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Background and Hypothesis Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, yet a significant proportion of individuals on clozapine continue to experience disabling symptoms, despite being treated with an adequate dose. There is a need for adjunct treatments to augment clozapine, notably for negative and cognitive symptoms. One such potential agent is the glutathione precursor N -acetylcysteine (NAC). Study Design A randomized double-blind, multi-center, placebo-controlled trial for clozapine patients with enduring psychotic symptoms (n = 84) was undertaken to investigate the efficacy of adjunctive NAC (2 g daily) for negative symptoms, cognition and quality of life (QoL). Efficacy was assessed at 8, 24, and 52 weeks. Study Results NAC did not significantly improve negative symptoms (P =.62), overall cognition (P =.71) or quality of life (Manchester quality of life: P =.11; Assessment of quality of life: P =.57) at any time point over a 1-year period of treatment. There were no differences in reported side effects between the groups (P =.26). Conclusions NAC did not significantly improve schizophrenia symptoms, cognition, or quality of life in treatment-resistant patients taking clozapine. This trial was registered with "Australian and New Zealand Clinical Trials" on the 30 May, 2016 (Registration Number: ACTRN12615001273572). [ABSTRACT FROM AUTHOR]

Background Coronavirus disease 2019 (COVID-19) struck the world by surprise by the rising numbers that required prompt governmental and hospital staff reaction to the ongoing crisis. A robust preparedness and personal protective equipment (PPE) were yet to be regarded as our best plan. Methods A survey study was conducted on 254 Egyptian house officers using an anonymous web-based questionnaire that was filled using Google Forms after obtaining online informed consent. Results The mean age of the participants was 25 years. Only 28.74% of the house officers were categorized as having a good preparedness, while 85.83% of them have a good PPE attitude. The preparedness and willingness were significantly associated with the overall worry related to the pandemic (P value = 0.012). Fear of contracting COVID-19 infection negatively affected their preparedness by 60% (odds ratio (OR) 0.40, 95% confidence interval (CI), 0.17–0.93, P value = 0.034). The House officers with family members at-risk for severe COVID-19 were less likely to be prepared and willing by 70% (OR 0.30, 95% CI 0.15–0.60, P value = 0.001). The house officers with good preparedness and willingness to deal with COVID-19 seemed to have a good PPE attitude (OR 11.48, 95% CI 2.43-54.34, P value = 0.002). Conclusion A significant number of house officers expressed low levels of preparedness, while most of them have a good PPE attitude. [ABSTRACT FROM AUTHOR]

Background The ongoing COVID-19 pandemic has resulted in a sharp rise in demand for healthcare workers worldwide. This has been coupled with reduced numbers of available medical professionals due to confirmed or suspected infections with SARS-CoV-2. To counteract these shortages, governments of several countries have considered the enrolment of medical students into the workforce in order to help to tackle the ongoing crisis. Methods Questionnaire-based study assessing the perceived role of medical students in assisting in the COVID-19 pandemic. The primary aim was to determine factors contributing to the willingness of medical students to actively assist in the pandemic. The secondary aim was to evaluate their perspectives regarding the associated changes in medical education. Results Out of 760 responses, 71.18% of medical students were willing to assist the medical workforce during the pandemic. Clinical year students were more likely to help in a medical capacity than pre-clinical students (OR = 0.384, 95%CI [0.167, 0.883, P  < 0.05)]. Respondents concerned about their own well-being were less likely to engage in clinical work (OR = 0.680, 95%CI [0.491, 0.941], P  < 0.020). Students who agreed that online lectures will negatively impact their education were inclined to think that the academic year should be extended (95%CI [0.065, 0.271], P  = 0.001). Conclusions Most students are willing to help in both a medical and non-medical capacity. Their primary concerns when working in a medical setting are the risk of infecting their relatives and patients, lack of protective equipment and necessary knowledge as well as legal uncertainty whilst working without a medical qualification. [ABSTRACT FROM AUTHOR]

Research on mortality associated with exposure to the Holocaust is relevant for a better understanding of the effects of genocides on survivors. To our knowledge, previous studies have not investigated the long-term cause-specific mortality of Holocaust survivors. We compared mortality rates among Israelis born in European countries controlled by the Nazis during World War II with those among Israelis of European descent who did not have this exposure. Records of 22,671 people (45% women; 5,042 survivors) from the population-based Jerusalem Perinatal Study (1964–1976) were linked to the Israeli Population Registry, which was updated through 2016. Cox models were used for analysis, with 2-sided tests of statistical significance. Risk of all-cause mortality was higher among exposed women (hazard ratio (HR) = 1.15, 95% confidence interval (CI): 1.05, 1.27) than in unexposed women. No association was found between Holocaust exposure and male all-cause mortality. In both sexes, survivors had higher cancer-specific mortality (HR = 1.17 (95% CI: 1.01, 1.35) in women and HR = 1.14 (95% CI: 1.01, 1.28) in men). Exposed men also had excess mortality due to coronary heart disease (HR = 1.39, 95% CI: 1.09, 1.77) and lower mortality from other known causes combined (HR = 0.86, 95% CI: 0.75, 0.99). In summary, experiencing the Holocaust was associated with excess all-cause and cancer-specific mortality in women and cancer- and coronary heart disease–specific mortality in men. [ABSTRACT FROM AUTHOR]

Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene-expression signature that can identify beneficiaries of IC.Methods: We screened chemosensitivity-related genes by comparing gene-expression profiles of patients with short-term tumor response or nonresponse to IC (n = 95) using microarray analysis. Chemosensitivity-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Tests of statistical significance are 2-sided.Results: We identified 43 chemosensitivity-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] = 0.87, sensitivity = 87.5%, specificity = 75.6%). We further found that IC conferred failure-free survival benefits only in patients in the benefit group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.34 to 0.87; P = .01) and not on those in the no-benefit group (HR = 1.25, 95% CI = 0.62 to 2.51; P = .53). In the clinical trial cohort, the 6-gene signature was also highly accurate at predicting the tumor response (AUC = 0.82, sensitivity = 87.5%, specificity = 71.8%) and indicated failure-free survival benefits. In the external independent cohort, similar results were observed.Conclusions: The 6-gene signature can help select beneficiaries of IC and lay a foundation for a more individualized therapeutic strategy for locoregionally advanced nasopharyngeal carcinoma patients. [ABSTRACT FROM AUTHOR]

Background: Over the past decades, many regions have experienced a steady increase in the incidence of cutaneous melanoma. Here, we report on incidence trends for subsequent primary melanoma.Methods: In this nationwide population-based study, patients diagnosed with a first primary cutaneous melanoma reported to the Swedish Cancer Registry were followed for up to 10 years for a diagnosis of subsequent primary melanoma. Patients were grouped with patients diagnosed with first melanoma in the same decade (1960s, 1970s, 1980s, 1990s, and 2000s, respectively). Frequencies, incidence rates (IRs), standardized incidence ratios (SIRs), and 95% confidence intervals (CIs) for second melanomas were calculated. All tests of statistical significance were 2-sided.Results: Of patients with melanoma, 54 884 were included and 2469 were diagnosed, within 10 years, with subsequent melanomas. Over the 5 decades, there was a statistically significant steady increase in the frequency, IR, and SIR for second primary melanoma. For example, in the 1960s cohort, less than 1% (IR = 1.0, 95% CI = 0.5 to 1.7, and IR = 1.1, 95% CI = 0.5 to 1.9 per 1000 person-years in women and men, respectively) had second primary melanoma, and this rose to 6.4% (IR = 7.5, 95% CI = 6.8 to 8.3, per 1000 person-years) in the women and 7.9% (IR = 10.3, 95% CI = 9.3 to 11.2, per 1000 person-years) in the men in the 2000s cohort. This rise was seen independent of age, sex, invasiveness, or site of the melanoma. Further, in patients diagnosed with a second melanoma, the frequency of those having more than 2 melanomas increased statistically significantly and was 0.0% in the 1960s and rose to 18.0% in the 2000s (P < .001).Conclusions: This is the first study to evaluate and report on a rising trend for subsequent primary melanoma. Additional primary melanomas worsen the patients' survival, and precautions are needed to turn this steep upgoing trend. [ABSTRACT FROM AUTHOR]

The article focuses on initiation of opioids for acute pain in the hospital can lead to unanticipated long-term opioid use. Topics include the opioids are effective for short-term nociceptive pain, little evidence for their use in chronic noncancer pain exists, and over time risks associated with opioid use accumulate, and the transition of care from the hospital into the community represents a high-risk period for medication management and especially in the setting of delayed or otherwise.

Objective To describe the diverse upper reference limits of serum thyroid stimulating hormone on the same platform for pregnant women in China. Methods The trimester-specific and population-specific TSH reference intervals for pregnant women were established, and then 5 reference intervals on the same platform in China were compared with the reference intervals derived from the present study and the manufacturer. Results The most striking difference in the upper reference limits of TSH among 5 reference intervals on the same platform was shown at the first trimester of pregnancy. The calculated regional prevalence rates of subclinical thyroid diseases varied using the data derived from 30,771 pregnant women who visited the largest obstetric center in our district from 2008 to 2018. Conclusion We reported differences among 7 reference intervals of TSH on the same platform and showed the changing population factors significantly affected them. [ABSTRACT FROM AUTHOR]

Limiting ultraviolet radiation exposure during early childhood can significantly reduce the risk of developing skin cancer, making early childhood a critical time for sun protection strategies. This study aimed to measure sun protection practices utilized in Australian early-childhood services over the past decade and evaluate the impact of Cancer Council Australia's SunSmart Early-Childhood Program. Results are presented from cross-sectional and repeated-measures survey data, completed by directors or other staff at randomly sampled early-childhood services in 2008, 2013 and 2018 (N  =   3243). Most sun protection practices were used by a significantly greater proportion of services in 2018 relative to earlier years, such as requiring the use of sunscreen (98.4%), and sun-protective hats (99.7%) and clothing (88.8%). However, only a small and declining proportion of services (16.3%–22.4%) required the use of specific items of sun-protective clothing. SunSmart program members reported enacting significantly more sun protection practices compared to non-members, while new members showed an increase in the use of those practices relative to services whose status did not change (d  =   0.48). The results demonstrate improvements in sun protection in Australian early-childhood settings, and highlight the benefits and limitations of the SunSmart program. [ABSTRACT FROM AUTHOR]

Background. People with low back pain (LBP) may display an altered lumbar movement pattern of early lumbar motion compared to people with healthy backs. Modifying this movement pattern during a clinical test decreases pain. It is unknown whether similar effects would be seen during a functional activity. Objective. The objective of this study was to examine the lumbar movement patterns before and after motor skill training, effects on pain, and characteristics that influenced the ability to modify movement patterns. Design. The design consisted of a repeated-measures study examining early-phase lumbar excursion in people with LBP during a functional activity test. Methods. Twenty-six people with chronic LBP received motor skill training, and 16 people with healthy backs were recruited as a reference standard. Twenty minutes of motor skill training to decrease early-phase lumbar excursion during the performance of a functional activity were used as a treatment intervention. Early-phase lumbar excursion was measured before and after training. Participants verbally reported increased pain, decreased pain, or no change in pain during performance of the functional activity test movement in relation to their baseline pain. The characteristics of people with LBP that influenced the ability to decrease early-phase lumbar excursion were examined. Results. People with LBP displayed greater early-phase lumbar excursion before training than people with healthy backs (LBP: mean = 11.2°, 95% CI = 9.3°-13.1°; healthy backs: mean = 7.1°, 95% CI = 5.8°--8.4°). Following training, the LBP group showed a decrease in the amount of early-phase lumbar excursion (mean change = 4.1°, 95% CI = 2.4°-5.8°); 91% of people with LBP reported that their pain decreased from baseline following training. The longer the duration of LBP (β = - 0.22) and the more early-phase lumbar excursion before training (β = - 0.82), the greater the change in early-phase lumbar excursion following training. Limitations. The long-term implications of modifying the movement pattern and whether the decrease in pain attained was clinically significant are unknown. Conclusions. People with LBP were able to modify their lumbar movement pattern and decrease their pain with the movement pattern within a single session of motor skill training. [ABSTRACT FROM AUTHOR]

Background. Physical therapy is an important treatment option for patients with low back pain (LBP). However, whether to refer patients for physical therapy and the timing of initiation remain controversial. Objective. The objective of this study was to evaluate the impact of receiving physical therapy and the timing of physical therapy initiation on downstream health care utilization and costs among patients with acute LBP. Design. The design was a retrospective cohort study. Methods. Patients who had a new onset of LBP between January 1, 2009, and December 31, 2013, in New York State were identified and grouped into different cohorts on the basis of whether they received physical therapy and the timing of physical therapy initiation. The probability of service use and LBP-related health care costs over a 1-year period were analyzed. Results. Among 46,914 patients with acute LBP, 40,246 patients did not receive physical therapy and 6668 patients received physical therapy initiated at different times. After controlling for patient characteristics and adjusting for treatment selection bias, health care utilization and cost measures over the 1-year period were the lowest among patients not receiving physical therapy, followed by patients with immediate physical therapy initiation (within 3 days), with some exceptions. Among patients receiving physical therapy, those receiving physical therapy within 3 days were consistently associated with the lowest health care utilization and cost measures. Limitations. This study was based on commercial insurance claims data from 1 state. Conclusions. When referral for physical therapy is warranted for patients with acute LBP, immediate referral and initiation (within 3 days) may lead to lower health care utilization and LBP-related costs. [ABSTRACT FROM AUTHOR]

There is a paucity in the literature examining the African American middle-class. Most studies of African Americans and Type 2 Diabetes Mellitus (T2DM) have concentrated on lower-SES individuals, or make no distinction between African Americans of varying socio-economic positions. Middle-class African Americans are vulnerable in ways often overlooked by researchers. This study quantitatively examines specific T2DM knowledge and perceptions of risk in middleclass African Americans (N=121). The majority of respondents, 70.2%, were unable to correctly identify all the warning signs of T2DM development. Only 3.3% of respondents correctly identified all risk factors provided as 'possible causes' of T2DMdevelopment. The difference between those participants who considered themselves to be at risk for T2DM development and their level of risk, according to the American Diabetes Associations' risk assessment, was not statistically significant (P=0.397). However, there were statistically significant differences between participants' perceptions of their weight and clinical definitions of overweight, a major risk factor in T2DM development, based on BMI (P=0.000). Middle-class African Americans are not inherently protected or exempt from developing T2DM. This study demonstrates gaps in knowledge and overall incongruent levels of perceived susceptibility, suggesting a need for additional research and health education in this segment of the population. [ABSTRACT FROM AUTHOR]

Background Promoting vaccination during pandemics is paramount to public health, yet few studies examined theoretical motivations for vaccination during pandemics. Thus, the relationships between dispositional pandemic worry, constructs of the health belief model (HBM) and vaccination during the H1N1 pandemic were studied. Methods Participants (N = 1377) completed surveys assessing dispositional pandemic worry, HBM variables and H1N1 vaccination. Principle axis factor analysis and point biserial correlations were conducted. Differences in worry and vaccination were assessed via independent samples t-tests. Relationships between vaccination, demographics and worry were investigated using hierarchical linear regression. PROCESS analysis was conducted to explicate the relationship between worry and vaccination intention. Results A two-factor structure of dispositional pandemic worry--worry frequency and worry severity--was confirmed. Dispositional worry was higher among those who intended to and received H1N1 vaccine. Worry frequency and worry severity were positively related to vaccination. Threat, benefits and barriers mediated the impact of worry severity and threat and barriers mediated the impact of worry frequency on vaccination intentions. Conclusions Messages increasing dispositional worry and benefits while decreasing barriers may boost vaccination behavior during a pandemic event. Future study of relationships between dispositional worry and HBM variables is warranted. [ABSTRACT FROM AUTHOR]

Background. For health care providers in the United States, the risk for nonfatal violence in the workplace is 16 times greater than that for other workers. Inappropriate patient sexual behavior (IPSB) is directed at clinicians, staff, or other patients and may include leering, sexual remarks, deliberate touching, indecent exposure, and sexual assault. Inappropriate patient sexual behavior may adversely affect clinicians, the organization, or patients themselves. Few IPSB risk factors for physical therapists have been confirmed. The US prevalence was last assessed in the 1990s. Objective. The objectives of this study were to determine career and 12-month exposure to IPSB among US physical therapists, physical therapist assistants, physical therapist students, and physical therapist assistant students and to identify IPSB risk factors. Design. This was a retrospective and observational study. Methods. An electronic survey was developed; content validity and test-retest reliability were established. Participants were recruited through physical therapist and physical therapist assistant academic programs and sections of the American Physical Therapy Association. Inappropriate patient sexual behavior risk models were constructed individually for any, mild, moderate, and severe IPSB events reported over the past 12 months. Open-ended comments were analyzed using qualitative methods. Results. Eight hundred ninety-two physical therapist professionals and students completed the survey. The career prevalence among respondents was 84%, and the 12-month prevalence was 47%. Statistical risk modeling for any IPSB over the past 12 months indicated the following risks: having fewer years of direct patient care, routinely working with patients with cognitive impairments, being a female practitioner, and treating male patients. Qualitative analysis of 187 open-ended comments revealed patient-related characteristics, provider-related characteristics, and abusive actions. Limitations. Self-report, clinician memory, and convenience sampling are limitations of this type of survey research. Conclusions. The extremely high prevalence of IPSB among physical therapist professionals warrants practitioner and student education as well as clear workplace policy and support. [ABSTRACT FROM AUTHOR]

In clinical trials it is not uncommon to face a multiple testing problem which can have an impact on both type I and type II error rates, leading to inappropriate interpretation of trial results. Multiplicity issues may need to be considered at the design, analysis and interpretation stages of a trial. The proportion of trial reports not adequately correcting for multiple testing remains substantial. The purpose of this article is to provide an introduction to multiple testing issues in clinical trials, and to reduce confusion around the need for multiplicity adjustments. We use a tutorial, question-and-answer approach to address the key issues of why, when and how to consider multiplicity adjustments in trials. We summarize the relevant circumstances under which multiplicity adjustments ought to be considered, as well as options for carrying out multiplicity adjustments in terms of trial design factors including Population, Intervention/Comparison, Outcome, Time frame and Analysis (PICOTA). Results are presented in an easy-to-use table and flow diagrams. Confusion about multiplicity issues can be reduced or avoided by considering the potential impact of multiplicity on type I and II errors and, if necessary pre-specifying statistical approaches to either avoid or adjust for multiplicity in the trial protocol or analysis plan. [ABSTRACT FROM AUTHOR]

Decline in both telomere length and physical fitness over the life course may contribute to increased risk of several chronic diseases. The relationship between telomere length and aerobic and muscular fitness is not well characterized. We examined whether there are cross-sectional associations of mean relative leukocyte telomere length (LTL) with objective measures of aerobic fitness, muscle strength, and muscle endurance, using data on 31-year-old participants of the Northern Finland Birth Cohort 1966 (n = 4,952-5,205, varying by exposureoutcome analysis). Aerobic fitness was assessed by means of heart rate measurement following a standardized submaximal step test; muscular fitness was assessed by means of a maximal isometric handgrip strength test and a test of lower-back trunk muscle endurance. Longer LTL was associated with higher aerobic fitness and better trunk muscle endurance in models including adjustment for age, sex, body mass index, socioeconomic position, diet, smoking, alcohol consumption, physical activity level, and C-reactive protein. In a sex-stratified analysis, LTL was not associated with handgrip strength in either men or women. LTL may relate to aspects of physical fitness in young adulthood, but replication of these findings is required, along with further studies to help assess directions and causality in these associations. [ABSTRACT FROM AUTHOR]

Objective. To conduct a replication study and meta-analysis involving the study of mtDNA variants in the radiographic progression of OA in different cohorts worldwide, including Cohort Hip and Cohort Knee (CHECK), the OA Initiative and a cohort from Spain. Methods. The influence of the haplogroups in the rate of radiographic progression at 96 months in 431 subjects from CHECK was assessed in terms of Kellgren and Lawrence (KL) grade. Progression was defined as a change from KL ≥ 1 at baseline to any higher grade during the follow-up. Extended Cox proportional hazard models were used to analyse the influence of mtDNA variants in the rate of radio-graphic knee OA progression. A subsequent meta-analysis of 1603 subjects following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted to combine the data of individual studies. A sensitivity analysis was performed to validate the stability of the results. Results. CHECK subjects carrying the haplogroup T showed the lowest rate of radiographic knee OA progression [hazard ratio (HR) 0.645 (95% CI 0.419, 0.978); P < 0.05]. When pooled, subjects within the superhaplogroup JT showed the same trend [HR 0.707 (95% CI 0.501, 0.965); P < 0.05]. BMI [HR 1.046 (95% CI 1.018, 1.073); P < 0.05] and bilateral OA [HR 2.266 (95% CI 1.733, 2.954); P < 0.05] at baseline are risk factors for radiographic knee OA progression as well. In the meta-analysis there was a reduced rate of radiographic progression in subjects with haplogroup T [HR 0.612 (95% CI 0.454, 0.824); P = 0.001] or in the superhaplogroup JT [HR 0.765 (95% CI 0.624, 0.938); P = 0.009]. Sensitivity analysis revealed that the results were robust. Conclusion. The mtDNA variants in the superhaplogroup JT associate with a reduced rate of radiographic OA progression. The mtDNA polymorphisms in the superhaplogroup JT emerge as potential complementary genetic biomarkers for disease progression. [ABSTRACT FROM AUTHOR]

Indoor tanning is associated with increased risk of melanoma, but most evidence comes from case-control studies. Using data from the Norwegian Women and Cancer Study, a large prospective cohort study, we investigated the associations of age at initiation of indoor tanning, duration of tanning-device use, and dose response with melanoma risk and examined the role of indoor tanning in age at melanoma diagnosis. We used Poisson regression to estimate relative risks and 95% confidence intervals for the relationship of indoor tanning to melanoma risk and linear regression to examine age of indoor tanning initiation in relation to age at diagnosis. During follow-up of 141,045 women (1991-2012; mean duration follow-up = 13.7 years), 861 women were diagnosed with melanoma. Melanoma risk increased with increasing cumulative number of tanning sessions (for highest tertile of use vs. never use, adjusted relative risk = 1.32, 95% confidence interval (CI): 1.08,1.63); P-trend = 0.006. Age at initiation <30 years was associated with a higher risk in comparison with never use (adjusted relative risk = 1.31, 95% CI: 1.07, 1.59). Moreover, women who started indoor tanning prior to 30 years of age were 2.2 years (95% CI: 0.9, 3.4) younger at diagnosis, on average, than never users. This cohort study provides strong evidence of a dose-response association between indoor tanning and risk of melanoma and supports the hypothesis that vulnerability to the harmful effects of indoor tanning is greater at a younger age. [ABSTRACT FROM AUTHOR]

We examined the proportions of multiple types of breast cancers in the population that were attributable to established risk factors, focusing on behaviors that are modifiable at menopause. We estimated the full and partial population attributable risk percentages (PAR%) by combining the relative risks and the observed prevalence rates of the risk factors of interest. A total of 8,421 cases of invasive breast cancer developed in postmenopausal women (n = 121,700) in the Nurses' Health Study from 1980-2010. We included the following modifiable risk factors in our analyses: weight change since age 18 years, alcohol consumption, physical activity level, breastfeeding, and menopausal hormone therapy use. Additionally, the following nonmodifiable factors were included: age, age at menarche, height, a combination of parity and age at first birth, body mass index at age 18 years, family history of breast cancer, and prior benign breast disease. When we considered all risk factors (and controlled for age), the PAR% for invasive breast cancers was 70.0% (95% confidence interval: 55.0, 80.7). When considering only modifiable factors, we found that changing the risk factor profile to the lowest weight gain, no alcohol consumption, high physical activity level, breastfeeding, and no menopausal hormone therapy use was associated with a PAR% of 34.6% (95% confidence interval: 22.7, 45.4). The PAR% for modifiable factors was higher for estrogen receptor-positive breast cancers (PAR% = 39.7%) than for estrogen receptor-negative breast cancers (PAR% = 27.9%). Risk factors that are modifiable at menopause account for more than one-third of postmenopausal breast cancers; therefore, a substantial proportion of breast cancer in the United States is preventable. [ABSTRACT FROM AUTHOR]

The mental health toll of the Iraq and Afghanistan Wars on military veterans has been considerable, yet little is known about the persistence of these adverse outcomes, especially relative to predeployment status. We pro-spectively examined posttraumatic stress disorder (PTSD) as a long-term consequence of warzone deployment, integrating data collected from 2003-2014. In the Neurocognition Deployment Health Study, we measured PTSD symptoms in US Army soldiers before and shortly after Iraq War deployment. We used the PTSD Checklist-Civilian Version and a structured clinical interview (i.e., Clinician-Administered PTSD Scale) to reassess PTSD in 598 service members and military veterans a median of 7.9 years (interquartile range, 7.2-8.5 years) after an index Iraq deployment. At long-term follow-up, 24.7% (95% confidence interval (CI): 21.5, 28.4) of participants met the case definition for PTSD, which was an absolute increase of 14.2% from the percentage assessed post-deployment (10.5%; 95% CI: 7.8, 13.7) and of 17.3% from the percentage assessed predeployment (7.4%; 95% CI: 5.5, 9.8). These findings highlight that PTSD is an enduring consequence of warzone participation among contemporary military personnel and veterans. The largest increase in PTSD cases occurred between the post-deployment and long-term follow-up assessments, which suggests that adverse stress reactions cannot necessarily be expected to dissipate over time and actually may increase. [ABSTRACT FROM AUTHOR]

Objective. To investigate widespread pressure hyperalgesia in the trigemino-cervical and extra-trigeminal (distant pain-free) regions in women with episodic and chronic migraine. Methods. Fifty-one women with episodic migraine, 52 women with chronic migraine, and 52 healthy women without headache history were recruited. Pressure pain thresholds (PPT) were bilaterally assessed over the trigeminal area (i.e., temporalis muscle), cervical area (i.e., C5/C6 zygapophyseal joint), and two extra-trigeminal areas (i.e., second metacarpal, tibialis anterior muscle) in a blinded design. Clinical features of migraine and anxiety/depression (Hospital Anxiety and Depression Scale, HADS) were also assessed. Results. The multivariate analysis of covariance (ANCOVA) revealed that PPTs were significantly decreased bilaterally over trigeminal and extra-trigeminal points in migraine patients compared to healthy women (all sites, P< 0.001). No differences between episodic and chronic migraine were observed (all, P> 0.919). The presence of neck pain (all, P> 0.282), anxiety (P> 0.425) or depression (all, P> 0.316) did not influence the results. The intensity of migraine pain was negatively associated with widespread pressure pain sensitivity: The greater the intensity of migraine attacks, the lower the widespread PPT levels, i.e., the greater the widespread sensitization. Conclusions. This study found similar widespread pressure hypersensitivity in women with episodic or chronic migraine suggesting that central manifestations are involved both in episodic and chronic migraine. [ABSTRACT FROM AUTHOR]

Background: The main aim of this study was to quantify and compare 6-year mortality risk attributable to smoking, hypertension and diabetes among English and Brazilian older adults. This study represents a rare opportunity to approach the subject in two different social and economic contexts. Methods: Data from the data from the English Longitudinal Study of Ageing (ELSA) and the Bambuí Cohort Study of Ageing (Brazil) were used. Deaths in both cohorts were identified through mortality registers. Risk factors considered in this study were baseline smoking, hypertension and diabetes mellitus. Both age-sex adjusted hazard ratios and population attributable risks (PAR) of all-cause mortality and their 95% confidence intervals for the association between risk factors and mortality were estimated using Cox proportional hazards models. Results: Participants were 3205 English and 1382 Brazilians aged 60 years and over. First, Brazilians showed much higher absolute risk of mortality than English and this finding was consistent in all age, independently of sex. Second, as a rule, hazard ratios for mortality to smoking, hypertension and diabetes showed more similarities than differences between these two populations. Third, there was strong difference among English and Brazilians on attributable deaths to hypertension. Conclusions: The findings indicate that, despite of being in more recent transitions, the attributable deaths to one or more risk factors was twofold among Brazilians relative to the English. These findings call attention for the challenge imposed to health systems to prevent and treat non-communicable diseases, particularly in populations with low socioeconomic level. [ABSTRACT FROM AUTHOR]

The U.S. federal Every Student Succeeds Act (ESSA) was enacted with goals of closing achievement gaps and providing all students with access to equitable and high-quality instruction. One requirement of ESSA is annual statewide testing of students in grades 3-8 and once in high school. Some students, including many deaf or hard-of-hearing (D/HH) students, are eligible to use test supports, in the form of accommodations and accessibility tools, during state testing. Although technology allows accommodations and accessibility tools to be embedded within a digital assessment system, the success of this approach depends on the ability of test developers to appropriately represent content in accommodated forms. The Guidelines for Accessible Assessment Project (GAAP) sought to develop evidence- and consensus-based guidelines for representing test content in American Sign Language. In this article, we present an overview of GAAP, review of the literature, rationale, qualitative and quantitative research findings, and lessons learned. [ABSTRACT FROM AUTHOR]

Objective. This study aims to determine 1) the epidemiology of perioperative opioid use; and 2) the association between patterns of preoperative opioid use and time-to-cessation of postoperative opioids. Design. Retrospective, cohort study. Setting. National, population-level study of Veterans Healthcare Administration (VHA) electronic clinical data. Subjects. All VHA patients (n564,391) who underwent surgery in 2011, discharged after stays of ≥1 day, and receiving ≥1 opioid prescription within 90 days of discharge. Methods. Patients' preoperative opioid use were categorized as 1) no opioids, 2) tramadol only, 3) shortacting (SA) acute/intermittent (≤ 90 days fill), 4) SA chronic (> 90 days fill), or 5) any long-acting (LA). After defining cessation as 90 consecutive, opioidfree days, the authors calculated time-to-opioid-cessation (in days), from day 1 to day 365, after hospital discharge. The authors developed extended Cox regression models with a priori identified predictors. Sensitivity analyses used alternative cessation definitions (30 or 180 consecutive days). Results. Almost 60% of the patients received preoperative opioids: tramadol (7.5%), SA acute/intermittent (24.1%), SA chronic (17.5%), and LA (5.2%). For patients opioid-free preoperatively, median time-to-cessation of opioids postoperatively was 15 days. The SA acute/intermittent cohort (HR51.96; 95% CI51.92-2.00) had greater risk for prolonged time-to-cessation than those opioid-free (reference), but lower risk than those taking tramadol only, SA chronic (HR5 9.09; 95% CI5 8.33-9.09), or LA opioids (HR59.09; 95% CI58.33-10.00). Diagnoses of chronic pain, substance-use, or affective disorders were weaker positive predictors. Sensitivity analyses maintained findings. Conclusion. Greater preoperative levels of opioid use were associated with progressively longer time to- cessation postoperatively. [ABSTRACT FROM AUTHOR]

Objective. Prolonged exposure to opioids is known to produce neuroplastic changes in animals; however, few studies have investigated the effects of short-term prescription opioid use in humans. A previous study from our laboratory demonstrated a dosage-correlated volumetric decrease in the right amygdala of participants administered oral morphine daily for 1 month. The purpose of this current study was to replicate and extend the initial findings. Methods. Twenty-one participants with chronic low back pain were enrolled in this double-blind, placebo-controlled study. Participants were randomized to receive daily morphine (n = 11) or a matched placebo (n = 10) for 1 month. High-resolution anatomical images were acquired immediately before and after the treatment administration period. Morphological gray matter changes were investigated using tensor-based morphometry, and significant regions were subsequently tested for correlation with morphine dosage. Results. Decreased gray matter volume was observed in several reward- and pain-related regions in the morphine group, including the bilateral amygdala, left inferior orbitofrontal cortex, and bilateral pre-supplementary motor areas. Morphine administration was also associated with significant gray matter increases in cingulate regions, including the mid cingulate, dorsal anterior cingulate, and ventral posterior cingulate. Conclusions. Many of the volumetric increases and decreases overlapped spatially with the previously reported changes. Individuals taking placebo for 1 month showed neither gray matter increases nor decreases. The results corroborate previous reports that rapid alterations occur in reward-related networks following short-term prescription opioid use. [ABSTRACT FROM AUTHOR]

Background. Balance problems are common in children who have cerebral palsy (CP) but are active and ambulant. Control of the whole-body center of mass is critical in maintaining dynamic stability during challenging mobility tasks, such as clearing an obstacle while walking. Objective. The objective of this study was to compare trunk and lower limb kinematics and center-of-mass control in children with CP and those in children with typical development during obstacle crossing. Design. This was a cross-sectional study. Thirty-four children who were 5 to 17 years of age (17 with CP and 17 with typical development) and matched in age and height completed 2 gait trials involving crossing a 10-cm obstacle. Methods. Three-dimensional kinematic and kinetic data were captured with a general-purpose 3-dimensional motion tracking system and forceplates. Trunk data were captured with a validated model. Results. All children cleared the obstacle with similar hip and knee kinematics, step length, and single-support duration. In children with CP, step width was increased by 4.81 cm, and center-of-mass velocity was significantly slower at lead limb toe-off (0.31 m/s) and during lead limb clearance (0.2 m/s). Children with CP showed altered trunk and pelvis movement, characterized by significantly greater pelvic obliquity, pelvic tilt, and trunk rotation throughout the task, increased lateral trunk lean during lead limb crossing (37°), and greater sagittal trunk movement as the trail limb crossed (5.1°). Limitations. The study was not powered to analyze differences between children with diplegia and those with hemiplegia. Conclusions. Children with CP required greater adjustments at the trunk and pelvis to achieve successful obstacle crossing. The increase in trunk movement could have been compensatory for reduced stability distally or for a primary problem reflecting poor proximal control. The findings suggest that rehabilitation should focus on both proximal trunk control and distal stability to improve balance. [ABSTRACT FROM AUTHOR]

Background. Previous retrospective studies have shown that physical functioning in older cancer survivors is affected after treatment, yet prospective data are lacking. The aim of this study was to assess change in physical functioning in different age groups of patients with hormone receptor-positive breast cancer who were enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) phase III trial. Methods. Two physical parameters were assessed. Physical functioning was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire 1 year (T1) and 2 years (T2) after diagnosis. Physical activity was measured in metabolic equivalent of task (MET) hours/week at T1 and T2. Physical activity before diagnosis (T0) was assessed retrospectively at the T1 questionnaire. Patients were divided into three age groups: <60, 60-69, and ≥70 years. Decline in physical functioning was assessed using linear regression analysis. Differences in mean values of physical activity levels were calculated using repeated-measures one way analysis of variance. Results. A total of 431 patients were included for analysis. In all age groups, physical activity levels at T1 and T2 were significantly lower than prediagnostic physical activity levels (T0) (p < .001 for all age groups). Age ≥70 years was independently associated with decline in physical functioning between T1 and T2 (β = 24.62, 95% confidence interval -8.73 to -0.51, p = .028). Conclusion. Patients aged 70 years or older treated with breast surgery and adjuvant hormonal therapy did not improve between years 1 and 2 after diagnosis to the same extent as did younger patients. [ABSTRACT FROM AUTHOR]

Diet quality index scores on Healthy Eating Index 2010 (HEI-2010), Alternative HEI-2010, alternative Mediterranean Diet Index, and the Dietary Approaches to Stop Hypertension (DASH) index have been inversely associated with all cause and cancer-specific death. This study assessed the association between these scores and colorectal cancer (CRC) incidence as well as CRC-specific mortality in the Women's Health Initiative Observational Study (1993-2012), a US study of postmenopausal women. During an average of 12.4 years of follow-up, there were 938 cases of CRC and 238 CRC-specific deaths. We estimated multivariate hazard ratios and 95% confidence intervals for relationships between quintiles of diet scores (from baseline food frequency questionnaires) and outcomes. HEI-2010 score (hazard ratios were 0.81, 0.77, and 0.73 with P values of 0.04, 0.01, and <0.01 for quintiles 3-5 vs. quintile 1, respectively) and DASH score (hazard ratios were 0.72, 0.74, and 0.78 with P values of <0.01, <0.01, and 0.03 for quintiles 3-5 vs. quintile 1, respectively), but not other diet scores, were associated with a lower risk of CRC in adjusted models. No diet scores were significantly associated with CRC-specific mortality. Closer adherence to HEI-2010 and DASH dietary recommendations was inversely associated with risk of CRC in this large cohort of postmenopausal women. [ABSTRACT FROM AUTHOR]

Background: depression is common in people with poor physical health, particularly within the acute medical in-patient setting. Co-morbid depression contributes to poor outcomes, and screening for depression in acute medical in-patients has been advocated. The Edinburgh Depression Scale (EDS) has been validated in a variety of general hospital patient groups, but not previously in older acute medical in-patients. Methods: one hundred and eighteen patients aged 65 and older on acute medical wards were assessed using a standardised diagnostic interview (Present State Examination--Schedules for Clinical Assessment in Neuropsychiatry) to identify depression according to ICD-10 criteria. They subsequently completed the EDS. The performance characteristics at a range of thresholds were compared, and receiver operating characteristic curve analysis was performed. Results: the optimal EDS cut-off for identifying ICD-10 depressive episode was 7/8, with a sensitivity of 88%, specificity of 77%, positive predictive value of 52% and negative predictive value of 96%. The area under the receiver operating characteristic curve was 0.91. Conclusion: the EDS was shown to be a useful instrument for detecting clinical depression in older people on acute medical wards in this study. Its performance was equivalent to other validated screening instruments in this population. Our findings add further weight to using the EDS as a screening instrument for depression in multiple general hospital settings. [ABSTRACT FROM AUTHOR]

Objective. The study aimed to evaluate the value of the Cervista human papillomavirus (HPV), Hybrid Capture 2 (HC-2), and careHPV tests in diagnosing cervical intraepithelial neoplasia grade 2 (CIN2) or worse in Xinjiang Uyghur women. Methods. Three high-risk human papillomavirus (HR-HPV) detection methods were studied on two different populations by different combination modes; a cytology specimen was obtained at the same time. An abnormal result of any test resulted in referral to colposcopy. Cervical biopsy was also performed. Results. In population 1, HR-HPV-positive rates were 57.6% and 54.3% as detected by HC-2 and Cervista, respectively; κ = 0.892 for consistency check of HC-2 and Cervista (p < .001). Area under the receiver operating characteristic curve (AUC) of HC-2 and Cervista was 0.744 (95% confidence interval [CI]:0.664~0.824,p< . 001) and 0.786 (95% CI: 0.715-0.858, p < .001), respectively, for diagnosing CIN2 1 .The A9 probe can detect six subtypes of HPV, including HPV16, HPV31, HPV33, HPV35, HPV52, and HPV58. If one or more of these subtypes are postitive, then A9 will be positive. A diagnosis of class A9 by the Cerevista test correlated with pathological interpretations (chi-square 5 43.063, p < .001). In population 2, HR-HPV-positive rates were 40.1% and 34.4%, respectively, by HC-2 and careHPV; κ value was 0.779 for the two tests (p < .001). AUC of HC-2 was 0.895 (95% CI: 0.849-0.940, p < .001), and careHPV was 0.841 (95% CI: 0.770-0.899, p < .001) for diagnosing CIN2 1 . Conclusion. Good consistency was shown between HC-2 and Cervista tests and also between the HC-2 and careHPV tests. In the detection of CIN21, Cervista showed better specificity than HC-2, and interpretation of the A9 subgroup showed high predicted value. The HC-2 test demonstrated better sensitivity than careHPV in detection of CIN21. HC-2, Cervista, and careHPV may be applied as a triage test for visual inspection with acetic acid/Lugol's iodine-positive or ThinPrep cytologic test-positive women. The careHPV test was comparatively economical and efficient and may be more suitable for resource-limited regions, such as Xinjiang. [ABSTRACT FROM AUTHOR]

Objective. Evaluate the human abuse potential (HAP) of an experimental, microsphere-in-capsule formulation of extended-release oxycodone (oxycodone DETERx®) (herein "DETERx). Design. Randomized, double-blind, double-dummy, positive- and placebo-controlled, single-dose, four-phase, four-treatment, crossover study. Setting. Clinical research site. Subjects. There were 39 qualifying subjects (72% male, 85% white, mean age of 27 years) with 36 completing all four Double-blind Treatment Periods. Methods. The four phases encompassed: 1) Screening; 2) Drug Discrimination; 3) Double-blind Treatment; and 4) Follow-up. Drug Discrimination tests ensured that subjects could distinguish placebo from opioid. The four Double-blind Treatments compared DETERx--administered as either a crushed intranasal (IN) or an intact oral (PO) preparation--with immediate-release oxycodone IN (OXY-IR IN) and with an intact IN and PO placebo DETERx control. Results. For primary pharmacokinetic (PK) assessments, abuse quotient (Cmax/Tmax) was lower with DETERx IN than DETERx PO; both treatments were substantially lower than OXY-IR IN (6.24, 8.60, and 69.6 ng/mL/h, respectively). For drug liking, the primary subjective pharmacodynamic (PD) endpoint, both DETERx IN and DETERx PO produced significantly lower scores than OXY-IR IN (P ≤ 0.0001 for each); DETERx IN was less liked than DETERx PO (P ≤ 0.05), mirroring the PK relationships. Objectively assessed pupillometry corroborated the more rapid and significantly greater effect of OXY-IR IN than either DETERx IN or DETERx PO (P ≤ 0.007 for each). Overall safety profiles of DETERx and OXY-IR were comparable and both were well tolerated. Conclusions. Pharmacokinetic and pharmacody-namic outcomes suggest that DETERx IN has relatively low HAP; continued research in larger populations is suggested. [ABSTRACT FROM AUTHOR]

Background Data. Few studies have investigated the long-term efficacy of percutaneous lumbar disc decompression (PLDD) with Dekompressor (Stryker, Kalamazoo, MI) for discogenic radicular pain that has failed conservative management. Objective. Determine long-term outcomes of Dekompressor PLDD for discogenic radicular pain. Methods. Prospective cohort study at a tertiary academic spine center of consecutive patients (12/2004-11/2005) with discogenic lumbosacral radicular pain who underwent PLDD with Dekompressor. Numerical Rating Scale (NRS) leg pain score and Oswestry Disability Index (ODI) score data were collected at 6 months and 1 year. These two measures, 5-point Likert scale patient satisfaction, and surgical rate data were collected at 8 years. Results. Seventy patients underwent PLDD. Forty and 25 patients were successfully contacted at 1-year and 8-year follow-up, respectively. Using intention to treat analysis, at 1 year and 8 years, NRS leg pain scores were reduced >50% in 47% (95% confidence interval [CI] 35%, 59%) and 29% (95% confidence interval [CI] 18%, 40%) of patients, respectively; ODI score improved >30% in 43% (CI 32%, 55%) and 26% (CI 19%, 41%) of patients, respectively. Of the patients who followed up at 8 years, 36% (CI 17%, 55%) had undergone surgery and the median satisfaction was "4" (interquartile range 2,5). Conclusions. While limited by loss-to-follow-up, this study suggests that treatment of discogenic lumbosacral radicular pain with Dekompressor results in decreased leg pain and disability and favorable satisfaction at long-term follow-up. Further study with adequate follow-up retention is needed to confirm that Dekompressor spares open spinal surgery. [ABSTRACT FROM AUTHOR]

Background and objective: adiponectin is an adipocyte-derived hormone with anti-obesity and anti-diabetic properties. However, higher circulating adiponectin levels are related to poor muscle function and physical disability, which suggests a potential link between adiponectin and risk of falls. Nevertheless, no direct association between circulating adiponectin levels and incident fall risk has been reported. Therefore, this study aimed to investigate the relationship between serum adiponectin levels and incident falls in a population of middle-aged and older adults. Design: a prospective cohort study. Setting: Oroshisho Center in Sendai City, Japan. Subjects: Japanese adults who were ≥45 years old (n = 430). Measurements: serum adiponectin levels were measured at baseline, and the subjects were divided into sex-specific tertiles. Data regarding a history of falls were collected via participant recall using a self-reported questionnaire. Incident falls were defined as falls that were experienced by people without a history of falls at baseline. Results: during the 2-year follow-up, 15.6% (67/430) of the subjects experienced an incident fall. In the univariate logistic regression analysis, incident falls were significantly more frequent across the increasing sex-specific serum adiponectin tertiles (P for trend = 0.008). Adjusted odds ratios (95% confidence interval) for incident falls were 2.31 (1.07-4.98) in the middle tertile and 3.61 (1.63-7.99) in the highest tertile; this risk was significantly higher than that for the lowest adiponectin tertile (P for trend = 0.002). Conclusions: the findings of this prospective cohort study indicate that higher serum adiponectin levels may be a predictor of incident falls. [ABSTRACT FROM AUTHOR]

Background. The use of gemcitabine as an adjuvant modality for cholangiocarcinoma (CC) is increasing, but limited data are available on predictive biomarkers of response. Human equilibrative nucleoside transporter 1 (hENT-1) is the major transporter involved in gemcitabine intracellular uptake. This study investigated the putative predictive role of hENT-1 localization in tumor cells of CC patients undergoing treatment with adjuvant gemcitabine. Methods. Seventy-one consecutive patients with resected CC receiving adjuvant gemcitabine at our center were retrospectively analyzed by immunohistochemistry for hENT-1 localization in tumor cells. The main outcome measure was disease-free survival (DFS). Hazard ratios (HRs) of relapse and associated 95% confidence intervals (CIs) were obtained from proportional hazards regression models stratified on quintiles of propensity score. Results. Twenty-three (32.4%) cases were negative for hENT-1, 22 (31.0%) were positive in the cytoplasm only, and 26 (36.6%) showed concomitant cytoplasm/membrane staining. Patients with membrane hENT-1 had a longer DFS (HR 0.49, 95% CI 0.24-0.99, p = .046) than those who were negative or positive only in the cytoplasm of tumor cells. Notably, the association between DFS and membrane hENT-1 was dependent on the number of gemcitabine cycles (one to two cycles: HR 0.96, 95% CI0.34-2.68; three to four cycles: HR 0.99,95% CI 0.34-2.90; five to six cycles: HR 0.27, 95% CI 0.10-0.77). Conclusion. hENT-1 localization on tumor cell membrane may predict response to adjuvant gemcitabine in CC patients receiving more than four cycles of chemotherapy. Further prospective randomized trials on larger populations are required to confirm these preliminary results, so that optimal gemcitabine-based chemotherapy may be tailored for CC patients in the adjuvant setting. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate the association between osmophobia and the characteristics of patients and their headaches, among migraine patients. Methods. This was a cross-sectional study. Patients who consecutively sought medical attendance in a primary care unit were asked about their headaches over the last 12 months. Those who had migraine were included. A semi-structured interview, the Headache Impact Test and the Hospital Anxiety and Depression Scale were used. Results. 147 patients had migraine; 78 had osmophobia; 60 had significant anxiety symptoms; and 78 had significant depression symptoms. The mean age of these patients was 43.2 years (± 13.7); 91.2% were women. The mean length of time with complaints of headache was 13.8 years (± 12). Among the migraine patients, those with anxiety, more years of headache history, and phonophobia presented significantly more osmophobia (multivariate logistic regression). Conclusion: Osmophobia in migraine patients is associated with significant anxiety symptoms, length of headache history, and phonophobia. [ABSTRACT FROM AUTHOR]

Low absolute lymphocyte count (ALC) to absolute monocyte count (AMC) ratio (ALC/AMC) is an independent prognostic factor in Hodgkin lymphoma (HL), but different cutoffs (1.1, 1.5, and 2.9) have been applied. We aimed to validate the prognostic significance of ALC/AMC in 537 homogenously treated (doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalents ± radiotherapy) classical HL patients at various cutoffs. The median ALC/AMC was 2.24 (0.44-20.50). The median AMC was 0.653 3 109/L (0.050-2.070). Lower ALC/AMC was associated with established markers of adverse prognosis. In total, 477 (89%), 418 (78%), and 189 (35%) patients had an ALC/AMC ratio of ≥1.1, ≥1.5, and ≥2.9; respectively; 20% had monocytosis (≥0.9 3 109/L).Ten-year time to progression (TTP) was 77% versus 55% for patients with ALC/AMC ≥1.1 and <1.1 (p = .0002), 76% versus 68% for ALC/AMC ≥1.5 and <1.5 (p = .049), 77% versus 73% for ALC/AMC ≥2.9 and <2.9 (p = .35), and 79% versus 70% for ALC/AMC ≥2.24 and <2.24 (p = .08), respectively. In stages IA/IIA and in patients ≥60 years old, ALC/AMC had no significant effect on TTP. In advanced stages, ALC/AMC was significant only at the cutoff of 1.1 (10-year TTP 67% vs. 48%; p = .016). In younger, advanced-stage patients, the differences were more pronounced. In multivariate analysis of TTP, ALC/AMC < 1.1 (p = .007) and stage IV (p < .001) were independent prognostic factors; ALC/AMC was independent of International Prognostic Score in another model. ALC/AMC was more predictive of overall survival than TTP. At the cutoff of 1.1, ALC/AMC had independent prognostic value in multivariate analysis. However, the prognostically inferior group comprised only 11% of patients. Further research is needed prior to the widespread use of this promising marker. [ABSTRACT FROM AUTHOR]

Purpose. From a global perspective, the rates of allogeneic hematopoietic cell transplantation (alloHCT) are closely related to the economic status of a country. However, a potential association with outcome has not yet been documented. Thegoal of this study was to evaluate effects of health care expenditure (HCE), Human Development Index (HDI), team density, and center experience on nonrelapse mortality (NRM) after HLA-matched sibling alloHCTfor adults with acute lymphoblastic leukemia (ALL). Patients and Methods. A total of 983 patients treated with myeloablative alloHCT between 2004 and 2008 in 24 European countries were included. Results. In a univariate analysis, the probability of day 100 NRM was increased for countries with lower current HCE (8% vs. 3%; p = .06), countries with lower HDI (8% vs. 3%; p = .02), and centers with less experience (8% vs. 5%; p = .04). In addition, the overall NRM was increased for countries with lower current HCE (21% vs. 17%; p = .09) and HDI (21% vs. 16%; p = .03) and for centers with lower activity (21% vs. 16%;p = .07). Ina multivariate analysis, the strongest predictive model for day 100 NRM included current HCE greater than the median (hazard ratio [HR], 0.39; p = .002). The overall NRM was mostly predicted by HDI greater than the median (HR, 0.65; p = .01). Both lower current HCE and HDI were associated with decreased probability of overall survival. Conclusion. Both macroeconomic factors and the socioeconomic status of a country strongly influence NRM after alloHCT for adults with ALL. Our findings should be considered when clinical studies in the field of alloHCT are interpreted. [ABSTRACT FROM AUTHOR]

Background. Patient blood management (PBM) programs are associated with reduced transfusion usage, reduced hospital costs, and improved patient outcomes. The application of PBM principles in patients with malignant disease might achieve similar results. However, this population presents unique challenges. The aim of the present study was to investigate the impact of a PBM program on blood usage and patient outcomes in cancer patients, particularly in the setting of restricted use of erythropoiesis-stimulating agents (ESAs). Materials and Methods. A retrospective observational study was performed of patients admitted with a primary diagnosis of malignancy treated at Eastern Maine Medical Center as inpatients or outpatients, or both, from January 2008 through July 2013. Results. The proportion of inpatients and outpatients receiving ESAs decreased from 2.9% in 2008 to 1.1% in 2013 (p < .001). During the same period, an increase occurred in the mean dose of intravenous (IV) iron from 447 mg (95% confidence interval [CI], 337-556) to 588 mg (95% CI, 458-718). The mean red blood cell (RBC) units transfused per inpatient and outpatient episode decreased from 0.067 to 0.038 unit (p < .001). In inpatients, significant increases occurred in the proportion of single-unit RBC transfusions (p < .001) and patients infused with IV iron (p = .02), and significant decreases in the mean pretransfusion hemoglobin (p = .02) and RBC transfusion rate (p = .04). In-hospital mortality and length of stay did not change significantly during this period. Conclusion. Despite the decreased use of ESA therapy, the implementation of a PBM program and outpatient anemia management protocol in cancer patients at our medical center was associated with significant reductions in RBC usage. [ABSTRACT FROM AUTHOR]

Background. A multidimensional geriatric assessment (GA) is recommended in older cancer patients to inventory health problems and tailor treatment decisions accordingly but requires considerable time and human resources. The G8 is among the most sensitive screening tools for selecting patients warranting a full GA but has limited specificity. We sought to develop and validate an optimized version of the G8. Patients and Methods. We used a prospective cohort of cancer patients aged ≥70 years referred to geriatricians for GA (2007-2012: n = 729 [training set]; 2012-2014: n = 414 [validation set]). Abnormal GA was defined as at least one impaired domain across seven validated tests. Multiple correspondence analysis, multivariate logistic regression, and bootstrapped internal validation were performed sequentially. Results. The final model included six independent predictors for abnormal GA: weight loss, cognition/mood, performance status, self-rated health status, polypharmacy (≥6 medications per day), and history of heart failure/coronary heart disease. For the original G8, sensitivity was 87.2% (95% confidence interval, 84.3-89.7), specificity 57.7% (47.3-67.7), and area under the receiver-operating characteristic curve (AUROC) 86.5% (83.5-89.6). The modified G8 had corresponding values of 89.2% (86.5-91.5), 79.0% (69.4-86.6), and 91.6% (89.3; 93.9), with higher AUROC values for all tumor sites and stable properties on the validation set. Conclusion. A modified G8 screening tool exhibited better diagnostic performance with greater uniformity across cancer sites and required only six items. If these features are confirmed in other settings, the modified tool may facilitate selection for a full GA in older patients with cancer. [ABSTRACT FROM AUTHOR]

Background: Cystatin C, a marker for early stage chronic kidney dysfunction, mediates the pathogenesis of cardiovascular diseases. Objective: To investigate whether serum cystatin C is an independent predictor of coronary heart disease (CHD) for patients without chronic kidney disease (CKD). Methods: In this cross-sectional study, we included 525 patients with CHD and 142 apparently healthy control individuals and acquired their demographic characteristics, medical histories, and listings of the concurrent medications they were taking. All patients with CHD underwent coronary angiography and other routine laboratory examinations. We quantified serum concentrations of cystatin Cvia particle-enhanced immunonephelometric assay. Results: Compared with controls, the patients with CHD had higher serum cystatin C levels (median: 1.17mg/L, interquartile range [IQR]: 1.01 to 1.46 mg/L vs median: 0.98 mg/L, IQR: 0.80 to 1.06 mg/L, P 5.001), lower levels of high-density lipoprotein cholesterol (P5.001), higher levels of low-density lipoprotein cholesterol (P5.001), triglyceride (P5.001), total cholesterol (P= .007) and high-sensitivity C-reactive protein (P5.001). No differences occurred in serum concentrations of creatinine or estimated glomerular filtration rate between CHD patients and healthy controls. Multivariate logistic regression indicated that levels of cystatin C (OR, 1.648; 95% confidence interval [CI], 1.454 to 1.868; P5.001) were most strongly correlated with CHD prevalence. Conclusions: Elevated serum cystatin C is a potential biochemical marker for the prediction of CHD, which suggests that mild preclinical renal dysfunction may be associated with the pathogenesis of CHD. [ABSTRACT FROM AUTHOR]

Background: Overweight and obesity are associated with breast cancer mortality. However, the relationship between postdiagnosis weight gain and mortality is unclear. We conducted a systematic review and meta-analysis of weight gain after breast cancer diagnosis and breast cancer-specific, all-cause mortality and recurrence outcomes.Methods: Electronic databases identified articles up through December 2014, including: PubMed (1966-present), EMBASE (1974-present), CINAHL (1982-present), and Web of Science. Language and publication status were unrestricted. Cohort studies and clinical trials measuring weight change after diagnosis and all-cause/breast cancer-specific mortality or recurrence were considered. Participants were women age 18 years or older with stage I-IIIC breast cancer. Fixed effects analysis summarized the association between weight gain (≥5.0% body weight) and all-cause mortality; all tests were two-sided.Results: Twelve studies (n = 23 832) were included. Weight gain (≥5.0%) compared with maintenance (<±5.0%) was associated with increased all-cause mortality (hazard ratio [HR] = 1.12, 95% confidence interval [CI] = 1.03 to 1.22, P = .01, I(2) = 55.0%). Higher risk of mortality was apparent for weight gain ≥10.0% (HR = 1.23, 95% CI = 1.09 to 1.39, P < .001); 5% to 10.0% weight gain was not associated with all-cause mortality (P = .40). The association was not statistically significant for those with a prediagnosis body mass index (BMI) of less than 25 kg/m(2) (HR = 1.14, 95% CI = 0.99 to 1.31, P = .07) or with a BMI of 25 kg/m(2) or higher (HR = 1.00, 95% CI = 0.86 to 1.16, P = .19). Weight gain of 10.0% or more was not associated with hazard of breast cancer-specific mortality (HR = 1.17, 95% CI = 1.00 to 1.38, P = .05).Conclusions: Weight gain after diagnosis of breast cancer is associated with higher all-cause mortality rates compared with maintaining body weight. Adverse effects are greater for weight gains of 10.0% or higher. [ABSTRACT FROM AUTHOR]

Background: Certain factors originating from the perinatal and childhood periods are suspected of contributing to the recent increasing trend of childhood type 1 diabetes (T1D) incidence. This study sought to investigate the relationships between various perinatal and childhood risk factors and T1D incidence in young children (<10 years). Methods: We used a nested case-control design based on 1 478 573 live births born in 2000-05 in Taiwan. Cases were 632 incident cases of T1D between 2000 and 2008. Ten matched controls for each case were randomly selected. Information on various perinatal risk factors was also identified from claim data. Multiple conditional logistic regression was employed to estimate odds ratio (OR) and 95 confidence interval (CI) of T1D. Results: Childhood infection was significantly associated with an increased risk of T1D (OR = 1.46, 95% CI = 1.23-1.73). Increased risk of T1D was also noted in children born to younger mothers (<25 years) (OR = 1.94, 95% CI = 1.34-2.81), older fathers (>30 years) (OR = 1.56 (95% CI = 1.16-2.10) to 1.57 (95% CI = 1.19-2.05), mothers with Caesarean section (CS) (OR = 2.35, 95% CI = 1.52-3.64), and mothers with gestational diabetes mellitus (OR = 4.36, 95% CI =2.76-7.77). Fathers with T1D (OR = 7.36, 95% CI = 1.02-57.21) or type 2 diabetes (OR = 1.54, 95% CI = 1.04-2.26) were observed to substantially increase the risk of offspring T1D. Conclusions: Certain modifiable perinatal factors such as infection and CS may predispose incidence of T1D in young children. [ABSTRACT FROM AUTHOR]

Background. In a previous pilot study, adrenal suppression was found to be common after antiemetic dexamethasone therapy in cancer patients.The objective of this large prospective multicenter study was to confirm the incidence and factors associated with secondary adrenal suppression related to antiemetic dexamethasone therapy in cancer patients receiving chemotherapy. Methods. Chemotherapy-naï ve patients who were scheduled to receive at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Patients with a suppressed adrenal response before chemotherapy or those administered corticosteroids within 6 months of enrollment in the study were excluded. Results. Between October 2010 and August 2014, 481 patients receiving chemotherapy underwent the rapid adrenocortico-tropic hormone (ACTH) stimulation test to assess eligibility; 350 of these patients were included in the final analysis. Fifty-six patients (16.0%) showed a suppressed adrenal response in the rapid ACTH stimulation test at 3 or 6 months after the start of the first chemotherapy. The incidence of adrenal suppression was affected by age, performance status, stage, and use of megestrol acetate in univariate analysis. Multivar-iate analysis revealed that secondary adrenal suppression associated with antiemetic dexamethasone therapy was significantly associated with megestrol acetate treatment (odds ratio: 3.06; 95% confidence interval: 1.60 to 5.86; p < .001). Conclusion. This large prospective study indicates that approximately 15% of cancer patients receiving chemotherapy with a normal adrenal response show suppressed adrenal responses after antiemetic dexamethasone therapy. This result was particularly significant for patients cotreated with megestrol acetate [ABSTRACT FROM AUTHOR]

Background. The survival benefit of combining sorafenib and transarterial chemoembolization (TACE) therapy compared with sorafenib monotherapy for patients with advanced hepatocellular carcinoma (HCC) and main portal vein tumor thrombosis (MPVTT) is unclear. Methods. Between January 2009 and June 2013,183 consecutive patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) and MPVTT were retrospectively reviewed. Of these, 89 patients with advanced HCC and MPVTT were enrolled in this study: 45 were treated with combination therapy (sorafenib-TACE group), and the other 44 treated with sorafenib monotherapy (sorafenib group). Results. The mean number of TACE sessions per patient was 2.6 (range: 1-5). The median duration of sorafenib in the sorafenib-TACE group and sorafenib group was 5.6 months and 5.4 months, respectively. The disease control rate was similar between the two groups. Median time to progression was 3.0 months (95% confidence interval [CI]: 2.2, 3.7) in the sorafenib-TACE group, and 3.0 months (95% CI: 2.1, 3.8) in the sorafenib group (p = .924). Median overall survival was 7.0 months (95% CI: 6.1, 7.8) and 6.0 months (95% CI: 4.7, 7.3) in the sorafenib-TACE group and the sorafenib group, respectively (p = .544). The adverse events related to sorafenib were comparable between the two groups. Twenty-one adverse events of grade 3-4 related to TACE occurred in 12 patients (26.7%), and 2 of them died (4.4%). Conclusion. This study demonstrated no advantage of combination therapy over sorafenib monotherapy. Considering the patients' morbidity after TACE, sorafenib monotherapy is appropriate for managing patients with advanced HCC and MPVTT. [ABSTRACT FROM AUTHOR]

Objective. Lateral epicondylalgia presents as lateral elbow pain provoked by upper limb tasks. An experimental model of elbow pain provoked by movement/ muscle contraction and maintained over several days is required to better understand the mechanisms underlying sustained elbow pain. This study investigated the time course and pain location induced by nerve growth factor (NGF) injection into a wrist extensor muscle, and whether movement and muscle contraction/stretch provoked pain. Methods. On Day 0 twenty-six painfree volunteers were injected with NGF (N513) or isotonic saline (randomized) into the extensor carpi radialis brevis (ECRB) muscle of the dominant arm. On Day 2 pain was induced in all participants by hypertonic saline injection into ECRB. A Likert scale and patientrated tennis elbow evaluation (PRTEE) was used to assess pain and functional limitation (Days 0-10). Pain intensity during contraction/stretch of ECRB, and pressure pain thresholds (PPTs) were recorded before and after injections on Days 0 and 2, and Days 4 and 10. Results. Compared with isotonic saline, NGF evoked: i) greater Likert pain ratings from 12 hours postinjection until Day 6, ii) greater PRTEE scores on Days 2 and 4, iii) greater pain during ECRB contraction/ stretch on Day 2, and iv) lower PPTs on Day 4. Conclusions. This article presents a novel experimental human pain model suitable to study the sustained effects of lateral elbow pain on sensorimotor function and to probe the mechanisms underlying persistent musculoskeletal pain. [ABSTRACT FROM AUTHOR]

Background. Soft tissue massage and exercise are commonly used to treat episodes of shoulder pain. Objective. The study objective was to compare the effects of soft tissue massage and exercise with those of exercise alone on pain, disability, and range of motion in people with nonspecific shoulder pain. Design. This was a randomized controlled trial. Setting. The study was conducted in public hospital physical therapy clinics in Sydney, New South Wales, Australia. Participants. The study participants were 80 people with an average age of 62.6 years (SD=12.2) who were referred to physical therapists for treatment of nonspecific shoulder pain. Intervention. Participants were randomly assigned to either a group that received soft tissue massage around the shoulder and exercises (n=40) or a group that received exercise only (n=40) for 4 weeks. Measurements. The primary outcome was improvement in pain, as measured on a 100-mm visual analog scale, 1 week after the cessation of treatment. Secondary outcomes were disability and active flexion, abduction, and hand-behind-back range of motion. Measurements were obtained at baseline, 1 week after the cessation of treatment, and 12 "weeks after the cessation of treatment. Results. The between-group difference in pain scores from the baseline to 12 weeks after the cessation of treatment demonstrated a small significant difference in favor of the group receiving exercise only (mean difference= 14.7 mm). There were no significant differences between groups in any other variable. Limitations. It was not possible to mask therapists or participants to group allocation. Diagnostic tests were not used on participants to determine specific shoulder pathology. Conclusions. The addition of soft tissue massage to an exercise program for the shoulder conferred no additional benefit for improving pain, disability, or range of motion in people with nonspecific shoulder pain. [ABSTRACT FROM AUTHOR]

Background and objective: previously, a randomised controlled exercise intervention study (RCT) showed that combined resistance and balance-jumping training (COMB) improved physical functioning and bone strength. The purpose of this followup study was to assess whether this exercise intervention had long-lasting effects in reducing injurious falls and fractures. Design: five-year health-care register-based follow-up study after a 1-year, four-arm RCT. Setting: community-dwelling older women in Finland. Subjects: one hundred and forty-five of the original 149 RCT participants; women aged 70-78 years at the beginning. Methods: participants' health-care visits were collected from computerised patient register. An injurious fall was defined as an event in which the subject contacted the health-care professionals or was taken to a hospital, due to a fall. The rate of injured fallers was assessed by Cox proportional hazards model (hazard ratio, HR), and the rate of injurious falls and fractures by Poisson regression (risk ratio, RR). Results: eighty-one injurious falls including 26 fractures occurred during the follow-up. The rate of injured fallers was 62% lower in COMB group compared with the controls (HR 0.38, 95% CI 0.17 to 0.85). In addition, COMB group had 51% less injurious falls (RR 0.49, 95% CI 0.25 to 0.98) and 74% less fractures (RR 0.26, 95% CI 0.07 to 0.97). Conclusions: home-dwelling older women who participated in a 12-month intensive multi-component exercise training showed a reduced incidence for injurious falls during 5-year post-intervention period. Reduction in fractures was also evident. These long-term effects need to be confirmed in future studies. [ABSTRACT FROM AUTHOR]

Background: while there is a trend towards a compression of disability, secular trends in physiological frailty have not been investigated. The aim of this paper was to report physiological frailty in two cohorts of 75-year olds examined in 1987 and 2005. Methods: a repeated cross-sectional study. Two population-based birth cohorts of community-dwelling 75-year olds from Gothenburg, Sweden, born in 1911-12 (n = 591) and 1930 (n = 637) were examined with identical methods in 1987 and 2005. Measures were three frailty criteria from Fried's frailty phenotype: low physical activity, slow gait speed and self-reported exhaustion. Results: seventy-five-year olds examined in 2005 were less frail according to the criteria low physical activity compared with those examined in 1987 (3 versus 18%, P < 0.001).This was seen both in women and in men, and among those with basic and more than basic educational level. Further, men with basic education were less frail in 2005 compared with those in 1987 in slow gait speed (non-significant when adjusted for body height) and low self-rated fitness, while no cohort differences were seen in men with more than basic education. Women with more than basic education were less frail in 2005 compared with those in 1987 in slow gait speed and self-rated fitness, while no cohort difference was seen in women with basic education. Conclusion: less 75-year olds were physiologically frail in 2005 compared with those in 1987, with the exception of women with low educational level, suggesting that this is a disadvantaged group that needs to receive particular attention with regard to physiological frailty. [ABSTRACT FROM AUTHOR]

Background: Violence in the workplace is a serious social and public health problem. The objective of this study was to estimate the prevalence of workplace violence and to identify potential predictors of workplace violence at Serbian Primary Health Care (PHC) centres. Methods: A cross-sectional study was conducted between October 2012 and July 2013. The sample consisted of medical and non-medical staff employed at PHC centres in Belgrade, Serbia. Among 1757 currently presented at work, 1526 returned the questionnaires. The data were collected by questionnaire Workplace Violence in the Health Sector—Country Case Studies, developed by the ILO/ICN/WHO/PSI. Binary logistic regression was conducted to assess the association between exposure to workplace violence and sociodemographic and work-related characteristics. Results: The prevalence of workplace violence, was 803 (52.6%), with 147 (18.3%), exposed to physical violence. Multiple logistic regression models indicated that the following work-related characteristics were positive associated of workplace violence with working between 18:00 and 07:00 h [odds ratio (OR): 1.37, 95% confidence interval (CI): 1.08-1.73], nurses as a professional group (OR: 1.91, 95% CI: 1.16-3.17), working with preschool children (OR: 0.56, 95% CI: 0.34-0.91). There was negative association of workplace violence with encouragement to report violence (OR: 0.61, 95% CI: 0.49-0.76) and the number of staff in the same work setting (OR: 0.73, 95% CI: 0.56-0.96). Conclusions: More than half of employees in Belgrade PHC centres were exposed to different types of workplace violence. There is a need for interventions to protect health workers and provide safer workplace environments. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) is an important and priority public health problem globally. Long working hours have been proposed as a modifiable risk factor for MetS, despite sparse epidemiological evidence. Thus, the aim of this study was to prospectively evaluate the associations between working hours and incidence of MetS and each of its components. Methods: We assessed 6845 participants of a Spanish dynamic prospective cohort of university graduates (the SUN project), initially free of any specific criteria of MetS, and followed-up for a median of 8.3 years. Weekly working hours were collected at baseline and grouped into four categories: >0-24, 25-39, 40-49 and ≥50 h. MetS was defined according to the updated harmonizing criteria. We estimated multivariable adjusted Relative Risks (RR) of MetS and their 95% Confidence Intervals (95% CI), using Poisson regression models. Results: The cumulative incidence of MetS was 6.0%. Working hours were not independently related to MetS (25-39 h/week = RR: 1.42, 95% CI 0.90-2.25; 40-49 h/week = RR: 1.45, 95% CI 0.91-2.30; ≥50 h/week = RR: 1.49, 95% CI 0.91-2.42, P for trend = 0.235) nor to any of its individual definition criteria. Conclusion: Our findings do not suggest that long working hours increase the risk of MetS development or each of its components. Further longitudinal studies in general population should be conducted to confirm these results. [ABSTRACT FROM AUTHOR]