Evaluation of U.S. Army Soldiers wearing a back exosuit during a field training exercise.

Back overuse injuries are a significant problem in the U.S. Army, responsible for nearly a quarter of musculoskeletal injuries. Back exosuits are wearable devices that relieve musculoskeletal strain, make lifting easier, and could potentially reduce Soldier overuse injuries. But published studies have not evaluated exosuits during realistic field operations to assess acceptability to Soldiers. We tested a back exosuit on field artillery Soldiers during a field training exercise. Afterward, Soldiers completed a survey to quantify their satisfaction, intent to use, and performance impact of the exosuit. Feedback was overwhelmingly positive: Approximately 90% of Soldiers reported that exosuits increased their ability to perform their duties, and 100% said that if the exosuit were further developed and made available to them, they would be likely to wear it. These numerical survey results indicated that exosuits can provide a practical and acceptable way to assist lifting and augment physical performance during realistic Army operations without interfering with other duties.

Selecting Patients with Favorable Risk, Grade Group 2 Prostate Cancer for Active Surveillance-Does Magnetic Resonance Imaging Have a Role?

PURPOSE: The National Comprehensive Cancer Network® recommends that selected men with grade group 2 prostate cancer be considered for active surveillance. However, selecting which patients with grade group 2 disease can be safely managed by active surveillance remains controversial. The aim of this study was to evaluate the association of multiparametric magnetic resonance imaging with adverse pathology in the radical prostatectomy specimen of men with favorable risk grade group 2 prostate cancer, which could help select patients for active surveillance. MATERIALS AND METHODS: We retrospectively analyzed a cohort of patients with favorable grade group 2 disease who underwent radical prostatectomy between 2010 and 2019. Preoperative multiparametric magnetic resonance imaging was scored as negative (no identifiable lesion), positive (identifiable lesion) or equivocal. We defined a multivariable logistic regression model with multiparametric magnetic resonance imaging score as the predictor and adverse pathology (up staging to T3a/b disease, upgrading to ≥grade group 3 or lymph node invasion) as the outcome, adjusting for preoperative prostate specific antigen, biopsy Gleason grade, clinical stage, and number of negative and positive prostate biopsy cores. Secondary outcomes of biochemical recurrence, grade group upgrading alone and the added value of incorporating multiparametric magnetic resonance imaging data into the nomogram were also investigated. RESULTS: We identified 1,117 patients with favorable risk grade group 2 disease who underwent radical prostatectomy. Positive multiparametric magnetic resonance imaging was associated with higher rates of adverse pathology (OR 2.55, 95% CI 1.75-3.40, p <0.0001) and upgrading (OR 3.89, 95% CI 2.00-7.56, p <0.0001). However, as our study included only grade group 2 patients who underwent radical prostatectomy, our cohort may represent a higher risk group than grade group 2 patients as a whole. Adding multiparametric magnetic resonance imaging results to a standard prediction model led to higher net benefit on decision curve analysis. An identifiable lesion on multiparametric magnetic resonance imaging was associated with an increased risk of aggressive pathological features in the radical prostatectomy specimen of patients with favorable risk grade group 2 prostate cancer who were potential active surveillance candidates. This information could be used to inform biopsy strategy, counsel patients on treatment options and guide strategies for those on active surveillance. CONCLUSIONS: Combining multiple magnetic resonance imaging modalities (multiparametric magnetic resonance imaging) provides a more accurate prediction of the risk presented by prostate cancer than current prediction methods. In this study, positive magnetic resonance imaging results approximately doubled the chances that a patient with favorable risk prostate cancer would be found to have adverse pathology when their prostate was removed. Thus, multiparametric magnetic resonance imaging could help select patients with favorable risk cancer who may be good candidates for active surveillance, and help guide biopsy and surveillance strategies for such patients.

Updated prostate imaging reporting and data system (PIRADS v2) recommendations for the detection of clinically significant prostate cancer using multiparametric MRI: critical evaluation using whole-mount pathology as standard of reference.

OBJECTIVES: To evaluate the recommendations for multiparametric prostate MRI (mp-MRI) interpretation introduced in the recently updated Prostate Imaging Reporting and Data System version 2 (PI-RADSv2), and investigate the impact of pathologic tumour volume on prostate cancer (PCa) detectability on mpMRI. METHODS: This was an institutional review board (IRB)-approved, retrospective study of 150 PCa patients who underwent mp-MRI before prostatectomy; 169 tumours ≥0.5-mL (any Gleason Score [GS]) and 37 tumours <0.5-mL (GS ≥4+3) identified on whole-mount pathology maps were located on mp-MRI consisting of T2-weighted imaging (T2WI), diffusion-weighted (DW)-MRI, and dynamic contrast-enhanced (DCE)-MRI. Corresponding PI-RADSv2 scores were assigned on each sequence and combined as recommended by PI-RADSv2. We calculated the proportion of PCa foci on whole-mount pathology correctly identified with PI-RADSv2 (dichotomized scores 1-3 vs. 4-5), stratified by pathologic tumour volume. RESULTS: PI-RADSv2 allowed correct identification of 118/125 (94 %; 95 %CI: 90-99 %) peripheral zone (PZ) and 42/44 (95 %; 95 %CI: 89-100 %) transition zone (TZ) tumours ≥0.5 mL, but only 7/27 (26 %; 95 %CI: 10-42 %) PZ and 2/10 (20 %; 95 %CI: 0-52 %) TZ tumours with a GS ≥4+3, but <0.5 mL. DCE-MRI aided detection of 4/125 PZ tumours ≥0.5 mL and 0/27 PZ tumours <0.5 mL. CONCLUSIONS: PI-RADSv2 correctly identified 94-95 % of PCa foci ≥0.5 mL, but was limited for the assessment of GS ≥4+3 tumours ≤0.5 mL. DCE-MRI offered limited added value to T2WI+DW-MRI. KEY POINTS: • PI-RADSv2 correctly identified 95 % of PCa foci ≥0.5 mL • PI-RADSv2 was limited for the assessment of GS ≥4+3 tumours ≤0.5 mL • DCE-MRI offered limited added value to T2WI+DW-MRI.

The use of granulocyte colony-stimulating factors in a Canadian outpatient setting.

BACKGROUND: Data on real-life utilization of granulocyte colony-stimulating factors (g-csfs) in Canada are limited. The objective of the present study was to describe the reasons for, and the patterns of, g-csf use in selected outpatient oncology clinics in Ontario and Quebec. METHODS: In a retrospective longitudinal cohort study, a review of medical records from 9 Canadian oncology clinics identified patients being prescribed filgrastim (fil) and pegfilgrastim (peg). Patient characteristics, reasons for g-csf use, and treatment patterns were descriptively analyzed. RESULTS: Medical records of 395 patients initiating g-csf therapy between January 2008 and January 2009 were included. Of this population, 80% were women, and breast cancer was the predominant diagnosis (59%). The most commonly prescribed g-csf was fil (56% in Ontario and 98% in Quebec). The most frequent reason for g-csf use was primary prophylaxis (42% for both fil and peg), followed by secondary prophylaxis (37% fil, 41% peg). Those proportions varied by tumour type and chemotherapy regimen. Delayed g-csf administration (more than 1 day after the end of chemotherapy) was frequently observed for fil, but rarely reported for peg, and that finding was consistent across tumours and concurrent chemotherapy regimens. CONCLUSIONS: The use of g-csf varies with the malignancy type and the provincial health care setting. The most commonly prescribed g-csf agent was fil, and most first g-csf prescriptions were for primary prophylaxis. Delays were frequently observed for patients receiving fil, but were rarely reported for those receiving peg.

Association between osteoporosis treatment change and adherence, incident fracture, and total healthcare costs in a Medicare Advantage Prescription Drug plan.

UNLABELLED: We examined the association between osteoporosis treatment change and adherence, incident fractures, and healthcare costs among Medicare Advantage Prescription Drug (MAPD) plan members. Treatment change was associated with a small but significant increase in adherence, but was not associated with incident fracture or total healthcare costs. Overall adherence remained low. INTRODUCTION: We examined the association between osteoporosis treatment change and adherence, incident fractures, and healthcare costs among MAPD plan members in a large US health plan. METHODS: We conducted a retrospective cohort study of MAPD plan members aged≥50 years newly initiated on an osteoporosis medication between 1 January 2006 and 31 December 2008. Members were identified as having or not having an osteoporosis treatment change within 12 months after initiating osteoporosis medication. Logistic regression analyses and difference-in-difference (DID) generalized linear models were used to investigate the association between osteoporosis treatment change and (1) adherence to treatment, (2) incident fracture, and (3) healthcare costs at 12 and 24 months follow-up. RESULTS: Of the 33,823 members newly initiated on osteoporosis treatment, 3,573 (10.6%) changed osteoporosis treatment within 12 months. After controlling for covariates, osteoporosis treatment change was associated with significantly higher odds of being adherent (medication possession ratio [MPR]≥0.8) at 12 months (odds ratio [OR]=1.18) and 24 months (OR=1.13) follow-up. However, overall adherence remained low (MPR=0.59 and 0.51 for the change cohort and MPR=0.51 and 0.44 for the no-change cohort at 12 and 24 months, respectively). Osteoporosis treatment change was not significantly associated with incident fracture (OR=1.00 at 12 months and OR=0.98 at 24 months) or total direct healthcare costs (p>0.4) in the DID analysis, but was associated with higher pharmacy costs (p<0.004). CONCLUSIONS: Osteoporosis treatment change was associated with a small but significant increase in adherence, but was not associated with incident fracture or total healthcare costs in the MAPD plan population. Overall adherence to therapy remained low.

Effect of androgen deprivation therapy on the expression of prostate cancer biomarkers MSMB and MSMB-binding protein CRISP3.

We have investigated the effects of short-term neoadjuvant and long-term androgen deprivation therapies (ADTs) on ß-microseminoprotein (MSMB) and cysteine-rich secretory protein-3 (CRISP3) expression in prostate cancer patients. We also studied if MSMB expression was related to genotype and epigenetic silencing. Using an Affymetrix cDNA microarray analysis, we investigated the expression of MSMB, CRISP3, androgen receptor (AR), KLK3 and Enhancer of Zeste Homologue-2 (EZH2) in tissue from prostate cancer patients receiving (n=17) or not receiving (n=23) ADT before radical prostatectomy. MSMB, CRISP3 and AR were studied in tissue from the same patients undergoing TURP before and during ADT (n=16). MSMB genotyping of these patients was performed by TaqMan PCR. MSMB and KLK3 expression levels decreased during ADT. Expression levels of AR and CRISP3 were not affected by short-term ADT but were high in castration-resistant prostate cancer (CRPC) and metastases. Levels of EZH2 were also high in metastases, where MSMB was low. Genotyping of the MSMB rs10993994 polymorphism showed that the TT genotype conveys poor MSMB expression. MSMB expression is influenced by androgens, but also by genotype and epigenetic silencing. AR and CRISP3 expression are not influenced by short-term ADT, and high levels were found in CRPC and metastases.

Genomic aberrations are rare in urothelial neoplasms of patients 19 years or younger.

Urothelial neoplasms in patients 19 years of age or younger are rare, and the data regarding clinical outcome are conflicting. Molecular data are not available. Urothelial tumours from 14 patients aged 4 to 19 years were analysed, including FGFR3 and TP53 mutation screening, comparative genomic hybridization (CGH), UroVysion FISH analysis, polymerase chain reaction for human papillomavirus (HPV), microsatellite analysis using the NIH consensus panel for detection of microsatellite instability (MSI) and six markers for loss of heterozygosity on chromosome arms 9p, 9q, and 17p and immunohistochemistry for TP53, Ki-67, CK20 and the mismatch repair proteins (MRPs) hMSH2, hMLH1, and hMSH6. Based on the 2004 WHO classification, one urothelial papilloma, seven papillary urothelial neoplasms of low malignant potential (PUNLMPs), five low-grade, and one high-grade papillary urothelial carcinoma were included. No multifocal tumours were found and recurrence was seen in only one patient with a urothelial papilloma. All patients were alive with no evidence of disease at a median follow-up of 3.0 years. We found no mutations in FGFR3, deletions of chromosome arms 9p, 9q or 17p, MSI or MRP loss, or HPV positivity in any of the patients. Three cases showed chromosome alterations in CGH analyses, urothelial dedifferentiation with CK20 overexpression, or aneuploidy, and one TP53 mutation with TP53 overexpression was found. Urothelial neoplasms in people younger than 20 years are predominantly low grade and are associated with a favourable clinical outcome. Genetic alterations frequently seen in older adults are extremely rare in young patients. Urothelial neoplasms in children and young adults appear to be biologically distinct and lack genetic instability in most cases.

Hepatosplenic gamma/delta T-cell lymphoma masquerading as alcoholic hepatitis and methadone withdrawal.

Hepatosplenic gamma/delta T-cell lymphoma is a rare neoplasm of mature gamma/delta T-cells with sinusoidal infiltration of spleen, liver, and bone marrow. Patients are predominantly adolescent and young adult males and usually present with marked hepatosplenomegaly. Pancytopenia is another common finding. Despite an initial response to treatment, patients have a median survival of one to two years. In this report, we document a case of alcoholic hepatitis and methadone withdrawal masquerading unsuspected, hepatosplenic gamma/delta T-cell lymphoma with unusual CD20 positivity.

Agreement between parent and child report of quality of life in children with attention-deficit/hyperactivity disorder.

BACKGROUND: There is little information in the research literature of agreement between parent and child in reports of child quality of life (QOL) for a sample of children diagnosed with attention-deficit/hyperactivity disorder (ADHD). The aim of our study was to determine whether parent and child concordance is greater for physical domains of QOL than for psychosocial domains; whether parents rate their child's QOL better or poorer than their child's ratings; and whether concordance is related to demographic, socioeconomic or clinical factors. METHODS: The study was a questionnaire survey of children aged 10-17 referred to the ADHD clinic and diagnosed with ADHD in the province of British Columbia (Canada) between November 2001 and October 2002 and their parent. RESULTS: Fifty-eight children diagnosed with ADHD and their parents completed our study questionnaire. The main outcome measure was the Child Health Questionnaire, which permitted comparisons on eight QOL domains and one single item. Intraclass correlation coefficients were moderate for five domains (range from 0.40 to 0.51), and good for three domains (range from 0.60 to 0.75). Children rated their QOL significantly better than their parents in four areas and poorer in one. Standardized Response Means indicated clinically important differences in mean scores for Behaviour and Self-esteem. Compared with population norms, across most domains, children with ADHD reported comparable health. Discrepancies between parent-child ratings were related to the presence of a comorbid oppositional/defiant disorder, a psychosocial stressor and increased ADHD symptoms. CONCLUSIONS: Although self-report is an important means of eliciting QOL data, in children with ADHD, given the discrepancies in this study between parent and child report, measuring both perspectives seems appropriate.

Treatment choices and experiences in attention deficit and hyperactivity disorder: relations to parents' beliefs and attributions.

BACKGROUND: Despite their potential to influence treatment decisions, parents' beliefs and attitudes regarding attention deficit hyperactivity disorder (ADHD) have not been widely studied. This research examined relations between parents' beliefs and attitudes and their experiences with different treatments for their children's ADHD. METHODS: Canadian parents of 73, 5- to 13-year-old, boys with ADHD completed questionnaires measuring beliefs about ADHD, attributions for ADHD behaviours, and treatment experiences. RESULTS: Parents reported using primarily behaviour management and stimulant medications in treating ADHD. Approximately half of the families also used diet/vitamin therapies. Parents were knowledgeable about ADHD and held generally accurate beliefs. They saw ADHD symptoms as predominantly internal to the child and as relatively enduring and pervasive. Parents' beliefs were related to their use of different treatments and parents who used less empirically supported treatments were more likely to see ADHD behaviours as internal to the child, enduring and pervasive. CONCLUSIONS: The findings highlight the importance of assessing parents' use of alternate treatments for ADHD and the potential role of parents' beliefs and attributions in shaping treatment choices.

Electrochemical behavior of nitinol alloy in Ringer's solution.

Corrosion behavior of Nitinol (nickel titanium) alloy has been examined in physiological Ringer's solution by means of electrochemical techniques (open-circuit potential measurement, potentiodynamic and potentiostatic polarizations) and capacitance measurements. The results show that the passive film is stable at open-circuit condition, but many of anodic current transients are observed at potentiodynamic and potentiostatic polarizations. The thickness of passive film decreased because of the occurrence of dissolution.

The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, II: characteristics of patients enrolled and not enrolled. COMS Report No. 17.

OBJECTIVES: To describe characteristics of patients evaluated for the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy for choroidal melanoma by enrollment status, and to compare characteristics of patients enrolled with those of patients with tumors of eligible size who did not enroll in order to assess the extent to which findings from the clinical trial can be generalized to future patients. METHODS: For all patients diagnosed with choroidal melanoma and evaluated for the clinical trial at COMS centers from November 1986 through July 31, 1998, selected data were transmitted to the COMS Coordinating Center, Baltimore, Md, where they were integrated and analyzed. Data included ophthalmic and medical history, examination findings, and visual acuity measurements recorded prior to enrollment; standardized A- and B-scan echographic examination findings; and wide-angle fundus photographs and fluorescein angiograms. RESULTS: Of 8712 patients with choroidal melanoma, 5046 had tumors of eligible size; of these, 2882 (57%) were eligible for enrollment, and 1317 (46% of eligible patients, 26% of patients with tumors of eligible size) enrolled. Most differences between eligible and ineligible patients corresponded to eligibility and exclusion criteria. However, ineligible patients were older and had thicker tumors than eligible patients. Eligible patients who enrolled were slightly older and had larger tumors than those who did not enroll. Nearly half (48%) of enrolled patients had choroidal melanoma with the apex located temporal to the fovea, compared with 40% of eligible patients not enrolled and 29% of ineligible patients. CONCLUSIONS: This trial was designed to yield internally valid treatment comparisons through random assignment to treatment at time of enrollment. Information from this and other studies document that enrolled patients were similar to other patients with choroidal melanoma who were treated with 125I brachytherapy. These findings support the external validity of the trial and applicability of treatment findings to all patients who meet the criteria used to judge eligibility for the trial.

The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18.

OBJECTIVES: To report initial mortality findings from the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy vs enucleation for treatment of choroidal melanoma. METHODS: Patients were evaluated for eligibility at 43 participating clinical centers in the United States and Canada. Eligible consenting patients were assigned randomly at the time of enrollment to enucleation or 125I brachytherapy. Patients were examined at specified intervals after enrollment for data collection purposes. Findings presented herein are based on data received by September 30, 2000. Data for each patient were analyzed with the treatment group to which the patient was assigned randomly at the time of enrollment. RESULTS: During the 11(1/2)-year accrual period, 1317 patients enrolled; 660 were assigned randomly to enucleation and 657 to 125I brachytherapy. Only 2 patients in the enucleation arm were found to have been misdiagnosed when histopathology was reviewed centrally. All but 17 patients (1.3%) received the assigned treatment. Adherence to the brachytherapy protocol was excellent, with 91% of patients treated per protocol. Based on time since enrollment, 1072 patients (81%) had been followed for mortality for 5 years and 416 (32%) for 10 years. A total of 364 patients had died: 188 (28%) of 660 patients in the enucleation arm and 176 (27%) of 657 patients in the brachytherapy arm. The unadjusted estimated 5-year survival rates were 81% and 82%, respectively; there was no clinically or statistically significant difference in survival rates overall (P =.48, log-rank test). The adjusted estimated risk ratio for 125I brachytherapy vs enucleation was 0.99 (95% confidence interval [CI], 0.80-1.22). Five-year rates of death with histopathologically confirmed melanoma metastasis were 11% and 9% following enucleation and brachytherapy, respectively; after adjustment, the estimated risk ratio was 0.91 (95% CI, 0.66-1.24). CONCLUSIONS: Mortality rates following 125I brachytherapy did not differ from mortality rates following enucleation for up to 12 years after treatment of patients with choroidal melanoma who enrolled in this COMS trial. The power of the study was sufficient to indicate that neither treatment is likely to increase or decrease mortality rates by as much as 25% relative to the other.

CT appearance of some colonic villous tumors.

OBJECTIVE: A review was made of the CT studies and pathology reports of four patients with surgically resected colonic villous adenomatous tumors, two of whom had focal carcinomatous invasion. CONCLUSION: Two patients had villous tumors with IV contrast-enhancing convolutional gyral patterns. The other two patients had tumor masses that showed oral contrast medium collecting in surface interstices, analogous to findings with barium enemas. One of the latter also had an unusual cluster of mesenteric vessels adjacent to the lesion.

Elevated expression of caveolin-1 in adenocarcinoma of the colon.

Caveolins 1, 2, and 3 are the principal proteins of caveolae, the vesicular invaginations of the plasma membrane. Several reports have suggested that caveolin-1 may have a role in cellular transformation and tumorigenesis. We studied the expression of caveolin-1 and caveolin-2 in normal epithelium, adenoma, and adenocarcinoma of the colon and their possible role in tumorigenesis. Formalin-fixed, paraffin-embedded sections of 41 cases of adenocarcinoma and 13 cases of adenoma of the colon were stained immunohistochemically with anti-caveolin-1 and anti-caveolin-2 antibodies. The expression of caveolin-1 was elevated in the overwhelming majority of the adenocarcinomas, while most normal colonic epithelium and adenomas showed little or no staining. There was significant statistical correlation of the expression of caveolin-1 with adenocarcinoma but not with tumor stage. Expression of caveolin-2 was undetectable in all of the normal colonic glands, adenomas, and carcinomas. We discuss the possible clinical implications of our findings within the context of caveolins and signal transduction.

Emotion knowledge as a predictor of social behavior and academic competence in children at risk.

Following leads from differential emotions theory and empirical research, we evaluated an index of emotion knowledge as a long-term predictor of positive and negative social behavior and academic competence in a sample of children from economically disadvantaged families (N = 72). The index of emotion knowledge represents the child's ability to recognize and label emotion expressions. We administered control and predictor measures when the children were 5 years old and obtained criterion data at age 9. After controlling for verbal ability and temperament, our index of emotion knowledge predicted aggregate indices of positive and negative social behavior and academic competence. Path analysis showed that emotion knowledge mediated the effect of verbal ability on academic competence. We argue that the ability to detect and label emotion cues facilitates positive social interactions and that a deficit in this ability contributes to behavioral and learning problems. Our findings have implications for primary prevention.

Intracoronary delivery of adenovirus encoding adenylyl cyclase VI increases left ventricular function and cAMP-generating capacity.

BACKGROUND: We tested the hypothesis that intracoronary injection of a recombinant adenovirus encoding adenylyl cyclase type VI (AC(VI)) would increase cardiac function in pigs. METHODS AND RESULTS: Left ventricular (LV) dP/dt and cardiac output in response to isoproterenol and NKH477 stimulation were assessed in normal pigs before and 12 days after intracoronary delivery of histamine followed by intracoronary delivery of an adenovirus encoding lacZ (control) or AC(VI) (1.4x10(12) vp). Animals that had received AC(VI) gene transfer showed increases in peak LV dP/dt (average increase of 1267+/-807 mm Hg/s; P=0.0002) and cardiac output (average increase of 39+/-20 mL. kg(-1). min(-1); P<0.0001); control animals showed no changes. Increased LV dP/dt was evident 6 days after gene transfer and persisted for at least 57 days. Basal heart rate, blood pressure, and LV dP/dt were unchanged, despite changes in cardiac responsiveness to catecholamine stimulation. Twenty-three hour ECG recordings showed no change in mean heart rate or ectopic beats and no arrhythmias. LV homogenates from animals receiving AC(VI) gene transfer showed increased AC(VI) protein content (P=0.0007) and stimulated cAMP production (P=0.0006), confirming transgene expression and function; basal LV AC activity was unchanged. Increased cAMP-generating capacity persisted for at least 18 weeks (P<0.0002). CONCLUSIONS: Intracoronary injection of a recombinant adenovirus encoding AC provides enduring increases in cardiac function.