possibly too small to result in a clinically meaningful difference in virological suppression. Second, a substantial number of the trials included in this meta-analysis were of relatively short duration. Moreover, volunteers for clinical trials are likely to be more adherent than their counterparts managed in routine clinical practice, and there may be more resources available to support adherence in clinical trial settings . For theThese results have several important practical implications. Currently, as all recommended regimens are highly potent, ART combinations should be selected based on factors such as tolerability, potential drug interactions, patient preference for dosing frequency, and pill burden, as well as structural factors  . EffortsIn a mathematical simulation, Walensky and colleagues showed that the future use of a once-daily regimen that includes generic efavirenz plus generic lamivudine plus branded tenofovir in the United States could yield savings of almost $1 billion per year to HIV programs . Our res2 > 50%). Also, by focusing on once-daily vs twice-daily dosing, our analysis may have masked regimen-specific effects  that have little to do with the frequency of dosing. Finally, the impact of regimen frequency and pill burden on adherence and virological outcomes in RCTs may not necessarily generalize to desimplification, in which patients may perceive that their regimen has been reduced in quality. Such a change could adversely affect adherence and/or treatment outcome, and, as noted above, specific studies to investigate this question are needed.Our study has several strengths. We performed a comprehensive search of several databases and sources to identify eligible RCTs that provide the highest quality of evidence. Three authors independently evaluated each study for inclusion and data extraction. Furthermore, we performed a trial sequential analysis; this is an efficient decision-making tool that is used to establish whether firm evidence of effect has been obtained . RegardiIn this meta-analysis of 19 RCTs, we confirmed that once-daily ART regimens increased adherence when compared with twice-daily regimens, but the difference was modest and not associated with a difference in virological suppression. Importantly, we found that higher pill burden was associated with lower rates of virological suppression regardless of dosing frequency. The nonlinear correlation between pill burden and adherence or virological suppression suggests that, while ART desimplification from once-daily STRs to once-daily multitablet regimens may have adverse effects on virological outcomes, separating out STRs and/or fixed-dose combinations into their constituents is not likely to have a major detrimental impact on virological outcomes . Nevertheless, further research is needed to directly investigate the impact of such a switch, in particular among patients who are virologically suppressed at baseline. In the meantime, our results suggest that pill burden should be a consideration in the selection of an antiretroviral regimen, independent of dosing frequency.Supplementary materials are available at Clinical Infectious Diseases online . Supplementary materials consist of data provided by the author that are published to benefit the reader. The posted materials are not copyedited. The contents of all supplementary data are the sole responsibility of the authors. Questions or messages regarding errors should be addressed to the author.


Locally advanced pancreatic duct carcinoma (PDAC) and metastatic PDAC, usually found the metastases over liver, peritoneum, or lung, have been shown to be with dismal prognosis. Brain metastasis is a rare entity and most cases reported before were found post-mortem. Intraductal papillary mucinous neoplasms of the pancreas (IPMN) has been deemed as a precursor of PDAC with very slow progression rate. Here we reported a case diagnosed with IPMN-derived PDAC with brain metastasis. After surgeries for PDAC and brain metastasis, subsequent chemotherapy and radiotherapy were also given. One and half year after surgery, this patient is still living with good performance status, which may warrant individualization of therapeutic strategy for PDAC with only brain metastasis.Pancreatic cancer is a lethal disease without effective treatments at present. It ranks as s as 4 Pancreatic duct adenocarcinoma (PDAC) is a lethal human malignancies with a very poor prognosis. PDAC ranks as the eighth and ninth most common cause of cancer-related mortality worldwide for men and women, respectively . The oveIntraductal papillary mucinous neoplasms of the pancreas (IPMN) has been deemed as a precursor of PDAC with very slow progression rate. Here we reported a case diagnosed with IPMN-derived PDAC with brain metastasis. After aggressive surgeries for PDAC and brain metastasis and subsequent chemotherapy and radiotherapy, this patient is still l living well at the time of writing, which may encourages an aggressive treatment strategy against patients with PDAC with brain metastasis.A 54-year-old male patient with an unexceptional medical history complained of several episodes of right-sided weakness and tripping in November, 2009. After one episode of tumbling on January 2, 2010, he was brought to our emergency department by his family. Data from blood biochemistry and other blood tests were all within normal ranges. Due to the presence of neurologic symptoms and signs, a computed tomography (CT) scan of the patient’s brain was performed. The scan revealed a 2.9-cm low-density mass over the left frontal lobe, with peripheral rim enhancement and extensive perifocal edema reaching the corpus callosum, and crossing the midline . Taken together, these findings suggested a final diagnosis of oncocytic-type intraductal papillary mucinous neoplasm (IPMN)-derived invasive oncocytic carcinoma with brain metastasis  and subsequent adjuvant chemoradiation. Two years later, brain metastasis occurred and gemcitabine-based chemotherapy was given [et al. recently reported that patients with adrenal metastasis from pancreatic cancer seemed to be benefited by resection of metastatic and origin sites [Here, we report a patient diagnosed with invasive oncocytic carcinoma derived from the oncocytic type of IPMN combined with sole brain metastasis, initially presenting with neurologic symptoms. As shown in a previous study, pancreatic cancer metastasizes predominantly to the liver and peritoneal cavity, as is usually found in locally advanced PDAC . The inctastasis . Recentlas given . To our as given . To the in sites . Patientin sites ,27. Usedin sites : 5-FU hain sites .In the present case, our patient initially presented with neurologic symptoms and so was treated initially on the assumption that he was suffering from a brain abscess. After serial examinations, PDAC with brain metastasis was highly suspected. Although radical therapy for this situation was not feasible, due to the previous subtotal excision of the metastatic brain lesion and the fact that no other metastasis was found after a series of examinations, after discussion with his family, the Whipple operation was conducted and his final local stage was, surprisingly, T3N0. Subsequent radiotherapy and a combination of cisplatin and 5-FU chemotherapy were given and, at present, this patient is still alive with good performance status 2 years after surgery.On the basis of this case, we suggest that an aggressive therapeutic strategy may benefit some IPMN-derived PDAC patients presenting solely with brain metastasis. IPMN-derived PDAC with sole brain metastasis warrants individual treatment.This study has been approved by Chang Gung memorial hospital IRB board. The approved IRB number is 100-2977B. A copy of the approval of IRB is available for review by the Editor-in-Chief of this journal.CCRT: Combined chemotherapy and radiotherapy; CDX2: Caudal-related homeobox transcription factor 2; CT: Computed tomography; 5-FU: 5-fluorouracil; IPMN: Intraductal papillary mucinous neoplasm; MR: Magnetic resonance; MRCP: Cholangiopancreaticography; PDAC: Pancreatic duct carcinoma; TTF1: Thyroid transcription factor 1; WHO: World Health Organization.The authors declare that they have no competing interests.K-cC and C-cY wrote the manuscript, J-rC and C-cH carried out the pathological examination, C-nY, L-wC, J-tH helped wrote the manuscript, C-sT and H-cC participated in helping data collection, Y-tH carried out the image reading, C-hW and H-yC finalized the manuscript. All authors read and approved the final manuscript.Huang-Yang Chen, Kun-Chun Chiang and Chi-Chang Yu are Co-first authors.


Turner Syndrome women are at high risk of vascular disease and the assessment of early risk factors in Turner Syndrome girls is an emerging focus of research. Our objective was to evaluate endothelial function (EF), a preclinical measure of atherosclerosis, in Turner Syndrome girls compared with controls.A cross-sectional case-control study of Turner Syndrome girls and healthy controls. Subjects underwent fasting insulin and glucose with calculation of HOMA-IR, fasting lipid profile, anthropometrics, and EF testing using peripheral arterial tonometry (PAT). Subjects, aged 10-18 years, had karyotype-confirmed Turner Syndrome; growth hormone (GH), thyroxine and estrogen use were not exclusion criteria. Controls were age- and BMI-matched healthy girls. Fifteen Turner Syndrome and 15 controls were recruited.Turner Syndrome girls had lower height, higher HDL and higher waist:height ratio than controls. PAT-hyperemia ratio (RH-PAT) scores were lower in Turner Syndrome  indicating impaired EF. Among Turner Syndrome, RH-PAT did not vary with estrogen therapy or with karyotype 45,XO compared with other karyotypes. However, endothelial function was better in GH-treated compared with GH-untreated Turner Syndrome  although there were no differences in HOMA-IR, adiponectin or IGF-1.Girls with Turner Syndrome exhibit impaired endothelial function compared with controls, which may explain higher risk for vascular disease. GH may protect endothelial function in Turner Syndrome. Turner Syndrome, a common genetic disorder affecting 1 in 2500 live-born females, is caused by complete or partial loss of × chromosome . HoweverAdolescents and young adults rarely experience cardiovascular events, and surrogate markers of cardiovascular disease are needed to evaluate asymptomatic patients. Impaired endothelial function is an initial step in the development of atherosclerosis, and represents an early and reversible step in the vascular disease process ,6. The mThe objectives of this study were to evaluate endothelial function, as a marker of early vascular disease, in a group of pediatric Turner Syndrome girls in relation to an age-, sex- and body mass index (BMI)-matched healthy control population, and to assess the impact of disease-related treatment factors and acquired cardiovascular risk factors on endothelial function in the Turner Syndrome study group.Institutional ethical approval was obtained for this case-controlled cross-sectional study. Inclusion criteria for Turner Syndrome subjects included: karyotype-confirmed diagnosis of Turner Syndrome; patients followed in our endocrinology clinic; and aged 10-18 years. Individuals receiving human growth hormone (GH), L-thyroxine or estrogen, or with a history of congenital heart disease, were eligible for inclusion. All patients taking L-thyroxine were on stable therapy with thyroid function within the normal range. Subjects took their medications as usual on the day of the study. Controls were healthy girls, age- and BMI-matched to TS subjects and recruited as part of previous studies using the same testing protocol. Exclusion criteria included: inability of the family and/or patient to comply with study protocol; previous diagnosis of Type 1 or Type 2 Diabetes Mellitus; taking medications for the treatment of disorders of glucose, insulin or lipid metabolism.Each subject attended the Hospital for Sick Children for full evaluation on two separate days. On one day, subjects had fasting bloodwork including cholesterol profile , adiponectin, insulin and glucose. Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated based on fasting insulin and glucose values: .2. Pubertal status was assessed by a single examiner according to the methods of Tanner  and GH-untreated [N = 8] Turner Syndrome girls were not different  and IGF-1 levels were not different between GH-treated and GH-untreated girls . Among the GH-treated Turner Syndrome girls, GH treatment duration was 4.6 ± 1.1 years, with prescribed GH doses 0.35 mg/kg/week. There were no statistical differences in HOMA-IR, adiponectin, lipid measurements or blood glucose between GH-treated and GH-untreated Turner Syndrome girls . Among girls with Turner Syndrome, RH-PAT scores did not vary with estrogen replacement therapy  or between those with 45,XO karyotype [N = 6] and other karyotypes [N = 9] . However, RH-PAT scores were higher in girls receiving GH therapy than in those not receiving GH therapy  and in Turner Syndrome girls receiving GH therapy, PAT scores were similar to control girls .In Turner Syndrome subjects, RH-PAT score did not correlate with any measures of glucose, adiposity or anthropometrics. In control subjects, RH-PAT correlated positively with age and systolic BP, and negatively with LDL and HDL.This study demonstrates that Turner Syndrome girls, compared with healthy age-, sex- and BMI-matched controls, have impaired endothelial function, an early, pre-clinical marker of vascular disease. We did not observe any significant correlations with acquired CVD risk factors present in our TS cohort, including lipid profile, BP or markers of insulin resistance.The increased risk of cardiovascular complications in Turner Syndrome patients is complex and encompasses both congenital and acquired lesions. Recent data from the UK observed that non-congenital circulatory disease accounted for 41% of absolute excess mortality in Turner Syndrome women compared with only 8% for congenital anomalies . Our stuWe identified higher HDL concentrations in Turner Syndrome subjects compared with controls, and no effect of GH treatment on any measured cholesterol parameter was observed. These results are different with respect to previous studies that have shown higher total cholesterol in TS subjects independent of age, BMI and karyotype  and highAdditionally, we identified a tendency towards a decrease in fasting insulin and HOMA-IR with GH therapy. Previous reports have been mixed. One study identified increased fasting insulin and glucose in TS girls on GH therapy  and anotWe did observe that girls with Turner Syndrome who were receiving GH therapy had higher RH-PAT scores than girls with Turner Syndrome who were not receiving GH therapy, suggesting that GH may offer some endothelial protection in girls with Turner Syndrome. This was seen in a small number of patients, yet differences in endothelial function were not noted with estrogen replacement. Using other measures of endothelial or vascular function, previous studies have identified a protective effect of GH therapy. Flow-mediated dilatation improves in GH deficient adults following 3-18 months of GH therapy . GH defiPhysiologically, inherent differences have been described as part of the vasculopathy associated with Turner Syndrome. The precise mechanisms underlying this are likely multi-factorial and related to endothelial injury; alterations in Turner Syndrome patients include abnormities of collagen  and impaSeveral features of this study warrant further comment. This report is limited by the small number of patients studied and by the absence of significant correlations between RH-PAT and known traditional cardiovascular risk factors in the Turner Syndrome cohort. We did not observe any significant correlations with acquired CVD risk factors present in our cohort, including abnormal lipid profile, hypertension or insulin resistance. However, our relatively small study size and the lack of wide variation in these variables may account for this finding. We also used historical healthy controls who had undergone previous endothelial function testing using the same measure and protocol. While this did allow for matching on the basis of several confounding variables including age, sex and BMI, data relating to pubertal status or markers of insulin resistance were not available for comparison in the healthy control group. Nonetheless, given the nature of Turner Syndrome, with requirements for pubertal induction, it is unlikely that groups could be matched simultaneously for age and pubertal status . FinallyOur findings suggest that that Turner Syndrome is an independent risk factor for impaired endothelial function at a young age, but GH therapy may be protective in the Turner Syndrome population. Considering this inherent vasculopathy, it is important to monitor and intervene in these patients to reduce the additional burden of acquired cardiovascular disease risk factors , which are commonly observed in adolescent and adult Turner Syndrome patients. Regular screening is essential so that sub-clinical treatable conditions can be identified, with the ultimate goal of improving morbidity and mortality.We identified evidence of impaired endothelial function in pediatric Turner Syndrome subjects, compared with age- and BMI-matched female controls. We suggest that pediatricians need to be aware of increased risk of early atherosclerosis in pediatric age range Turner Syndrome patients, and to intervene with diet and lifestyle modifications and medications as needed. We also suggest that longitudinal studies are required to follow Turner Syndrome girls throughout the age spectrum into adulthood to identify and follow evidence of atherosclerosis.PAT: Peripheral Arterial Tonometry; BMI: Body Mass Index; HOMA-IR: Homeostasis Model Assessment - Insulin Resistance; RH-PAT: PAT-hyperemia ratio; HDL: High Density Lipoprotein cholesterol; GH: Growth Hormone; IGF1: Insulin-Like Growth Factor 1; LDL: Low Density Lipoprotein; BP: Blood Pressure; Kg: kilograms; M: metres; CV: coefficient of variation; SD: Standard deviation.The authors declare that they have no competing interests.CSOG designed the study, collected the data, analysed the data, wrote the manuscript. CS co- collected data and co-analysed data. TB co-designed the study and co-analysed the data. JH participated in study design, data analysis and preparation of the manuscript. FHM conceived the study, designed the study, analysed the data and co-wrote the final manuscript. All authors read and approved the final manuscript.


HIV/AIDS is associated with an increased burden of undernutrition among children even under antiretroviral therapy (ART). To treat undernutrition, WHO endorsed the use of Ready to Use Therapeutic Foods (RUTF) that can reduce case fatality and undernutrition among ART-naïve HIV-positive children. However, its effects are not studied among ART-treated, HIV-positive children. Therefore, we examined the association between RUTF use with underweight, wasting, and stunting statuses among ART-treated HIV-positive children in Dar es Salaam, Tanzania.This cross-sectional study was conducted from September-October 2010. The target population was 219 ART-treated, HIV-positive children and the same number of their caregivers. We used questionnaires to measure socio-economic factors, food security, RUTF-use, and ART-duration. Our outcome variables were underweight, wasting, and stunting statuses.Of 219 ART-treated, HIV-positive children, 140 (63.9%) had received RUTF intervention prior to the interview. The percentages of underweight and wasting among non-RUTF-receivers were 12.4% and 16.5%; whereas those of RUTF-receivers were 3.0% (P = 0.006) and 2.8% (P = 0.001), respectively. RUTF-receivers were less likely to have underweight (Adjusted Odd Ratio (AOR) =0.19, CI: 0.04, 0.78), and wasting , compared to non RUTF-receivers. Among RUTF receivers, children treated for at least four months (n = 84) were less likely to have underweight (P = 0.049), wasting (P = 0.049) and stunting (P < 0.001).Among HIV-positive children under ART, the provision of RUTF for at least four months was associated with low proportions of undernutrition status. RUTF has a potential to improve undernutrition among HIV-positive children under ART in the clinical settings in Dar es Salaam, Tanzania. Management of undernutrition among HIV-positive children is complicated. This is mostly due to a weakened immunity  which leAmong RUTF-treated children, severe undernutrition status can be improved among hospitalized antiretroviral therapy (ART) naïve HIV-positive children . CompareThe combination of RUTF and ART treatments might improve undernutrition and reduce case fatality rates among HIV-positive children. This is because ART improves immunity, reduces energy loss, and may improve child’s appetite to food -12. So fTanzania is one of the countries hardest hit by both HIV/AIDS and child undernutrition. In 2009, HIV prevalence was 5.9% in Tanzania . In the To ameliorate such high undernutrition rate, Ministry of Health and other development partners established the RUTF intervention in selected HIV/AIDS Care and Treatment Centers (CTCs) as a pilot intervention in Tanzania. Although studies among ART naïve populations showed effectiveness of RUTF, we could not find similar studies among ART-treated children elsewhere. Furthermore, since the start of RUTF intervention as a pilot project in Tanzania, no studies have evaluated its efficacy among ART-treated HIV-positive children. Therefore, we conducted this study to examine the association of RUTF intervention with stunting, wasting, and underweight statuses among the ART-treated, HIV-positive children in Dar es Salaam, Tanzania.We conducted this cross sectional study in Dar es Salaam, where HIV prevalence was 8.9% in 2009. It accounts for about 300,000 people living with HIV/AIDS. The city has 44 HIV/AIDS care and treatment centers (CTCs) which provide ART programs to care about 4,000 children .Participants of this study included pairs of 219 under-five ART-treated, HIV-positive children and their caregivers. These children were attending CTCs that provide RUTF treatment to severe undernourished children. In Dar es Salaam, a total of six out of 44 CTCs provide RUTF to such children. We excluded the CTC of the Muhimbili National Hospital (MNH). MNH is the referral center for complicated cases from the Northern zone and beyond. Being the highest tertiary hospital, its CTC also cares for more complicated and severe cases from the outside of the region. As a result, we selected five CTCs: Amana, Temeke, Mwananyamala, IDC, and Pasada CTCs. Children under five years of age in the selected CTCs totaled 1719. Amana CTC registered 350 children, Temeke CTC 396, IDC 250, Pasada 373, and Mwananyamala 350.Of the total, about 58% of the children enrolled in CTCs were on ART. We excluded children with missing medical and ART-related information and those whose parents did not consent to participate in the study. We selected each alternative participant of this study from the list of the eligible participants (n = 670). We used Epi-Info Version 6  to calculate the minimum required sample size. We estimated that the ratio of children exposed to RUTF to those who were not exposed to RUTF in the intervention clinics to be 2:1. The proportion of underweight among ART-treated HIV-positive children was considered at 13.6% . We therWe defined ART-treated HIV-positive children as children whose sero-status was confirmed to be positive using standard laboratory methods and were taking Highly Active Antiretroviral Therapy (HAART). According to the national guidelines for pediatric HIV/AIDS care in Tanzania, children are typically treated with a combination therapy consisting of three antiretroviral medicines, hence HAART .RUTF Plumpynut® is given to children with severe wasting (Weight-for-height Z-score (WHZ) < −3SD) or underweight (Weight-for-age Z-score (WAZ) < −3SD) or both severe wasting and underweight . Such chWe measured children’s weight by two methods. For children who could not stand alone, we used a standardized hanging Salter scale® (UK) calibrated to 0.1 kg. For children who could stand alone we used a standardized Seka® digital scale . We measured height for the 24 months and older children  using a Low HAZ, WAZ, and WHZ are the measures of stunting, underweight, and wasting, respectively . StuntinAccording to the WHO Global Database on Child Growth and Malnutrition, an abnormal anthropometry is defined as a value of Z-score below −2 Standard Deviation (SD) or above +2SD. Z-scores less than -2SD are defined as moderate undernutrition, while less than -3SD are defined as severe undernutrition . These cWe adopted the socio-demographic variables pertaining to children and their caregivers from the Tanzania Demographic and Health Survey (TDHS), women and household questionnaires . InformaWe assessed food security by using the 6-item Household Food Security Scale (HFSS) . HFSS haWe assessed economic status by using a Weighted Wealth Index incorporating household durable assets ownership such as paraffin lamp, television, radio, telephone, flat iron, refrigerator, bicycle, motor car, farm and electricity; housing and dwelling characteristics, such as main floor materials, house ownership, fuel for lighting and cooking, type of toilet, source of water, feeding characteristics, and household food satisfaction . Then, wWe hired five nurse counselors and trained them for one day on interviewing technique and questionnaire contents. The first author and trained research assistants pretested the questionnaire. To ensure good interviewing environment, we recruited all research assistants from the clinics and assigned them to conduct data collection. We collected data by face-to-face interview with caregivers and anthropometric measurements of the children attending the clinic between September and October 2010.P-value <0.05. We conducted analyses using PASW 18 .We conducted descriptive analysis using Chi-square test and Independent sample T-tests to compare characteristics and nutrition status of children who were treated versus those who were not treated with RUTF. We conducted multivariate analysis to examine the effectiveness of RUTF on nutritional status of HIV positive children after adjusting other covariates and important confounders including ART treatment duration. Among RUTF treated children, we used bivariate analysis to evaluate the association of undernutrition and RUTF treatment duration; since the proportion of wasting and underweight was small for multivariate regression analysis. We set the statistical significance at We obtained ethical clearance from the Ethical Committees of the University of Tokyo and Muhimbili University of Health and Allied Sciences to conduct this study. We also obtained permission to conduct research from health departments and facilities used for the study. Participation was voluntary, and confidentiality was ensured. Caregivers gave the written informed consent before starting the interview.Out of 219 HIV positive children recruited for this study, 140 (63.9%) had received the RUTF intervention. Children who received and those who did not receive the intervention did not have any significant difference in age, sex, orphan hood state, and birth weight (Table Table Table Table This study found that RUTF treated HIV-positive children under ART had lower proportions of underweight and wasting compared to RUTF naïve HIV-positive children under ART. Furthermore, children treated by RUTF for at least four months had lower proportions of underweight, wasting, and stunting compared to their counterparts. Our study is the first to show the effect of RUTF treatment duration on both acute and chronic undernutrition in the era of ART scaling up.In this study, about 97% of children treated with RUTF were found to have normal weight-for-age and weight-for-height. This is an important achievement. This is because, all of these children were either severely wasted or underweight or both at the baseline. Compared with RUTF-naïve, the RUTF treated children had a significantly better nutrition status. Such significant achievement of RUTF treatment can be explained as follows. First, RUTF ingredients are energy dense, with lipids and proteins , which pWhile our results showed low wasting and underweight proportions among RUTF treated children compared to RUTF naïve children, proportions of stunting were not significantly different among them. Stunting has many persistent determinants including poverty, food insecurity ,43, and Apart from RUTF intervention, this study also found other factors associated with undernutrition among ART treated children. These factors include male sex, low birth weight, lower economic status, and food insecurity. Previous study conducted among ART-treated children in Tanzania  and amonOur results should be interpreted with care owing to some limitations. First, the cross-sectional design would limit direction of causal relationship. Using this design, it may be difficult to examine the effect of food in a population that has high food insecurity. In our multivariate analyses, however, we controlled for food insecurity and other factors that were found to be associated with undernutrition in a previous study in the same region . MoreoveIn conclusion, among HIV-positive children under ART, provision of RUTF was associated with low proportions of wasting and underweight statuses. Furthermore, RUTF treatment for at least four months was associated with lower proportions of underweight, wasting and stunting. This result suggests that supplementation with RUTF at least for four months has a potential to improve undernutrition among HIV-positive children under ART in the clinical settings. RUTF may be useful in countries like Tanzania and others with high proportion of undernutrition among ART-treated HIV-positive children . It is tAIDS: Acquired immunodeficiency syndrome; AOR: Adjusted odd ratio; ART: Antiretroviral therapy; CI: Confidence interval; CTC: Care and treatment center; ENA: Emergency nutrition assessment; HAZ: Height for age z-score; HFSS: Household food security scale; HIV: Human immunodeficiency virus; PCA: Principal component analysis; RUTF: Ready to use therapeutic foods; TDHS: Tanzania demographic and health survey; WAZ: Weight for age z-score; WHO: World Health Organization; WHZ: Weight for height z-score.Authors declare that they have no competing interests.BFS conceived the research question, designed the study, conducted the fieldwork, analyzed data, and prepared the manuscript draft. KCP was involved to conceptualize the study and contributed to the study design, statistical analysis, interpretation of the data, and revisions of the manuscript. LBM conducted the fieldwork, data entry, and preparation of the manuscript. KO was involved in the study design. JY was involved in the study design and revision of the manuscript. DPU was involved in logistic preparation for fieldwork, supervision of the fieldwork, and revision of the manuscript. NPM was involved in fieldwork, logistics support, and revision of the manuscript. MJ monitored the study progress, contributed to design of the study, and revised the manuscript. All authors read and approved the final manuscript draft.


Hispanics are the fasting growing population in the U.S. and disproportionately suffer from chronic diseases such as hypertension and diabetes. Little is known about the complex interplay between acculturation and chronic disease prevalence in the growing and increasingly diverse Hispanic population. We explored the association between diabetes and hypertension prevalence among distinct U.S. Hispanic subgroups by country of origin and by degree of acculturation.We examined the adult participants in the 2001, 2003, 2005, and 2007 California Health Interview Survey (CHIS). Using weighted logistic regression stratified by nativity, we measured the association between country of origin and self-reported hypertension and diabetes adjusting for participants’ demographics, insurance status, socio-economic status and degree of acculturation measured by citizenship, English language proficiency and the number of years of residence in the U.S.There were 33,633 self-identified Hispanics . After multivariable adjustment, we found significant heterogeneity in self-reported hypertension and diabetes prevalence among Hispanic subgroups. Increasing years of U.S. residence was associated with increased disease prevalence. Among all foreign-born subgroups, only Mexicans reported lower odds of hypertension after adjustment for socioeconomic and acculturation factors. Both U.S.-born and foreign-born Mexicans had higher rates of diabetes as compared to non-Hispanic whites.We found significant heterogeneity among Hispanics in self-reported rates of hypertension and diabetes by acculturation and country of origin. Our findings highlight the importance of disaggregation of Hispanics by country of origin and acculturation factors whenever possible. Hispanics are the fastest growing minority group in the U.S., comprising 15% of the population -8. TheseWhile disease prevalence has been shown to vary by Hispanic subgroups -14, few Since the Hispanic population in California is two times greater than that of the remainder of the U.S. (36.2% versus 15.1%) , we examWe examined the adult participants in the 2001, 2003, 2005, and 2007 CHIS, the largest health survey conducted in any state. CHIS is a population-based random-digit dial telephone survey of California’s population conducted every other year since 2001. CHIS employs a multi-stage sample design and includes cellphone-only households. In addition, interviews are conducted in English, Spanish, and three Asian languages. Using CHIS allows sampling of non-Carribean Hispanics in larger numbers than what is possible through national datasets. A detailed description of the history, design, data collection, and available data for CHIS is available at the website .Patient demographic characteristics included age, sex, self-reported race , federal poverty level (FPL) , insurance , and education level . Self-identified Hispanics were categorized by country of origin: Mexican, Salvadorean, Guatemalan, Central American, South American, Puerto Rican, Hispanic European, Hispanics having two or more countries of origin (2+ Hispanic), and Other Hispanic. We merged Salvadorean, Guatemalan and Central American into one category to account for smaller sample size. Other Hispanic included those who self-identified as this category and those who identified as Hispanic European. We did not include Puerto Ricans in our analyses due to small sample size.Given the multiple metrics for measuring acculturation , we examSelf-reported hypertension and diabetes were ascertained by the questions: “Has a doctor ever told you that you have high blood pressure?” and “Other than during pregnancy, has a doctor ever told you that you have diabetes or sugar diabetes?” Body mass index (BMI) was calculated by CHIS based on self-reported participant’s weight and height. Smoking habits were assessed with two questions: “Altogether have you smoked at least 100 or more cigarettes in your entire lifetime?” and “Do you now smoke cigarettes every day, some days or not at all?” Based on examination of distribution plots, self-reported intensity of utilization of clinical services in the past 12 months was defined into three categories: no visits, 1–11 visits, greater than 11 visits.a priori to conduct separate sensitivity analyses stratifying the aforementioned regression models by age greater than 45 years. Finally, separate interaction analyses were conducted between Hispanic country of origin subgroups and two acculturation variables (years of residence in the U.S. and English language ability).We used the chi-square test to compare the distribution of participants’ demographic and clinical characteristics of self-reported hypertension and diabetes. Weighted logistic regression models were created for participants’ self-reported hypertension and diabetes. All models were adjusted for participants’ demographic characteristics, insurance status, socioeconomic level, clinical characteristics, and acculturation factors . NHW was used as a reference group. Models were stratified by nativity status because prior work has shown that significant differences exist between foreign- and U.S.-born Hispanics . BecauseDue to the complex sampling design of CHIS, SUDAAN 9.2 statistical software  was used for all analyses. Special sample weights provided by CHIS were included in the analysis to adjust for oversampling, non-response bias and post-stratification population totals. All p values reported are for 2-tailed tests and a value of <0.05 was considered statistically significant. All p values were adjusted for multiple comparisons between subgroups using the Bonferroni method.The current study was deemed exempt by the Massachusetts General Hospital Institutional Review Board because the data were de-identified by CHIS and are publicly available.There were 33,633 self-identified Hispanics and 126,448 NHWs. There were 13,645 U.S.-born Hispanics  or people who identify as biracial or bi-ethnic . The self-identity of Hispanics is complex and is influenced by the country of origin and nativity status . Future A major strength of our study is its large sample size of Hispanics over a seven-year period that used the same sampling and data collection methodology in a state with one of the largest Hispanic populations. The survey questions allowed for a more detailed analysis of self-identified Hispanics by country of origin and acculturation factors than has been available in previous studies. We were able to assess acculturation in four dimensions . In addition, California’s Hispanic demographic patterns allowed for a larger and more representative sample of Hispanics from Central and South America, groups traditionally underrepresented in other datasets. Importantly, our data allowed for statistical analyses that controlled for important confounders such as intensity of clinical services utilization.Our study had several limitations. First, our data are cross-sectional and thus associations found are not proof of causality. Second, the self-reported nature of hypertension and diabetes may cause underestimation of disease rates, particularly because many Hispanics are uninsured and have less access to regular sources of healthcare. However, self-reported data for hypertension and diabetes have been shown to be highly correlated with physicians’ records -36. SimiIn conclusion, we found significant differences in rates of self-reported hypertension and diabetes by Hispanic subgroups, nativity, and acculturation. Our findings underscore the importance of exploring within-group differences and heterogeneity among Hispanics in the U.S., differences that may account for the mixed and paradoxical associations between acculturation and various health indicators. Finally, better standardized data collection strategies that incorporate Hispanic subgroups and acculturation factors will allow for improved tracking of health status among Hispanics, which may better inform public health interventions.BMI: Body mass index; CHIS: California Health Interview Survey; CVD: Cardiovascular disease; NHW: Non-Hispanic white.The authors declare that they have no competing interests.FR contributed to the data interpretation and manuscript preparation. LH contributed to the study design and conception a well as manuscript revisions. LL contributed to the conception and study design, data acquisition and interpretation, statistical analyses, and manuscript drafting. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/12/768/prepub


Adult T-cell leukemia (ATL) is a T-cell malignancy caused by HTLV-1. In ATL, chemotherapeutic responses are generally poor, which has suggested the existence of chemotherapy-resistant cancer stem cells (CSCs). The HTLV-I transactivator, Tax, initiates ATL-like disease (mATL) in Tax transgenic mice. Recently, the CSCs of mATL were identified. The CSCs in a side population, could consistently regenerate the original lymphoma and overlapped with a minor population of CD38(-)/CD71(-)/CD117(+) cells, suggesting that the eradication of cancer stem cells will be necessary to improve the outcome of treatment for mATL. In designing specific regimens for CSCs, antibody-based therapy appears to be a promising way to destroy CSCs. A small number of target antigens on cancer stem cells have been described. It remains to be determined, however, whether these and other targets will distinguish cancer stem cells from normal tissues.In this study, a proteomic approach was used to identify proteins differentially expressed in CSCs of mATL. The CSCs of mATL were isolated using cell sorting, and analyzed by label-free LC-MS/MS to compare protein profiles in CSCs and no-CSCs. More than 700 proteins were detected. The levels of 53 proteins were increased in CSCs. An interesting finding is that these proteins included one membrane protein, which might potentially serve as a new target of antibody-based therapy. Flow cytometry validated expression of the membrane protein. Taken together, the data presented provide a significant new protein-level insight into the biology of cancer stem cells of mATL, a key population which are involved in mATL development.


Both low birth weight, an indicator of intrauterine growth restriction, and low grade systemic inflammation depicted by high sensitivity C-reactive protein (hs-CRP) have emerged as independent predictors of cardiovascular (CV) disease and type 2 diabetes. However, information linking low birth weight and hs-CRP in a biracial (black/white) population is scant. We assessed a cohort of 776 black and white subjects  aged 24-43 years (mean 36.1 years) enrolled in the Bogalusa Heart Study with regard to birth weight and gestational age data were retrieved from Louisiana State Public Health Office.Black subjects had significantly lower birth weight than white subjects  and higher hs-CRP level . After adjusting for sex, age, body mass index (BMI), smoking status and race , the hs-CRP level decreased across quartiles of increasing birth weight in white subjects (p = 0.001) and the combined sample (p = 0.002). Adjusting for sex, age, BMI, smoking status and race for the total sample in a multivariate regression model, low birth weight was retained as an independent predictor variable for higher hs-CRP levels in white subjects (p = 0.004) and the total sample (p = 0.007). Conversely, the area under the receiver operative curve (c statistic) analysis adjusted for race, sex, age, smoking status and BMI yielded a value of 0.777 with regard to the discriminating value of hs-CRP for predicting low birth weight.The deleterious effect of low birth weight on systemic inflammation depicted by the hs-CRP levels in asymptomatic younger adults may potentially link fetal growth retardation, CV disease and diabetes, with important health implications. The growth of an undernourished fetus results in adaptive fetal programming or metabolic imprinting, with permanent changes in structure, metabolism and physiology of fetal organs and related pathophysiologic consequences in later life ,2. StudiInflammation plays an important role in the pathogenesis of atherosclerosis -9. Risk The study sample was derived from a cohort of 1203 subjects aged 23 to 43 examined as a part of a longitudinal follow-up survey. Of these, information on 908 singletons with hs-CRP measurement, birth weight, gestational age and body mass index (BMI) data were available. The exclusion of 132 singletons born premature (<37 weeks of gestation) and/or had conditions (with or without medication) of diabetes, hypertension and dyslipidemia left 776 eligible participants . Birth weight and gestational age data were retrieved from Louisiana State Public Health Office. Tulane University Medical Center Institutional Review Board approved the study, and informed consent was obtained from all participants.Standardized techniques and protocols were used by trained examiners. Height and weight were measured twice and the mean values were used to calculate BMI as a measure of adiposity. Information on smoking status was obtained by questionnaires. Those who had smoked at least one cigarette per week during the past one year or more were identified as current smokers, and the remainder as non-smokers. Plasma high sensitivity hs-CRP levels were measured by latex particle-enhanced immunoturbidemetric assay on a Hitachi 902 Automatic Analyzer . The reproducibility of hs-CRP measurement checked with 10% of randomly assigned pairs of blind duplicate analysis, which gave an intraclass correlation coefficient of 0.99.Statistical analyses were done with SAS software, version 9.1 . As the hs-CRP level was not normally distributed, log transformation was used to approach normality. Analyses were performed where appropriate on transformed data. Analysis of variance for race difference in mean values of continuous variables and chi-square test for categorical variables were used. Because of a strong association between gestational age and birth weight, the latter was adjusted by regression analysis models to the mean values of the former in each race-sex group. For categorical analysis, quartiles of gestational age-adjusted birth weight were defined by using cut-off points in race-sex groups. Covariates adjusted mean values of hs-CRP were calculated by general linear models and used for analysis of birth weight by quartiles. Multiple regression analysis was used to determine the independent association of birth weight with hs-CRP in relation to the measured covariates. Two steps were followed in the regression model: the logarithm of hs-CRP was used in both cases as a dependent variable to determine the association between birth weight and hs-CRP. Model 1 was adjusted for age, sex, smoking and race  and the model 2 was adjusted for the above variables along with the potential confounding variable, BMI. In addition, a multivariate c-statistic model was used to determine the ability of hs-CRP to predict low birth weight (defined as <2500 gm). The area under the receiver-operating characteristic curve (c-statistic) was evaluated after adjusting for the covariates race, sex, age, smoking status and BMI. C-statistic of >0.5 indicated increased predictive ability.Table Figure Table Figure This community-based study demonstrates an inverse and independent association between birth weight and hs-CRP, a widely used biomarker of systemic inflammation. In addition, female sex, BMI and smoking were independent adverse correlates of hs-CRP. It is noteworthy that these findings support the emerging concept of intrauterine imprinting and its pathophysiologic consequences later in life by linking low birth weight to excess hs-CRP ,2.Although previous study in children has failed to find significant association between birth weight and hs-CRP , our epiAlthough observational studies like this cannot address the issue of causality, several putative mechanisms might link low birth weight to underlying perturbation in inflammatory pathways in utero. Undernutrition in utero causes permanent impairment in growth, structure, and function of muscle ,20, fat As in previous studies ,32, obesIn conclusion, low birth weight for gestational age is characterized by increased hs-CRP levels. In conjunction with earlier studies, these findings support the view that low birth weight, albeit a crude surrogate indicator of adaptive fetal programming, is a potential early risk factor for the emergence of disorders related to the activation of inflammatory pathways. As stated by Barker , primaryhs-CRP: high sensitivity C-reactive protein; BMI: body mass index.The authors declare that they have no competing interests.ARB participated in study design, data analysis and manuscript preparation. SRB, WC and GSB contributed to study concept and design, data collection, acquisition of funding and manuscript preparation. MJA involved in manuscript preparation. All authors listed have made substantial contributions on this article