Long-term trends in critical care admissions in Wales*.

As national populations age, demands on critical care services are expected to increase. In many healthcare settings, longitudinal trends indicate rising numbers and proportions of patients admitted to ICU who are older; elsewhere, including some parts of the UK, a decrease has raised concerns with regard to rationing according to age. Our aim was to investigate admission trends in Wales, where critical care capacity has not risen in the last decade. We used the Secure Anonymised Information Linkage Databank to identify and characterise critical care admissions in patients aged ≥ 18 years from 1 January 2008 to 31 December 2017. We categorised 85,629 ICU admissions as youngest (18-64 years), older (65-79 years) and oldest (≥ 80 years). The oldest group accounted for 15% of admissions, the older age group 39% and the youngest group 46%. Relative to the national population, the incidence of admission rates per 10,000 population in the oldest group decreased significantly over the study period from 91.5/10,000 in 2008 to 77.5/10,000 (a relative decrease of 15%), and among the older group from 89.2/10,000 in 2008 to 75.3/10,000 in 2017 (a relative decrease of 16%). We observed significant decreases in admissions with high comorbidity (modified Charlson comorbidity index); increases in the proportion of older patients admitted who were considered 'fit' rather than frail (electronic frailty index); and decreases in admissions with a medical diagnosis. In contrast to other healthcare settings, capacity constraints and surgical imperatives appear to have contributed to a relative exclusion of older patients presenting with acute medical illness.

Reliability of frailty assessment in the critically ill: a multicentre prospective observational study.

Demand for critical care among older patients is increasing in many countries. Assessment of frailty may inform discussions and decision making, but acute illness and reliance on proxies for history-taking pose particular challenges in patients who are critically ill. Our aim was to investigate the inter-rater reliability of the Clinical Frailty Scale for assessing frailty in patients admitted to critical care. We conducted a prospective, multi-centre study comparing assessments of frailty by staff from medical, nursing and physiotherapy backgrounds. Each assessment was made independently by two assessors after review of clinical notes and interview with an individual who maintained close contact with the patient. Frailty was defined as a Clinical Frailty Scale rating > 4. We made 202 assessments in 101 patients (median (IQR [range]) age 69 (65-75 [60-80]) years, median (IQR [range]) Acute Physiology and Chronic Health Evaluation II score 19 (15-23 [7-33])). Fifty-two (51%) of the included patients were able to participate in the interview; 35 patients (35%) were considered frail. Linear weighted kappa was 0.74 (95%CI 0.67-0.80) indicating a good level of agreement between assessors. However, frailty rating differed by at least one category in 47 (47%) cases. Factors independently associated with higher frailty ratings were: female sex; higher Acute Physiology and Chronic Health Evaluation II score; higher category of pre-hospital dependence; and the assessor having a medical background. We identified a good level of agreement in frailty assessment using the Clinical Frailty Scale, supporting its use in clinical care, but identified factors independently associated with higher ratings which could indicate personal bias.

Defining sepsis on the wards: results of a multi-centre point-prevalence study comparing two sepsis definitions.

Our aim was to prospectively determine the predictive capabilities of SEPSIS-1 and SEPSIS-3 definitions in the emergency departments and general wards. Patients with National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled over a 24-h period in 13 Welsh hospitals. The primary outcome measure was mortality within 30 days. Out of the 5422 patients screened, 431 fulfilled inclusion criteria and 380 (88%) were recruited. Using the SEPSIS-1 definition, 212 patients had sepsis. When using the SEPSIS-3 definitions with Sequential Organ Failure Assessment (SOFA) score ≥ 2, there were 272 septic patients, whereas with quickSOFA score ≥ 2, 50 patients were identified. For the prediction of primary outcome, SEPSIS-1 criteria had a sensitivity (95%CI) of 65% (54-75%) and specificity of 47% (41-53%); SEPSIS-3 criteria had a sensitivity of 86% (76-92%) and specificity of 32% (27-38%). SEPSIS-3 and SEPSIS-1 definitions were associated with a hazard ratio (95%CI) 2.7 (1.5-5.6) and 1.6 (1.3-2.5), respectively. Scoring system discrimination evaluated by receiver operating characteristic curves was highest for Sequential Organ Failure Assessment score (0.69 (95%CI 0.63-0.76)), followed by NEWS (0.58 (0.51-0.66)) (p < 0.001). Systemic inflammatory response syndrome criteria (0.55 (0.49-0.61)) and quickSOFA score (0.56 (0.49-0.64)) could not predict outcome. The SEPSIS-3 definition identified patients with the highest risk. Sequential Organ Failure Assessment score and NEWS were better predictors of poor outcome. The Sequential Organ Failure Assessment score appeared to be the best tool for identifying patients with high risk of death and sepsis-induced organ dysfunction.

Turns while walking among individuals with Parkinson's disease following overground locomotor training: A pilot study.

BACKGROUND: Individuals with Parkinson's disease are challenged in making turns while walking, evidenced by reduced intersegmental coordination and reduced dynamic postural stability. Although overground locomotor training previously improved ambulation among people with Parkinson's disease, its effect on walking turns remained unknown. We sought to understand the effects of overground locomotor training on walking turns among individuals with mild-Parkinson's disease. METHODS: Twelve participants with Parkinson's (7 Males/5 Females; Age: 68.5 ± 6.4 years) completed twenty-four sessions lasting approximately 60 min and over 12-15 weeks. Baseline and follow-up assessments included the ten-minute walk test using wearable sensors. Primary outcomes included changes to intersegmental coordination, measured by peak rotation and normalized peak rotation, and dynamic postural stability, measured by peak turn velocities in the frontal and transverse planes. Statistical analysis included one-tailed paired t-tests and Cohen's d effect sizes with α = 0.05. FINDINGS: No effects of overground locomotor training on mean peak thoracic rotation (+0.23 ± 4.24°; Cohen's d = 0.05; P = 0.45) or mean normalized peak thoracic rotation (-0.59 ± 5.52 (unitless); Cohen's d = 0.10; P = 0.45) were observed. Moderate and small effects of overground locomotor training were observed on mean peak turn velocities in the frontal (+1.59 ± 2.18°/s; Cohen's d = 0.43; P = 0.01) and transverse planes (+0.88 ± 3.18°/s; Cohen's d = 0.25; P = 0.18). INTERPRETATION: This pilot study provides preliminary evidence suggesting that individuals with mild-Parkinson's moderately improved frontal plane dynamic postural stability after overground locomotor training, likely attenuating the perturbations experienced while turning. CLINICAL TRIAL REGISTRATION: NCT03864393.

A short overview of bubbles in foods and chocolate.

The incorporation of bubbles in foods has created a positive market response from consumers since their first introduction over 70 years ago and has resulted in an expanding market over this period. However, although the physics and chemistry of most ingredients in commercial food products are reasonably well understood, the behaviour of bubbles in foods are much less established and their behaviour not fully appreciated. In fact, bubbles are perhaps the least studied of all food ingredients even though aeration is still one of the fastest growing unit operations in processing. Although many of these manufactured aerated food products are perceived as lighter with lower calorific values, problems in manufacturing remain even today and it is generally difficult to optimize the size, the size distribution, the deviation the from spherical shapes and the stability of the bubbles during the different stages of the processing. In this review, we discuss the dispersion of the various food ingredients and the different processes involved in introducing bubbles into the melt, producing well dispersed multiphase systems. The second part of this review focusses on aerated chocolate and the above aspects are particularly important and are discussed in some detail since it has been well established that the bubble size and size distribution can influence the texture, the mouthfeel, the crispness, the melting temperature, and the brittleness of the product. Understanding the science involved in the transformation from the liquid state containing dispersed bubbles to a solid chocolate foam, stabilization of the bubbles and the control of the bubble size are highlighted. Although CO2 is usually used to generate bubbles in chocolate, several different gases including N2O, Ar and N2 have also been evaluated. One of the research aims of food companies is to improve control over the stability of the systems. This has been investigated with respect to drainage, by carrying out experiments under zero gravity conditions.

Prevalence of chronic viral hepatitis in people of south Asian ethnicity living in England: the prevalence cannot necessarily be predicted from the prevalence in the country of origin.

The prevalence of hepatitis B and hepatitis C in immigrant communities is unknown. Immigrants from south Asia are common in England and elsewhere, and the burden of viral hepatitis in these communities is unknown. We aimed to determine the prevalence of viral hepatitis in immigrants from south Asia living in England, and we therefore undertook a community-based testing project in such people at five sites in England. A total of 4998 people attending community centres were screened for viral hepatitis using oral fluid testing. The overall prevalence of anti-hepatitis C virus (HCV) in people of south Asian origin was 1.6% but varied by country of birth being 0.4%, 0.2%, 0.6% and 2.7% in people of this ethnic group born in the UK, India, Bangladesh and Pakistan, respectively. The prevalence of hepatitis B surface antigen was 1.2%-0.2%, 0.1%, 1.5% and 1.8% in people of this ethnic group born in the UK, India, Bangladesh and Pakistan, respectively. Analysis of risk factors for HCV infection shows that people from the Pakistani Punjab and those who have immigrated recently are at increased risk of infection. Our study suggests that migrants from Pakistan are at highest risk of viral hepatitis, with those from India at low risk. As prevalence varies both by country and region of origin and over time, the prevalence in migrant communities living in western countries cannot be easily predicted from studies in the country of origin.

Value of targeting at-risk populations at outreach venues: findings from a local sauna.

An assessment of the need to increase access to an outreach venue, the local sauna in Walsall, UK, frequented only by men who have sex with men, was undertaken. A case-notes review of the clients who attended the monthly outreach sessions at the sauna in the year 2007 was performed. Among the 287 men seen at the 12 outreach sessions, 37% had a sexually transmitted infection (STI). Of those tested positive, 88% had never had a previous STI. Twenty-one men had syphilis and a further six tested positive for HIV. Hepatitis B vaccination was completed for 41% of the clients seen. Those who tested positive for an STI said they would not have attended a conventional setting but accepted screening at the sauna. This confirmed the need to increase access at this outreach venue, and further funding has now been provided to have outreach sessions twice a month.

Incidence and risk factors for alopecia in survivors of critical illness: A multi-centre observational study.

PURPOSE: To investigate the incidence, nature and risk factors for patient-reported alopecia in survivors of critical illness. MATERIALS AND METHODS: A multi-centre, mixed methods observational study in the intensive care units (ICU) of ten hospitals in Wales. All patients with an ICU stay of 5 days or more, able to give consent were included. Demographic variables and risk factors were collected. A pre-designed survey was completed at three months post-ICU discharge. Statistical analysis included numbers and percentages (categorical variables) and medians and interquartile ranges (continuous variables). Comparisons between patients with and without alopecia were made using Fisher's Exact test (categorical variables) and Mann Whitney U test (continuous variables). Multivariate logistic regression analysis was used to determine the risk factors for alopecia. RESULTS: The survey was completed by 123 patients with alopecia reported in 44 (36%) patients. The only risk factor for alopecia on analysis was sepsis / septic shock (p < .001; OR: 5.1, 95%CI: 2.1-12.4). CONCLUSIONS: Limited research exists examining the incidence, nature and risk factors for patient-reported alopecia in adult survivors of critical illness. The results of this study highlight the need to discuss the potential for alopecia with survivors of critical illness, who had sepsis / septic shock.

Diagnostic specificity of a real-time RT-PCR in cattle for foot-and-mouth disease and swine for foot-and-mouth disease and classical swine fever based on non-invasive specimen collection.

Foot-and-mouth disease virus (FMDV) and classical swine fever virus (CSFV) are highly contagious and can cause great economic losses when introduced into disease-free regions. Accurate estimates of diagnostic specificity (Sp) are important when considering the implementation of surveillance for these agents. The purpose of this study was to estimate diagnostic Sp of a real-time reverse-transcriptase PCR assay developed for detection of FMDV in cattle and domestic swine and CSFV in domestic swine based on non-invasive specimen collection. One thousand and eighty-eight range beef cattle were sampled from thirteen geographic locations throughout Texas. One thousand and one hundred market hogs and cull sows were sampled. Results for both FMDV and CSFV were considered positive if amplification occurred at or before 40 PCR cycles, inconclusive between 40 and 45 cycles and negative otherwise. Ten cattle had nonspecific PCR amplifications for FMDV, but none were classified as positive and only one as inconclusive. Specificity (95% confidence interval) was estimated as 100% (99.7, 100). There were 19 nonspecific PCR amplifications for FMDV in sampled swine with 1 classified as positive, 6 as inconclusive, and 12 as negative. Specificity (95% confidence interval) was estimated as 99.9% (99.5, 100). There were 21 nonspecific PCR amplifications for CSFV, and 1 was classified as positive. Specificity (95% confidence interval) was estimated as 99.9% (99.5, 100). These assays have high Sp, but nonspecific PCR amplifications can occur.

Syphilis outbreak in Walsall, UK: lessons for control and prevention.

An assessment of risk-taking behaviour among men who have sex with men (MSM) attending a sauna venue was undertaken, using a standardized questionnaire, after which outreach screening was introduced targeting MSM. The epidemiology of the continuing outbreak of syphilis was reviewed to determine the factors driving the outbreak and assess the benefit of continuing outreach screening. Findings among the 163 respondents at the sauna included a high rate of casual sex and a tendency not to disclose HIV status. Over 12 months, 51 cases of early syphilis were recorded. Our review showed a decline in incidence in MSM after outreach screening, but an increase in heterosexual spread. Given the frequent anonymous nature of syphilis transmission, traditional contact tracing is ineffective. Outreach screening is required at gay venues and other community settings to target at-risk populations.

An innovative solution to raise public awareness using a mobile colorectal clinic - The 'bowel bus'.

INTRODUCTION: Colorectal cancer is the fourth most common cancer in the United Kingdom; however, figures show that the uptake for bowel cancer screening lags behind other cancer screening programmes. METHODS: This is a report of a multi-staged development of an outreach colorectal clinical community service provided through a Mobile Unit (a Bowel Bus). The unit delivers a one-stop colorectal clinic that provides a rapid access pathway to members of the public who have concerns about, or symptoms of, bowel cancer. The aims of the project were to increase public awareness about colorectal cancer and to provide an outreach clinic as a supplement to the hospital based colorectal clinic. This service is a result of collaborative efforts between Tenovus Cancer Care (TCC) and the colorectal surgery department of the local NHS Hospital. RESULTS: During one year, the Bowel Bus has provided services to 772 members of the local community. 244 patients were examined by the colorectal nurse specialist including 66 drop-in patients and 135 patients referred by the GPs. The service led to decrease in the waiting list for routine referrals to be seen in the colorectal clinic at the hospital from a mean of 10.5 weeks-5.9 weeks. A feedback questionnaire from 180 patients, used to audit the quality of the service, has confirmed an overwhelming satisfaction with the service. CONCLUSION: The Mobile Unit is a novel solution to addressing the ever increasing demand for specialist outpatient services without compromising the quality of care whilst enhancing the patient experience.

The crisis in sexual health and developing genitourinary medicine services: lessons from a primary care trust.

The House of Commons Health Select Committee recently described a national crisis in sexual health. Alarmed by dramatic increases in the rates of sexually transmitted infections (STIs) and appalled by over-stretched, under-resourced genitourinary (GU) medicine services, the committee has called for urgent action. The increasing rates of STIs locally, a significant cluster of syphilis cases, and an over-burdened GU medicine service prompted Walsall primary care trust to undertake an evaluation of local service provision. The results were used to inform the development of GU medicine services locally and Walsall's sexual health strategy. This paper reports the results of the evaluation and the implications for service development. The Walsall GU medicine service was evaluated using three approaches, based on standards for GU medicine service provision identified from the literature. Routine data were used to analyse trends in STIs and service activity, including access times. These data further informed the evaluation process. Local stakeholder views on GU medicine service provision were sought using semi-structured interviews. Most standards relating to the provision of core services, including those for the management of patients with HIV infection, were met. High levels of patient satisfaction were reported. However, under-staffing, inadequate clinic facilities, and limited joint working with other agencies were highlighted as key concerns. Tackling sexual health inequalities and improving the sexual health of the population requires investment in resources and manpower, improved partnership working, and configuring services around the needs of patients. In addition, and perhaps most importantly, it will require a shift in how both health professionals and the public perceive and utilize sexual health services.

Fatty acid and sensory characteristics of beef from three biological types of cattle grazing cool-season forages supplemented with soyhulls.

Over two consecutive years, the effects of allocating divergent biological types of cattle (n=107) to fescue pasture without supplementation, or fescue or orchardgrass pasture with soyhull supplementation on chemical, fatty acid and sensory characteristics were investigated. Cattle from the two supplemented treatments produced beef that had increased (P<0.05) percentage lipid and decreased (P<0.05) polyunsaturated and n-3 fatty acids compared to the control. However, the n-6 to n-3 ratio was still less than four in beef from the supplemented cattle. Additionally, supplementation did not decrease (P>0.05) the CLA present in the longissimus, which can commonly occur when forage-fed cattle are supplemented concentrates. Although supplementation did not impact (P>0.05) Warner-Bratzler shear force or tenderness, supplementation of soyhulls reduced (P<0.05) the grassy flavor intensity of rib steaks when compared to the control. Biological type did not have a significant influence on most traits analyzed in this study. These results suggest that supplementation of soyhulls to cattle grazing forage can reduce grassy flavor intensity without decreasing CLA proportions, but can reduce the n-3 fatty acid proportions present in the longissimus.

Survival of patients with metastatic breast cancer treated with either combination or sequential chemotherapy.

One hundred twenty-one patients with metastatic adenocarcinoma of the breast were randomized to concurrent combination therapy or single-drug chemotherapy administered sequentially. Although response frequency and duration of response were significantly increased in patients receiving the combination regimen, survival was not significantly prolonged when compared to those receiving sequential treatment. For the 69 patients free of liver metastasis, median survival was comparable in both treatment arms (14.4 months sequential versus 12.8 months combination). These results indicate that a large subset of patients with metastatic breast cancer may benefit from less aggressive therapeutic regimens. Furthermore, these results illustrate that conclusions of chemotherapy trials in breast cancer based only on response frequency and duration of response represent preliminary results subject to change when final survival information becomes available.

The LH1-RC core complex of Rhodobacter sphaeroides: interaction between components, time-dependent assembly, and topology of the PufX protein.

Mutant strains of the photosynthetic bacterium Rhodobacter sphaeroides, lacking either LH1, the RC or PufX, were analysed by mild detergent fractionation of the cores. This reveals a hierarchy of binding of PufX in the order RC:LH1 > LH1 > RC. The assembly of photosynthetic membranes was studied by switching highly aerated cells to conditions of low aeration in the dark. The RC-H subunit appears before other components, followed by the pufBALMX then pufBA transcripts. Synthesis of the PufX polypeptide precedes that of LH1alpha and beta, which suggests that PufX associates with a limited amount of LH1alpha, beta and the RC, and prior to the encirclement of the RC by the rest of the LH1 complex. The topology of PufX within the intracytoplasmic membrane was determined by proteolytic treatment of membrane vesicles followed by protein sequencing; PufX is N-terminally exposed on the cytoplasmic surface of the photosynthetic membrane.

Combination chemotherapy, glucocorticoids, and interferon alfa in the treatment of multiple myeloma: a Southwest Oncology Group study.

PURPOSE: Standard therapy for multiple myeloma consists of cytotoxic chemotherapy plus glucocorticoids. Interferon (IFN) alfa maintenance is reported to prolong chemotherapy-induced remissions and survival. This study evaluates induction chemotherapy, glucocorticoids, and interferon maintenance in myeloma. PATIENTS AND METHODS: Five hundred twenty-two previously untreated myeloma patients were randomized to three chemotherapy regimens with differing glucocorticoid intensities. Patients who achieved remission were randomized to receive IFN or observation until relapse. Patients who failed to respond to chemotherapy received IFN alfa plus dexamethasone (DEX). RESULTS: Five hundred nine patients were eligible for induction chemotherapy. Chemotherapy with higher dose-intensity glucocorticoids yielded higher response rates and improved survival (P = .02 for the three-group comparison; P < .05 for each higher glucocorticoid arm v vincristine, melphalan, cyclophosphamide, and prednisone alternating with vincristine, carmustine [BCNU], doxorubicin, and prednisone [VMCP/VBAP]). One hundred ninety-three patients who achieved remission were randomized to receive IFN alfa 3 MU three times weekly or observation. IFN was not superior to observation for relapse-free (P = .95) or overall survival (P = .39) from start of maintenance. Eighty-eight induction failures received 5 MU of IFN three times weekly plus DEX. Patients who received IFN/DEX had a median survival duration of 48 months from start of IFN/DEX. CONCLUSION: Higher-dose glucocorticoids increases frequency of response to chemotherapy and prolong survival in myeloma. IFN maintenance with the dose schedule used in this trial did not prolong relapse-free or overall survival. We cannot exclude a small effect of IFN, as most individual trials do not have sufficient statistical power. Meta-analysis of randomized trials evaluating IFN maintenance in myeloma might be of value. While IFN appeared ineffective, addition of higher-dose glucocorticoids improved outcome in myeloma.

Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest Oncology Group study.

PURPOSE: Southwest Oncology Group (SWOG) protocol 8228 is a prospective trial designed to investigate the prognostic significance of progesterone receptor (PgR) levels in estrogen receptor (ER)-positive breast cancer patients who were treated with tamoxifen. This study was undertaken because the value of PgR measurements in advanced breast cancer had been assessed previously only in studies that were small, retrospective, or included heterogeneously treated patients. METHODS: Receptor assays were performed only in the laboratories that met strict quality control guidelines. Of the 398 patients entered, 342 patients were eligible and assessable for the study end points of objective clinical response, time to treatment failure, and overall survival. RESULTS: Multivariate analysis shows that elevated PgR levels significantly and independently correlated with increased probability of response to tamoxifen, longer time to treatment failure, and longer overall survival. Overall response rate (defined as complete response [CR], partial response [PR], or stable disease [SD] for greater than 6 months) in this trial was 54%. Response rates to tamoxifen were 43%, 53%, and 61% in subsets of patients with less than 10, 10 to 99, and more than 100 fmol/mg PgR, respectively. Exploratory subset analysis using PgR and other prognostic variables identified ER-positive patient subsets with response rates to tamoxifen ranging from 24% (premenopausal patients) to 86% (postmenopausal patients with ER greater than 38 and PgR greater than 329 fmol/mg). No groups of ER-positive patients were identified who had such a low response rate as to absolutely preclude considering the use of tamoxifen. Multivariate analysis showed the independent, statistically significant predictors were: for response to tamoxifen, menopausal status, PgR, and ER; for time to treatment failure, menopausal status, disease-free interval (DFI), PgR, and ER; and for overall survival DFI, PgR, ER, site of disease, and history of adjuvant therapy. CONCLUSION: We conclude that knowledge of PgR levels together with other clinical information can improve the pretreatment assessment of ER-positive breast cancer patients with metastatic disease.

bcl-2, p53, and response to tamoxifen in estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group study.

PURPOSE: To test the hypothesis that high bcl-2 expression and accumulation of p53 protein, both of which should inhibit apoptosis, are associated with a poorer tamoxifen response and a more aggressive clinical course in estrogen receptor (ER)-positive metastatic breast cancer. METHODS: A total of 205 paraffin-embedded tumor blocks were evaluated for nuclear p53 (a marker of p53 inactivation) and cytoplasmic bcl-2 by immunohistochemistry (IHC). All patients received tamoxifen as initial therapy for metastatic disease. The study began in 1982 and follow-up duration of the 24 patients last known alive is 8 years. RESULTS: Response to tamoxifen and time to treatment failure (TTF) were not significantly associated with p53 status, although patients with higher p53 had a worse survival (P = .008; median, 36 v 20 months). Higher bcl-2 expression was associated with higher levels of ER (P = .02), better response to tamoxifen (62% v 49%; P = .07), longer TTF (median, 9 v 5 months; P = .002), and better survival (median, 40 months v 25 months; P = .009). In multivariate analyses, including ER, progesterone receptor (PgR), and p53, high bcl-2 remained significantly associated with a longer TTF (P = .007) and survival (P = .07). p53 status was a significant factor for shorter survival (P = .05), but not for TTF (P = .61). CONCLUSION: p53 status, as determined by IHC is not significantly associated with response to tamoxifen, although tumors with altered p53 protein are inherently more aggressive. Contrary to expectation, high bcl-2 identifies a relatively indolent phenotype of ER-positive metastatic breast cancer, in which patients experience a better clinical response to tamoxifen and a longer survival.

Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22.

PURPOSE: The National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a randomized trial (B-22) to determine if intensifying but maintaining the total dose of cyclophosphamide (Cytoxan, Bristol-Myers Squibb Oncology, Princeton, NJ) in a doxorubicin (Adriamycin, Pharmacia, Kalamazoo, MI)-cyclophosphamide combination (AC), or if intensifying and increasing the total dose of cyclophosphamide improves the outcome of women with primary breast cancer and positive axillary nodes. PATIENTS AND METHODS: Patients (N = 2,305) were randomized to receive either four courses of standard AC therapy (group 1); intensified therapy, in which the same total dose of cyclophosphamide was administered in two courses (group 2); or intensified and increased therapy, in which the total dose of cyclophosphamide was doubled (group 3). The dose and intensity of doxorubicin were similar in all groups. Disease-free survival (DFS) and overall survival were determined using life-table estimates. RESULTS: There was no significant difference in DFS (P = .30) or overall survival (P = .95) among the groups through 5 years. At 5 years, the DFS of women in group 1 was similar to that of women in group 2 (62% v 60%, respectively; P = .43) and to that of women in group 3 (62% v 64%, respectively; P = .59). The 5-year survival of women in group 1 was similar to that of women in group 2 (78% v 77%, respectively; P = .86) and to that of women in group 3 (78% v 77%, respectively; P = .82). Grade 4 toxicity increased in groups 2 and 3. Failure to note a difference in outcome among the groups was unrelated to either differences in amount and intensity of cyclophosphamide or to dose delays and intervals between courses of therapy. CONCLUSION: Intensifying or intensifying and increasing the total dose of cyclophosphamide failed to significantly improve either DFS or overall survival in any group. It was concluded that, outside of a clinical trial, dose-intensification of cyclophosphamide in an AC combination represents inappropriate therapy for women with primary breast cancer.

Experimental techniques for studying the structure of foams and froths.

Several techniques are described in this review to study the structure and the stability of froths and foams. Image analysis proved useful for detecting structure changes in 2-D foams and has enabled the drainage process and the gradients in bubble size distribution to be determined. However, studies on 3-D foams require more complex techniques such as Multiple-Light Scattering Methods, Microphones and Optical Tomography. Under dynamic foaming conditions, the Foam Scan Column enables the water content of foams to be determined by conductivity analysis. It is clear that the same factors, which play a role in foam stability (film thickness, elasticity, etc.) also have a decisive influence on the stability of isolated froth or foam films. Therefore, the experimental thin film balance (developed by the Bulgarian Researchers) to study thinning of microfilms formed by a concave liquid drop suspended in a short vertical capillary tube has proved useful. Direct measurement of the thickness of the aqueous microfilm is determined by a micro-reflectance method and can give fundamental information on drainage and thin film stability. It is also important to consider the influence of the mineral particles on the stability of the froth and it have been shown that particles of well defined size and hydrophobicity can be introduced into the thin film enabling stabilization/destabilization mechanisms to be proposed. It has also been shown that the dynamic and static stability can be increased by a reduction in particle size and an increase in particle concentration.