Racial and ethnic differences in patients enrolled in the national bronchiectasis and nontuberculous mycobacteria research registry.

Demographic and socioeconomic factors are recognized to contribute to disparities in healthcare outcomes. Originally, bronchiectasis was described in a population of predominantly White ethnic group of patients in which racial disparity could not be identified. The U.S. Bronchiectasis Research Registry (BRR), a centralized database of adult patients with bronchiectasis and/or NTM from 18 clinical institutions across the U.S., was created to support the research of this condition. The aim of this study is to describe the racial and ethnic distribution of patients enrolled in the BRR and evaluate factors associated with healthcare disparities within manifestations of and/or the care delivered to this population. At the time of this study, 3600 patients with bronchiectasis and/or NTM were enrolled in the BRR. Of those, 3510 participants were included in these analyses. The population was predominantly non-HispanicWhite (n = 3143, 89.5%), followed by Hispanic or Latino (n = 149, 4.3%), Asian (n = 130, 3.7%) and non-Hispanic Black (n = 88, 2.5%) participants. Testing for cystic fibrosis, immunoglobulin deficiency, and mycobacteria was not different between races, but non-Hispanic Black patients were tested less frequently for alpha-1 antitrypsin (A1AT) deficiency compared to other groups (P = 0.01). The four groups did not differ in the proportion of Pseudomonas aeruginosa or Hemophilus influenzae. There was no statistically significant difference in use of high-frequency chest wall oscillation, pulmonary rehabilitation services, or suppressive macrolide treatment across the groups (P > 0.05). There is a disproportionately high percentage of non-Hispainc White patients compared to non-Hispanic Black patients and Hispanic or Latino patients in the BRR. However, we found an overall similarity of care of BRR patients, regardless of racial and ethnic group.

Micro-CT scouting for transmission electron microscopy of human tissue specimens.

Transmission electron microscopy (TEM) provides sub-nanometre-scale details in volumetric samples. Samples such as pathology tissue specimens are often stained with a metal element to enhance contrast, which makes them opaque to optical microscopes. As a result, it can be a lengthy procedure to find the region of interest inside a sample through sectioning. We describe micro-CT scouting for TEM that allows noninvasive identification of regions of interest within a block sample to guide the sectioning step. In a tissue pathology study, a bench-top micro-CT scanner with 10 µm resolution was used to determine the location of patches of the mucous membrane in osmium-stained human nasal scraping samples. Once the regions of interest were located, the sample block was sectioned to expose that location, followed by ultra-thin sectioning and TEM to inspect the internal structure of the cilia of the membrane epithelial cells with nanometre resolution. This method substantially reduced the time and labour of the search process from typically 20 sections for light microscopy to three sections with no added sample preparation.

Children with dermatological conditions admitted to paediatric intensive care: analysis of a national clinical audit database.

There is little published literature about dermatological conditions in paediatric intensive care units (PICUs). The aim of this study was to describe the range of skin disorders in children admitted to PICUs in the UK and Ireland using data from a national audit. An analysis was conducted using data for 2002 - 2010 from the Paediatric Intensive Care Audit Network (PICANet). In total, 999 admissions of 882 children were identified, representing 0.8% of all PICU admissions. The most frequent dermatological conditions were skin infections, including cellulitis and necrotizing fasciitis, and inflammatory conditions. In 28% of cases, the dermatological diagnosis was considered the reason for PICU admission, in 35% it was a manifestation of systemic disease and in 37% it was considered incidental. Overall mortality was similar to the general PICU population, with 52 deaths (5.2%), but was greater in children with vascular/haematological conditions.

Observational study of children admitted to United Kingdom and Republic of Ireland Paediatric Intensive Care Units after out-of-hospital cardiac arrest.

AIMS: To estimate the prevalence of children admitted after out-of-hospital cardiac arrest (OHCA) to UK and Republic of Ireland (RoI) Paediatric Intensive Care Units (PICUs) and factors associated with mortality to inform future clinical trial feasibility. METHOD: Observational study using a prospectively collected dataset of the Paediatric Intensive Care Audit Network (PICANet) of 33 UK and RoI PICUs (January 2003 to June 2010). Cases (0 to <16 years), with documented OHCA surviving to PICU admission and requiring mechanical ventilation were included. Main outcomes were prevalence for admission and death within PICU. Factors associated with mortality were examined with multiple logistic regression analysis. RESULTS: 827 of 111,170 admissions (0.73%; 95% CI [0.48 to 0.98%]) were identified as children admitted following OHCA. PICU mortality for OHCA was 50.5% (418/827). Recruitment into an adequately sized clinical trial would not be feasible with the current prevalence rate. Characteristics at PICU admission associated with increased risk of death included; bilateral unreactive pupils, genetically inherited condition, inter-hospital transfer to PICU, requirement for vasoactive drugs and greater base deficit. Factors associated with reduced risk of death were submersion or a respiratory aetiology and pre-existing respiratory or cardiac conditions. CONCLUSIONS: Less than 120 children a year are admitted to PICUs in the UK and RoI after OHCA, limiting options for conducting UK intervention trials. The risk factors associated with mortality identified in this study will allow risk stratification in future studies.

Anaphylaxis admissions to UK critical care units between 2005 and 2009.

Anaphylaxis is a life-threatening emergency that may necessitate admission to a critical care unit. There are no reports of the frequency of admission to critical care units for patients with anaphylaxis or indeed any description of their demographic characteristics or outcomes. We analysed all physician-diagnosed cases of anaphylaxis over a 5-year period in national audit data from critical care units across the UK. Over the period 2005-2009, there were 81 paediatric and 1269 adult admissions with anaphylaxis admitted to UK critical care units (0.1% of admissions to paediatric units and 0.3% of admissions to adult units). Absolute numbers in both children and adults rose year on year. There were comparable proportions of admissions in female and male children (female = 47% and male = 53%; rate ratios (RR) = 0.88, 95% CI 0.64-1.20), but a greater proportion of adult female admissions (female = 65% and male = 35%; RR = 1.83, 95% CI 1.68-1.99). Survival to unit discharge was 95% (77/81) for children, and survival to hospital discharge was 92% (1166/1269) for adults. Each UK critical care unit is likely to see at least one anaphylaxis case per year. The number of admissions has risen in both children and adults. Although admission ratios between the sexes were comparable in children, there was a female preponderance in adult life. Survival rates were high at over 90%.

The use of a measure of acute irritation to predict the outcome of repeated usage of hand soap products.

BACKGROUND: Healthcare-associated infection is an important worldwide problem that could be reduced by better hand hygiene practice. However, an increasing number of healthcare workers are experiencing irritant contact dermatitis of the hands as a result of repeated hand washing. This may lead to a reduced level of compliance with regard to hand hygiene. OBJECTIVES: To assess whether a measure of acute irritation by hand soaps could predict the effects of repeated usage over a 2-week period. METHODS: In a double-blind, randomized comparison study, the comparative irritation potential of four different hand soaps was assessed over a 24-h treatment period. The effect of repeated hand washing with the hand soap products over a 2-week period in healthy adult volunteers on skin barrier function was then determined by assessment of transepidermal water loss (TEWL), epidermal hydration and a visual assessment using the Hand Eczema Severity Index (HECSI) at days 0, 7 and 14. RESULTS: A total of 121 subjects from the 123 recruited completed phase 1 of the study. All four products were seen to be significantly different from each other in terms of the irritant reaction observed and all products resulted in a significantly higher irritation compared with the no-treatment control. Seventy-nine of the initial 121 subjects were then enrolled into the repeated usage study. A statistically significant worsening of the clinical condition of the skin as measured by HECSI was seen from baseline to day 14 in those subjects repeatedly washing their hands with two of the four soap products (products C and D) with P-values of 0·02 and 0·01, respectively. Subclinical assessment of the skin barrier function by measuring epidermal hydration was significantly increased from baseline to day 7 after repeated hand washing with products A, B and D but overall no significant change was seen in all four products tested by day 14. A statistically significant increase in TEWL at day 14 was seen for product A (P = 0·02) indicating a worsening of skin barrier function. This effect was also seen initially for product D at day 7 although this was then lost at day 14. Further regression analysis was then performed to see if the acute irritant test data for each product correlated with the skin barrier data from the repeated usage component of the study. This showed that the results of acute irritant testing of the individual products did not predict the results of chronic use of hand soaps. CONCLUSIONS: The results from phase 2 of our study confirm the work of previous studies that show that regular exposure to irritants in daily life leads to stratum corneum damage and impairment of the skin barrier. Although significant differences were seen between the products in phase 1 of the study, regression analysis showed that the results of patch testing of the individual products did not predict the results of chronic use of hand soaps. When designing a study to assess the effects of cumulative use of a product on the skin, the study should mirror the use conditions of the product as closely as possible.

The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients.

BACKGROUND: The proportion of epithelial and stromal cells in tumours is thought to have an important role in the progression of epithelial malignancy. We aimed to determine whether the relative proportion of tumour (PoT) was related to survival in colorectal cancer. METHODS: The PoT at the luminal surface was measured by point counting using virtual tissue sections in a series of 145 colorectal cancer cases. The relationship of PoT to clinicopathological parameters including cancer-specific survival was analysed. Modified receiver operating characteristic curves were used to determine the optimum cut off points to dichotomise the data for survival analyses. RESULTS: Tumours with PoT-low (

A double-blind, randomized study to assess the effectiveness of different moisturizers in preventing dermatitis induced by hand washing to simulate healthcare use.

BACKGROUND: Healthcare-associated infection is an important worldwide problem that could be reduced by better hand hygiene practice. However, irritant contact dermatitis of the hands as a result of repeated hand washing is a potential complication that may be preventable by the regular use of an emollient. OBJECTIVES: To assess the effect of moisturizer application after repeated hand washing (15 times daily) vs. soap alone. METHODS: In a double-blind, randomized study, the effect of five different moisturizers on skin barrier function was determined by assessment after repeated hand washing over a 2-week period in healthy adult volunteers. Assessments of transepidermal water loss (TEWL), epidermal hydration and a visual assessment using the Hand Eczema Severity Index (HECSI) were made at days 0, 7 and 14. RESULTS: In total, 132 patients were enrolled into the study. A statistically significant worsening of the clinical condition of the skin as measured by HECSI was seen from baseline to day 14 (P = 0.003) in those subjects repeatedly washing their hands with soap without subsequent application of moisturizer. No change was seen in the groups using moisturizer. Subclinical assessment of epidermal hydration as a measure of skin barrier function showed significant increases from baseline to day 14 after the use of three of the five moisturizing products (P = 0.041, 0.001 and 0.009). Three of the five moisturizers tested led to a statistically significant decrease in TEWL at day 7 of repeated hand washing. This effect was sustained for one moisturizing product at day 14 of hand washing (P = 0.044). CONCLUSIONS: These results support the view that the regular application of moisturizers to normal skin offers a protective effect against repeated exposure to irritants, with no evidence of a reduction in barrier efficiency allowing the easier permeation of irritant substances into the skin as has been suggested by other studies. Regular use of emollient in the healthcare environment may prevent the development of dermatitis.

Factors predicting outcome for advanced gastroesophageal cancer in elderly patients receiving palliative chemotherapy.

AIMS: Most patients with advanced gastroesophageal cancer are elderly, but current standard regimens have emerged from trials predominantly involving patients with a median age <65 years. The aim of this study was to assess the factors influencing survival outcome for an elderly gastroesophageal cancer non-trial population. MATERIALS AND METHODS: We reviewed the case notes of all patients in our centre over the age of 65 years who received palliative chemotherapy for gastroesophageal cancer over a period of 3.5 years. Patients were classified as having received standard, non-standard combination or single-agent chemotherapy. After an initial univariate analysis, a multivariate analysis of the most significant prognostic factors was carried out. RESULTS: In total, 120 patients were suitable for analysis. The median overall survival for patients receiving standard chemotherapy was 8.1 months, non-standard combination 8.3 months and single-agent fluoropyrimidines 3.9 months. Poor prognosis was predicted by two independent factors: poor performance status (hazard ratio 2.402; 95% confidence interval 1.53-3.77, P<0.001) and the presence of cancer symptoms (hazard ratio 2.235; 95% confidence interval 1.32-3.79, P=0.003). CONCLUSIONS: An assessment of the performance status and the level of symptoms is vital in this vulnerable group of patients. Prospective randomised trials to assess the benefit of chemotherapy in elderly patients with gastroesophageal cancer are required.

Interleukin-4 -590 (C>T), toll-like receptor-2 +2258 (G>A) and matrix metalloproteinase-9 -1562 (C>T) polymorphisms in pre-eclampsia.

Functional single nucleotide polymorphisms (SNPs) of interleukin (IL)-4 -590 (C>T), toll-like receptor (TLR)-2 +2258 (G>A) and matrix metalloproteinase (MMP)-9 -1562 (C>T) were examined by polymerase chain reaction-restriction fragment length polymorphism to identify their merit as genetic markers for pre-eclampsia. One hundred and seventeen pre-eclamptic women and 146 control subjects with uncomplicated singleton pregnancies participated in this study, conducted at Leeds General Infirmary and St James's University Hospital. While the TLR-2 +2258 (G>A) and MMP-9 -1562 (C>T) SNPs failed to present any significant association with pre-eclampsia, there was a marked trend for an association between the IL-4 -590 (C>T) SNP and pre-eclampsia (chi(2)= 5.87, P = 0.055), with a prevalence of TT homozygous women in this group (OR 4.455, 95% CI 1.286-15.350).

Predictors of return to work following carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is an important part of secondary prevention in selected patients following a transient ischaemic attack or stroke. A key marker of success, return to work following surgery, was assessed in a retrospective cohort study. METHODS: Patients from the UK aged less than 65 years at operation were sent a questionnaire concerning return to work after CEA. Data were analysed using univariable tests and logistic regression. RESULTS: Some 174 (64.4 per cent) of 270 patients responded; their median age was 60 (range 35-64) years and 124 were men. Seventy-five per cent of respondents employed preoperatively returned to work following CEA. Newly retiring patients were older (62 versus 58 years; P < 0.001). Univariable analysis confirmed that age and preoperative stroke influenced return to work. The adjusted odds ratio for patients with versus without a preoperative stroke was 0.46 (95 per cent confidence interval 0.22 to 0.97) (P = 0.040). Median convalescence was 4 weeks, but was shorter in the self-employed (P = 0.039) and prolonged in patients with symptomatic cardiovascular disease (P = 0.023) and those who required postoperative critical care (P = 0.039). CONCLUSION: Return to work following CEA was influenced by age and preoperative stroke.

Comparison of the collagen VI content within the islet-exocrine interface of the head, body, and tail regions of the human pancreas.

Efficient islet isolation depends on the use of collagenase to digest the extracellular matrix within the islet-exocrine interface, the molecular structure of which is poorly understood. Recently it has been reported that transplantable yields of islets can be isolated from the tail segment of the pancreas alone. This study aimed to quantify and compare the amount of collagenase-resistant collagen VI within the islet-exocrine interface of the head, body, and tail of the human pancreas. Human adult pancreata (n = 5) were retrieved from heart-beating donors (age range, 40-62 years; cold ischemia times <10 hours). Tissue blocks from the head, body, and tail region of each pancreas were fixed in formalin and processed for immuno-labelling of collagen VI, which was quantified in the islet-exocrine interface using a Zeiss KS-400 image analysis system. Data were expressed as area of collagen at the interface relative to the islet area. Statistical analysis was done using paired t test. The mean islet areas in the head, body, and tail regions were not significantly different. Collagen VI was uniformly present within the islet-exocrine interface of all regions of the pancreas and was 0.326 +/- 0.064, 0.324 +/- 0.060, and 0.334 +/- 0.052 microm(2)/islet area (P = .441) in the head, body, and tail, respectively. The content of collagen VI within the islet-exocrine interface was uniform throughout all parts of the adult pancreas. Targeting this collagen subtype with novel collagenase blends may result in consistently improved islet yields and enable a wider number of available donor pancreata to be used.

Development of a novel digestion chamber for human and porcine islet isolation.

BACKGROUND: The current technique of human pancreas digestion for islet isolation relies on selective distribution of collagenase delivered via the pancreatic duct to produce digestion and removal of peri-acinar fibrous tissue. However, the collagenase has relatively little effect on the interlobular fibrous tissue, which must therefore be broken down by mechanical means within the digestion chamber so as to release the contained acini and islets. The current way of achieving this in the Ricordi chamber is to place five or six stainless steel balls within the chamber and shake vigorously. The shaking presumably breaks down the interlobular fibrous tissue by a combination of shear force induced by the movement of tissue through the shaking process, assisted by numerous blows from the steel balls. Intuitively, one would expect some islets would be destroyed rather than released by such a battering. METHODS: In an attempt to improve the efficiency of islet isolation we have designed a new digestion/filtration chamber that consists of a glass cylinder, sealed with Teflon plates holding in mesh filters at each end, secured in place by a central threaded tie-rod and external knurled nuts. A ring-shaped piston within the cylinder can be pushed up and down the travel by two rods passing out through sealed ports in the Teflon disk at one end and connected to an external handle. The handle is used to gently push the piston up and down the travel of the cylinder, which pushes the fluid and tissue through the central lumen of the ring-piston. A series of hooks attached to the central tie-rod catch the fibrous strands of the passing tissue; the shearing forces produced cause disruption by a process thought to be similar to teasing the tissue apart with fine forceps. RESULTS: A series of initial experiments with human pancreas showed the prototype to be too large, causing temperature control problems, and a redesigned smaller chamber was produced, maintaining the crucial design features. Experience processing five human pancreata has now demonstrated that in three of five pancreata the new chamber produced a good yield (>200,000 I.E.) of remarkably well separated and intact islets, the entire dispersion process being under 1 hour. However, in two isolations the collagenase digestion was poor, with few free islets. A copy of the new chamber (reserved for porcine work only) has been produced, as well as a copy of the Ricordi chamber. We have confirmed that the new chamber can isolate porcine islets in large numbers (>5000 islets/g pancreas [n = 2], but note that pig islets are small). CONCLUSION: These preliminary studies are sufficiently encouraging to justify further direct comparison with the Ricordi chamber for the purpose of animal and human islet isolation.

Serum prolactin and TSH in an in vitro fertilization population: is there a link between fertilization and thyroid function?

PURPOSE: Measurements of TSH and prolactin are generally included in the evaluation of female infertility, but their value in women coming to in vitro fertilization (IVF) has been questioned. METHODS: In this study, we sought to investigate whether prolactin or TSH, measured in 509 specimens collected prior to therapy, predicted outcome in a prospective study of couples undergoing IVF between 1994 and 2001. RESULTS: TSH was higher in women whose fertility problem was attributed to a male factor, and prolactin was lower if the measurement was taken during menses. TSH and prolactin were positively correlated (p < 0.0001). Neither TSH nor prolactin levels correlated with overall IVF outcome; however, TSH levels were significantly higher among women who produced oocytes that failed to be fertilized and this finding persisted after adjustment for several covariates, including sperm motility. Among women who had a least one oocyte inseminated, the likelihood that they would have fewer than 50% of their eggs fertilized was significantly related to higher TSH levels in a multivariate model. CONCLUSION: We conclude that TSH may predict poor fertilization in IVF and reflect the importance of thyroid hormones in oocyte physiology.

Transplantation of mouse pancreatic islets into primates--in vivo and in vitro evaluation.

BACKGROUND: Islets transplanted from other species to man has the potential to cure diabetes but whether islets are subject to hyperacute rejection after xenotransplantation is contentious. We transplanted mouse pancreatic islets of mouse beneath the primate renal capsule and assessed natural xenoantibody binding, complement activation and cell lysis in vitro. METHODS: Freshly isolated mouse islets were transplanted in a blood clot under the renal capsule of cynolmogus monkeys. The graft was removed after 24 hr for histological and ultrastructural analysis. Freshly isolated mouse pancreatic islets were analyzed in vitro by immunohistochemistry for Gal(alpha1,3)Gal and Von Willebrand factor expression and for IgG, IgM, C3, C4, and C5b-9 binding after incubation in 100% human serum. Complement mediated cell lysis was evaluated by 51Cr release assays after incubation of islets for 4 hr in human serum, plasma, and lymph with and without added neutrophils. RESULTS: Mouse islets transplanted under the renal capsule of cynomolgus monkeys were destroyed within 24 hr by a process involving necrosis with neutrophil and mononuclear cell infiltration. Gal(alpha1,3)Gal was strongly positive on only 10% of islet cells. After islet incubation in 100% human serum before frozen section, human IgG and IgM, C3, C4, and C5b-9 was deposited on islets with increased intensity in the periphery. Measurement of 51Cr release from labeled fresh islets after four hours incubation in 100% human serum showed 17% lysis and was not changed by addition of neutrophils. CONCLUSION: These results indicate that mouse islets in a primate recipient undergo rapid destruction by a process that has features similar to hyperacute rejection in vascularized organs and we propose the same term be used.

Recent trends in assisted reproductive techniques and associated outcomes.

OBJECTIVE: We examined recent trends in success rates for assisted reproduction and determined the influence of changes in patient selection and treatment characteristics on these trends. METHODS: We collected baseline information and abstracted treatment-related details and outcomes on 1244 couples accepted for in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) at three clinics in greater Boston from 1994-1998. RESULTS: Delivery rates per initiated cycle improved significantly from 14.9% for IVF and 20.6% for GIFT in 1994-1995 to 22.5% for IVF and 28.0% for GIFT in 1997-1998 (P < or = .001). After adjusting for female age, the two treatment-related variables that appeared most likely to explain this trend were decreased use of GnRH agonists in short course (flare) regimens and increased use of highly purified forms of urinary gonadotropins. CONCLUSION: There were significant improvements in the success rates for IVF and GIFT from 1994-1998 that correlated with changes in ovulation induction regimens.

Gonadotropin-releasing hormone agonist use in assisted reproduction cycles: the influence of long and short regimens on pregnancy rates.

OBJECTIVE: To compare the efficacy of GnRH agonists used in either the flare (short) or down-regulation (long) regimen as part of IVF or GIFT treatment cycles. DESIGN: Observational study. SETTING: Three IVF clinics. PATIENT(S): One thousand two hundred forty-four couples accepted for IVF or GIFT treatment at participating clinics. INTERVENTION(S): In vitro fertilization or GIFT protocols standard to each clinic were recorded. MAIN OUTCOME MEASURE(S): Treatment cycle characteristics and outcomes, including E2 level, number of oocytes retrieved, and clinical pregnancy rate. RESULT(S): At site 1, there were 146 clinical pregnancies in 980 flare cycles, for a pregnancy rate of 14.9%, compared with 148 clinical pregnancies in 650 down-regulation cycles, for a pregnancy rate of 22.8%. This difference persisted after adjustment for age, primary infertility diagnosis, GIFT or IVF therapy, and year of treatment, and appeared to be mediated largely by the number of oocytes retrieved (mean, 9.8 for downregulation and 8.7 for flare in the first cycle). Despite having fewer oocytes retrieved, women who received flare regimens had higher E2 levels before hCG administration. CONCLUSION(S): Women who received GnRH agonists in a flare regimen had 11% fewer oocytes retrieved and a 35% reduction in the clinical pregnancy rate compared with those who received them in a down-regulation regimen; this difference was not explained by patient selection factors.