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There is significant uncertainty about the potential role of temperature control in the intensive care unit (ICU) in general, but more specifically in septic shock patients.1,2 Common techniques for temperature control have been limited by minimal effect (eg, paracetamol, fans or air blankets), undesirable side effects (eg, non-steroidal anti-inflammatories), or being burdensome (eg, heavy sedation, paralysis with surface cooling; intravascular cooling devices3). In contrast, the potential of newer-generation surface-cooling devices to achieve temperature control more simply has created the possibility of studying temperature modulation in the septic ICU population.

To determine the association between relationship distress and menopausal symptoms.A retrospective analysis was conducted of questionnaires completed by women 40-65 years of age seeking menopause or sexual health consultation between May, 2015 and May, 2017.Associations between menopausal symptoms assessed using the Menopause Rating Scale (MRS) and relationship distress measured on the Kansas Marital Satisfaction Scale (KMSS) were evaluated with two-sample t-tests. Linear regression was used to assess associations after adjusting for potential confounders.The sample of 1884 women averaged 53 years of age (SD = 6.1); most were white (95%), employed (66%), married (90%), and well-educated (≥ college graduate, 64%). Women reporting no relationship distress (KMSS ≥ 17) had less severe menopausal symptoms overall compared with women reporting relationship distress (total MRS score 13.1 vs 16.0, P 0.001), with similar findings in each MRS domain. In multivariable analyses, this relationship persisted for total MRS scores and for psychological symptoms among women with no relationship distress, who scored an estimated 1.15 points (95% CI 0.52-1.78) lower on the total MRS and 0.82 points (95% CI 0.53-1.10) lower in the psychological symptom.The absence of relationship distress was associated with less severe menopausal symptoms, particularly in the psychological domain, in women presenting to a women's health clinic. Given the cross = sectional design, the direction of the relationship is unknown.

Background & Aims Patients with cirrhosis are growing older. The overlap between minimal hepatic encephalopathy (MHE) and predementia mild cognitive impairment (MCI) could affect quality of life (QOL). We investigated the performance of elderly patients with cirrhosis on tests for MHE and MCI and their effects on QOL. Methods We recruited outpatients with cirrhosis (n = 109) and without cirrhosis (controls, n = 100), 65 years or older, at 4 centers (derivation cohort). All study participants were assessed for psychometric hepatic encephalopathy score (PHES), EncephalApp score, and QOL. MCI was tested in patients with cirrhosis using the repeatable battery for assessment of neuropsychological status and assigned to the following groups: unimpaired, MCI only, MHE only, and MCI+MHE. We created adjusted norms to detect MHE using PHES and EncephalApp scores from the controls. Findings were validated using data from a separate cohort of 77 patients with cirrhosis (mean age, 69.49 ± 4.36 y; 72% men) at the same study sites. Results Controls were older but were more educated, performed better cognitively, and had better QOL. Among patients with cirrhosis, age, education, model for end-stage liver disease score, EncephalApp score, and QOL were similar, but PHES and repeatable battery for assessment of neuropsychological status differed among sites. In the derivation cohort, the presence of MHE, with or without MCI, was associated with poor QOL, which was lowest in the MCI+MHE group. When we adjusted for age, sex, and education, 49% of patients with cirrhosis had MHE based on the EncephalApp and 8% had MHE based on the PHES. A similar pattern (49% MHE based on EncephalApp and 6% MHE based on PHES) was found in a validation cohort. Conclusions In a multicenter study of patients with cirrhosis (>65 y) and controls, the presence of MHE, regardless of MCI, was associated with poor cognition and QOL. We created adjusted norms that defined the high sensitivity of EncephalApp for the detection of MHE in older individuals and validated it in a separate cohort.

Approximately 50% of older adults receiving care at VA are Veterans with chronic pain (V-CP). While physical activity can reduce chronic pain and increase mobility, little is known about group exercise (GE) effects for V-CP. We hypothesized that attrition may limit GE effectiveness. In this study, we retrospectively compared program attrition and participant mobility at three-months of Gerofit GE. At baseline, Older V-CP (N=21) had lower mobility assessment scores (gait speed, 6MW, chair stands, TUG: 1.04 m/s, 443 yd, 11, 9.35s vs. 1.09 m/s, 463 yd, 12, 8.19s respectively) compared to unaffected Veterans. Three-month attrition was higher for older V-CP (54% vs 39%). For those completing three months GE, gains in mobility were similar. We conclude that Veterans with chronic pain are less likely to persist in group exercise but those who persist benefit much like those without pain. Further study is needed to understand successful exercise adherence.

Background & Aims Inpatients with cirrhosis are prone to develop acute-on-chronic liver failure (ACLF). ACLF is associated with dysbiosis of the intestinal microbiota, which might serve as a prognostic factor. We investigated whether features of the intestinal microbiota associate organ failure, transfer to intensive care, and mortality within 30 days in patients admitted to the hospital with cirrhosis. Methods Stool samples were collected from 181 patients with cirrhosis (age 56 years; mean model for end-stage liver disease score, 21; 43% with infections) at time of admission, from multiple hospitals in North America. Patients were followed for 30 days for development of ACLF, extra-hepatic organ failures, and death or hospice care. Microbiota were analyzed by 16s rRNA sequencing for alpha diversity (within groups), beta diversity (between groups), cirrhosis dysbiosis ratio (CDR), and taxa that differed between groups with vs without negative outcomes (individual organ failures, transfer to intensive care, ACLF, death, or hospice). Regression analyses were performed using microbial and clinical variables for each outcome. Results ACLF developed in 8% of study subjects; 16% were transferred to intensive care and 21% died. Beta diversity of the intestinal microbiome was significantly different, whereas alpha diversity was similar, between subjects with vs without outcomes. The CDR was lower in subjects who developed ACLF, especially among those with renal failure. Taxa belonging to phylum Proteobacteria (Enterobacteriaceae, Campylobacteriaceae, and Pasteurellaceae) and Firmicutes (Enterococcaceae and Streptococcaceae) were associated with development of negative outcomes, whereas other Firmicutes members (Lachnospiraceae and Clostridiales) reduced risk of negative outcomes. Changes in the microbiota associated with extra-hepatic organ failure, transfer to intensive care, ACLF, and death, independently on logistic regression analyses. Conclusion In hospitalized patients with cirrhosis, dysbiosis of the intestinal microbiota on admission (particularly changes in Protebacteria constituents) associates with increased risk of extra-hepatic organ failure, ACLF, and death, independent of clinical factors. Strategies to reduce gut dysbiosis might improve outcomes of patients with cirrhosis.

While conducting a larger project along the continental shelf off central California in June 2006, we encountered a large patch of sea whips (Halipteris willemoesi) in an area that was actively fished by vessels using otter trawls. A total of 10 transects were conducted using a remotely operated vehicle (ROV) to collect video imagery of seafloor communities. Video records allowed us to quantify sea whip density and to calculate the densities of upright and damaged or broken sea whips. Though the transects were sited within a dense aggregation of trawl tracks, we recorded significant variability in sea whip densities across transects. While subtle differences in water depth among transects may have contributed to the variability in sea whip density, we suggest that the distribution of trawling effort is a more likely explanation.

Background:Centers for Disease Control (CDC) data suggest that Latinos are less likely to be physically active and more likely to be overweight and suffer from resulting complications than are Whites and that within the Latino population, Latina women are especially at risk. Therefore, promoting physical activity among Latinos, and understanding gender participation patterns within that population, is particularly important. One strategy for encouraging physical activity is to promote active uses of public parks.Methods:A national, multiyear, multisite study funded by the USDA Forest Service sought to understand use of public parks by Latinos and Latinas in Los Angeles, Minneapolis, and Chicago.Results:More than 50% of our sample visited parks to engage in physical activity, and in part, activity choice was related to gender. Furthermore, nearly half of all respondents walked to city park sites, whereas few or none walked to state or regional park sites.Conclusions:Our data suggest that Latinos are using some parks repeatedly and, in the case of city parks, are using them for physical as well as social activity. Therefore, we suggest specific ways that parks could be managed to encourage more physical activity while taking into account gender variations.

OBJECTIVE To describe an association between renal cell carcinoma (RCC) and multiple myeloma (MM) in patients with both disorders, and suggest possible explanations for the association. PATIENTS AND METHODS We retrospectively reviewed the records of patients with MM and RCC at the Cleveland Clinic between 1990 and 2005, and identified 1100 with MM, 2704 with RCC and eight with concomitant MM and RCC. The medical records of these eight patients were reviewed. RESULTS In four of the eight patients, RCC was diagnosed after the MM at 3, 8, 23 and 46 months, respectively; in the remaining four, the RCC was diagnosed before MM by 108, 35, 13 and 1 months, respectively. The number of cases of RCC expected in the present 1100 patients with MM over 15 years was lower than the four recorded (P

Women's leisure time sport participation was examined in relation to resistance, bodies and community. Fifteen interviews were conducted with participants and coaches in two all-women's triathlon training groups in Austin, Texas. Qualitative methods and grounded theory guided the interviewing and data analyses. The results indicate that all-women's leisure time sport groups are capable of providing an atmosphere for women, particularly sport novices, to recreate and reappropriate their bodies and their sport.

Clonotypic B lymphocytes may underlie relapse of patients with multiple myeloma. Rituximab, a CD20 monoclonal antibody, may result in eradication of the monoclonal B cells. We conducted a phase II study of rituximab in combination with melphalan and prednisone therapy (MP) followed by rituximab maintenance in newly diagnosed multiple myeloma patients. Sixteen patients (35%) had CD20 positive bone marrow plasma cells, while 9 patients (20%) had unknown CD20 status. No patient had a complete remission, 26 patients (58%) had a partial response, 6 patients (13%) had a minimal response, and 8 patients (18%) had stable disease. The median event-free survival was 14 months, and the 7-year overall survival was 30%. The toxicity of the combination was overall manageable and consistent with what is generally noted with MP chemotherapy. The combination of rituximab to MP therapy did not result in improved response rate or event-free survival.

Luke was one of only a couple second graders who took a systematic approach to generating combinations of frog characteristics from a list.

Background: The International Myeloma Working Group (IMWG) proposed response and progression criteria using serum free light chain (sFLC) testing for patients with nonsecretory multiple myeloma (MM). We attempt to validate these criteria by comparing paraprotein responses with sFLC responses in patients with secretory myeloma. Patients and Methods: Prospectively entered data for 89 patients with MM enrolled on various clinical trials at the Cleveland Clinic between April 2004 and December 2006 were reviewed. Results: By standard paraprotein criteria, 4 patients had complete remission (CR), 22 had partial remission (PR), 34 had stable disease (SD), 26 had progressive disease (PD), and 3 were inevaluable. Only 43 patients (48%) had an involved sFLC ≥ 10 mg/dL (which is considered evaluable by the IMWG), of which 14 had PR, 8 had SD, 18 had PD, and 3 were inevaluable. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for sFLC in predicting response were 81%, 83%, 64%, and 92% respectively. The sensitivity, specificity, PPV, and NPV for sFLC in predicting progression were 93%, 80%, 72%, and 95% respectively. Conclusion: sFLC reliably predicts response and progression in MM. However, half of the patients had inevaluable disease by sFLC, thus limiting the utility of sFLC testing in patients with nonmeasurable disease by electrophoretic methods.

OBJECTIVE To evaluate the efficacy and safety of adding thalidomide to the pegylated liposomal doxorubicin, vincristine, and decreased-frequency dexamethasone (DVd) regimen for multiple myeloma. PATIENTS AND METHODS Patients newly diagnosed as having active multiple myeloma and those with relapsed-refractory disease were studied between August 2001 and October 2003. Patients received DVd as previously described. Thalidomide was given at 50 mg/d orally and the dose increased slowly to a maximum of 400 mg/d. At the time of best response, patients received maintenance prednisone, 50 mg orally every other day, and daily thalidomide at the maximum tolerated dose for each patient. The primary end point was the rate of complete responses plus very good partial responses as defined by the European Group for Blood and Marrow Transplantation criteria and the Intergroupe Francais du Myelome, respectively. RESULTS Of 102 eligible patients, 53 were newly diagnosed as having multiple myeloma, and 49 had been previously treated for multiple myeloma. The complete response plus very good partial response rate was 49% and 45%, with an overall response rate of 87% and 90% for patients with newly diagnosed and previously treated multiple myeloma, respectively. Furthermore, better responses were associated with improved progression-free and overall survival. The most common grade 3 and 4 adverse events were thromboembolic events (25%), peripheral neuropathy (22%), and neutropenia (14%). CONCLUSIONS The addition of thalidomide to the DVd regimen significantly improves the response rate and quality of responses compared with the DVd regimen alone. This improvement is associated with longer progression-free and overall survival. The rate of observed quality responses is comparable to responses seen with high-dose therapy.

Single-agent arsenic trioxide has shown promising results in patients with relapsed or refractory multiple myeloma (MM). Because preclinical data suggested greater activity with dexamethasone and ascorbic acid, a phase 2 trial of the combination of arsenic trioxide, dexamethasone, and ascorbic acid in patients with relapsed or refractory MM was conducted. Twenty patients in whom no more than two previous therapies had failed were enrolled. The mean age was 62 yr, and 55% of the patients had refractory disease. The regimen consisted of 14- or 15-wk cycles, with the first cycle considered induction, followed by one or two consolidation cycles with a reduced steroid schedule and then a maintenance cycle in responding patients. The overall response rate was 30%, with at least stable disease in 80% of patients. Median progression-free survival was 316 d in all patients and 584 d in those with a response. The regimen was well tolerated, with most adverse events being mild or moderate. This study showed the clinical efficacy and tolerability of the combination of arsenic trioxide, dexamethasone, and ascorbic acid. Further study is warranted.

According to recent state standardized test reports, Heidi is an average to slightly-above-average fifth-grade math student. She works hard to complete her assignments and follow directions, and this year she had all A's in her grade-level mathematics class. She confidently applies standard algorithms for all operations. Here, Murray discusses how Heidi uses concepts in her mathematical thinking.

Background: Arsenic trioxide (ATO) has shown activity in relapsed/refractory multiple myeloma (MM). An uncommon but life-threatening side effect of ATO is arrhythmia such as torsade de pointes (TdP), especially when QT or QTc (heart-rate corrected) intervals >500 milliseconds (ms). We evaluated the incidence and predictors of QT and QTc prolongation in MM patients treated with ATO. Methods: We reviewed prospectively collected demographic, laboratory and 766 weekly-ECG data on 48 patients treated in phase II trials with ATO. Patients received a median of 1.7 cycles (range 1–8) of 0.1–0.25 mg/Kg of IV ATO. Cycles consisted of 12 weeks of ATO (5-days/week for 1 week, then twice weekly for 11 weeks). Electrolytes were aggressively repleted to keep serum electrolytes as follows: K > 4 mEq/L, Mg > 2 mg/dL and Ca > 8.5 mg/dL. Endpoints included number of patients with QT and QTc prolongation (> 450 ms in males and > 470 ms in females), percentage of QT and QTc > 500 ms, and arrhythmia incidence. Predictors for QT and QTc prolongation were analyzed using a logistic regression model. Results: Median patient age was 67.4 years. 85% were Caucasians, 64 % were males, and 37% achieved a response to ATO (CR or PR). Throughout the study, median values for K, Mg, Ca were 4.3 (4.0, 4.5), 2.1 (1.9, 2.2), and 9.1 (8.6, 9.4), respectively. Prolonged QT and QTc intervals at any time during the study occurred in 6/48 patients (12.5%) and in 25/48 patients (52%), respectively. ATO therapy was held based on ECG changes in 2 patients. One of whom had both QT and QTc > 500 ms and was found to be on a phenothiazine derivative; the other patient had only QTc > 500 ms and was found to have severe hypomagnesemia and hypocalcemia. After discontinuing the offensive drug and correcting electrolytes, therapy was restarted without any further QT or QTc prolongation. Overall, QT and QTc intervals returned to baseline with subsequent doses indicating the absence of a cumulative dose-effect. The factors influencing QT and QTc considered in the statistical analyses were age, race, gender, and response. In univariate and multivariate analyses, the only variable associated with QT and QTc prolongation was male gender (p Conclusion: ATO can result in prolongation of QT and to a higher degree QTc interval. QT and QTc are rarely prolonged > 500 ms. Males were more likely to develop QT and QTc prolongation. With repeated administration, a dose-cumulative effect does not seem to further prolong QT or QTc. ATO can be safely administered to patients with MM when electrolytes and concomitant medications are appropriately managed. Decisions based on ECG occurred in two patients during the first 12 weeks of therapy, utilizing 2/766 ECG’s (0.003%). Weekly ECG’s may therefore not be warranted in this clinical setting.

ATO is a novel anticancer agent whose unique multifaceted mechanisms of action offer a scientific rationale for investigation in different hematologic malignancies. 2 phase II studies of ATO in advanced, heavily treated MM reported ≥25% decrease(40–50% of treated pts) in serum M-protein concentrations. Data from both studies suggest that long term therapy might result in enhanced quality of responses. It has been shown that ATO sensitizes myeloma cells to Dex in-vitro and AA potentiates the effect of ATO on different myeloma and human cell lines. We therefore initiated a phase II trial combining ATO with Dex & AA. MM pts with active, progressive disease who failed < 2 different regimens were eligible for enrollment. SWOG response criteria was used to assess efficacy to therapy. Treatment regimen consisted of 12 weeks (wks) treatment blocks with the 1st block considered induction, containing intense steroid schedule, and 1–2 more 12 wks blocks for consolidation with reduced steroid schedule. Regimen details;Cycle 1:Wk 1, loading with ATO at 0.25mg/kg IV d1-5,AA 1000mg IV within 30 minutes after each ATO infusion & Dex 40 mg orally d1-4. Wks 2 through 12; ATO at 0.25mg/kg IV twice weekly,AA 1000mg IV within 30 minutes after each ATO infusion & Dex 40 mg orally d11–14,29–32,39–42,57–60,& 67–70. Wks 13 through 15, is a rest period. Cycles 2 & 3 are the same as cycle 1 except Dex frequency is reduced to once a month (m) as follows;Dex 40 mg orally d1–4,29–32,57–60,& 67–70. Pts achieving SD or better were initiated on maintenance with the regimen administered for 5 wks with a 2m break and steroids given once a month. 20 pts were enrolled & evaluable for response and toxicity. Median age is 64,β2 microglobulin 3.2mg/dl & median serum albumin is 3.85. Six,7,2 & 5 patients were on study for a median duration of 58, 151, 351 and 511 days respectively.17 pts were taken off study;14 for disease progression,1 for grade 4 painful neuropathy,1 for refusal of therapy &1 developed colon cancer. Median survival for the 14 pts alive is 18.3 m (2.5–24.2). The regimen was well tolerated with 6 pts experiencing either grade 3 hyperglycemia, headaches, burning at IV site, neutropenia, dehydration, syncope, or fatigue. 1 patient experienced grade 4 painful neuropathy and was taken off study with the event resolving in 4 wks without any therapy. 3/5 pts who proceeded to maintenance decided against the 3rd consolidation cycle because of travel logistics, absence of further reduction of protein, or normalization of performance status. The most common cause to reduce the number of loading dose days and the biweekly treatment during maintenance is grade 2 paraesthesia that resolved with dose reduction. 8 pts achieved >50% reduction of the m-protein following cycle 1 of therapy;2CR,1NCR,5PR,10SD & 3PD. None of the pts but 1 showed further improvement in the m-protein after the1st cycle of therapy. Mean duration of therapy was 1.9 years. TAD results in an over all response rate of 45% & 85% SD or better with a mean survival of 18.3 months. Further expansion of the study to confirm this data is warranted, and utilizing the complementary mechanism of action of other immunomodulatory agents such as thalidomide with this regimen is ongoing.