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Exploratory pharmacodynamics and efficacy of PF-06817024 in a Phase 1 study of patients with chronic rhinosinusitis and atopic dermatitis

PF-06817024 is a humanized antibody against interleukin-33 that has the potential to inhibit type 2 inflammation. An exploratory analysis of the pharmacodynamics and clinical effects of single and repeat doses of PF-06817024 was assessed in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and patients with moderate-to-severe atopic dermatitis (AD), respectively, as part of a Phase 1, first-in-human study. Rhinosinusitis symptoms were improved, and nasal polyps were decreased in size following treatment with PF-06817024 in patients with CRSwNP. In patients with AD, PF-06817024, in aggregate, reduced disease severity and improved symptoms, as demonstrated by greater percentage decrease from baseline in Eczema Area and Severity Index (EASI) scores and reduced pruritus numerical rating scores, compared with placebo. The efficacy in AD appeared to be bimodal with a sub-group of participants exhibiting high levels of improvement (EASI75 and EASI90) for a sustained period of time after dosing. In patients with CRSwNP, a consistent trend of decrease in eosinophil levels was observed in the PF-06817024 group, compared with placebo. Further research would be needed to confirm the clinical benefit and safety of PF-06817024 as a treatment for allergic diseases.Trial registration ClinicalTrials.gov, NCT02743871. Registered 15 April 2016, https://clinicaltrials.gov/study/NCT02743871?term=NCT02743871&rank=1.

Anti-Angiogenic Screening of Moringa Oleifera Leaves Extract Using Chorioallantonic Membrane Assay

Background: Angiogenesis is defined as the formation of new blood vessels. However, angiogenesis in cancer will lead to tumour growth and metastasis. Therefore, anti-angiogenesis is one of the ways to slow down growth and spreading of tumour. Moringa oleifera is also known as a “Miracle tree” which has high nutritive value and various therapeutics effect in different parts of the plant. This study aims to determine the anti-angiogenic property of Moringa oleifera leaves extract by using chick chorioallantoic membrane (CAM) assay. Materials and Methods: The extracts were prepared by decoction method using methanol and water. The qualitative phytochemical screening was carried out for both methanol and aqueous extracts. The fertilised chicken eggs were divided into six groups which include negative control group (phosphate-buffer saline with pH 7.4), positive control group (sunitinib), 50% and 100% methanol extract, 50% and 100% aqueous extract. The anti-angiogenic effect of Moringa oleifera leaves extract was determined by calculating the number and percentage decrease in blood vessels in post-24 and post-48 hours of treatment. Results: Statistical analysis by one-way ANOVA has shown significant (p<0.05) percentage reduction in the blood vessels between each treatment group after 48 hours of treatment. Among all the extracts, 100% aqueous extract of Moringa oleifera was found to have highest anti-angiogenic effect with the greater percentage decrease in blood vessels (81.33%) in post-48 hours of treatment. Furthermore, the anti-angiogenic effect of Moringa oleifera leaves was found to increased when the concentration of the Moringa oleifera extract was increased. Conclusion: Moringa oleifera leaves with various phytochemicals was found to possess anti-angiogenic potential.

Association Between Proposed Definitions of Clinical Remission/Response and Well-Being in Patients With Crohn's Disease.

Background and AimsPatient-reported outcomes are recommended endpoints in Crohn’s disease [CD] trials. The association between patient-reported general well-being relative to symptoms of diarrhoea and abdominal pain [AP] in patients with moderate to severe CD was explored.MethodsPatients from three randomized, placebo-controlled, double-blind adalimumab or upadacitinib studies with average daily very soft/liquid stool frequency [SF] ≥4 and/or AP score ≥2 at baseline were included. Using electronic diaries, patients reported general well-being [seven-point Likert scale; 1 = worst; 7 = best] in item 10 of the Inflammatory Bowel Disease Questionnaire [IBDQ]. Changes in well-being and clinical outcomes of SF and AP from baseline to week 12 or 16, and the relationship between well-being and clinical outcomes were evaluated using cumulative distribution function and probability density function curves.ResultsIn total, 858 patients with CD were included [adalimumab, n = 695; upadacitinib, n = 163]. Patients who achieved clinical remission [SF ≤2.8, AP score ≤1.0, neither worse than baseline] were more likely than those not in clinical remission to report IBDQ item 10 response in the 6–7 group category but not IBDQ categories ≤5. Higher IBDQ score for item 10 [6–7] was associated with lower SF and AP score. Greater point increases in IBDQ item 10 were associated with a greater percentage decrease in clinical parameters; a ≥25–30% decrease in SF or AP was associated with a ≥1-point improvement in IBDQ.ConclusionsAn association between improvements in patient-reported general well-being and clinical remission/response was observed using outcomes of SF and AP, supporting the clinical remission/response endpoint definitions used in clinical studies of CD. Clinical Trial Registrations [ClinicalTrials.gov]: NCT00077779 [CHARM]; NCT00348283 [EXTEND]; NCT02365649 [CELEST].

Chronic Inflammation in Ulcerative Colitis Causes Long-Term Changes in Goblet Cell Function.

Background & AimsOne of the features of ulcerative colitis (UC) is a defect in the protective mucus layer. This has been attributed to a reduced number of goblet cells (GCs). However, it is not known whether abnormal GC mucus secretion also contributes to the reduced mucus layer. Our aims were to investigate whether GC secretion was abnormal in UC and exists as a long-term effect of chronic inflammation.MethodsColonoids were established from intestinal stem cells of healthy subjects (HS) and patients with UC. Colonoids were maintained as undifferentiated (UD) or induced to differentiate (DF) and studied as three-dimensional or monolayers on Transwell filters. Total RNA was extracted for quantitative real-time polymerase chain reaction analysis. Carbachol and prostaglandin E2 mediated mucin stimulation was examined by MUC2 IF/confocal microscopy and transmission electron microscopy.ResultsColonoids from UC patients can be propagated over many passages; however, they exhibit a reduced rate of growth and transepithelial electrical resistance compared with HS. Differentiated UC colonoid monolayers form a thin and non-continuous mucus layer. UC colonoids have increased expression of secretory lineage markers ATOH1 and SPDEF, along with MUC2 positive GCs, but failed to secrete mucin in response to the cholinergic agonist carbachol and prostaglandin E2, which caused increased secretion in HS. Exposure to tumor necrosis factor α (5 days) reduced the number of GCs, with a greater percentage decrease in UC colonoids compared with HS.ConclusionsChronic inflammation in UC causes long-term changes in GCs, leading to abnormal mucus secretion. This continued defect in GC mucus secretion may contribute to the recurrence in UC.

Impact of the COVID-19 pandemic on radiology physician work RVUs at a large subspecialized radiology practice

PurposeAs the COVID-19 pandemic continues, efforts by radiology departments to protect patients and healthcare workers and mitigate disease spread have reduced imaging volumes. This study aims to quantify the pandemic's impact on physician productivity across radiology practice areas as measured by physician work Relative Value Units (wRVUs). Materials and methodsAll signed diagnostic and procedural radiology reports were curated from January 1st to July 1st of 2019 and 2020. Physician work RVUs were assigned to each study type based on the Medicare Physician Fee Schedule. Utilizing divisional assignments, radiologist schedules were mapped to each report to generate a sum of wRVUs credited to that division for each week. Differential impact on divisions were calculated relative to a matched timeframe in 2019 and a same length pre-pandemic time period in 2020. ResultsAll practice areas saw a substantial decrease in wRVUs from the 2020 pre- to intra-pandemic time period with a mean decrease of 51.5% (range 15.4%–76.9%). The largest declines were in Breast imaging, Musculoskeletal, and Neuroradiology, which had decreases of 76.9%, 75.3%, and 67.5%, respectively. The modalities with the greatest percentage decrease were mammography, MRI, and non-PET nuclear medicine. ConclusionAll radiology practice areas and modalities experienced a substantial decrease in wRVUs. The greatest decline was in Breast imaging, Neuroradiology, and Musculoskeletal radiology. Understanding the differential impact of the pandemic on practice areas will help radiology departments prepare for the potential depth and duration of the pandemic by better understanding staffing needs and the financial effects.

Plasma Dehydroepiandrosterone Sulfate and Cardiovascular Disease Risk in Older Men and Women.

Lower dehydroepiandrosterone-sulfate (DHEA-S) levels have been inconsistently associated with coronary heart disease (CHD) and mortality. Data are limited for heart failure (HF) and association between DHEA-S change and events. Assess associations between low DHEA-S/DHEA-S change and incident HF hospitalization, CHD, and mortality in older adults. DHEA-S was measured in stored plasma from visits 4 (1996-1998) and 5 (2011-2013) of the Atherosclerosis Risk in Communities study. Follow-up for incident events: 18 years for DHEA-S level; 5.5 years for DHEA-S change. General community. Individuals without prevalent cardiovascular disease (n = 8143, mean age 63 years). Associations between DHEA-S and incident HF hospitalization, CHD, or mortality; associations between 15-year change in DHEA-S (n = 3706) and cardiovascular events. DHEA-S below the 15th sex-specific percentile of the study population (men: 55.4 µg/dL; women: 27.4 µg/dL) was associated with increased HF hospitalization (men: hazard ratio [HR] 1.30, 95% confidence interval [CI], 1.07-1.58; women: HR 1.42, 95% CI, 1.13-1.79); DHEA-S below the 25th sex-specific percentile (men: 70.0 µg/dL; women: 37.1 µg/dL) was associated with increased death (men: HR 1.12, 95% CI, 1.01-1.25; women: HR 1.19, 95% CI, 1.03-1.37). In men, but not women, greater percentage decrease in DHEA-S was associated with increased HF hospitalization (HR 1.94, 95% CI, 1.11-3.39). Low DHEA-S and change in DHEA-S were not associated with incident CHD. Low DHEA-S is associated with increased risk for HF and mortality but not CHD. Further investigation is warranted to evaluate mechanisms underlying these associations.

Evaluation of the bactericidal potential of 2780-nm ER,CR:YSGG and 940-nm diode lasers in the root canal system

Successful endodontic therapy relies on chemomechanical debridement. Laser-assisted irrigation techniques are available for debridement. However, there are limited studies demonstrating the effectiveness of dual lasers for root canal disinfection. Hence, the aim of the present study is to determine if laser activation irrigation using the Er,Cr:YSGG and 940-nm diode laser is as effective as positive pressure needle irrigation using sodium hypochlorite (NaOCl) and ethylenediamine tetraacetic acid (EDTA). Fifty-two caries-free premolars were divided into six groups: G1, sterile water via positive pressure irrigation; G2, EDTA and NaOCl via positive pressure irrigation; G3, sterile water and the Er,Cr:YSGG cleaning and disinfection step; G4, sterile water and the Er,Cr:YSGG cleaning and disinfection step followed by disinfection with the 940-nm diode; G5, sterile water and the Er,Cr:YSGG cleaning step followed by a disinfection step with the Er,Cr:YSGG and diode laser together; and G6, negative controls. S1 samples were validated in both negative and positive control groups via culturing. All teeth, except the negative controls, were inoculated with Enterococcus faecalis. S2 sampling after treatments was completed and tested for bacterial presence via culturing and SEM and CLSM analysis. The data demonstrated that the traditional irrigation group (G2) and the dual laser group (G5) showed the greatest percentage decrease in bacterial counts from the S1 to the S2 group. The data demonstrates that the combination of the Er,Cr:YSGG and 940-nm diode laser wavelengths is safe and more effective than either laser alone and is comparable to needle irrigation with sodium hypochlorite and EDTA.

Annual and seasonal trends in mortality rates from cardiovascular diseases in Hungary between 1984 and 2013.

The aim of this study was to investigate annual and seasonal trends in mortality rates from cardiovascular diseases in Hungary between 1984 and 2013. Annual and monthly mortality and population data were obtained from the Hungarian Central Statistical Office. The annual mortality data by gender and age were available for the following disease classifications of the circulatory system: all cardiovascular diseases, all diseases of the heart, hypertension, coronary heart disease, and cerebrovascular diseases. Six age groups were defined for both sexes. Negative binomial regression was carried out to analyse annual trends in age-standardized mortality rates. The Walter-Elwood method was used to identify seasonal variation using monthly numbers of deaths. Significant decreases in annual mortality rates for all cardiovascular diseases were found, but not for hypertension. Age-standardized death rates were higher for men for all causes, except for hypertension. The greatest sex difference in the average risk of death was observed in the middle-aged groups. The greatest percentage decrease in death rates during the study period was seen for both sexes in the under 35 age group. The lowest percentage change was observed among people aged over 75. Significant seasonality was found in monthly death rates from all causes, with a peak in February. In spite of a decreasing trend in the annual mortality rates for cardiovascular diseases, the Hungarian mortality rate is still high. Moreover, this study demonstrated a significant winter peak in mortality from cardiovascular diseases over a thirty-year period.

(P009) Assessment of Lumpectomy Cavity Radiotherapy Boost Volume With Repeat CT Simulation

Lumpectomy cavity (LC) radiotherapy boost after breast conserving surgery and whole breast irradiation (WBRT) reduces local cancer recurrence. Radiotherapy boost correlates with increased rates of fibrosis and may have worse cosmetic outcomes. LC volumes and subsequent boost volumes may decrease with increasing time from surgery. This study evaluates the timing of CT simulation and radiotherapy technique for cavity directed radiotherapy boost. We seek to determine if repeat CT simulation results in smaller boost volumes which may minimize treatment related toxicity and maximize local tumor control. A retrospective chart review examined 47 consecutive patients receiving WBRT with LC boost after breast conserving surgery. All patients underwent CT simulation prior to WBRT and repeat CT simulation prior to LC boost. The WBRT prescription dose ranged from 4240-5040cGy and boost from 1000-1600cGy. The LC was contoured on the pre and post CT images and delineated by surgical clips and seroma cavity. 40 of 47 patients reviewed were found to have decreased LC volumes. The mean initial and repeat LC volumes were 71.1cc and 42.6cc respectively. Initial volumes greater than 60cc had a greater percentage decrease in LC volume at time of repeat simulation, 42% vs 30% (p=0.01). Patients who underwent initial LC evaluation less than 4 weeks after surgery had a greater percent decrease in mean repeat cavity volumes compared to those greater than 4 weeks out from surgery, 53% vs 24%. Patients undergoing WBRT with LC radiotherapy boost were found to have decreased cavity volume with repeat CT simulation. Factors that correlate to reduced volume are larger initial cavity volume and shorter time interval from surgery. These factors help to identify patients who will benefit from repeat CT simulation prior to boost planning and will subsequently have smaller volumes of radiation to normal breast tissue.

Sources and transformations of anthropogenic nitrogen along an urban river–estuarine continuum

Abstract. Urbanization has altered the fate and transport of anthropogenic nitrogen (N) in rivers and estuaries globally. This study evaluates the capacity of an urbanizing river–estuarine continuum to transform N inputs from the world's largest advanced (e.g., phosphorus and biological N removal) wastewater treatment facility. Effluent samples and surface water were collected monthly along the Potomac River estuary from Washington D.C. to the Chesapeake Bay over a distance of 150 km. In conjunction with box model mass balances, nitrate stable isotopes and mixing models were used to trace the fate of urban wastewater nitrate. Nitrate concentrations and δ15N-NO3− values were higher down-estuary from the Blue Plains wastewater outfall in Washington D.C. (2.25 ± 0.62 mg L−1 and 25.7 ± 2.9 ‰, respectively) compared to upper-estuary concentrations (1.0 ± 0.2 mg L−1 and 9.3 ± 1.4 ‰, respectively). Nitrate concentration then decreased rapidly within 30 km down-estuary (to 0.8 ± 0.2 mg L−1), corresponding to an increase in organic nitrogen and dissolved organic carbon, suggesting biotic uptake and organic transformation. TN loads declined down-estuary (from an annual average of 48 000 ± 5000 kg day−1 at the sewage treatment plant outfall to 23 000 ± 13 000 kg day−1 at the estuary mouth), with the greatest percentage decrease during summer and fall. Annually, there was a 70 ± 31 % loss in wastewater NO3− along the estuary, and 28 ± 6 % of urban wastewater TN inputs were exported to the Chesapeake Bay, with the greatest contribution of wastewater TN loads during the spring. Our results suggest that biological transformations along the urban river–estuary continuum can significantly transform wastewater N inputs from major cities globally, and more work is necessary to evaluate the potential of organic nitrogen and carbon to contribute to eutrophication and hypoxia.

Ultrasound‐guided femoral arterial access in pediatric cardiac catheterizations: A prospective evaluation of the prevalence, risk factors, and mechanism for acute loss of arterial pulse

The objectives of this study were to describe the prevalence, mechanisms, and identify risk factors for acute loss of arterial pulse (LOP) in children who had ultrasound-guided femoral arterial access (UGFAA) during cardiac catheterization. LOP is a known complication in children following femoral arterial (FA) access for cardiac catheterization. The prevalence of LOP requiring treatment ranges between 4% and 8%. A prospective study was performed including 486 cardiac catheterizations using UGFAA in children ≤18 years over a 3 years period. Ultrasound and Doppler evaluations were performed prior to and at the end of the procedure. LOP was identified in 33 cases (6.8%) with 23 (4.7%) requiring treatment. For children ≤6 months, the prevalence of LOP requiring treatment was 13.6%. FA diameter <3mm was the only significant independent predictor for LOP (OR: 8.44, 95% CI: 2.07-34.5, P < 0.001). Smaller patient size, number of access attempts, time required for access, operator experience, sheath size, and length of procedure were not found to be significant predictors. Children with LOP had a greater percentage decrease in vessel diameter (median 62% vs 18%, P < 0.001) compared to those without LOP. FA thrombus was diagnosed only in 9 patients (27% of those with LOP). The prevalence of LOP requiring treatment is 4.7% when UGFAA is used during pediatric cardiac catheterizations. Arterial spasm was more common than thrombus as a cause of LOP. FA diameter <3mm was the only independent predictor for LOP in this carefully designed prospective study. © 2016 Wiley Periodicals, Inc.

Implementing the Next Accreditation System: Results of the 2014-2015 Annual Data Review.

Implementing the Next Accreditation System: Results of the 2014-2015 Annual Data Review.

Intravenous Hydralazine in Hospitalized Children and Adolescents with Hypertension

To explore the efficacy and safety of intravenous (IV) hydralazine in hospitalized children with hypertension. Data were retrospectively collected on hospitalized children treated with IV hydralazine. Percent changes in blood pressure (BP) were calculated, and linear regression was used to investigate associations between BP change and pertinent clinical and demographic variables. Bivariate logistic regression was used to investigate associations between the same covariates and the outcomes of ideal clinical response (ICR), a 10%-25% reduction in mean arterial pressure (MAP), and excess response (ER), a 25% reduction in MAP. A total of 141 initial doses of IV hydralazine (median dose, 0.10mg/kg [IQR, 0.09-0.11; range, 0.02-0.37]) were analyzed. Median age was 8 years (IQR, 2-15; range, 0-24); most patients had renal disease, malignancy, or were organ transplant recipients. The mean MAP reduction was 19%±12%. An ICR occurred in 66 patients (47%). Higher initial MAP and increased hydralazine dose were associated with greater percentage decrease in MAP. No association was found between ICR and the covariates of interest; higher initial MAP was associated with greater odds of ICR. ER occurred in 44 children (31%). Among this group, higher initial MAP and higher hydralazine dose were associated with increased odds of ER, and administration of other antihypertensive drugs was associated with decreased odds of ER. Four adverse effects possibly related to IV hydralazine, including 2 episodes of hypotension, were recorded. IV hydralazine reduced BP in the majority of children. However, a substantial proportion of children experienced potentially excessive BP reduction.

A Comparative Evaluation of the Effectiveness of Three Different Irrigating Solution on Microorganisms in the Root Canal: An Invivo Study

An infected root canal system either due to caries exposure or trauma cannot be eliminated by the host defense mechanisms alone or in combination with systemic antibiotic therapy. It can be treated through professional endodontic intervention using both chemical and mechanical procedures. To suggest triple antibiotic solution containing tetracycline, ornidazole and ciprofloxacin as a new endodontic irrigant that may possess superior antibacterial activity in comparison with chlorhexidine solution. This study was carried out on 60 teeth from 40 children with anterior tooth fracture, asymptomatic, non-vital and necrotic in nature. Patients were randomly divided into three groups of 20 teeth each depending upon the type of irrigant. After access opening microbial samples were obtained: a) Pre- irrigation i.e. sample after pulp extirpation and before irrigation, b) Post-irrigation i.e. sample after irrigation, stored in sterile containers and immediately transferred to microbiological laboratory. After incubation of samples aerobically at 37(0)C for 24 hours, the samples were streaked on blood agar culture media and incubated for 48 hours. After 48 hours, the colony forming units were counted using a colony counter. Statistical analysis was carried out using Kruskal-Wallis test, Wilcoxson signed rank test and Mann-Whitney test. On intra group comparison, highly significant differences in the colony forming units were found between pre-irrigation and post-irrigation sample for all the three groups. On inter group comparison, statistical difference was found between saline and chlorhexidine (p ≤ 0.001), saline and triple antibiotic paste (p< 0.001). The greatest percentage decrease was obtained in samples treated with Chlorhexidine solution (Group 2) i.e.73.91. The triple antibiotic irrigating solution group showed percentage decrease of 66.22 followed by Group 1 (Saline) 15.04. The difference found amongst the groups was statistically insignificant. It was concluded that triple antibiotic irrigating solution can be used as an irrigating solution. The antibacterial action of triple antibiotic irrigating solution is comparable with chlorhexidine. Although saline may not be effective in the antimicrobial action but its flushing action may be able to decrease some microbial load.

The impact of restraint reduction meetings on the use of restrictive physical interventions in English residential services for children and young people.

The aim was to examine the impact of post restraint reduction meetings upon the frequency and restrictiveness of restraint use in English children's residential services. Attention has been drawn to the misuse, overuse and safety of some techniques used to physically restrain children in residential services. Successful interventions to reduce restraints have been reported, mostly from the USA. Demonstrate a significant overall reduction in both, frequency and restrictiveness of restraints; the greatest percentage decrease in the most restrictive floor restraints. Whilst five services reduced both frequency and restrictiveness, five services showed some increases in frequency and/or restrictiveness of restraints employed. Restraint reduction is most effectively reduced through employing multiple strategies and that post restraint reduction meetings maybe one useful component. Organisations seeking to promote restraint reduction meetings need to allocate sufficient priority and resources to support these.

Trihalomethanes in public drinking water and stillbirth and low birth weight rates: an intervention study

During 2003–2004, United Utilities water company in North West England introduced enhanced coagulation (EC) to four treatment works to mitigate disinfection by-product (DBP) formation. This enabled examination of the relation between DBPs and birth outcomes whilst reducing socioeconomic confounding. We compared stillbirth, and low and very low birth weight rates three years before (2000–2002) with three years after (2005–2007) the intervention, and in relation to categories of THM change.We created exposure metrics for EC and trihalomethane (THM) concentration change (n=258 water zones). We linked 429,599 live births and 2279 stillbirths from national birth registers to the water zone at birth. We used Poisson regression to model the differences in birth outcome rates with an interaction between before/after the intervention and EC or THM change.EC treatment reduced chloroform concentrations more than non-treatment (mean -29.7µg/l vs. -14.5µg/l), but not brominated THM concentrations. Only 6% of EC water zones received 100% EC water, creating exposure misclassification concerns. EC intervention was not associated with a statistically significant reduction in birth outcome rates. Areas with the highest chloroform decrease (30 – 65μg/l) had the greatest percentage decrease in low -9 % (-12, -5) and very low birth weight -16% (-24, -8) rates. The interaction between before/after intervention and chloroform change was statistically significant only for very low birth weight, p=0.02. There were no significant decreases in stillbirth rates.In a novel approach for studying DBPs and adverse reproductive outcomes, the EC intervention to reduce DBPs did not affect birth outcome rates. However, a measured large decrease in chloroform concentrations was associated with statistically significant reductions in very low birth weight rates.

Central venous-to-arterial carbon dioxide partial pressure difference in early resuscitation from septic shock

Central venous-to-arterial carbon dioxide partial pressure difference (ΔPCO2) can be used as a marker for the efficacy of venous blood in removing the total CO2 produced by the tissues. To date, this role of ΔPCO2 has been assessed only in patients after resuscitation from septic shock with already normalised central venous oxygen saturation (ScvO2 ≥70%). There are no reports on the behaviour of ΔPCO2 and its relationship to cardiac index (CI) and clinical outcome before normal ScvO2 has been achieved. To investigate the behaviour of ΔPCO2 and its relationship to CI, blood lactate concentration and 28-day mortality during resuscitation in the very early phase of septic shock. To examine whether patients who normalise both ΔPCO2 and ScvO2 during the first 6 h of resuscitation will have a greater percentage decrease in blood lactate concentration than those who only achieve normal ScvO2. Prospective observational study. Intensive Care Unit (ICU) in a university hospital. Eighty patients with septic shock were consecutively recruited. Patients were resuscitated in accordance with the recommendations of the Surviving Sepsis Campaign. Blood lactate concentrations, and haemodynamic and oxygen-derived variables were obtained at ICU admission (T0) and 6 h after admission (T6). Lactate decrease was defined as the percentage decrease in lactate concentration from T0 to T6. All cause 28-day mortality was also recorded. Data are presented as median (interquartile range). At T0, there were significant differences (P < 0.0001) between normal (ΔPCO2 ≤0.8 kPa) and high ΔPCO2 groups for CI (3.9 [3.3 to 4.7] vs. 2.9 [2.3 to 3.1] l min m) and ScvO2 (73 [65 to 80] vs. 61 [53 to 63]%). The correlation between changes in CI and ΔPCO2 was r = -0.62, P < 0.0001. Patients who reached a normal ΔPCO2 at T6 had larger decreases in blood lactate concentration and Sequential Organ Failure Assessment scores on day 1. The lactate decrease was greatest in the subgroup achieving both normal ScvO2 and ΔPCO2 at T6. Lactate decrease, unlike ΔPCO2 and ScvO2, was an independent predictor of 28-day mortality. Monitoring ΔPCO2 may be a useful tool to assess the adequacy of tissue perfusion during resuscitation. The normalisation of both ΔPCO2 and ScvO2 is associated with a greater decrease in blood lactate concentration than ScvO2 alone. The lactate decrease is an independent predictor of 28-day mortality. Further research is needed to confirm this hypothesis.

Impaired Peripheral Circulation in Veterans with Claudication is Associated with Smoking

We compared the peripheral vascular function of veterans and non-veterans with peripheral artery disease (PAD) and claudication. The circulation of the lower extremities was assessed under rest and reactive hyperemia conditions in 413 veterans and in 83 non-veterans. Veterans had more severe PAD as measured by a lower ankle/ brachial index (p<0.001). Following the occlusive test, veterans had a greater relative percentage decrease in ankle systolic blood pressure (p=0.015), a greater percentage decrease in calf transcutaneous oxygen tension (p=0.035), and a blunted percentage increase in calf blood flow (p=0.031). After adjustment for current smoking status, these measures were no longer statistically different between the veterans and non-veterans. We conclude that veterans with PAD and claudication have greater impairments in macrovascular and microvascular function of the lower extremities, and greater severity of PAD than compared to non-veterans, and that these factors were primarily associated with their higher prevalence of smoking. The greater compromise in peripheral vascular measures in veterans is particularly noteworthy given that the prevalence of diabetes, hypertension, and dyslipidemia were not higher.

Effect of a hydrogymnastics program on the serum levels of high-sensitivity C-reactive protein amongst elderly women

The aim of this study was to evaluate the effect of a hydrogymnastics training program on highsensitivity C-reactive protein in elderly women. The subjects were randomly divided into the experimental group who participates in the hydrogymnastics training program and the control group who was not involved in the training and remained sedentary. The serum levels of highsensitivity C-reactive protein were determined by immunoturbidimetry using C-reactive protein (CRP), the training protocol consisted of hydrogymnastics sessions 5 times per week during 12 weeks of intervention, executed in a pool of 1.3 meters divided into three phases: a 10-minute warm-up, 30 minutes of aerobic exercise at 50%-60% of maximum heart rate (monitored by heart rate monitor) and a 10-minute cool down. As a statistical method to compare the results between groups of variables pre and post training, the analysis of variance (ANOVA) mixed 2 × 2 (group × measurement) test was done using SPSS version 17. The founds showed significant changes in the level of high-sensitivity C-reactive protein, and a greater percentage decrease of hs-CRP (Δ%= -37%, p = 0.001) in the experimental group in relation to the control group.Therefore, it can be inferred that a hydrogymnastics program is effective in reducing the metabolic rate of high-sensitivity C-reactive protein amongst elderly women.

HCV Triple Therapy, The Non-study Experience: A Single Center Analysis Comparing African American to White Americans

Purpose: To evaluate qualitative and quantitative differences between African Americans and White Americans in the treatment of HCV in a non-study based setting; the real world experience. Methods: A retrospective case study analysis at a single center that evaluated the efficacy of triple HCV therapy in non study setting. Clinical response and quantitative laboratory values were compared between African-American and non African-American patients throughout the duration of treatment. Patients were included if they started triple therapy treatment after July 2011 and are not a part of any other clinical/pharmaceutical trials. Results: African-Americans were found to have significantly higher BMI and HCV RNA quantitative viral loads at initiation of treatment with triple therapy (either boceprevir or telaprevir; Table 1). Throughout the course of treatment, African Americans had a greater percentage decrease in their baseline hemoglobin and platelet count, and a corresponding reduction in their baseline ribavirin dose. However, treatment outcomes (defined as virus negative at the conclusion of treatment) were not found to be statistically significant between African American and White Americans. A subset analysis (Table 2) revealed that patients who were virus negative at the end of treatment (either telaprevir or boceprevir) were less likely to have received blood transfusions throughout the duration of treatment.Table: Table. HCV triple therapy—African vs white AmericansTable: Table. Treatment outcomesConclusion: Treatment dosages of ribavirin are based upon a patients weight, which corresponds with BMI. Higher doses of ribavirin are more likely to cause cytopenia compared to smaller doses of ribavirin. As a result, patients with higher BMI are more likely to have decreased hemoglobin and platelet counts. In the event a patient develops severe cytopenia, blood transfusion may be necessary. As evidenced in this study, blood transfusion was statistically significant in treatment outcomes - if a patient requires blood transfusions, they are less likely to complete treatment and achieve virus negativity. Larger studies, with greater power, are needed in order to explore other prognostic indicators in the treatment of chronic HCV.