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Biomedical subjects

R Mullins

Publications and source records attributed to R Mullins.

At least 19 recordsLinked to original sources

The association between synthetic bedding and adverse respiratory outcomes among skin-prick test positive and skin-prick test negative children.

BACKGROUND: Synthetic bedding has been associated with increased child wheeze and also higher allergen levels in several studies. We aimed to examine whether the association between synthetic bedding and adverse respiratory outcomes was more evident among skin-prick test (SPT) positive children. METHODS: A cross-sectional survey involving a population sample of 758 (81% of eligible) school children aged 8-10 years from randomly selected schools in the Australian Capital Territory in 1999. Parental questionnaires for ISAAC respiratory symptoms and child bedding were obtained. SPT results of 10 common allergens were available on 722 of the subjects (77% of those eligible). Synthetic pillow or quilt use was termed synthetic upper bedding. RESULTS: Synthetic quilt use was associated with asthma (Adjusted Odds Ratio 1.67 (1.05, 2.65)), recent wheeze (AOR 1.63 (1.03, 2.59)) and allergic rhinoconjunctivitis (AOR 2.11 (1.33, 3.34)) among SPT-positive children. However, these associations were not apparent for SPT-negative children. Similarly, increasing synthetic upper bedding use was associated with more than 12 episodes of wheeze among SPT-positive children (AOR 1.69 (1.08, 2.64), P=0.02, per category) but not SPT-negative children (AOR 0.77 (0.26, 2.21), P=0.6, per category). CONCLUSION: The apparent association between synthetic upper bedding and adverse respiratory outcomes was evident among SPT-positive but not SPT-negative children. Prospective intervention studies that aim to examine the effect of upper bedding composition on child asthma among SPT-positive children are required.

Asthma↗

Non-secretion of mutant proteins of the glaucoma gene myocilin in cultured trabecular meshwork cells and in aqueous humor.

Until recently, very little was known about the molecular mechanisms responsible for the development of glaucoma, a leading cause of blindness worldwide. Mutations in the glaucoma gene myocilin (MYOC, GLC1A) are associated with elevated intraocular pressure and the development of autosomal dominant juvenile glaucoma and a subset of adult-onset glaucoma. MYOC is expressed in the trabecular meshwork (TM), a tissue responsible for drainage of aqueous humor from the eye, and the tissue involved in elevated intraocular pressure associated with glaucoma. To better understand the role of MYOC in glaucoma pathogenesis, we examined the expression of normal and mutant myocilin in cultured ocular (TM) and non-ocular cells as well as in the aqueous humor of patients with and without MYOC glaucoma. Normal myocilin was secreted from cultured cells, but very little to no myocilin was secreted from cells expressing five different mutant forms of MYOC. In addition, no mutant myocilin was detected in the aqueous humor of patients harboring a nonsense MYOC mutation (Q368X). Co-transfection of cultured cells with normal and mutant myocilin led to suppression of normal myocilin secretion. These studies suggest that MYOC glaucoma is due either to insufficient levels of secreted myocilin or to compromised TM cell function caused by congestion of the TM secretory pathway.

Animals↗

The relationship between low level nitrogen dioxide exposure and child lung function after cold air challenge.

BACKGROUND: Nitrogen dioxide (NO(2)) or home gas appliance use has been inconsistently associated with adverse respiratory outcomes in childhood. OBJECTIVES: (i) To examine the contribution of home gas appliance type and personal NO(2) exposure. (ii) To examine the relationship between NO(2) exposure and child lung function and respiratory history. (iii) To assess whether these relationships vary by house dust mite sensitization status. METHODS: A cross-sectional survey of 344 children (71% of the eligible group) with a mean age of 9.1 years from four randomly selected schools in the Australian Capital Territory from July to September 1999. Study measurements included a parental questionnaire, NO(2) exposure by passive gas samplers, skin prick testing for 10 aeroallergens and lung function at rest and after cold air challenge. RESULTS: Total NO(2) exposure was low with a mean concentration of 10.1 ppb. No associations were found between NO(2) exposure or gas appliance use and asthma, wheeze or baseline lung function. Personal NO(2) exposure was associated with a reduction in forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) after cold air challenge (adjusted difference - 0.12% (- 0.23% to - 0.01%) per 1 ppb increase). After exclusion of children who had home heating changed because of asthma, gas heater use was also significantly associated with a reduction in this measure (adjusted difference - 2.0% (- 3.7% to - 0.2%)). There was some evidence that these reductions were greater among the non-mite-sensitized children. CONCLUSIONS: The effect of low-level NO(2) exposure on these respiratory outcomes was not marked. The possible effect of low-level NO(2) exposure on non-specific bronchial reactivity requires confirmation. Future studies on NO(2) and respiratory health should include measures of house dust mite sensitization and bronchial hyper-responsiveness.

Air↗

Long-term benefits in self-reported health status of nasal continuous positive airway pressure therapy for obstructive sleep apnoea.

Doubt has been expressed about the efficacy of nasal continuous positive airways pressure (NCPAP) therapy for sleep apnoea. Recent evidence from a randomized controlled trial of 1 month duration, suggested that NCPAP therapy can have a substantial impact on subjective and clinical outcomes in the short term, but data was not available to determine whether these effects were sustained over the long term. This study, an extension of the original trial, examined whether the beneficial impacts of NCPAP continued over the longer term. Patients were followed-up 1 month after being placed on active or sub-therapeutic NCPAP. They completed health status measures and a clinical test of sleepiness. After this period, all patients were placed on NCPAP and followed up 5 months later. The beneficial impact of NCPAP on sleep apnoea was sustained on all measures at follow-up. Furthermore, those who had initially been in the sub-therapeutic arm gained scores after 5 months of NCPAP similar to those of the active group. The impact of NCPAP appears sustained in the longer term. Subjective health status instruments have been advocated as important outcome points in randomized trials. This study would support such a use, and shows the important role of patient report in the evaluation of health care.

Follow-Up Studies↗

Clinical utility of monitoring tacrolimus blood concentrations in liver transplant patients.

The relationship between the dose of tacrolimus, trough tacrolimus blood concentration, and selected clinical endpoints (acute rejection, nephrotoxicity, and other toxicities) were examined in a prospective, multicenter clinical trial to validate the use of an enzyme-linked immunosorbent assay (ELISA) for monitoring whole-blood concentrations of tacrolimus in liver transplant patients. A total of 111 subjects from six transplant centers were evaluated over 12 weeks posttransplantation. In addition to trough tacrolimus blood concentrations, hematocrit, ALT, AST, GGTP, alkaline phosphatase, total bilirubin, serum creatinine, BUN, serum potassium, serum magnesium, blood glucose, and serum albumin were also measured. The relationship between trough tacrolimus blood concentrations and clinical endpoints was analyzed using both a logistic regression model and a Cox proportional hazard model. By logistic regression analysis, a statistically significant (p = 0.0465) relationship between increasing trough tacrolimus blood concentrations and decreasing risk of acute rejection was demonstrated over a 7-day time window. Nephrotoxicity and other toxicities also demonstrated statistically significant relationships with trough tacrolimus blood concentrations. The results of the Cox analysis were consistent with the logistic regression analysis. Using receiver operator characteristic curves, trough tacrolimus concentrations as measured by the ELISA method were able to differentiate the occurrence of nephrotoxicity and toxicity from nonevents. To minimize nephrotoxicity of tacrolimus, it is necessary to maintain trough blood concentrations below 15 ng/ml. This study demonstrates that the ELISA method used to measure tacrolimus blood concentrations in this study provides information of predictive value for managing the risk of nephrotoxicity, other toxicity, and rejection in liver transplant patients.

Administration, Oral↗

Management of the geriatric trauma patient at risk of death: therapy withdrawal decision making.

HYPOTHESIS: The management of geriatric injured patients admitted to a trauma center includes the selective decision to provide comfort care only, including withdrawal of therapy, and a choice to not use full application of standard therapies. The decision makers in this process include multiple individuals in addition to the patient. DESIGN: Retrospective review of documentation by 2 blinded reviewers of the cohort of patients over a recent 5-year period (1993-1997). SETTING: Trauma service of a level I trauma center. PATIENTS: A convenience sample of patients aged 65 years and older who died, and whose medical record was available for review. MAIN OUTCOME MEASURES: Patients were categorized as having withdrawal of therapy, and documentation in the medical record of who made the assessment decisions and recommendations, and to what extent the processes of care were documented. RESULTS: Among 87 geriatric trauma patients who died, 47 had documentation interpreted as indicating a decision was made to withdraw therapy. In only a few circumstances was the patient capable of actively participating in these decisions. The other individuals involved in recommendations for withdrawal of therapy were, in order of prevalence, the treating trauma surgeon, family members (as proxy reporting the patient's preferences), or a second physician. Documentation regarding the end-of-life decisions was often fragmentary, and in some cases ambiguous. Copies of legal advance directives were rarely available in the medical record, and ethics committee participation was used only once. CONCLUSIONS: Withdrawal of therapy is a common event in the terminal care of geriatric injured patients. The process for reaching a decision regarding withdrawal of therapy is complex because in most circumstances patients' injuries preclude their full participation. Standards for documentation of essential information, including patients' preferences and decision-making ability, should be developed to improve the process and assist with recording these complicated decisions that often occur over several days of discussion.

Advance Directives↗

Which derivative from overnight oximetry best predicts symptomatic response to nasal continuous positive airway pressure in patients with obstructive sleep apnoea?

The cost and inconvenience of polysomnography for the investigation of obstructive sleep apnoea (OSA) has led to the search for simpler and cheaper alternatives. These are usually compared to an apnoea/hypopnoea index (AHI) derived from oro-nasal airflow and ribcage/abdominal effort sensors. However, AHI is not a proven gold standard for the identification of clinically important OSA. Recent work has shown that correctly analysed oximetry indices not only mimic AHI with considerable accuracy, but also predict the symptomatic response to nasal continuous positive airway pressure (nCPAP) at least as well as conventional polysomnographic indices. This current study looks at 10 different derivatives of all-night oximeter tracings in 81 patients with OSA, and compares their ability to predict the improvement in subjective sleepiness after 6 months of nCPAP therapy. Sleep apnoea in this study was defined as a > 4% SaO2 dip rate of > 10 h(-1), and an Epworth sleepiness score (ESS) of > 10 on presentation. Subjects took part in a placebo-controlled trial of nCPAP for 1 month and thereafter were all supplied with nCPAP set at an effective pressure. All night SaO2 was sampled every 2 sec and later analysed for mean, median, mean nadir of SaO2 dip, time below 90%, 2 and 12 sec delta index (an average measure of SaO2 change across these two time periods), rapid resaturation index (rises in SaO2 > 3% within 10 sec per hour), and > 4, > 3, and > 2% dips per hour. These indices were then correlated with the change in ESS seen after 6 months on nCPAP. Median compliance for the group was 5.8 (5/95% range, 1.5-8.0) h night(-1). The two best correlates of improvement in ESS were the > 4% SaO2 dips h(-1) (Spearman's r = -0.33 P=0.002) and the delta 12 sec index (r = -0.33, P = 0.003). Cumulative time below 90% SaO2 was almost as good (r = -0.29, P = 0.009). The worst correlate was the > 2% SaO2 dips h(-1) (r = 0.01, not significant). This study has identified which of several analyses of overnight oximeter recordings best identify nCPAP responsive OSA. Both > 4% SaO2 dips and 12 sec delta index are equally predictive and presumably the most appropriate derivatives to calculate from overnight records of SaO2.

Adult↗

Randomised prospective parallel trial of therapeutic versus subtherapeutic nasal continuous positive airway pressure on simulated steering performance in patients with obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) impairs vigilance and may lead to an increased rate of driving accidents. In uncontrolled studies accident rates and simulated steering performance improve following treatment with nasal continuous positive airway pressure (NCPAP). This study seeks to confirm the improvement in steering performance in a randomised controlled trial using subtherapeutic NCPAP as a control treatment. METHODS: Fifty nine men with OSA (Epworth Sleepiness Score (ESS) of > or =10, and > or =10/h dips in SaO(2) of >4% due to OSA) received therapeutic or subtherapeutic NCPAP ( approximately 1 cm H(2)O) for one month. Simulated steering performance over three 30-minute "drives" was quantified as: standard deviation (SD) of road position, deterioration in SD across the drive, length of drive before "crashing", and number of off-road events. The reaction times to peripheral target stimuli during the drive were also measured. RESULTS: Subtherapeutic NCPAP did not improve overnight >4% SaO(2) dips/h compared with baseline values, thus acting as a control. The SD of the steering position improved from 0.36 to 0.21 on therapeutic NCPAP, and from 0.35 to 0.30 on subtherapeutic NCPAP (p = 0.03). Deterioration in SD of the steering position improved from 0.18 to 0.06 SD/h with therapeutic NCPAP and worsened from 0.18 to 0.24 with subtherapeutic NCPAP (p = 0.04). The reaction time to target stimuli was quicker after therapeutic than after subtherapeutic NCPAP (2.3 versus 2.7 seconds, p = 0.04). CONCLUSIONS: Therapeutic NCPAP improves steering performance and reaction time to target stimuli in patients with OSA, lending further support to the hypothesis that OSA impairs driving, increases driving accident rates, and that these improve following treatment with NCPAP.

Accidents, Traffic↗

Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised prospective parallel trial.

BACKGROUND: Nasal continuous positive airway pressure (NCPAP) is widely used as a treatment for obstructive sleep apnoea. However, to date there are no randomised controlled trials of this therapy against a well-matched control. We undertook a randomised prospective parallel trial of therapeutic NCPAP for obstructive sleep apnoea compared with a control group on subtherapeutic NCPAP. METHODS: Men with obstructive sleep apnoea, defined as an Epworth sleepiness score of 10 or more and ten or more dips per h of more than 4% SaO2 caused by obstructive sleep apnoea on overnight sleep study, were randomly assigned therapeutic NCPAP or subtherapeutic NCPAP (about 1 cm H2O) for 1 month. Primary outcomes were subjective sleepiness (Epworth sleepiness score), objective sleepiness (maintenance of wakefulness test), and SF-36 questionnaire measurements of self-reported functioning and well-being. FINDINGS: 107 men entered the study: 53 received subtherapeutic NCPAP and 54 therapeutic NCPAP. Use of NCPAP by the two treatment groups was similar: 5.4 h (therapeutic) and 4.6 h (subtherapeutic) per night. Subtherapeutic NCPAP did not alter the overnight number of SaO2 dips per h compared with baseline, and thus acted as a control. Therapeutic NCPAP was superior to subtherapeutic NCPAP in all primary outcome measures. The Epworth score was decreased from a median of 15.5 to 7.0 on therapeutic NCPAP, and from 15.0 to 13.0 on subtherapeutic NCPAP (between treatments, p<0.0001). Mean maintenance-of-wakefulness time increased from 22.5 to 32.9 min on therapeutic NCPAP and, not significantly, from 20.0 to 23.5 min on subtherapeutic NCPAP (between treatments p<0.005). Effect sizes for SF-36 measures of energy and vitality were 1.68 (therapeutic) and 0.97 (subtherapeutic) NCPAP (between treatments p<0.0001). For mental summary score, the corresponding values were 1.02 and 0.4 (between treatments p=0.002). INTERPRETATION: Therapeutic NCPAP reduces excessive daytime sleepiness and improves self-reported health status compared with a subtherapeutic control. Compared with controls, the effects of therapeutic NCPAP are large and confirm previous uncontrolled clinical observations and the results of controlled trials that used an oral placebo.

Adult↗

Analysis of whole blood tacrolimus concentrations in liver transplant patients exhibiting impaired liver function.

In transplant patients with impaired liver function, HPLC methodologies have been suggested for monitoring whole blood tacrolimus concentrations because of the reported inaccuracy of immunoassay for whole blood tacrolimus concentrations. One hundred fifty whole blood samples from 50 subjects enrolled in a multicenter liver transplant trial were chosen for HPLC/MS/MS analysis without consideration of the clinical status of the patient at the time of sampling. These samples were chosen to represent the sampling intervals during the 12-week posttransplantation period. Retrospectively, the authors identified a subset of 39 samples from 27 subjects exhibiting impaired liver function as demonstrated by bilirubin concentrations > 3.0 mg/dL (mean +/-SD = 7.5 +/- 5.6 mg/dL). The authors compared the agreement of concentrations obtained from the PRO-Trac II ELISA and HPLC/MS/MS by least squares linear regression analysis and Bland/Altman analysis, in this subset against the agreement of concentrations for 76 samples with normal bilirubin. In the samples obtained from patients with impaired liver function the resulting regression equation was: ELISA = 1.19(HPLC) + 0.7; r = 0.9. The mean difference (HPLC/MS/MS - ELISA) was -2.5 ng/mL +/- 2.9 ng/mL (mean +/- SD). While 71% of samples agreed within 3 ng/mL, 3% (n = 1) exhibited a difference >10 ng/ml. The corresponding evaluation of the samples with normal bilirubin concentrations resulted in the regression equation ELISA = 0.96(HPLC) + 0.9; r = 0.9, and a mean difference of -0.6 ng/mL +/- 2.3 ng/mL. The authors conclude that while a small subset of patients with cholestasis may require closer evaluation with a more specific methodology, the majority of the patients may be satisfactorily monitored with the PRO-Trac II ELISA.

Adult↗

A strategy for involving general practitioners in smoking control.

OBJECTIVE: In 1991, the Victorian Smoking and Health Program introduced a simple intervention strategy for general practitioners that could be integrated conveniently and inexpensively into the routine care of patients who smoke. The aim of this study was to determine whether there had been a change over time in whether or not GPs advised their patients not to smoke. METHOD: The extent to which smokers remembered GPs talking to them about smoking was assessed in population-based surveys of adults in Victoria in 1990 (prior to the implementation of the intervention) and in 1992, 1994 and 1996. RESULTS: Over time there was a significant increase in the proportion of smokers who reported that their GP had provided them with help or information to stop smoking (chi 2 = 17.58, p < 0.001). In 1996, 9% of smokers said their doctor had advised them to contact Quit. CONCLUSION: Levels of recalled advice and provision of information regarding smoking cessation have increased by 10% over the past six years. However, nearly half the smokers in this study reported that they had been given inappropriate advice or no advice at all. IMPLICATIONS: A brief intervention by GPs, supplemented by appropriate referrals, has the potential to assist significant numbers of smokers to quit and may be more practical for GPs who are unable to personally provide all of the support smokers may need to quit.

Chi-Square Distribution↗

Trends in environmental tobacco smoke restrictions in the home in Victoria, Australia.

OBJECTIVE: To assess the extent to which smokers and non-smokers in Victoria, Australia attempt to keep their homes smoke free and to determine whether the proportion of people attempting to do so has changed over time. DESIGN: Face to face surveys conducted in Victoria each year from 1989 to 1997. PARTICIPANTS: Approximately 2500 randomly selected adults each year. MAIN OUTCOME MEASURES: Proportion of respondents who discourage their visitors from smoking; proportion of smokers who always smoke outside their own homes; behaviour of smokers when they are around children. Changes in each of these measures over time. RESULTS: Reports of visitors being discouraged from smoking rose from 27% in 1989 to 53% in 1997. Smokers who reported always smoking outside the home rose from 20% in 1995 to 28% in 1997. Not smoking in the presence of children rose from 14% in 1989 to 33% in 1996. Indoor restrictions on smoking were associated with the presence of children in the household and even more strongly with the presence of non-smoking adults. People who worked in places where smoking was totally banned were more likely to ask their visitors not to smoke than those who worked where smoking was allowed. CONCLUSIONS: The results indicate a strong move towards homes and towards protecting children from smoke. Efforts to support and facilitate this social change should be further encouraged.

Adolescent↗

Analytical validation of the PRO-Trac II ELISA for the determination of tacrolimus (FK506) in whole blood.

BACKGROUND: The analytical validation of multiple lots of the PRO-Trac II ELISA (DiaSorin) for the determination of tacrolimus in whole blood is described. METHODS: The analytical parameters assessed included analytical sensitivity, dilution linearity, functional sensitivity, values in samples containing no tacrolimus, intra- and interassay precision, supplementation and recovery, metabolite cross-reactivity, interference studies, and method comparisons HPLC-tandem mass spectrometry (HPLC/MS/MS) and the IMx Tacrolimus II multiparticle enzyme immunoassay. Where appropriate, assessments were performed according to NCCLS guidelines. RESULTS: The mean analytical detection limit was <0.25 microg/L for all lots, whereas the functional sensitivity was 1.0 microg/L. Excellent linear correlation (r = 0.985) was observed for dilution linearity. The intraassay imprecision was <7%, and the total imprecision by ANOVA was <10%. Recovery was 109% +/- 11%. Metabolite cross-reactivity was consistent with previous reports for this antibody. No interference was observed for 35 tested drugs. Method comparison with HPLC/MS/MS showed no statistically significant differences. Samples exhibited stability through four freeze/thaw cycles and for 1 week at room temperature. CONCLUSION: These data demonstrate that the PRO-Trac II ELISA is a robust, accurate, and precise tool for the assessment and management of tacrolimus blood concentrations in transplant patients.

Chromatography, High Pressure Liquid↗

Smoking and smoking cessation among men whose partners are pregnant: a qualitative study.

Smoking among partners of non-smoking pregnant women has been linked to adverse pregnancy outcome, including low birthweight. Paternal smoking also increases the risk of infant respiratory infections and sudden infant death syndrome, irrespective of maternal smoking status. Furthermore, men's smoking habits are probably one of the strongest influences on the extent to which women are able to quit smoking in pregnancy and maintain cessation post birth. In four focus group discussions, male smokers whose partners were pregnant discussed their beliefs about passive smoking in pregnancy, the barriers they perceived to quitting in pregnancy and their preparedness to support maternal cessation. Men were largely unaware that their own smoking could pose a specific risk to the fetus, but when pregnant women are smokers, men believed their own smoking habits were unimportant. For men, barriers to quitting during their partners' pregnancy were: lack of understanding as to how passive smoking can affect the fetus, including a belief that the fetus is "protected" inside its mother; lack of motivation to quit early in pregnancy due to the baby not being "real"; and concern about stress-induced marital discord associated with cigarette withdrawal. These findings are discussed with regard to messages and strategies which may influence men to quit during their partners' pregnancy.

Female↗

Prevalence of workplace smoking bans in Victoria.

Restrictions on smoking in the Victorian workplace have been measured since 1988. This paper investigates whether the trend of increasing prevalence of total bans found between 1988 and 1992 has continued. Estimates are based on workers' reports of the restrictions on smoking that apply at their workplaces. For indoor workers a total ban on smoking restrictions in the workplace has increased from 58% in 1992 to 66% in 1995. White collar workers continue to enjoy a higher rate of protection than blue collar workers. Factories, warehouses, hotels and restaurants are the worksites least likely to have restrictions. Bans result in considerable exiled smoking: half the smokers reported going out to smoke during working hours on their last work day.

Data Collection↗