Once-daily fluticasone furoate 50 mcg in mild-to-moderate asthma: a 24-week placebo-controlled randomized trial.

BACKGROUND: Inhaled glucocorticosteroids (ICS) are the mainstay of treatment in asthma. Fluticasone furoate (FF) is a novel, once-daily ICS asthma therapy. This study investigated the efficacy and safety of FF 50 mcg in patients with mild-to-moderate persistent asthma. METHODS: A 24-week, multicenter, randomized, placebo-controlled and active-controlled, double-blind, double-dummy, parallel-group phase III study. Three hundred and fifty-one patients (aged ≥12 years; uncontrolled by non-ICS therapy) were randomized to treatment (1 : 1 : 1) with once-daily FF 50 mcg dosed in the evening, twice-daily fluticasone propionate (FP) 100 mcg or placebo. The primary endpoint was change from baseline in evening trough forced expiratory volume in 1 s (FEV1 ) at Week 24. Secondary endpoints were change from baseline in the percentage of rescue-free 24-h periods (powered endpoint), change from baseline in evening and morning peak expiratory flow, change from baseline in the percentage of symptom-free 24-h periods and number of withdrawals due to lack of efficacy. RESULTS: Evening trough FEV1 at Week 24 was not statistically significantly increased with FF 50 mcg once-daily (37 ml [95% CI: -55, 128]; P = 0.430), but was with FP 100 mcg twice daily (102 ml [10, 194]; P = 0.030), vs placebo. No consistent trends were observed across other endpoints, including the powered secondary endpoint. No safety concerns were raised for either active treatment. CONCLUSIONS: FP 100 mcg twice daily improved evening trough FEV1 in patients with mild-to-moderate persistent asthma, but FF 50 mcg once daily did not demonstrate a significant effect. Secondary endpoints showed variable results. No safety concerns were identified for FF or FP.

Assessing the impact of diabetes on the quality of life of older adults living in a care home: validation of the ADDQoL Senior.

AIMS: Around a quarter of UK care-home residents have diabetes. Diabetes is known to impact quality of life but existing diabetes-specific quality of life measures are unsuitable for elderly care-home residents. We aimed to develop and evaluate a new measure for use with older adults, to be particularly suitable for use with care-home residents: the Audit of Diabetes-Dependent Quality of Life (ADDQoL) Senior*. METHODS: Content and format changes were made to the 19-domain ADDQoL, informed by related measures for people with visual impairments (12 domain-specific items were retained, four items were revised/added and three items were removed). This revision was modified further following cognitive debriefing interviews with three older adults living in a care home. Psychometric evaluation of the newly developed 17-domain ADDQoL Senior was conducted using data from 90 care-home residents with diabetes who took part in a broader intervention study. RESULTS: The life domains most impacted by diabetes were 'independence' and 'freedom to eat as I wish'. The ADDQoL Senior demonstrated good factor structure and internal consistency (Cronbach's alpha = 0.924). Domain scores were, as expected, significantly intercorrelated. CONCLUSIONS: The ADDQoL Senior measures the perceived impact of diabetes on quality of life in older adults, and has been found to be suitable for those living in care homes if administered by interview. The scale has demonstrated acceptability and excellent psychometric properties. It is anticipated that the number of items may be reduced in the future if our current findings can be replicated.

Treatment and secondary prevention effects of the probiotics Lactobacillus paracasei or Bifidobacterium lactis on early infant eczema: randomized controlled trial with follow-up until age 3 years.

BACKGROUND: Allergic disease has been associated with altered intestinal microbiota. Therefore, probiotics have been suggested as a potential treatment for eczema. OBJECTIVE: We investigated whether dietary supplementation of infants with eczema at age 3-6 months with Lactobacillus paracasei CNCM I-2116 or Bifidobacterium lactis CNCM I-3446 had a treatment effect or altered allergic disease progression. METHODS: Primary outcome included eczema severity (SCORing Atopic Dermatitis, SCORAD) 3 months post-randomization. Secondary: SCORAD (other visits); infant dermatitis quality of life (IDQoL); gastrointestinal permeability; urinary eosinophilic protein X; allergen-sensitization; allergic symptoms (age 12, 18, 36 months). A total of 208 infants aged 3-6 months with physician-diagnosed eczema were recruited; 137/208 (SCORAD ≥ 10, consuming ≥ 200 mL standard formula/day) were randomized to daily supplements containing L. paracasei or B. lactis or placebo for a 3-month period, while receiving extensively hydrolysed whey-formula (dairy-free diet). There were two open observational groups, one group exclusively breastfed (n = 22) and the other, standard formula-fed (n = 49). TRIAL NUMBER: ISRCTN41490500. RESULTS: Eczema severity decreased significantly over time in all groups. No significant difference was observed between randomized groups after 12-week treatment-period (SCORAD-score pre-/post-intervention: B. lactis 25.9 [95% CI: 22.8-29.2] to 12.8 [9.4-16.6]; L. paracasei 25.4 [22.1-29] to 12.5 [9.2-16.4]; placebo 26.9 [23.4-30.6] to 11.8 [9.6-14.3]; P = 0.7). Results were similar when analysis was controlled for allergen-sensitization, or when only sensitized infants were analysed. No differences were found for secondary outcomes. No difference was observed in SCORAD-score between randomized and observational groups. CONCLUSION AND CLINICAL RELEVANCE: We found no benefit from supplementation with B. lactis or L. paracasei in the treatment of eczema, when given as an adjunct to basic topical treatment, and no effect on the progression of allergic disease from age 1 to 3 years.

Body mass index in young children and allergic disease: gender differences in a longitudinal study.

BACKGROUND: The increase in allergic diseases has occurred in parallel with the obesity epidemic, suggesting a possible association. OBJECTIVE: We investigated the relationship of body mass index (BMI) up to age 8 years with allergic disease within a birth cohort. METHODS: Children were followed from birth and were reviewed at age 3, 5 and 8 years (n=731; male 406). Parents completed questionnaires; children were weighed, measured, skin prick tested and examined. RESULTS: Increasing BMI at 3, 5 and 8 years increased the risk of current wheezing at the corresponding age (odds ratio [95% confidence interval] per standardized deviation score: age 3, 1.26 [1.04-1.53], P=0.02; age 5, 1.33 [1.06-1.67], P=0.02; age 8, 1.27 [1.0-1.62], P=0.05). The effect of BMI on wheeze at age 8 years differed between boys and girls, with a significant positive association in girls, but not in boys (P=0.04 for interaction). The effect of BMI at earlier ages on current or subsequent wheezing did not differ significantly between genders. Increasing BMI significantly increased the risk of physician-diagnosed eczema at age 5 (1.23 [1.04-1.47], P=0.02) and 8 (1.23 [1.03-1.45], P=0.02), with a significant interaction between gender and BMI at age 5 (P=0.04). There was no association between BMI and sensitization. Being overweight at age 3 years was significantly associated with late-onset wheeze (3.83 [1.51-9.75], P=0.005), persistent wheeze (4.15 [2.07-8.32], P<0.001) and persistent eczema (1.79 [1.03-3.13], P=0.04) in both boys and girls. CONCLUSIONS: Being overweight is associated with an increased risk of allergic disease in childhood. However, the strength of the association varies with the gender, age and atopic phenotype.

Differences in both prevalence and titre of specific immunoglobulin E among children with asthma in affluent and poor communities within a large town in Ghana.

BACKGROUND: Reports from several African countries have noted an increasing prevalence of asthma in areas of extensive urbanization. OBJECTIVE: To investigate the relevance of allergen-specific sensitization and body mass index (BMI) to asthma/wheezing and exercise-induced bronchospasm (EIB) among children from affluent and poorer communities within a large town in Ghana. METHODS: Children with physician-diagnosed asthma and/or current wheezing aged 9-16 years (n=99; cases) from three schools with differing socio-economic backgrounds [urban affluent (UA), urban poor (UP) or suburban/rural (SR)] were recruited from a cross-sectional study (n=1848) in Kumasi, Ghana, and matched according to age, sex and area of residence with non-asthmatic/non-wheezy controls. We assayed sera for IgE antibodies to mite, cat, dog, cockroach, Ascaris and galactose-α-1,3-galactose. RESULTS: Children from the UA school had the lowest total serum IgE. However, cases from the UA school had a higher prevalence and mean titre of sIgE to mite (71.4%, 21.2 IU/mL) when compared with controls (14.3%, 0.8 IU/mL) or cases from UP (30%, 0.8 IU/mL) and SR community (47.8%, 1.6 IU/mL). While similar findings were observed with EIB in the whole population, among cases there was no difference in IgE antibody prevalence or titre between children with or without EIB. BMI was higher among UA children with and without asthma; in UP and SR communities, children with EIB (n=14) had a significantly higher BMI compared with children with asthma/wheezing without EIB (n=38) (18.2 vs. 16.4, respectively, P<0.01). CONCLUSIONS AND CLINICAL RELEVANCE: In the relatively affluent school, asthma/wheezing and EIB were associated with high titre IgE antibodies to mite, decreased total IgE, and increased BMI. This contrasted with children in the urban poor school and suggests that changes relevant to a Western model of childhood asthma can occur within a short geographical distance within a large city in Africa.

Patient-reported outcomes following islet cell or pancreas transplantation (alone or after kidney) in Type 1 diabetes: a systematic review.

AIMS: For selected individuals with complex Type 1 diabetes, pancreatic islet transplantation (IT) offers the potential of excellent glycaemic control without significant hypoglycaemia, balanced by the need for ongoing systemic immunosuppression. Increasingly, patient-reported outcomes (PROs) are considered alongside biomedical outcomes as a measure of transplant success. PROs in IT have not previously been compared directly with the closest alternate treatment option, pancreas transplant alone (PTA) or pancreas after kidney (PAK). METHODS: We used a Population, Intervention, Comparisons, Outcomes (PICO) strategy to search Scopus and screened 314 references for inclusion. RESULTS: Twelve studies [including PRO assessment of PAK, PTA, islet-after kidney (IAK) and islet transplant alone (ITA); n = 7-205] used a total of nine specified and two unspecified PRO measures. Results were mixed but identified some benefits which remained apparent up to 36 months post-transplant, including improvements in fear of hypoglycaemia, as well as some aspects of diabetes-specific quality of life (QoL) and general health status. Negative outcomes included short-term pain associated with the procedure, immunosuppressant side effects and depressed mood associated with loss of graft function. CONCLUSIONS: The mixed results may be attributable to limited sample sizes. Also, some PRO measures may lack sensitivity to detect actual changes, as they exclude issues and domains of life likely to be important for QoL post-transplantation and when patients may no longer perceive themselves to have diabetes. Thus, the full impact of islet/pancreas transplantation (alone or after kidney) on QoL is unknown. Furthermore, no studies have assessed patient satisfaction, which may highlight further advantages and disadvantages of transplantation.

Parents' views about pre-school immunization: an interview study in southern England.

BACKGROUND: National Health Service immunization statistics for England indicate that uptake of the first plus second dose of measles, mumps and rubella (MMR) vaccine, and pre-school booster against diphtheria, tetanus, polio and pertussis, is lower than for the primary course alone. This qualitative study aimed to explore parents' views about pre-school immunization and to identify possible reasons for lower pre-school uptake compared with the primary course. METHODS: Semi-structured interviews were conducted with 21 parents of children aged 2-5 years from 19 family units. The parents were recruited from nine playgroups and pre-schools in three locations in southern England. Data collection and analysis were guided by a modified Grounded Theory approach. RESULTS: Although most parents believed pre-school immunization to be important and most intended to immunise, a minority questioned whether it was necessary based on their understanding of the duration of protection provided by the primary course. Compared with primary immunization, parents typically received no information about pre-school doses prior to their invitation to attend and had little or no contact with healthcare professionals. Other barriers included minor illness, apprehension about taking an older child for vaccinations and work or childcare commitments. CONCLUSIONS: Parents reported uncertainties, anxieties and time constraints, all of which may contribute to poor attendance for pre-school immunization. These findings have important implications for providing parents with timely information about boosters and the two-dose MMR programme. They indicate the potential value of playgroup or pre-school involvement and the need for improved communication with children about immunization.

Household characteristics and allergen and endotoxin levels in Aleppo, Syrian Arab Republic.

Few data are available from Eastern Mediterranean countries about levels of domestic allergens and endotoxins. Dust samples were collected from mattresses and floors of 457 homes in the Syrian city of Aleppo and analysed for antigens and endotoxins. The most important predictors for detectable levels of house-dust mite allergen Der p 1 were Arabic-style houses (OR 3.21) and newer houses (OR 1.56). In homes without cats, rubber mattresses were associated with detectable cat allergen Fel d 1 in mattress dust (OR 1.6). Cockroach allergen Bla g 2 was significantly more likely to be detected in houses over 20 years old than newer houses. Endotoxin levels were significantly higher in wool/cotton mattresses and older houses.

Sex differences and predictors of objective cough frequency in chronic cough.

BACKGROUND: Women are consistently over-represented in specialist cough clinics and known to have a more sensitive cough reflex than men. Whether female sex and other patient characteristics are associated with higher cough rates is not known. A study was conducted to determine the predictors of objective cough frequency in patients presenting to a tertiary referral clinic with chronic cough. METHODS: 100 subjects (65 women) of mean (SD) age 55.8 (11.0) years and median cough duration 4 years (IQR 2.0-10.0) with unexplained chronic cough completed flow-volume loops (mean (SD) forced expiratory volume in 1 s 103 (15.2)% predicted; forced expiratory flow (FEF(50)) 68.8 (24.1)% predicted), methacholine challenge (42% positive), citric acid cough reflex sensitivity (C5; 0.12 M (IQR 0.06-0.50)) and the Leicester Cough Questionnaire. 24-h ambulatory cough monitoring was performed in 86 subjects; manually counted coughs were quantified as the number of explosive cough sounds per hour. RESULTS: Women coughed significantly more than men (geometric mean 16.6 coughs/h (95% CI 13.1 to 21.0) vs 9.4 coughs/h (95% CI 6.4 to 13.9), p = 0.01)). The cough reflex was also more sensitive in women than in men (median logC5 -0.9 M vs -0.6 M, p = 0.002), but cough-related quality of life was similar in women and men (12.0 (3.6) and 12.2 (3.2), respectively, p = 0.76). Linear regression analysis showed that 38.6% of the variation in cough rate was predicted by sex (p = 0.01), logC5 (p<0.001) and age (p = 0.002) but not lung function or bronchial hyper-reactivity. CONCLUSIONS: Ambulatory objective cough monitoring provides novel insights into factors modulating chronic cough. These findings suggest that effects of sex and age must be taken into account in the study of cough and when designing clinical trials testing novel antitussive agents.

The effect of mindfulness meditation on cough reflex sensitivity.

BACKGROUND: Chronic cough is common, and medical treatment can be ineffective. Mindfulness is a psychological intervention that aims to teach moment-to-moment non-judgemental awareness of thoughts, feelings and sensations. METHOD: 30 healthy subjects and 30 patients with chronic cough were studied in two sequential trials. For both studies, cough reflex sensitivity to citric acid (C5) was measured on two occasions, with urge to cough rated following each inhalation; between challenges subjects were randomised to (1) no intervention, (2) mindfulness or (3) no intervention but modified cough challenge (subjects suppress coughing). For the healthy volunteers, measures were 1 h apart and mindfulness was practised for 15 min. For the patients with chronic cough measures were 1 week apart and mindfulness was practised daily for 30 min. RESULTS: In healthy volunteers, median change (interquartile range (IQR)) in cough reflex sensitivity (logC5) for no intervention, mindfulness and suppression was +1.0 (0.0 to +1.3), +2.0 (+1.0 to +3.0) and +3.0 (+2.8 to +3.0) doubling concentrations (p = 0.003); there were significant reductions for both mindfulness (p = 0.043) and suppression (p = 0.002) over no intervention. In patients with cough, median change (IQR) in logC5 for no intervention, mindfulness training and voluntary suppression was 0.0 (-1.0 to +1.0), +1.0 (-0.3 to +1.0) and +1.0 (+1.0 to +2.0) doubling concentrations (p = 0.046); there was a significant reduction for suppression (p = 0.02) but not mindfulness (p = 0.35). Urge to cough did not change after mindfulness compared with control in either healthy subjects (p = 0.33) or those with chronic cough (p = 0.47). CONCLUSION: Compared with control, mindfulness decreased cough reflex sensitivity in healthy volunteers, but did not alter cough threshold in patients with chronic cough. Both groups were able to suppress cough responses to citric acid inhalation.

Dietary antioxidant intake, allergic sensitization and allergic diseases in young children.

BACKGROUND: Allergic diseases have risen in prevalence over recent decades. The aetiology remains unclear but is likely to be a result of changing lifestyle and/or environment. A reduction in antioxidant intake, consequent to reduced intake of fresh fruits and vegetables, has been suggested as a possible cause. OBJECTIVE: To investigate whether dietary antioxidant intake at age 5 was related to atopy at 5 and 8 years of age amongst children in an unselected birth cohort. METHODS: Children were followed from birth. Parents completed a validated respiratory questionnaire and children were skin prick tested at 5 and 8 years of age. Serum IgE levels were measured at age 5. At age 5, antioxidant intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). A nutrient analysis program computed nutrient intake, and frequency counts of foods high in the antioxidant vitamins A, C and E were assessed. RESULTS: Eight hundred and sixty-one children completed both the respiratory and FFQ. Beta-carotene intake was associated with reduced risk of allergic sensitization at age 5 [0.80 (0.68-0.93)] and 8 [0.81 (0.70-0.94)]. In addition, beta-carotene intake was negatively associated with total IgE levels (P = 0.002). Vitamin E intake was associated with an increased risk of allergic sensitization [1.19 (1.02-1.39)], only at age 5. There was no association between antioxidant intakes and wheeze or eczema. CONCLUSION: Increased beta-carotene intake was associated with a reduced risk of allergic sensitization and lower IgE levels, in 5- and 8-year-old children. Dietary antioxidants may play a role in the development of allergic sensitization.

Deep layer of sediments in alpine lake in the tropical mid-pacific.

Sediments from a unique high-altitude lake on Hawaii indicate ash falls and other airborne and waterborne materials for a period estimated to extend into the Pleistocene.

Can lay people deliver asthma self-management education as effectively as primary care based practice nurses?

OBJECTIVES: To determine whether well trained lay people could deliver asthma self-management education with comparable outcomes to that achieved by primary care based practice nurses. DESIGN: Randomised equivalence trial. SETTING: 39 general practices in West London and North West England. PARTICIPANTS: 567 patients with asthma who were on regular maintenance therapy. 15 lay educators were recruited and trained to deliver asthma self-management education. INTERVENTION: An initial consultation of up to 45 min offered either by a lay educator or a practice based primary care nurse, followed by a second shorter face to face consultation and telephone follow-up for 1 year. MAIN OUTCOME MEASURES: Unscheduled need for healthcare. SECONDARY OUTCOME MEASURES: Patient satisfaction and need for courses of oral steroids. RESULTS: 567 patients were randomised to care by a nurse (n = 287) or a lay educator (n = 280) and 146 and 171, respectively, attended the first face to face educational session. During the first two consultations, management changes were made in 35/146 patients seen by a practice nurse (24.0%) and in 56/171 patients (32.7%) seen by a lay educator. For 418/567 patients (73.7%), we have 1 year data on use of unscheduled healthcare. Under an intention to treat approach, 61/205 patients (29.8%) in the nurse led group required unscheduled care compared with 65/213 (30.5%) in the lay led group (90% CI for difference -8.1% to 6.6%; 95% CI for difference -9.5% to 8.0%). The 90% CI contained the predetermined equivalence region (-5% to +5%) giving an inconclusive result regarding the equivalence of the two approaches. Despite the fact that all patients had been prescribed regular maintenance therapy, 122/418 patients (29.2%) required courses of steroid tablets during the course of 1 year. Patient satisfaction following the initial face to face consultation was similar in both groups. CONCLUSIONS: It is possible to recruit and train lay educators to deliver a discrete area of respiratory care, with comparable outcomes to those seen by nurses.

Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood.

BACKGROUND: Patterns of wheezing during early childhood may indicate differences in aetiology and prognosis of respiratory illnesses. Improved characterisation of wheezing phenotypes could lead to the identification of environmental influences on the development of asthma and airway diseases in predisposed individuals. METHODS: Data collected on wheezing at seven time points from birth to 7 years from 6265 children in a longitudinal birth cohort (the ALSPAC study) were analysed. Latent class analysis was used to assign phenotypes based on patterns of wheezing. Measures of atopy, airway function (forced expiratory volume in 1 s (FEV(1)), mid forced expiratory flow (FEF(25-75))) and bronchial responsiveness were made at 7-9 years of age. RESULTS: Six phenotypes were identified. The strongest associations with atopy and airway responsiveness were found for intermediate onset (18 months) wheezing (OR for atopy 8.36, 95% CI 5.2 to 13.4; mean difference in dose response to methacholine 1.76, 95% CI 1.41 to 2.12 %FEV(1) per mumol, compared with infrequent/never wheeze phenotype). Late onset wheezing (after 42 months) was also associated with atopy (OR 6.6, 95% CI 4.7 to 9.4) and airway responsiveness (mean difference 1.61, 95% CI 1.37 to 1.85 %FEV(1) per mumol). Transient and prolonged early wheeze were not associated with atopy but were weakly associated with increased airway responsiveness and persistent wheeze had intermediate associations with these outcomes. CONCLUSIONS: The wheezing phenotypes most strongly associated with atopy and airway responsiveness were characterised by onset after age 18 months. This has potential implications for the timing of environmental influences on the initiation of atopic wheezing in early childhood.

How to quantify coughing: correlations with quality of life in chronic cough.

Different methods are used for quantifying coughing in sound recordings, but as yet no method has been shown to be more valid than any other. In the present study, the relationships between three different units of cough were examined and their ability to predict subjective ratings of cough and cough-related quality of life were evaluated. In total, 70 subjects (mean+/-SD age 55+/-11.7 yrs, 51 (73%) females) with chronic unexplained cough (median duration 4.8 yrs, interquartile range 2.5-10.1 yrs) performed fully ambulatory 24-h sound recordings, which were manually counted by trained observers and quantified by 1) explosive phases, 2) cough seconds and 3) cough epochs. Subjects also completed cough visual analogue scales (VAS) and the Leicester Cough Questionnaire (LCQ). All units of cough were strongly correlated; explosive phases and cough seconds correlated slightly more strongly than cough seconds with cough epochs or explosive phases with cough epochs. LCQ scores correlated moderately with explosive phases and seconds; epochs correlated slightly less well. Cough VAS scores showed a similar pattern. Explosive phases and seconds are interchangeable units of cough, moderately related to subjective measures and cough-related quality of life; epochs are a less satisfactory alternative.

Effect of age related macular degeneration on the Eger macular stressometer photostress recovery time.

AIM: To assess the repeatability of Eger macular stressometer (EMS) measures of photostress recovery and determine their association with other measures of visual function. METHODS: EMS photostress recovery time was measured in 90 patients with bilateral exudative age related macular degeneration (AMD), 19 with bilateral atrophic AMD and 47 with both forms of the condition (mean age 79 (SD 13) years). Measurements were made on two occasions separated by 1 year. Intrasession repeatability was assessed by repeating the measures after a 10 minute recovery period at the first visit. Distance visual acuity was measured with a logMAR chart, near visual acuity with a MNRead chart at 25 cm, contrast sensitivity with a Pelli-Robson chart, and the presence of central visual disturbance assessed with an Amsler grid. A questionnaire was used to assess self reported difficulties with glare recovery. RESULTS: The average EMS recovery time was 11.0 (SD 8.9) seconds, decreasing by 1.6 (5.2) seconds on repeated measurement (p<0.05). EMS photostress recovery was not correlated with visual function measures or subjective difficulties with lights (p>0.05). EMS photostress recovery time did not predict those whose vision decreased over the following year compared with those among whom it remained stable. CONCLUSIONS: The EMS test is not a useful tool in determining the severity or progression of AMD.

Abacavir compared to protease inhibitors as part of HAART regimens for treatment of HIV infection: patient satisfaction and implications for adherence.

The purpose of this study was to compare treatment satisfaction with triple nucleoside reverse transcriptase inhibitor (NRTI) highly active antiretroviral treatment (HAART) regimens including abacavir (ABC) to HAART regimens that include protease inhibitors (PIs) and to estimate the relationship between patient satisfaction and adherence to HAART. Three open-label clinical trials comparing ABC-including HAART regimens with PI-including HAART regimens were completed, two with patients previously untreated with antiretroviral therapy and one with patients successfully treated with PI-including HAART regimens. The HIV Treatment Satisfaction Questionnaire (HIVTSQ) was completed at several time points during each trial. Levels of patient satisfaction with the ABC and PI regimens were compared for all three trials. The correlation between adherence and patient satisfaction scores was measured using data from an adherence questionnaire in one of the studies. In all three clinical trials, patient satisfaction scores were significantly higher with an ABC-including triple NRTI HAART regimen than with a PI-including HAART regimen. The difference was apparent by week 4 of the trial and was maintained throughout the trial time period. Inspection of the item responses in the patient satisfaction questionnaire indicated that treatment convenience, flexibility, impact on lifestyle, and side effects were key factors in the difference in satisfaction between the treatment groups. In addition, patient satisfaction was shown to be significantly correlated with adherence defined as taking 95% or more of prescribed doses. Greater satisfaction was reported by patients given an ABC-including HAART regimen than those given a PI-including HAART regimen. Patient satisfaction may be an indicator for better treatment adherence.

Preemptive treatment for the prevention of cytomegalovirus disease: in lung and heart transplant recipients.

BACKGROUND: Rapid quantifiable diagnostic techniques for the diagnosis of cytomegalovirus (CMV) infection may predict patients at risk of CMV pneumonitis and allow preemptive antiviral treatment. METHODS: Using CMV antigenemia as a prospective surveillance technique for CMV infection, we compared the outcome of preemptive treatment (PT) with ganciclovir, 10 mg/kg/day for 21 days directed by "high levels" of CMV antigenemia (PT group, n= 19), with the outcome in a group of historical controls (n=18) treated with ganciclovir when CMV illness occurred. Greater than 50 antigen-positive cells per 2 x 10(5) polymorphonuclear leukocytes was considered to be high-level antigenemia. RESULTS: Nine of the 18 controls developed high-level CMV antigenemia at a median of 33 days (range: 13-65 days) and 5 of the 9 developed CMV disease. Ten of the 19 PT group had high levels of CMV antigenemia detected at a median of 47 days (range: 20-63 days) and were given ganciclovir; none developed CMV disease. There was a significantly lower incidence of CMV disease in the PT group in comparison to controls (0 of 19 vs. 5 of 18: P=0.019). CONCLUSION: We have reduced the incidence of CMV disease using preemptive treatment, and because of a 100% negative predictive value, we omitted unnecessary antiviral prophylaxis for many at-risk patients.

Hypertonic citrate solution as an alternative to modified Euro-Collins' solution for lung preservation.

In a canine model of acute ischemic lung injury, a hypertonic citrate solution (HTC) widely used for renal preservation in the United Kingdom, was compared with modified Euro-Collins' solution (ECS) currently the most widely clinically used pulmonary perfusate. Ten beagle dogs underwent left thoracotomy and exclusion of the left lung in situ. The lung was flushed with 30 ml/kg of either HTC or ECS and subjected to 60 min of warm ischemia. The circulation to the lung was then restored, the contralateral lung excluded, and the animal ventilated at a fixed FiO2 of 0.4 for 4 hr. Lung function was assessed by arterial oxygenation and hemodynamic measurements and, following sacrifice, by lung weight gain, bronchoalveolar lavage, and ultrastructural studies. Flush perfusion with HTC was associated with significantly less severe reperfusion injury, as determined by superior arterial oxygenation (PaO2 at 1 hr: HTC--152 mmHg [(95% confidence interval) CI] [122-182], ECS--59 [47-70]; PaO2 at 4 hr: HTC--124 [100-149], ECS--51 [42-61]), lower pulmonary vascular resistance index (PVRI at 4 hrs: HTC--838 dynes sec cm-5m-2 [651-1075], ECS--1233 [963-1588]); and lower lung weight (HTC--85 g [66-107], ECS--146 [114-184]). Bronchoalveolar lavage studies demonstrated an influx of neutrophils following reperfusion that was significantly less marked in the HTC group (increase in % neutrophils: HTC 24 [19-29], ECS 77 [72-82]). Lung injury assessed by electron microscopy tended to be less severe in the HTC animals. We conclude that HTC may offer an alternative superior to ECS for lung preservation.

Amelioration of lung ischemic injury with prostacyclin.

The single-flush technique of lung preservation is thought to be enhanced by prostaglandin treatment. In order to test this hypothesis, ten beagle dogs underwent thoracotomy and in situ flush perfusion of the excluded left lung with 30 ml/kg of cold, modified Euro-Collins' solution. Group 1 (n = 5) received pretreatment with 30 ng/kg/min of PGI2 by infusion and as an additive to the flush (20 micrograms/L). Group 2 (n = 5) received no PGI2 and served as controls. Following 60 min of warm ischemia, the left lung was reperfused, the contralateral lung excluded, and the animal ventilated at a fixed FiO2 of 0.4 for 4 hr. The severity of reperfusion injury was assessed by arterial oxygenation and hemodynamic measurements and, following sacrifice, by lung weight gain and bronchoalveolar lavage and ultrastructural studies. PGI2 therapy resulted in significant amelioration of reperfusion injury, with superior oxygenation at both 1 and 4 hr (PaO2 at 1 and 4 hr, respectively; PGI2: 145 mmHg +/- 17.0 and 114 +/- 11.2; no PGI2: 59 mmHg +/- 5.8 and 51 +/- 4.5; P less than 0.01 at both times), lower pulmonary vascular resistance index at 4 hr (PVRI; PGI2: 913 dynes sec cm-5m-2 +/- 91; no PGI2: 1239 +/- 68; P less than 0.05) and lower lung weight (PGI2: 76 g +/- 4; no PGI2: 146 +/- 10; P less than 0.001). Bronchoalveolar lavage studies revealed an influx of neutrophils following reperfusion that was less marked in the PGI2 group (increase in % neutrophils; PGI2: 50.4 +/- 6.7; no PGI2: 76.9 +/- 6.0; P less than 0.05). Lung injury score assessed by electron microscopy was lower in the PGI2 group (PGI2: 5.2 +/- 1.1; no PGI2; 8.1 +/- 0.5; P less than 0.05). It is concluded that PGI2 treatment is protective against ischemic lung injury in this model.