This study examined the status of radiation-induced liver injury in adjuvant or palliative gastric cancer radiation therapy (RT), identified risk factors of radiation-induced liver injury in gastric cancer RT, analysed the dose-volume effects of liver injury, and developed a liver dose limitation reference for gastric cancer RT.Data for 56 post-operative gastric cancer patients and 6 locoregional recurrent gastric cancer patients treated with three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) from Sep 2007 to Sep 2009 were analysed. Forty patients (65%) were administered concurrent chemotherapy. Pre- and post-radiation chemotherapy were given to 61 patients and 43 patients, respectively. The radiation dose was 45–50.4 Gy in 25–28 fractions. Clinical parameters, including gender, age, hepatic B virus status, concurrent chemotherapy, and the total number of chemotherapy cycles, were included in the analysis. Univariate analyses with a non-parametric rank test (Mann–Whitney test) and logistic regression test and a multivariate analysis using a logistic regression test were completed. We also analysed the correlation between RT and the changes in serum chemistry parameters  after RT.The Child-Pugh grade progressed from grade A to grade B after radiotherapy in 10 patients. A total of 16 cases of classic radiation-induced liver disease (RILD) were observed, and 2 patients had both Child-Pugh grade progression and classic RILD. No cases of non-classic radiation liver injury occurred in the study population. Among the tested clinical parameters, the total number of chemotherapy cycles correlated with liver function injury. V35 and ALP levels were significant predictive factors for radiation liver injury.In 3D-CRT for gastric cancer patients, radiation-induced liver injury may occur and affect the overall treatment plan. The total number of chemotherapy cycles correlated with liver function injury, and V35 and ALP are significant predictive factors for radiation-induced liver injury. Our dose limitation reference for liver protection is feasible. Gastric cancer is one of the most common cancers in China, and patients with lymph node-positive disease have a 5-year survival rate as low as 15–20%. Even node-negative patients have a 5-year survival rate of only 45–55% if the T stage is advanced (T3-T4N0) [Moreover, patients with advanced stages of cancer require radiation therapy (RT) and chemotherapy. The advantage of oral chemotherapy drugs, such as capecitabine and S-1, has been shown in a randomized clinical trial –5; howevA number of models have been used to predict the risk of radiation-related liver injury. The probability of radiation-induced liver disease (RILD) using the Lyman-Kutcher-Burman model of normal tissue complication probability (NTCP) for primary liver cancer (PLC) treated with three-dimensional conformal radiation therapy (3D-CRT) was established by Dawson et al. and Xu et al. ,8. The rThe aims of current study were to investigate the predictive factors of radiation-induced liver injury in adjuvant and palliative gastric cancer RT, analyse the dose-volume effects of liver injury in gastric cancer RT, and offer a dose limitation reference for gastric cancer RT.All data were collected from consenting individuals according to the protocols approved by the Ethics Review Board at the Fudan University Shanghai Cancer Center. The consents were verbal, and we recorded the participant consents on our follow-up record to confirm that he/she wanted to join the study. The ethics committee approved this consent procedure. From Sep 2007 to Sep 2009, a total of 90 consecutive and non-selected gastric cancer patients underwent post-operative adjuvant or palliative RT at the Fudan University Shanghai Cancer Center. Among them, 76 patients with locally advanced post-operative gastric cancer and 14 patients with locoregional recurrence and non-metastatic gastric cancer patients underwent radiotherapy. Twenty-eight patients were excluded from the current study due to incomplete dosimetric parameters (12 patients) or insufficient follow-up data (16 patients). Thus, the data from a total of 62 patients were included in this study, including 56 post-operative patients who underwent adjuvant chemoradiotherapy and 6 locoregional recurrent patients who received palliative chemoradiotherapy. Out of this total, 45 patients were male, and 17 patients were female, with a median age of 56 years . Forty patients (65%) were administered concurrent chemotherapy, including 21 patients given capecitabine and 19 patients given 5-FU. Pre- and post-radiation chemotherapy were administered to 61 patients and 43 patients, respectively, with 1–10 (median 5) cycles and a chemotherapy regimen of ECF or modified ECF (EOF or EOX).For post-operative patients, the target volume for RT included the tumour bed, anastomosis, gastric remnant (pT3-T4), and regional draining lymph nodes . The target volume was determined from the pre-operative CT scan, surgical clips, and barium examination. For patients with locoregional recurrence, the target volume for RT included the recurrent lesions only and was determined from the enhanced-contrast CT scan. Treatment was delivered using 3D-CRT or intensity-modulated radiation therapy (IMRT) technology. Respiratory movement was estimated by fluoroscopy and repeated CT scanning. The PTV was an expansion of CTV because of the respiratory motion and inter-fractional uncertainty. Active Breathing Coordinator (ABC) technology was used to reduce organ movement in patients with a large displacement (>1 cm) due to breathing. The prescription dose was 45–50.4 Gy in 25–28 fractions. Three-dimensional dose calculations were performed using Pinnacle 3  with a tissue density inhomogeneity correction. The goal of the treatment plan was to ensure that the prescription dose covered at least 95% of the PTV and that 95% of the prescription dose covered at least 99% of the PTV. The dose constraints for the organs at risk (OAR) included each kidney V15 (volume receiving ≥15 Gy) <50%, a mean dose of each kidney <16 Gy, liver V30 (volume receiving ≥30 Gy) <30%, a mean liver dose (MLD) less than 23 Gy and a spinal cord maximum dose <45 Gy. If the aim of the treatment plan could not be met because of geometry size, position of the PTV or critical structures, a compromise was made for clinical purposes. Radiation therapy was delivered with a 6-MV linear accelerator, and IMRT was delivered with a step-and-shoot technique.All patients were required to undergo follow-up according to the protocol, including weekly meetings during RT and at least 4 monthly meetings after treatment completion. Follow-up examinations, including history and physical examination, were routinely performed, and all patients were evaluated for liver function, including bilirubin , alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and serum albumin (ALB). Baseline liver functions and post-RT changes in liver function were evaluated with the Child-Pugh score system. We recorded the classic and non-classic RILD cases according to the definition of Pan et al. . We defiClinical parameters, including gender, age, hepatic B virus status, concurrent chemotherapy, and the total number of chemotherapy cycles, were used in the analysis, and the dose volume histogram (DVH) of the treatment plan was recorded for each patient. The fractions of the liver receiving more than 5, 10, 15, 20, 30, 35, 40, and 45 Gy, MLD and maximal dose to the liver were computed for each patient from the liver DVH.A univariate analysis using a non-parametric rank test (Mann–Whitney test) and logistic regression test and a multivariate analysis using the logistic regression test were completed. A p-value of 0.05 was considered significant for the rank tests and logistic analysis. We analysed the correlation between RT and the changes in serum chemistry parameters  after RT.Out of the 62 patients, 58 patients were Child-Pugh grade A, and 4 patients were Child-Pugh grade B before RT. Fourteen patients were Child-Pugh grade B, and 45 patients were Child-Pugh grade A after RT. The Child-Pugh grade progressed from grade A to grade B after RT in 10 patients. A total of 16 cases of classic RILD (with elevation of ALP only) were observed. Two patients had both Child-Pugh grade progression and classic RILD (with elevation of ALP only). Non-classic radiation liver injury was not observed in any of the patients.The results of the univariate analysis evaluating the association between clinical and dose-volumetric parameters are summarized in A multivariate analysis  was perfWe analysed the correlation between dose-volumetric parameters and abnormal serum chemistry parameters  after RT. We found that AST, D-TB and TB were not related to delivery dose. The relationship between the other three parameters and the DVH parameters is summarized in This is the first investigation reporting the correlation between clinical parameters, DVH and liver function injury in gastric cancer RT. Our study showed that radiation-induced liver injury occurred in 3D-CRT for gastric cancer patients. Among the assessed clinical parameters, the total number of chemotherapy cycles correlated with liver function injury, and V35 and ALP were significant predictive factors for radiation-induced liver injury.The majority of previously applied normal liver tissue constraints in radiotherapy planning were based on the studies of liver toxicity after radiotherapy for primary or metastatic liver cancer. The radiation-induced hepatic injury differs between liver cancer and gastric cancer patients. More patients with gastric cancer had normal liver function before radiotherapy, and the dose distribution in the liver varied. Moreover, the treatment strategies and methods differ between liver cancer and gastric cancer patients. This straightforward study aimed to correlate clinical outcome with irradiated liver volume and increase the details for the liver tolerance guidelines. Thus, this study has merit.Our results showed that the response to liver radiation in gastric cancer RT was not as strong as in liver cancer RT. For whole liver RT, the prescription dose was limited to the whole-liver tolerance dose, which corresponded with a 5% risk of RILD after a whole-liver dose delivery of 30–35 Gy in 2 Gy per fraction . For parThe evaluation criterion used was different for patients with liver cancer and gastric cancer. Liver cancer, the most common liver toxicity after RT, includes a clinical syndrome of anicteric hepatomegaly, ascites, and elevated liver enzymes (ALP more than the transaminases) occurring typically between 2 weeks to 3 months after completion of RT. Most research uses the Cancer Therapy Evaluation Program and Common Terminology Criteria for Adverse Events (CTCAE) to evaluate liver toxicity after RT. The liver function of the majority of patients with gastric cancer was better compared with patients with liver cancer. The high-dose delivery to the liver in gastric cancer RT was less, and none of the patients suffered from serious liver toxicity in the current study.The dose distribution in liver during gastric cancer RT differs from liver cancer RT. Sparing the normal liver in patients with liver cancer was more difficult. In gastric RT, IMRT technology can be used to spare more liver volume, which may be beneficial for patients. In liver radiation, the target of radiation is always surrounded by normal liver parenchyma, which inevitably increases the normal liver dose. According to Jackson’s report, the liver was composed of independent functional subunits; thus, the distribution of dose may influence liver function .The relationship between treatment planning and serum chemistry parameters was established by recording and analysing dosimetric and clinical data. Our results show 2 effects of radiation. First, ALT and ALP were sensitive to a low-dose radiation volume if the volume of 3.5 Gy covered nearly the whole liver; therefore, these two parameters will reach abnormal levels after radiation. This result indicates that ensuring a part of liver does not receive radiation during the therapy may decrease the incidence of liver toxicity. This phenomenon was also described by Liang et al. . We alsoMany studies have used NTCP to estimate the risk of radiation-related liver complications. This method assumes a sigmoidal relationship between the dose of uniform radiation given to a volume of an organ and the chance of a complication occurring ,21. NTCPWe consider our results far from conclusive, and several important issues need to be addressed. First, the determination of the dose limitations for radiation therapy for gastric cancer patients is limited because of the retrospective study design. Second, the patient characteristics are not homogeneous in this study. Third, from a modelling point of view, this is a unique situation because of the wide spectrum of DVH shapes; however, this variability requires more patients to be enrolled in the study. Lastly, the chemotherapy regimen and cycles differed among patients, and the observation of a significant relationship between the number of chemotherapy cycles and liver dysfunction may have been influenced by confounding non-radiation-based factors. More clinical trials, preferably in a prospective design, are needed to determine the threshold value of the DVH parameters that can predict liver function.S1 Table(DOC)Click here for additional data file.


Assessing current fatigue of athletes to fine-tune training prescriptions is a critical task in competitive sports. Blood-borne surrogate markers are widely used despite the scarcity of validation trials with representative subjects and interventions. Moreover, differences between training modes and disciplines  have rarely been studied within a consistent design. Therefore, we investigated blood-borne fatigue markers during and after discipline-specific simulated training camps. A comprehensive panel of blood-born indicators was measured in 73 competitive athletes  at 3 time-points: after a run-in resting phase (d 1), after a 6-day induction of fatigue (d 8) and following a subsequent 2-day recovery period (d 11). Venous blood samples were collected between 8 and 10 a.m. Courses of blood-borne indicators are considered as fatigue dependent if a significant deviation from baseline is present at day 8 (Δfatigue) which significantly regresses towards baseline until day 11 (Δrecovery). With cycling, a fatigue dependent course was observed for creatine kinase , urea , free testosterone  and insulin linke growth factor 1 . For urea and IGF-1 95% confidence intervals for days 1 and 11 did not overlap with day 8. With strength and high-intensity interval training, respectively, fatigue-dependent courses and separated 95% confidence intervals were present for CK  only. These results indicate that, within a comprehensive panel of blood-borne markers, changes in fatigue are most accurately reflected by urea and IGF-1 for cycling and by CK for strength training and team sport players. Training load and competition frequency of elite athletes are steadily increasing and performance differences between race winners and “also-ran” are becoming more and more marginal. Consequently, athletes and coaches face the difficult task of maximizing training load and adaptation whilst avoiding insufficient recovery, which would lead to maladaptation, loss of performance and possibly to non-functional overreaching or the overtraining syndrome. In this situation, assessing the current fatigue status of an individual athlete is a critical task in order to fine-tune training prescriptions. The pivotal and most relevant objective characteristic of fatigue in competitive athletes is a decline in discipline specific performance . HoweverBlood-borne parameters are particularly attractive surrogate markers for training-induced fatigue because of a minimal interference with the training process, high accuracy and precision of measurements and, in most cases, a clear physiological concept concerning their connection with exercise and fatigue . HoweverThe study was a prospective, short-term training trial with follow-up testing. Tests were conducted at baseline following two days of rest , after induction of fatigue by a discipline specific, six day strenuous training program  as well as following an additional two day rest period . An overview of the general design is given in All tests were conducted in a University department . For cyclists and ballgame players, tests were conducted during the respective preparation periods . Strength athletes, not involved in competitions, were also studied during the summer season. The present investigation was carried out in accordance with the declaration of Helsinki and approved by the local ethics committee . All participants provided written informed consent prior to participation. Data are provided as supplemental material .Competitive cyclists , team sport players , and strength athletes (n = 23) were studied. All athletes were examined during their respective preparatory season. For cyclists only holders of a national competition license were eligible for this trial. Analogously, ballgame players were eligible if they participated in a regional league organized by the respective federation. No competition level was required for strength athletes.Blood-born parameters were included in the lab panel if they fulfilled the following criteria: 1) Evidence for an association with exercise training related fatigue. 2) Existing physiological insights into the mechanisms underlying this relationship. 3) Practicable sampling and analytical methodology, potentially enabling implementation on a routine basis. The resulting panel of blood-born indicators includes standard (creatine kinase (CK), urea, free-testosterone, c-reactive protein (CRP), cortisol ,11) as wVenous blood samples were collected at the beginning of testing days. After reporting to the laboratory at a standardized time  subjects rested in the supine position for 10 min prior to blood collection. A winged cannula was inserted into the antecubital vein during a short stasis (max. 30 sec.). Samples were processed immediately. Serum aliquots were frozen at -80°C within 60 min from blood collection and stored for later analysis.Blood count was performed immediately after sampling using an AcT 5 diff AL . CK, urea and CRP were analysed within 60 min by automated routine techniques . Free-testosterone, IGF-1, IGF-BP3, TNF and ACTH were analysed in one run from frozen serum samples using commercially available ELISA kits . The respective protocols supplied by the manufacturer were meticulously followed. Each sample was analysed in double and the mean of the two measurements was used as estimate of sample concentration. Gln and Glu were determined by an accredited commercial laboratory using immunochemical methods .Stepwise, incremental exercise tests to exhaustion were conducted in all athletes to estimate maximum aerobic capacity and enable comparative characterization of subgroups. Discipline specific performance was assessed on all testing days to verify effective induction of a reversible increase in fatigue. An overview over testing procedures and parameters is given in The 6 day training intervention comprised 11 training sessions and was designed to induce a detectable decline in discipline specific performance (fatigue) while still being tolerated by well-trained athletes from the respective disciplines. Care was taken to implement a realistic, training-stage like design for every exercise mode. An overview over the training schedules for the three subgroups is provided in The Statistica 7 software package  was used for data analysis. Changes from day 1 to day 8 (Δfatigue) as well as from day 8 to day 11 (Δrecovery) were calculated for all parameters. Normal distribution could be verified for all outcome parameters with the exception of CRP and changes in discipline specific performance with strength training (Shapiro-Wilks test). The normally distributed variables are given as mean ± standard deviation if not otherwise specified. Differences between the 3 time points were tested using repeated measures analysis of variance  with post-hoc Scheffé-test were appropriate. Associations between changes in normally distributed parameters were tested using Pearson product moment correlation. CRP and changes in maximum isometric contraction force are provided as median . Differences between time points were tested using Friedman ANOVA with post-hoc Wilcoxon test were appropriate. The significance level for the α-error was set at p < 0.05 for all tests.The course of a blood-born parameter is considered to reflect changes in fatigue status if a reversible, fatigue dependent deviation from baseline is present . Only parameters which fulfilled this criterion were included in the correlation analysis. Furthermore, non-overlap of 95% confidence intervals for values from day 8 with days 1 and 11, respectively, is considered to indicate diagnostic value of individual measurements.General subject characteristics for the 3 subgroups are presented in For all 3 exercise modes a significant decline in discipline specific performance over the simulated training camp could be confirmed . The restoration of performance over the recovery period was significant for cycling (p<0.001) and HIIT (p = 0.024) but failed to reach statistical significance for the strength training group (p = 0.094). Performance data for the male and female subgroups are provided as supplemental material .With the expectable exception of free-testosterone concentrations, no differences between males and females could be observed for the courses of blood-borne parameters. Therefore, data were pooled over sex for further analysis.For fatiguing endurance training, reversible deviations from baseline could be demonstrated for CK, urea, CRP, free-testosterone, IGF-1 as well as for the ratios of free-testosterone/cortisol and ACTH/cortisol. For urea and IGF-1, 95% confidence intervals from day 8 did not overlap with values from day 1 and day 11 . For HIIA significant test-by-discipline interaction, indicating different courses of the respective blood-borne markers between disciplines, was present for the following parameters: CK (p<0.001), urea (p<0.001), IGF-1 (p = 0.004), IGF-BP 3 (p<0.001), and ACTH (p = 0.010).No significant correlations could be found between changes in blood-born markers and changes in discipline specific performance . This analysis was confined to fatigue-dependent parameters.The main aim of the present study was to characterize changes in blood-borne indicators of fatigue induced by a period of standardized, discipline-specific training and the subsequent recovery period. In cyclists, representing high-volume endurance training, a reversible, fatigue dependent deviation from baseline was seen for urea, IGF-1, CK, free-testosterone and CRP. For urea and IGF-1, which both reflect the metabolic aspect of fatigue, 95% confidence intervals for fatigued and recovered time points did not overlap. For strength and HIIT training a reversible, fatigue-dependent deviation from baseline was seen for CK and CRP (strength training only). The magnitude of changes in CK, which reflect muscle fiber damage, was much higher with HIIT and strength training, respectively, compared to cycling cp.  and 95% The subgroup-dependent sets of blood-borne indicators for which a fatigue-dependent time course could be confirmed plausibly reflect the physical strain characterizing the respective training modes. Overload training in cyclists is mainly associated with a marked increase in caloric expenditure, temporal depletion of carbohydrate stores and subsequent protein breakdown for gluconeogenesis and ATP production . These cStrength training and HIIT in running are characterized by a considerable proportion of eccentric force production and high muscular tension. This leads to muscle fiber damage resulting in leakage of the enzyme creatine kinase (CK) from the sarcoplasm into the blood stream. This effect is known for a long time and makes CK a classical blood-borne marker of strain and fatigue in the relevant disciplines ,5,11. ThOnly previously proposed blood-borne indicators with a plausible physiological connection to exercise-induced fatigue were studied in this trial. Despite these criteria, the majority of parameters failed to show fatigue-dependent time courses, in particular for HIIT and strength training. In some cases, numerical differences in a direction consistent with previous reports and hypotheses were present but failed to reach statistical significance. This was the case for IGF-1, IGF-BP3 and HGH in strength-training as well as for IGF-1 in HIIT. As already stated above, IGF-1, IGF-BP3 and HGH are functionally connected and mainly represent the metabolic aspect of fatigue. A lesser involvement of the these processes in HIIT and strength training as compared to endurance training may therefore partly explain smaller effect sizes of fatigue-induced changes. Effect sizes for hormone levels were generally low  despite Another picture emerges for the serum concentrations of the amino acids glutamine (Gln) and glutamate (Glu) of which the time courses mostly failed to resemble the expected pattern ,14. LoweFrom the number of cytokines and regulatory molecules which have been reported to be influenced by exercise training  InterleuIn competitive athletes the ultimate aim of fatigue assessment is the individualized fine tuning of training recommendations to balance maximized training load and adaptation on the one hand side and sufficient recovery on the other. Therefore, the accurate characterization of the current fatigue status in an individual athlete is more important for the practical value of a fatigue marker than significant differences in means for recovered vs. fatigued time points. In the present trial, despite a run-in resting phase and a standardized induction of fatigue, inter-individual variability was high for measured values at the respective time points  as well The design of this trial is based on discipline-specific, standardized training interventions aiming at the induction of an equally standardized degree of fatigue. This experimental approach is adequate for the characterization of fatigue-induced changes in blood-borne markers. However, it has to be kept in mind that standardized training does not necessarily imply standardized fatigue. Otherwise, assessment of fatigue would be dispensable if training load is known. Therefore, in an effort to verify the achieved degree of fatigue on an individual basis, discipline specific performance has been assessed as gold-standard. A reversible, fatigue-induced reduction in discipline specific performance was apparent for all exercise modes examined. However, the variability of fatigue-induced changes was large and no significant correlation with changes in blood-borne markers could be found. Potential explanations for this finding include methodological as well as biological aspects. Although reliability was a key aspect in choosing performance indicators ,19,20,21A main advantage of the present trial is the comparative assessment of fatigue markers for contrasting exercise modes within a homogeneous methodological framework. However, this is associated with challenges regarding the standardization sports-related subject characteristics and training interventions between groups. As only specifically trained athletes were eligible for the respective study arms, exact equivalence of sport-specific subject characteristics  between subgroups is difficult to ensure or even to assess. In view of individual performance testing and relative training intensities, slight differences in these characteristics seem unlikely to impact relevantly on main outcomes. However, minor influences on between-group comparisons may not be ruled out.Analogously to subject characteristics, stringent standardization of training load, strain and fatigue between exercise modes is not feasible. Therefore, comparability between groups is based on discipline specific training schedules at the upper limit of what may be implemented in real-world training camps. With regard to discipline specific performance, differences between criterion parameters also have to be taken into account. This becomes apparent when looking at the restoration of performance over the recovery period in the strength training group which, in contrast to the other groups, is incomplete and fails to reach statistical significance. Potential explanations for this discrepancy include physiological as well as statistical aspects. From the physiological perspective the substantial (ultra-) structural muscle damage with strength-training or HIIT (supported by the large increase in CK) may lead to more time-consuming repair processes as compared to endurance training. Together with the maximal muscle tension required during performance testing in the strength training group this may at least partly explain the incomplete return to baseline in these subjects. From the statistical perspective it has to be kept in mind that, in contrast to measures of discipline specific performance in the endurance and HIIT groups, maximum voluntary isometric contraction force (MVIC) was not normally distributed and therefore non-parametric test with inherently lower statistical power had to be applied.The most promising blood-borne indicators of fatigue are urea and IGF-1 for endurance training (cycling) and CK for HIIT (team sports) and strength training, respectively. However, even in these parameters, the interindividual variability of measured values and fatigue induced changes is considerable, pointing to the potential value of an individualized interpretation. Moreover, it has to be kept in mind that only one point on the recovery-fatigue continuum for the 3 exercise modes has been studied and generalization to other fatigue states or training regimes may not be justified.S1 Fig(JPG)Click here for additional data file.S1 PDF(PDF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S1 Text(DOCX)Click here for additional data file.


Physical activity contributes to older adults’ autonomy, mobility, and quality of life as they age, yet fewer than 1 in 5 engage in activities as recommended. Many older adults track their exercise using pencil and paper, or their memory. Commercially available physical activity monitors (PAM) have the potential to facilitate these tracking practices and, in turn, physical activity. An assessment of older adults’ long-term experiences with PAM is needed to understand this potential.To assess short and long-term experiences of adults >70 years old using a PAM (Fitbit One) in terms of acceptance, ease-of-use, and usefulness: domains in the technology acceptance model.This prospective study included 95 community-dwelling older adults, all of whom received a PAM as part of randomized controlled trial piloting a fall-reducing physical activity promotion intervention. Ten-item surveys were administered 10 weeks and 8 months after the study started. Survey ratings are described and analyzed over time, and compared by sex, education, and age.P=.001); usefulness ; and acceptance . Differences in ratings by sex or educational attainment were not statistically significant at either time point. Most participants 80+ years of age  agreed or strongly agreed with survey items at long-term follow-up, however their ratings were significantly lower than participants in younger age groups at both time points.Participants were mostly women , 70 to 96 years old, and had some college education . Most participants  agreed or strongly agreed that the PAM was easy to use, useful, and acceptable both 10 weeks and 8 months after enrolling in the study. Ratings dropped between these time points in all survey domains: ease-of-use  to use PAMs when self-tracking their physical activity, and provide a basis for developing recommendations to integrate PAMs into promotional efforts. Clinicaltrials.gov NCT02433249; https://clinicaltrials.gov/ct2/show/NCT02433249 (Archived by WebCite at http://www.webcitation.org/6gED6eh0I)  Physical activity (PA) confers health benefits across older adult populations, including those with chronic conditions, and supports their autonomy and quality of life as they age . Fewer tMany older adults currently track their exercise, weight, or diet using pencil and paper or their memory . Self-trThere is growing evidence refuting the perception that older adults are not interested in, or do not have the ability to use, technology in their everyday life. Older adults report having interests in using technology, particularly when it is easy to use, convenient , and benefits their health and wellness . In a 20Given that older adults practice self-tracking and have interests in (and the abilities to use) technology, researchers have begun to examine their acceptance of PAMs. Initial findings suggest that older adults evaluate PAMs positively in terms of comfort, ease of installation, and usefulness . Particiacceptance) to use a new technology such as a PAM depends on their perceptions of its ease-of-use and its usefulness [The purpose of this study was to assess the short-term (10 week) and long-term (8 month) experiences of community-dwelling older adults using a popular, commercially available PAM (Fitbit One) to self-track their PA. The technology acceptance model (TAM) guided this assessment. The TAM posits that a person’s intention  testing a fall-reducing PA promotion intervention in community-dwelling older adults . All stuThe 95 participants in this study were community-dwelling older adults recruited via newspaper advertisements and flyers, which were placed in locations frequented by older adults living in Minneapolis, Minnesota between April and August 2014. Eligibility criteria included being 70 years old or greater, having the ability to walk, having the ability to speak English, having levels of PA below recommended guidelines [Fitbit Ones were used in this study for four reasons. First, their displays provide data about several PA indicators . This level of detail makes them usable as stand-alone PAMs for individuals who cannot, or prefer not to, access the Internet. Second, there is an emerging body of evidence regarding the accuracy of the Fitbit One to sense PA -17 and eParticipant feedback during the first few weeks of the study informed the refinement of PAM-related protocols. The first refinement was to decrease the manufacturer-set goals within the PAM  to be safe and more relevant for older adult populations . The second was to use display characteristics most valued by older adults in this study, including greetings , chatter , steps, distance, and a flower that grows with continuous activity. Finally, participants were given the option to use graphing worksheets developed for those wanting to visualize their PA trends, but without access to (or willingness to use) the Internet for visualizing their PA dashboards.Participants received a basic orientation when first enrolling into the RCT, assistance with troubleshooting for the next 10 weeks, and limited assistance after that. Upon enrollment, participants received a 15-30 minute basic orientation introducing the purpose of the PAM and demonstrating its core functions: charging, wearing, and reading displays. Participants were encouraged to demonstrate the skills they just learned and to ask questions. Individuals were also encouraged to use the project telephone number when in need of troubleshooting assistance or advanced orientation for operations, such as changing personal goals within the PAM and using a smartphone app to visualize their data. After being in the RCT for 10 weeks, participants received only limited troubleshooting assistance via the project telephone number. Approximately 10 individuals called during this time-frame with questions and challenges solvable by phone. Examples include getting their PAM out of its sleep mode, replacing lost or damaged PAMs, and synchronizing difficulties.Research assistants (RA) collected data during one-on-one interviews using standardized procedures at three time points. The first time point was within one week of enrolling into the RCT; RAs administered a baseline characteristic questionnaire comprised of clinical and demographic variables. The second and third time points were 10 weeks and 8 months post-RCT enrollment; RAs administered technology surveys. Research Electronic Data Capture (REDCap) is a secure, web-based application designed to support data capture and management for research studies hosted at the UMN, that was used to collect and manage all data .ease-of-use, perceived usefulness, and acceptance), using a 5-point Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree). Perceived ease-of-use is the degree to which a person believes technology use is free of effort. This TAM domain, linked to the research question asking if older adults believe that PAM are easy to use [usefulness is the degree to which a person believes a technology provides useful information. This TAM domain, linked to the second research question about older adults' beliefs regarding the value and usefulness of data provided by a PAM [Acceptance is the degree to which a person intends to use technology. This TAM domain, linked to the third research question regarding whether older adults intend to continue using a PAM to self-track their PA [Baseline characteristic questionnaires included the following demographic and clinical variables: self-reported age, sex, educational attainment, race, ethnicity, technology experience, and health conditions. The 10-item technology survey, adapted from previous usability and acceptability studies ,22 addrey to use ,22, was by a PAM , was meatheir PA , was meaThe online designer within REDCap enabled the creation of user-friendly case report forms for the baseline characteristic questionnaire and the technology survey see  with reaDe-identified data from aggregated case report forms were exported into SPSS 22 and analyzed in two phases. First, univariate analyses were conducted to summarize participants’ baseline characteristics and survey scores. The distributions of individual mean scores within each survey domain, assessed by visual inspection of histograms, were not normally distributed. Therefore, the second phase of analysis used non-parametric inferential statistics. Median differences in ratings between 10-week and 8-month time points were analyzed using the Wilcoxon signed-rank test, a non-parametric analog to the paired samples t-test. The Mann-Whitney U and the Kruskal-Wallis tests, non-parametric analogs to independent-samples t-tests and one-way analysis of variance, were used to test median differences between multiple groups  at the same time point. Groupings for educational attainment  and age  are consistent with Smith’s survey of older adults and technology use [Ninety-five community-dwelling older adults participated in the study, most of whom were women  with some college education , ranging in age from 70 to 96 years of age . See ease-of-use domain positively at 10 weeks (median 4.60/5) and 8 months (median 4.20/5). Median differences between these time points were statistically significant as indicated by a Wilcoxon signed-rank test, P<.001. Follow-up tests revealed ratings of three items dropped significantly: Most people, like me, could easily learn to use a Fitbit One ; I look at my Fitbit One at least once per day ; and I have sufficient information to help me get my personal data from my Fitbit One . Most participants  continued to agree or strongly agree with items in this domain after 8 months of ownership. Overall, participants rated the usefulness domain positively at 10 weeks (median 4.13/5) and 8 months (median 3.98/5). Median differences between these time points were not statistically significant as indicated by a Wilcoxon signed-rank test (P=.19). Most participants  continued to agree or strongly agree with items in this domain after 8 months of ownership. Overall, participants rated the perceived acceptance domain positively at 10 weeks (median 4.54/5) and 8 months (median 4.25/5). Median differences in ratings between these time points were statistically significant as indicated by a Wilcoxon signed-rank test, P=.025. Although ratings declined, most participants  continued to agree or strongly agree with this item after 8 months of use. Overall, participants rated the ease-of-use at 10 weeks  and 8 months ; usefulness at 10 weeks  and 8 months ; and acceptance at 10 weeks  and 8 months .Differences between men and women’s median ratings of the three survey domains were not statistically significant as evidenced by Mann-Whitney U tests for ease-of-use at 10 weeks  and 8 months ; usefulness at 10 weeks  and 8 months ; and acceptance 10 weeks  and 8 months .Differences in ratings between participants in the three education attainment groups  were not statistically significant, as evidenced by the Kruskal-Wallis test of mean rank differences for: ease-of-use, χ22 = 13.83, P=.002; usefulness, χ22 = 20.41, P<.001; and acceptance χ22 = 12.52, P=.002. Follow-up pairwise comparisons revealed lower ratings for the ease-of-use domain among participants in the 80+ age group (mean rank 33) compared to those in the 70-74 age group , and those in the 75-79 age group . Participants in the 80+ age group also rated the usefulness domain lower (mean rank 31) than those in the 70-74 age group , and the 75-79 age group . Finally, participants in the 80+ age group also rated the acceptance domain lower (mean rank 36) than those in the 70-74 age group  and the 75-79 age group .Differences in ratings between participants in the three age groups were statistically significant at 10 weeks for all three survey domains: ease-of-use, χ22 = 6.89, P=.032; usefulness, χ22 = 6.90, P=.032; and acceptance χ22 = 13.56, P=.001. Follow-up pairwise comparisons revealed lower ratings for the ease-of-use domain among participants in the 80+ age group (mean rank 39) compared to those in the 70-74 age group . Analyses also revealed lower ratings for acceptance among participants in the 80+ age group (mean rank 37), compared to those in the 70-74 age group . However, differences between age groups in ratings of the usefulness domain were not statistically significant (P>.067). Although ratings among participants in the 80+ age group were lower compared to younger age groups, most participants in this oldest age group  agreed or strongly agreed that the PAM was easy to use, useful, and acceptable after 8 months of ownership.Differences in ratings between participants in the three age groups at 8 months were also statistically significant for easy to use, useful, and acceptable with and without structured support. Although the ease-of-use and acceptance ratings decreased over time, and ratings were lower among those who were >80 years old compared to younger age groups, most ratings were positive.The purpose of this study was to assess older adults’ short and long-term experiences using PAM to self-track their PA. Overall, older adults evaluated the PAM as ease-of-use, usefulness, and acceptance) were positive and consistent with previous research [”, which was 4%. Lower rates of abandonment by participants in this study may have been, in part, because of the structured support they received during the first 10 weeks of the study. It is also possible that older adults, more than younger populations, find PAMs have long-term utility.Short-term (10 week) participant ratings across all three survey domains  . One posbit Ones . These dbit Ones , and thabit Ones . These fusefulness and perceived ease-of-use. Additional drivers may be important to consider in older adult populations, such as health benefits and emotional satisfaction [This study had several limitations. The experiences of older adults in this sample were assessed using just one popular PAM; ratings of PAM usage and acceptance may vary over time and by model. A second limitation was that PAM usage in this study was in a context of high support, at least during the initial 10-week period. This level of support exceeds what new owners of commercially available PAMs typically acquire, such as tailoring manufacturer-set goals within PAMs to be consistent with typical goals of older adults, and providing participants who preferred not to use the Internet with tools to aid their visualizations of aggregate data. A third limitation is that TAM, the conceptual model used in this study, posits that the two main drivers of technology acceptance are perceived sfaction ,26. Finasfaction .The findings of this study support future research to examine the facilitating potential of PAM activity trackers on older adults’ PA, and hint at opportunities for new designs to optimize meaningful use. It is unlikely that ownership of a PAM, alone, will elicit changes in PA behavior . Thus, eeasy to use and useful for self-tracking their PA. Thus, despite design and marketing strategies of PAMs that primarily target younger populations, it is feasible for older populations (70-90+ years of age) to use PAMs in ways that support their unique PA goals. These results support the potential of PAM technology to facilitate PA in older adults and provide a basis for developing recommendations for promoting such use.This study provides valuable insights into older adults’ short and long-term experiences with a commercially available PAM for self-tracking PA, the Fitbit One. Older adults with little technology experience, low levels of PA, as well as diverse PA goals and abilities, found the PAM


Women scored higher than men on the total DGI-2013 and all components except for dairy. Those who were from a rural area (men only), working full-time (men only), with lower education, smoked, did not meet physical activity guidelines, and who had a higher BMI, scored lower on the DGI-2013, highlighting a group of older adults at risk of poor health. The DGI-2013 is a tool for assessing compliance with the Australian Dietary Guidelines. We demonstrated associations between diet quality and a range of participant characteristics, consistent with previous literature. This suggests that the DGI-2013 continues to demonstrate convergent validity, consistent with the original Dietary Guideline Index.The Dietary Guideline Index, a measure of diet quality, was updated to reflect the 2013 Australian Dietary Guidelines. This paper describes the revision of the index (DGI-2013) and examines its use in older adults. The DGI-2013 consists of 13 components reflecting food-based daily intake recommendations of the Australian Dietary Guidelines. In this cross-sectional study, the DGI-2013 score was calculated using dietary data collected via an 111-item food frequency questionnaire and additional food-related behaviour questions. The DGI-2013 score was examined in Australian adults (aged 55–65 years;  The Dietary Guideline Index (DGI)  is a comIncreased longevity combined with the ageing of the baby boomers is leading to growth in the proportion of older people worldwide . Older aThe aims of this paper are to revise the Dietary Guideline Index (DGI-2013) and to examine the diet quality of peri-retirement aged adults by examining the DGI-2013’s associations with key sociodemographic characteristics, health-related behaviours and body mass index (BMI).The data was sourced from the Wellbeing Eating and Exercise for Long Life (WELL) study, a cohort study of Australian adults aged 55–65 years . This stThe Deakin University Human Research Ethics Committee approved the WELL study protocol  and all participants provided informed consent, as a requirement to obtain approval.Dietary intake was assessed using a 111-item Food Frequency Questionnaire (FFQ). The FFQ was developed for and used in the 1995 Australian National Nutrition Survey , has beeSelf-reported sociodemographic data including age, place of birth, employment status and education as well as health-related behaviours were collected. Participants reported their current smoking status  and physical activity in the seven days prior to the survey was assessed using the long version of the International Physical Activity Questionnaire (IPAQ) . IPAQ co2; Overweight: BMI ≥ 25 to < 30 kg/m2; Obese: BMI ≥ 30 kg/m2) [BMI was calculated using self-reported height and weight and categorized according to the World Health Organization criteria  .The DGI-2013 was developed to reflect compliance with the 2013 Australian Dietary Guidelines. It is based on the previous Dietary Guideline Index . It was The DGI-2013 is comprised of 13 components . Each coThe DGI-2013 contains indicators that reflect adequate intake of nutritious foods from core food groups , cereal, dairy and alternatives and meat and alternatives) as well as the food variety within these core groups . These aThe DGI-2013 also reflect recommendations for moderation or limited intake of discretionary foods. “Discretionary foods” describe energy-dense food and drink that are not essential to nutrition  and wereA new component, moderate unsaturated fat is included in the DGI-2013 to reflect the new guidelines that makes allowances for moderate intake of poly- and mono-unsaturated fat intake. There is good evidence to suggest that replacing dietary saturated fatty acids with unsaturated fatty acids is associated with improved blood lipid profiles and reduced inflammation markers .The DGI-2013 was applied to the WELL study sample using the food-based recommendations specific for 51–70 years old to determine cut-off values. The total daily intake of food groups was calculated by summing the daily intake frequency of the food or beverage items within the group. To avoid over-estimation of fruit and vegetable intake based on the FFQ responses , daily iThe level of wholegrain or high fiber cereal consumption was determined by the behavioural question “what type of bread do you usually eat?” Scores were given according to the amount of fiber typically in the bread type reported, with the following options; I don’t eat bread, high fiber white bread, white bread, wholemeal bread, rye bread, multigrain bread and other bread.t-tests. The percentage meeting the recommendations were calculated and compared between gender using chi-square. Associations between the DGI-2013 score and participant sociodemographic variables, health-related behaviours and BMI were investigated using chi-square for categorical data and analysis of variance for continuous data, stratified by sex.Of the 4082 participants, 1667 men and 1801 women aged 55–65 years old had complete data required to calculate the DGI-2013 as well as complete participant characteristics used for this analysis. Mean total DGI-2013 score and mean scores for each component were calculated and compared between gender using The distributions of participant characteristics are shown in vs. 81.5 ± 0.4, respectively; p < 0.001)  89.7 ± 0.3 < 0.001)  and on a< 0.001) . Men andThe results indicated that those with a lower DGI-2013 were more likely to be from rural areas (men only), working full-time (men only), have achieved a lower level of education, smoked, not meeting the physical activity guidelines and have a higher BMI .The DGI-2013 is a revised tool that can be used for assessing diet quality of Australian adults based on the Australian Dietary Guidelines. In a sample of peri-retirement aged Australians, a higher diet quality was associated with being female, higher education, not smoking, meeting physical activity guidelines and a lower BMI. These results are consistent with previous studies ,13. AmonOur results suggest that men from urban areas had higher diet quality than those from rural areas. Perhaps men are influenced by rural-related disadvantage such as access and availability of nutritious food , while wWe found a higher diet quality was associated with lower BMI. This is consistent with previous cross-sectional  and longAnother key finding of this study is that only 31% of men and 53% of women were meeting the daily intake recommendation for lean meat and alternatives, a protein-rich food group. This is substantially lower than earlier results reported from an Australian adult population (19 years old) in which 87%–90% of men and women met the previous guideline . Low comvs. mono- unsaturated fatty acid consumption and similarly for omega-3 fatty acid vs. omega-6 [There are a number of considerations to address when developing and using diet quality indices, including decisions regarding the components or indicators for inclusion in the index . Previou omega-6 , and per omega-6 . In addi omega-6 ,48,49. H omega-6 .vs. 61% in full time or part time employment) and they were marginally more highly educated (28% vs. 19% completing a university degree or higher). Participants were less likely to be overweight or obese in comparison to national data (64% vs. 74%) and were less likely to be current smokers (12% vs. 15%) [vs. 11%) and vegetable (61% vs. 56%) recommendations compared to the national population of the same age [This study has a number of strengths and limitations. Firstly, the results were limited by the modest response rate (38%); however, the participant characteristics were comparable to national population statistics. For example, the WELL study participants had similar levels of employment in comparison to national figures (60% vs. 15%) ,50,51. Ssame age .The cross-sectional nature limits this study, as a causal relationship cannot be assumed. The applications of the DGI-2013 in the WELL study was also limited by the available dietary intake data, in particular, there was no information collected on portion sizes to compliment the FFQ data; however, this is consistent with previous applications of the DGI  minimisiin vivo [The use of the food-based index to assess diet quality is a significant strength as diet research has shifted from exploring individual nutrients to whole foods and food patterns, to account for the interactions of the nutrients and non-nutrient components of foods in vivo . Anotherin vivo ,4,5,6. Tin vivo ,8. ExploAdults aged 55–65 years demonstrated poor diet quality according to the DGI-2013. Those at risk of the poorest diet quality were those who reported lower education, negative health behaviours including smoking and low physical activity, and a higher BMI, highlighting a group of peri-retirement aged adults at risk of poor health. This study demonstrated expected associations between diet quality and a range of participant characteristics including BMI consistent with previous literature. This suggests that the DGI-2013 continues to demonstrate convergent validity, consistent with the original DGI. Further investigation of the DGI-2013 and other health outcomes are required to confirm these findings, particularly in longitudinal studies.


Trauma exposure depends of the type of trauma and can result in the development of posttraumatic stress disorder (PTSD). The type of traumatization (such as Holocaust experiences and other sources of trauma) and specific symptoms of PTSD have influences on the outcome, and specific symptoms of PTSD influence personal and professional outcomes. Another factor is the role of the victim in their traumatization. Some patients are actively traumatized through being victims of torture, while others are passively traumatized by witnessing the traumatization of others.We compared two groups of victim/witness trauma sufferers (PTSD vs. Holocaust-experience PTSD (HE-PTSD)) with regard to PTSD symptoms, educational and working capacity, and functional outcome parameters.HE-PTSD survivors with victim/witness trauma experience showed substantially more specific PTSD symptoms and higher symptom-specific intensities but had high social function and education levels. The intensity and type of intrusive memories and sociodemographic factors do not seem to have a prognostic influence on working or educational outcomes.Identifying the combined victim/witness experience seems to play an important prognostic role in the assessment of PTSD victims. Further studies should consider these findings within other specific traumatization groups. Exposure to a traumatic event or psychological stress can result in posttraumatic stress disorder (PTSD). PTSD is classified based on five parameters: a person’s exposure to a traumatic event, re-experiencing the event with intrusive memories that are typically reported as “flash-back experiences” by the individual, persistent avoidance of trauma reminders, reduced emotional response after trauma, and persistent symptoms of increased arousal. Education and working abilities and social functioning are impaired in PTSD traumatized persons ,2.Moreover, in PTSD, resilience structures are diminished . ResiliePatients who have experienced trauma can be divided into groups depending on the type of trauma. One subgroup of PTSD patients is Holocaust survivors (HE-PTSD). Traumatization during the Holocaust was formative for these individuals’ personality and resilience structures ,8,9. TheHE-PTSD and PTSD have never been analyzed separately and have not been systematically compared with each other in the context of educational and working capacity outcomes.The comparative study was approved by the local ethical committee and then conducted with 80 HE-PTSD survivors  and 40 PTSD victims . All participants gave written consent to participate.HE-PTSD and PTSD were categorized according to the DSM-IV-R criteria. When evaluating the files, sociodemographic data and sociodemographic outcome parameters, such as gender, age, and school education (years), quality of school education, and years in job were evaluated. Additionally, the type of traumatization (witness or victim); occurrence of flashback-experiences, which were classified by the type of intrusive memory ; and their intensity , were analyzed. All participants provided a structured clinical interview to examine (HE-) PTSD-specific symptoms.t tests for unpaired samples. Non-normally distributed data were compared using the Mann-Whitney U test, and group differences  were tested for significant group bias. For significant group differences, Fisher’s least significant difference (LSD) post hoc test was administered. Significance was assumed, consequently, at p < 0.05.For data analysis, we used the statistical program SPSS 22.0, . We tested the data for normal distribution using the Kolmogorov-Smirnov test. For dichotomous variables, the chi-square test or Fisher’s exact test was used, as appropriate. For normally distributed data, variance testing was conducted using Levene’s test. Normally distributed data were compared using p < 0.001), 5 (2%) patients were only witnesses of violent acts against others, and only one patient (0.4%) fulfilled both the victim and witness criteria.Within the group of Holocaust survivors, all patients (100%) were both victims and witnesses of traumatization. Thirty-four PTSD patients (85%) were only victims (p < 0.001).Forty-seven patients (58.8%) of the HE-PTSD group and 31 (77.5%) of the PTSD group had multiple flashbacks or intrusive memory experiences per day. Furthermore, 23 patients (28.8%) in the HE-PTSD group had visual and acoustic intrusive memory experiences, compared to 38 (15.2%) in the PTSD group (p = 0.273), (see Table Thirty-seven participants (46.3%) in the HE-PTSD group and 31 participants (77.5%) in the PTSD group had completed basic or primary school; 33 (41.3%) HE-PTSD patients and 5 (12.5%) PTSD-patients had completed high school. Ten (12.5%) HE-PTSD patients and 4 (10%) PTSD-patients obtained university entrance diplomas. There were no significant differences with regard to years of employment between the two groups (Our findings suggest that HE-PTSD survivors have a higher professional qualification level than PTSD patients. One important aspect of PTSD outcome assessment is to consider the symptom complex, which is characterized by the multifactorial influence of traumatization -16. AnotThe other factors examined, such as the intensity and type of reported intrusive memories and sociodemographic factors, such as gender and age, do not seem to have a prognostic influence on work or educational outcomes. It remains unclear whether passive experiences compared to more active victim-witness traumatization are responsible for reduced social functioning and working capacity.post hoc testing, which is the suitable test in random samples of that size. The most remarkable finding is that identification of the combined victim/witness experience seems to play an important prognostic role in the assessment of PTSD victims.It is a limitation of our examination that both the HE-PTSD and PTSD groups are quite heterogeneous, especially concerning mean age and gender. Thus, the influence of age- and gender-related bias cannot completely be eliminated, although the sample group was controlled by LSD The question arises which other prognostic influence factors, such as medical and psychological treatment, influence the educational and social function levels of PTSD victims and affect personal resilience structures.Our study is limited by the absence of an extended examination of these potentially important factors in the multifactorial PTSD complex and by differences in the age and gender proportions. It is a natural fact that control groups with equal median ages are difficult to find. There are also more women who survived torture and prosecution within the holocaust experience , especiaFurther studies with larger participant groups are needed to address these points. Other groups that have experienced other types of trauma should be examined in the context of victim and witness experiences.


In March 2012, the Xpert MTB/RIF assay (Xpert) was introduced in three provincial public hospitals in Indonesia as a novel diagnostic to detect tuberculosis and rifampicin resistance among high risk individuals.This study assessed the effects of using Xpert in place of conventional solid and liquid culture and drug-susceptibility testing on case detection rates, treatment initiation rates, and health system delays among drug-resistant tuberculosis (TB) patients.Cohort data on registration, test results and treatment initiation were collected from routine presumptive patient registers one year before and one year after Xpert was introduced. Proportions of case detection and treatment initiation were compared using the Pearson Chi square test and median time delays using the Mood’s Median test.A total of 975 individuals at risk of drug-resistant TB were registered in the pre-intervention year and 1,442 in the post-intervention year. After Xpert introduction, TB positivity rate increased by 15%, while rifampicin resistance rate reduced by 23% among TB positive cases and by 9% among all tested. Second-line TB treatment initiation rate among rifampicin resistant patients increased by 19%. Time from client registration to diagnosis was reduced by 74 days to a median of a single day (IQR 0–4) and time from diagnosis to treatment start was reduced by 27 days to a median of 15 days (IQR 7–51). All findings were significant with p<0.001.Compared to solid and liquid culture and drug-susceptibility testing, Xpert detected more TB and less rifampicin resistance, increased second-line treatment initiation rates and shortened time to diagnosis and treatment. This test holds promise to improve rapid case finding and management of drug-resistant TB patients in Indonesia. In December 2010, the World Health Organization (WHO) recommended the use of Xpert MTB/RIF (Xpert) as a new automated molecular test to rapidly and simultaneously detect TB and rifampicin resistant (RR-)TB, which can be a good proxy for multidrug-resistant (MDR-)TB . Xpert iIncluded were all individuals at risk of MDR-TB registered between 1 March 2011 and 31 March 2013 at three clinics offering PMDT services in West-, Central- and East-Java. Primary data sources were the electronic presumptive client registers. Individual patient data were transferred to a database in Microsoft Excel: client registration date, identification number, sex, birth date (or age), address, referring health facility, MDR-TB risk group, specimen identification number, smear microscopy/culture/DST/Xpert result and release date, and treatment registration number and start date. Laboratory registers were used to verify and complete test results and dates. Treatment registers and consultations with PMDT doctors helped to validate and complete treatment information. The various registers were linked by matching unique identification numbers or sex, age and address. Inconsistencies were discussed with laboratory and hospital staff and solved on-site. After registration, individuals were followed for at least three months to record treatment start, culture and DST results. Records were excluded if individuals were entered double , or if second-line treatment was started before testing. Data analysis was done using IBM SPSS Statistics 21. Differences in TB and RR-TB positivity rates and second-line treatment initiation rates between Year 1 and 2 were compared using the Pearson Chi square test with a 5% significance level. Median time between registration, test result release and treatment start before and after the intervention were compared using the Mood’s Median test with a 95% confidence interval (CI) and 5% significance level. Censored cases were RR-TB cases not treated at the end of the observation period. Comparing Xpert results with culture and DST as a diagnostic workup in Year 2 was done by calculating the percentage of agreement (concordance) of Xpert and culture to detect TB, and of Xpert and DST to detect RIF resistance.Ethical clearance for this study was received from the Health Research Ethics Committee at the Medical Faculty of Padjadjaran University in Bandung, West-Java, Indonesia under number 181/UN6.C2.1.2/KEPK/PN/2012. Informed consent was not obtained as the intervention was done as a programmatic change in routine care. Further, data were de-identified and analyzed anonymously.After excluding double entries , a total of 975 individuals were registered in the year before (Year 1) and 1,442 in the year after (Year 2) introduction of Xpert, which is a relative increase of 47.9% . In YearIn further analysis, 15 (1.5%) and 32 (2.2%) people were excluded from Year 1 and 2 respectively, because they received second-line treatment before being tested. In Year 1 and 2, 90.7% (871/960) and 91.7%  of individuals received a diagnostic test for TB, respectively. Test and treatment results for individuals tested with and without Xpert in Year 2 were compared to Year 1 as different cohorts . When inDelays in detection and treatment of RR-TB were compared among those tested with culture and DST in Year 1 versus those tested by Xpert in Year 2. One month after initial registration of a person at risk of MDR-TB, 6% of patients diagnosed with conventional DST and 42% of those diagnosed with Xpert were started on second-line treatment . ExpressIn Year 2, 70.8% (549/775) of Xpert TB positives and 57.4% (105/183) of Xpert TB negatives received culture and DST workup . ConcordXpert was introduced in Indonesia with the main aim to shorten time to diagnosis and treatment of MDR-TB patients. This study found that post-intervention time to treatment was greatly reduced by almost 2.5 months, likely as a result of a shorter time for testing with Xpert than with culture and DST. Also, it took less time to send Xpert results back to clinicians, because the test was done in the PMDT hospital laboratory itself while culture and DST was performed in a reference laboratory located some distance away from the clinic. Another important finding was that after Xpert was introduced, a considerably larger proportion of RR-TB patients started second-line MDR-TB treatment. It is probable that this was an effect of the more rapidly available result of Xpert. Nevertheless, the treatment initiation rate remained below 60%. Some of the missing patients could have returned to local clinics and remained on first-line treatment, while others could have been switched from second- to first-line treatment on the basis of follow-on culture and DST results. These patients should have been classified as lost or referred, but this was often not recorded. This reflects an urgent gap between diagnosis and treatment and the need to strengthen patient registration, follow-up and monitoring alongside the introduction of Xpert. This finding adds onto recent concerns about patient management after Xpert diagnosis expressed in global guidance .Concordance between Xpert and culture as a diagnostic workup post-intervention was limited due to a substantial proportion of Xpert TB positive culture TB negative test results. This may represent the occurrence of false-negative culture results caused by unviable bacilli in sputum samples as a result of over-decontamination or delays in transportation or inoculation. Laboratory staff confirmed that delays in culture inoculation after receiving samples were a problem throughout Year 2 due to shortage of staff in a reference laboratory serving two of the three Xpert sites. This could also explain why the culture TB positivity rate decreased by 14.7% from Year 1 to Year 2. Alternatively, some tests could have been false-positive for TB with Xpert as a result of the different nature of genotypic versus phenotypic tests and the fact that Most individuals had recent previous TB treatment. It is likely that after multiple first-line treatment cycles, retreatment patients had either dead or damaged bacteria in their lungs that are positively identified on a molecular test like Xpert, but cannot grow on culture. This would be in line with recent findings from South Africa [Overall agreement between Xpert and phenotypic DST for detection of RIF resistance was good. In some cases, Xpert could have been false-negative for RIF as it has a sensitivity for RIF resistance of 95% . Xpert fThis study was unique in that it evaluated the effects of Xpert within a strictly programmatic setting: besides the physical placement of the new test, revision of registers and training of medical staff, national TB guidelines were unchanged. However, a programmatic intervention study involves inherent limitations.The main limitation was that the pre-post intervention design might have introduced selection bias and performance bias. Immediately and consistently after Xpert was introduced almost 50% more individuals at risk of MDR-TB were tested than the year before. Clinicians confirmed that the excitement of a new rapid test led to more attention for PMDT and increased referral of presumptive MDR-TB patients, which may have influenced the type of individuals being sent for testing as well as the treatment decision-making process. Although no significant shift in MDR-TB risk groups was observed post-intervention, it is still possible that clinicians sent presumptive MDR-TB clients earlier for diagnosis, e.g. presumptive relapse patients at the first suspicion of TB symptoms instead of at a second or third patient visit. This would explain why the total number of RR-TB diagnosed cases remained similar in Year 1 and 2. Further, it cannot be excluded that the increase in treatment initiation rate and reduction in time delays were partly caused by clinicians tracing patients more actively to start treatment, in addition to the rapid turn-around-time of Xpert results.A second limitation was the large proportion of missing follow-on culture and DST results among Xpert-tested individuals in Year 2, which could have introduced partial verification bias. If culture was considered as the gold standard and we would correct for bias using a population TB prevalence of 54.6%, a possible overestimation of concordance to detect TB of 4.6% (60.4% vs. 65.0%) was found. In particular, the proportion of Xpert TB negative culture TB positive patients may have been underestimated by as much as 15.8% (33.9% vs. 18.1%). Missing culture results were due to delays in culture inoculation as mentioned above and results becoming available only beyond the period of data collection.The results of this study indicate that the introduction of Xpert has helped to start more RR-TB patients on second-line treatment and initiate treatment sooner as compared to using conventional culture and DST. Fast turn-around of results likely resulted in less drop-out during the diagnostic process. In addition, clinician’s treatment decision-making could have been positively influenced by the excitement of a new rapid test. Still, the overall proportion of RR-TB patients that started second-line treatment was low and merits special attention from the national TB control program. Proper engagement of clients at high risk of MDR-TB is essential to prevent pre-treatment loss to follow-up. Further analysis is needed to clarify the increase in TB case detection and decrease in RIF resistance using Xpert compared to culture and DST. In conclusion, Xpert holds promise to improve RR-TB case finding and treatment in Indonesia, but its implementation should coincide with improved patient management to optimize PMDT services.S1 Table(DOCX)Click here for additional data file.


Until recently the most accepted technique of doing root canal treatment stresses multiple visit procedure. Most schools also concentrated upon teaching the multi-visit concept. However, it has now been reported that the procedure of single visit treatment is advocated by at least 70% of schools in all geographical areas. It was therefore the aims of the present study to find the incidence of post-obturation flare-ups following single and multiple visit endodontic treatment procedures, and to establish the relationship between pre-operative and post-obturation pain in patients referred for endodontic therapy in a Nigerian teaching Hospital.st, 7th and 30th day. The presence or absence of pain, or the appropriate degree of pain was recorded for each recall visits and the interval between visits. The compiled data were analysed using chi-square where applicable. P level ≤ 0.05 was taken as significant.Data collected included pulp vitality status, the presence or absence of pre-operative, inter-appointment and post-obturation pain. Pain was recorded as none, slight, or moderate/severe. Flare-ups were defined as either patient's report of pain not controlled with over the counter medication or as increasing swelling. The patients were recalled at three specific post-obturation periods, 1Ten endodontic flare-ups (8.1%) were recorded in the multiple visit group compared to 19 (18.3%) flare-ups for the single visit group, P = 0.02. For both single and multiple visit procedures, there were statistically significant correlations between pre-operative and post-obturation pain (P = 0.002 and P = 0.0004 respectively). Teeth with vital pulps reported the lowest frequency of post-obturation pain (48.8%), while those with nonvital pulps were found to have the highest frequency of post-obturation pain (50.3%), P = 0.9.The present study reported higher incidences of post-obturation pain and flare-ups following the single visit procedures. However, single visit endodontic therapy has been shown to be a safe and effective alternative to multiple visit treatment, especially in communities where patients default after the first appointment at which pain is relieved. Until recently the most accepted technique of doing endodontic treatment stresses multiple visit procedures. Most schools also concentrated upon teaching the multi-visit concept. However, it has now been reported that the procedure of single visit treatment is advocated by at least 70% of schools in all geographical areas .Some of the problems of root canal treatment are post-obturation pain, inter-appointment pain and swelling. Although these in most cases do not last long, but could be a source of embarrassment to the dentist and annoying for the patient, more so if the tooth was symptomless before the commencement of treatment. Literature review revealed varied opinions on the incidence and severity of post-obturation pain. Some authors reported slightly more post-obturation pain following single visit than with multiple visit procedures ,3. Otherst, 7th, and 30th post-obturation days, and to compare these results with those reported in previous studies.Endodontic treatment in Nigeria is carried out in the department of restorative dentistry of the four dental schools and in few private dental clinics located in major cities, health centres and general hospitals. Previous report revealed that few cases of root canal treatment were undertaken and that root canal treatment was completed in multiple visits, specifically three visits for about half the teeth treated . ReasonsConsenting patients referred to the department of Restorative Dentistry for root canal therapy within a period of twelve months were randomly assigned for either single visit or multiple visit procedures. For the multiple visit procedures, Patients that defaulted after the first appointment (incomplete treatment) were excluded from the study. For each tooth treated, the clinical factors and conditions existing before, during and after the completion of treatment were recorded. This data included pulp vitality status, the presence or absence of pre-operative pain, post-obturation flare-ups and degree of post-obturation pain. For patients requiring root canal treatment on more than one tooth, the treatment of each tooth was separated by a period of at least four weeks to allow for proper evaluation. The pulp vitality was determined by an electric pulp tester  in combination with the presence of pulpal haemorrhage.st, 7th and 30th day. At each post-obturation recall visit, the patients were interviewed to determine whether or not there were symptoms at the present visit and whether or not there had been symptoms during the interval between the present visit and the previous one. The presence or absence of pain, or the appropriate degree of pain was recorded for each recall visit and the interval between visits. Pain was recorded as none, slight, or moderate/severe. Slight pain was defined as any discomfort no mater how brief in duration that did not require medication and that did not impair masticatory function in any way. Moderate/severe pain was defined as pain requiring medication or other palliative treatment. Impairment of masticatory function (discomfort in chewing) was recorded as moderate/severe pain. Endodontic flare-ups were defined as either patient's report of pain not controlled with over the counter medication and or increasing swelling.The patients were recalled at three specific post-obturation periods, the 1The root canals were obturated with multiple gutta-percha cones and a zinc oxide-eugenol based sealer, using the lateral condensation technique. The compiled data were analysed using chi-square where applicable. P level ≤ 0.05 was taken as significant.st post-obturation day, of these 107 were completed in single visit and 136 were completed in multiple visit. Eighty-six (86) had vital pulps and 157 had nonvital pulp canal contents. Two hundred and twenty seven (227) reported for check-up on the 7th post-obturation day, of these 104 was completed in single visit and 123 completed in multiple visit. Two hundred and twenty two reported for check-up on the 30th post-obturation day, 102 completed in single visit and 120 in multiple visit.Two hundred and eighty three (283) teeth in 255 patients were treated in all, given a ratio of 1.11 teeth per patient. Of these 56 were excluded from the study due to non-availability of patients at post-obturation recall visit. These exclusions were randomly distributed between treatment groups, with no differential loss to follow-up . The treatment groups were fairly comparable, with similar distribution of tooth types between treatment groups, Table 2 = 9.04, p = 0.002). For the multiple visit procedures, 88 teeth presented with pre-operative pain out of which 55 (62.5%) reported post-obturation pain. 48 teeth had no pre-operative pain out of which 6 (12.5%) had post-obturation pain . These show that for both single and multiple visit procedures, there were statistically significant correlations between pre-operative and post-obturation pain , that is patients presenting with pain not controlled by over the counter medication and or increasing swelling, were recorded in the multiple visit group compared to 19 18.3%) flare-ups for the single visit group. This shows a significant difference , Table % flare-uTeeth with vital pulps reported the lowest frequency of pain 48.8%), while those with nonvital pulps were found to have the highest frequency of pain (50.3%), Table 8.8%, whist and 7th days respectively 35.5% and 16.3% were higher than those in the multiple visit group 30.2% and 9.8%. Chi square test indicated no statistically significant differences  whose pulps were non-vital.Many authorities in the field of endodontics advice against the completion of root canal treatment in single visit in order to prevent post-obturation pain, especially in cases presenting with pre-operative pain ,12.In the present study more flare ups occurred in the single visit group (18.3%) than in the multiple visit group (8.1%), showing a disadvantage for single visit treatment at a 95% confidence level, Table . This isPrevious studies have shown that there is a strong positive correlation between pre-operative and post-obturation pain ,14,15. Tth day in both groups, these present a strong indication that practitioners should not overreact to early post-obturation symptoms by immediately initiating endodontic retreatment procedures or extraction of the involved tooth. Apart from the reported higher incidence of flare-ups in the single visit group, the post-obturation pain experienced by the patients in both groups compares favourably well with each other. Therefore the higher incidence should not be taken as condemnation for the single visit endodontic therapy, it should however stress the fact that a thorough understanding of the basic endodontic principles is important in considering each case on an individual basis before making a decision as to whether or not it can be completed in one visit [Despite the high percentages of post-obturation pain reported on the first post-obturation day in both groups Table , seven dne visit . As it iThe present study reported higher incidences of post-obturation pain and flare-ups following the single visit procedures. However, single visit endodontic therapy has been shown to be a safe and effective alternative to multiple visit treatment, especially in communities where patients default after the first appointment at which pain is relieved.The author(s) declare that they have no competing interests.AOO conceived of the study, participated in its design, performed the statistics, and participated in the final write-up of the manuscript. CIU participated in the design, collected the data, drafted the initial manuscript, and participated in the final write-up of the manuscript.The pre-publication history for this paper can be accessed here:


Malnutrition is often present in vascular surgery patient during hospital admission. The present evidence of the consequence malnutrition has on morbidity and mortality is limited.The purpose of this study was to determine the effect of nutritional status on out-of-hospital mortality in vascular surgery patients.An observational cohort study was performed, studying non-cardiac vascular surgery patients surviving hospital admission 18 years or older treated in Boston, Massachusetts, USA. The exposure of interest was nutritional status categorized as well nourished, at-risk for malnutrition, nonspecific malnutrition or protein-energy malnutrition. The all cause 90-day mortality following hospital discharge was the primary outcome. Adjusted odds ratios were estimated by multivariable logistic regression models.This cohort included 4432 patients comprised of 48% women and a mean age 61.7 years. After evaluation by a registered dietitian, 3819 patients were determined to be well nourished, 215 patients were at-risk for malnutrition, 351 had non-specific malnutrition and 47 patients had protein-energy malnutrition. After adjustment for age, sex, ethnicity, medical versus surgical Diagnosis Related Group type, Deyo-Charlson index, length of stay, and vascular Current Procedural Terminology code category, the 90-day post-discharge mortality odds ratio for patients with non-specific malnutrition OR 1.96  and for protein-energy malnutrition OR 3.58 , all relative to patients without malnutrition.Nutritional status is a strong predictor of out-of-hospital mortality. This suggests that patient with vascular disease suffering from malnutrition could benefit from more intensified In-hospital and out-of-hospital dietary guidance and interventions. Malnutrition in hospitalized patients is common and associated with adverse outcomes yet is undervalued and often underreported –7. MalnuData describing the effects of malnutrition on mortality and other adverse events in vascular surgery patients are limited to small studies , 15, 16.Therefore we performed an observational study on inpatients who underwent vascular surgery and survived hospitalization. We utilized data determined by a registered dietitian (RD) evaluation to study the association of nutrition status and post-discharge outcomes. We hypothesized that patients who underwent vascular surgery and survived hospitalization, malnutrition would independently be associated with mortality and other adverse events following hospital discharge.Administrative and laboratory data were extracted from individuals admitted to Brigham and Women’s Hospital (BWH) in Boston, Massachusetts, USA. BWH is a 793 bed primary and tertiary care facility that provides full spectrum vascular surgery to an ethnically and socioeconomically diverse population within eastern Massachusetts and the surrounding area.Data on eligible patients were obtained through the Research Patient Data Registry (RPDR) between 2004 and 2012. The RPDR is a computerized registry that serves as a central data warehouse for all inpatient and outpatient records at Partners HealthCare sites , 20 inclPatients eligible for inclusion were hospitalized adults aged ≥18 years who were admitted to intensive care unit (ICU) or in-patient care ward and who underwent non-cardiac vascular surgery during their hospitalization and survived to hospital discharge. All patients were assigned at least one Current Procedural Terminology (CPT) code for vascular surgery  S1 FileS1 File, 2, basal metabolic rate is calculated based on body surface area [2 adjusted weight for obesity is calculated and used to calculate the basal metabolic rate based on body surface area and age, then activity and stress factors are applied based on severity of illness, similar to the approach for patients with a BMI < 30 kg/m2 . Critically ill patients with BMI 35–50 kg/m2 are fed at 14 kcal/kg dry weight, and those with BMI > 50 kg/m2 are fed at 25 kcal/kg ideal body weight [Malnutrition is diagnosed at BWH by an RD based on patient level data related to insufficient nutrient intake of energy or protein, wasting of muscle mass, and subcutaneous fat and unintentional weight loss , 9, 22. ace area  and age,y weight .Nutrition diagnoses were categorized a priori into malnutrition absent, at risk for malnutrition, nonspecific malnutrition, or any protein-energy malnutrition . PatientDRG type was defined as medical or surgical and incorporates the Diagnostic Related Grouping (DRG) methodology, devised by the Centres for Medicare & Medicaid Services and is reflective of case mix and resource utilization –23, 30. The primary end point was 90-day all-cause mortality following hospital admission. Information on mortality was obtained through the Social Security Administration Death Master File which has previously been validated in our dataset for in-hospital and out-of-hospital mortality . Death MSecondary outcomes were unplanned 30-day hospital readmission to the BWH or MGH, discharge to a care facility and 365-day mortality. Thirty-day hospital readmission was determined from RPDR hospital admission data as previously described  and defi90-day post-discharge hospital mortality would increase a relative 50% in patients with malnutrition (7.5%) compared to those without malnutrition (5%). With an alpha error level of 5% and a power of 80%, the minimum sample size thus required for our primary end point is 4,096 total patients.Based on prior studies , 42, 43,Categorical covariates were described by frequency distribution and compared across nutrition status groups using contingency tables and chi-square testing. Continuous covariates were examined graphically and in terms of summary statistics and compared across nutrition status groups using one-way analysis of variance (ANOVA). Unadjusted associations between nutrition status groups and outcomes were estimated by bivariable logistic regression analysis. Adjusted odds ratios  were estIn Patient characteristics were stratified according to nutritional status categories . Signifi2 8.4, P = 0.40) and good discrimination for 90-day post-discharge mortality .In the analytic cohort (N = 4432) comprising survivors of hospitalization, nutrition status was a significant predictor mortality 90 days following hospital discharge , Table 3Next, the association of malnutrition status and mortality following hospital discharge was analysed separately for men and women. Nonspecific malnutrition and specific protein-calorie malnutrition groups were combined due to low power. The 90-day post-discharge mortality rates were 3.3% in women and 3.9% in men. The adjusted associations of 90-day post-discharge mortality in patients with nonspecific malnutrition or protein-energy malnutrition had similar directionality, effects sizes and significance in both men and women . There iFinally, we analysed the association of malnutrition status with other outcomes following hospital discharge. Univariate data show that malnourished patients were significantly less likely to be discharged to home and more likely to be readmitted to hospital Tables  & 5. SucMalnutrition in hospitalized patients is a robust risk factor for adverse outcomes . In our The ACC-AHA Guidelines for the Management of Patients with peripheral artery disease (PAD) recommend that patients should be treated with an interdisciplinary care team including a dietitian and should be prescribed a heart-healthy diet like all other cardiovascular disease patients . AlthougThere is no specific evidence presented on nutritional diagnostics or interventions and consequently no recommendations are made in the ACC-AHA Guidelines. The current dietary evidence to prevent or treat vascular disease consists of retrospective and cross-sectional studies mainly with the outcome walking distance but lacks successful interventional clinical trials –52. In tThe knowledge of how nutrition might influence post-discharge outcomes after vascular surgery can help surgeons to improve risk stratification and personalize postoperative care. If patients are electively admitted, prior dietary optimization could lower perioperative risk. Understanding what the risk of death comprises following vascular surgery is vital in the decision-making process for surgeon, patient and their family . UnfortuNutritional status is a potentially modifiable risk factor. In the postoperative setting, nutritional status optimization may help vascular surgery patients who are more likely to develop adverse events. This is collaborated by our findings that patients with malnutrition had a lower chance of discharge to home as well as higher mortality risk. These patients may benefit from an intensified follow-up in the care facility or in their own home. For example, in cardiac surgery patients who are discharged from the hospital, frequent home visits by a hospital nurse practitioner in the post-discharge period improved readmission and mortality rates , 58. ThePotential limitations of this study include ascertainment bias as only vascular surgery patients deemed at nutritional risk were fully evaluated by an RD. This can limit the generalizability of the study findings. Despite multivariable adjustment, residual confounding is likely to be present. By determining covariates on the basis of ICD-9 codes it is likely that comorbidities are underestimated . Though The study has several strengths. The cohort contains a large number of vascular surgery patients which results in ample statistical power to detect a clinically relevant difference in 90-day post-discharge mortality if one exists. Linkage to the SSA Master Death file allows for out of hospital follow-up with high accuracy which was previously validated in our dataset . The RPDThese data demonstrate that in vascular surgery patients, malnutrition is associated with increased post-discharge mortality. Further, those with malnutrition are more likely not to be discharged to home and to be readmitted to the hospital within 30 days. As malnutrition is a potentially modifiable risk factor, improvement of nutritional status may be a target for intervention in the already vulnerable vascular surgery patient population.S1 File(DOCX)Click here for additional data file.S2 File(DOCX)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.