Confidence Limits For Difference Research Articles

P212 Parasternal Intercostal Electromyography To Assess Neural Respiratory Drive In Healthy Adult Subjects

Neural respiratory drive (NRD), measured using the parasternal intercostal muscle electromyogram (EMGpara), relates to lung disease severity as quantified by conventional methods in a range of diseases. Reference data from healthy populations are required for the technique to be used as an independent measure of lung disease severity. EMGpara has previously been expressed as a percentage of that obtained during a maximal inspiratory effort (EMGpara%max), restricting the use of the technique to subjects able to reliably perform such manoeuvres. The aim of this study was to investigate variability of both raw EMGpara (rEMGpara) and EMGpara%max in healthy adults. EMGpara was measured during tidal breathing in 43 healthy adult non-smokers (25 females, median (range) age 32 (19–79)years, mean (SD) BMI 23.4 (3.5) kg/m 2 ), using surface electrodes positioned bilaterally over the second interchondral space. Measurements were made with and without a mouthpiece/pneumotachograph in situ in 20 participants. Repeated measures were obtained within the same testing session in 27 subjects, and at least seven days later in 13 individuals. Spirometry, height, weight, BMI, fat free mass (FFM) via bioelectrical impedance and measures of regional fat distribution (waist/hip ratio and neck circumference) were also recorded. Mean (SD) EMGpara%max and rEMGpara were 5.88 (3.63)% and 5.06 (2.26)µV respectively. Significant relationships were observed between anthropometric measures and rEMGpara and EMGpara%max (Table 1). rEMGpara and EMGpara%max were unrelated to spirometry variables. Median (range) rEMGpara and EMGpara%max increased significantly with the pneumotachograph in place (4.86 (2.11–8.19)µV versus 5.62 (2.47–10.98) µV and 4.77(1.68–17.00)% versus 6.78 (2.35–20.94)%, both p Analysis of variance by subject was used to assess within-subject variability. Measurement error was higher for EMGpara%max than rEMGpara (upper 95% confidence limit of difference between repeat measures of EMGpara%max 3.14%, versus 2.35 µV for rEMGpara; within-subject coefficient of variation EMGpara%max 30.8% versus rEMGpara 24.5%). rEMGpara appears to be a reproducible marker of NRD. Both rEMGpara and EMGpara%max are influenced by subjects’ anthropometry. Further investigation is required to determine whether these influences are technical or physiological and must be considered when the technique is applied clinically or for research, or when developing reference values.

Antibiotic Therapy for Streptococcal Pharyngitis Revisited

Infectious Diseases| August 01 2008 Antibiotic Therapy for Streptococcal Pharyngitis Revisited AAP Grand Rounds (2008) 20 (2): 15–16. https://doi.org/10.1542/gr.20-2-15 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Antibiotic Therapy for Streptococcal Pharyngitis Revisited. AAP Grand Rounds August 2008; 20 (2): 15–16. https://doi.org/10.1542/gr.20-2-15 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: amoxicillin, antibiotic therapy, penicillin, sore throat, streptococcal, pharyngitis Source: Lennon DR, Farrell E, Martin DR, et al. Once-daily amoxicillin versus twice-daily penicillin V in group A β-haemolytic streptococcal pharyngitis. Arch Dis Child. 2008;93(6):474–478; doi:10.1136/adc.2006.113506 Investigators from New Zealand enrolled children 5–12 years of age in a prospective, randomized (1:1), nonblinded study to determine if oral once-daily amoxicillin (1500 mg if >30 kg, 750 mg if ≤30 kg; n=177) was noninferior to oral twice-daily penicillin V (500 mg if >30 kg, 250 mg if ≤ 30 kg; n=176) for treatment of group A β-hemolytic streptococcal (GAβHS) pharyngitis. Both drugs were given for 10 days. Children were enrolled between May 1996 and November 1998 if they presented with a sore throat and signs and symptoms suggestive of acute pharyngitis at a school clinic and had a throat culture positive for GAβHS. Noninferiority was defined as the upper confidence limit (CL) of a less than 10% difference in treatment effect between the two arms. Exclusion criteria included receipt of antibiotics in the previous 72 hours; history of acute rheumatic fever (ARF), cardiac or kidney disease; a rash suggestive of scarlet fever or mononucleosis; immunocompromised state, neoplasia, terminal illness, or neutropenia; and inclusion in the study during the prior 12 weeks. Children were seen for follow-up evaluations three additional times: days 3–6, days 12-16, and days 26–36. Throat cultures were performed on all follow-up visits and all GAβHS isolates were serotyped to determine failure (same serotype as initial isolate), relapse (same serotype as previous isolate with an intervening negative culture), or new acquisition (different serotype from the initial isolate). Impact of therapy on clinical course was also evaluated at each follow-up visit. A total of 353 patients were enrolled. Half the patients were Maori and a third were Pacific Islanders. Eleven children in the amoxicillin and seven in the penicillin group did not complete their course of treatment. Both drugs were well tolerated and adherence was 97% for the amoxicillin group and 98% for the penicillin group for receiving ≥80% of their doses. Amoxicillin was not inferior to penicillin V for bacteriologic failure at any follow-up visit. On the first follow-up visit, the treatment failure rate was 5.8% in the amoxicillin group and 6.2% in the penicillin group, while at the second follow-up visit, the treatment failure or relapse rate was 12.7% for the amoxicillin group and 11.9% for the penicillin group (upper 95% CL for difference between the groups of 6.5%). At the third follow-up visit the treatment failure or relapse rate was 10.7% in the amoxicillin group and 11.3% in the penicillin group (upper 95% CL for difference between the groups of 8.5%). The higher rate of positive cultures at the second and third follow-up visits compared with the first follow-up visit was primarily due to relapse. No significant differences in resolution of symptoms were noted between treatment groups. The authors conclude that once-daily amoxicillin is noninferior to twice-daily penicillin for the treatment of GAβHS pharyngitis in this population. Drs. Rathore and Barton have disclosed... You do not currently have access to this content.

Effects of the CYP2D6 Gene Duplication on the Pharmacokinetics and Pharmacodynamics of Tramadol

The analgesic drug tramadol is bioactivated by CYP2D6 to the opioid receptor agonist O-desmethyltramadol. Case reports indicated that carriers of the CYP2D6 gene duplication may be at high risk for opioid adverse events. However, the effects of the CYP2D6 duplication on kinetics and dynamics of tramadol have not been systematically studied. Pharmacokinetics and effects were monitored after a single dose of 100 mg racemic tramadol in 11 carriers of a CYP2D6 gene duplication allele (ultrarapid metabolizer [UM]) and compared with 11 carriers of 2 active CYP2D6 genes (extensive metabolizer [EM]). Pharmacodynamics was measured by cold pressure test, pupillometry, and standardized adverse event recording. The maximum plasma concentrations of the active metabolite (+)R,R-O-desmethyltramadol were significantly higher in the UM group compared with the EM group (P = 0.005; t test) with a mean difference of 14 ng/mL (95% confidence limit of difference, 2-26 ng/mL). Median (+)R,R-tramadol area under the curve was 786 and 587 mug.h.L in EMs and UMs, and the corresponding median (+)R,R-O-desmethyltramadol area under the curve was 416 and 448 mug.h.L (P = 0.005, t test). There was an increased pain threshold and pain tolerance and a stronger miosis after tramadol in UMs compared with EMs. Almost 50% of the UM group experienced nausea compared with only 9% of the EM group. In conclusion, pharmacokinetic differences between EMs and UMs were smaller than expected; nevertheless, UMs were more sensitive to tramadol than EMs. Therefore, tramadol may frequently cause adverse effects in southern European and Northern African populations with a high proportion of UMs.

Randomized Placebo-Controlled Study of Low-Dose Warfarin for the Prevention of Central Venous Catheter–Associated Thrombosis in Patients With Cancer

In this multicenter, randomized, placebo-controlled clinical trial, we studied whether warfarin 1 mg daily reduces the incidence of symptomatic central venous catheter (CVC) -associated thrombosis in patients with cancer. Two hundred fifty-five patients with cancer who required a CVC for at least 7 days were randomly assigned to receive warfarin 1 mg or placebo. There were 11 (4.3%) symptomatic CVC-associated thromboses among 255 patients, with no difference in the incidence of symptomatic CVC-associated thrombosis between patients taking warfarin 1 mg daily (six of 130 patients; 4.6%) and patients taking placebo (five of 125 patients; 4.0%; hazard ratio, 1.20; 95% CI, 0.37 to 3.94). Warfarin had no effect on CVC life span (84 days v 63 days in control and warfarin groups, respectively; 95% confidence limit, -16 to 55 days; P = .09), and it did not affect the number of premature CVC removals (23.2% v 25.4% in control and warfarin groups, respectively; 95% confidence limit of difference -8.34 to 12.71; P = .68) or the frequency of major bleeding episodes (2% v 0% in control and warfarin groups, respectively; P = .5, Fisher's exact test). Symptomatic CVC-associated thrombosis in patients with cancer, although significant, is less common than previously reported. In this study, the administration of warfarin 1 mg daily did not reduce the incidence of symptomatic CVC-associated thrombosis in patients with cancer. However, the low rate of symptomatic CVC-associated thrombosis means that a much larger trial is required to address this issue definitively.

Infection by CagA-positive Helicobacter pylori strains in patients with ischemic heart disease: prevalence and association with exercise-induced electrocardiographic abnormalities.

The role of H. pylori infection in increasing the risk of ischemic heart diseases (IHD) is still debated. We determined serologically the prevalence of overall H. pylori and CagA-positive H. pylori infection in 63 consecutive patients with IHD and 189 gender- and age-matched controls. We also determined in patients the influence of the infection and the CagA serological status on the results of an exercise ECG test and other parameters considered possible variables that may enhance the risk of IHD. The prevalence of H. pylori infection in patients and controls was 79.3% and 73.0%, respectively (P = 0.403) and that of CagA-positive H. pylori infection was 69.8% and 42.3%, respectively (P = 0.0002). The scores of the ECG S-T segment and T-wave abnormalities in the course of an exercise ECG in uninfected patients and in patients infected by CagA-negative and CagA-positive H. pylori strains were (mean +/- SD): 1.59 +/- 0.67, 1.92 +/- 0.64, and 2.19 +/- 0.70, respectively; (P = 0.011, 95% confidence limits of difference 0.15-1.07, CagA-positive infected vs uninfected patients). There was no intergroup difference in the levels of peripheral white blood cells, glucose, cholesterol, triglycerides, creatinine, and systolic and diastolic pressure. In conclusion, genetic heterogeneity of H. pylori could possibly explain some conflicting results concerning the association of H. pylori infection with IHD. Coronary vessels of IHD patients infected by CagA-positive H. pylori strains may be damaged more severely than those of uninfected patients.

Evaluation of a single dose of half strength inactivated influenza vaccine in healthy adults

Because of delays in the manufacturing of the 2000–2001, trivalent inactivated influenza vaccine in the US, there were concerns that there might be shortages of vaccine supply in the US. Therefore, we conducted a prospective, randomized, open-label, multicenter trial at six academic medical centers in the US, to evaluate the immunogenicity of a half dose of inactivated vaccine in healthy adults. Healthy adults between the ages of 18 and 49 were randomized to receive either a full 0.5 ml (15.5 μg of each HA antigen) dose or a 0.25 ml (7.75 μg of each HA antigen) dose of the 2000–2001 trivalent inactivated influenza vaccine by intramuscular injection. Sera were obtained for assessment of hemagglutination-inhibiting antibody to each of the three strains contained in the vaccine before and 21 days after vaccination. The proportions of individuals achieving a post-vaccination titer of ≥1:40, the geometric mean titers (GMTs) of post-vaccination antibody, and the proportions of individuals with a four-fold or greater increase in antibody were lower for all three strains in those receiving 0.25 ml of vaccine compared to those receiving 0.5 ml. However, the differences were small for all three antigens. The upper 95% confidence limits for differences between 0.25 and 0.5 ml doses were less than 20% for rates of achieving a titer of ≥1:40 and four-fold response, and less than 1.5 for the ratios of GMTs between dose groups, for all three vaccine antigens. These results suggest that when vaccine is in short supply, a strategy using a half dose in healthy adults could increase the number of people vaccinated with relatively little adverse impact on vaccine immunogenicity.

Gastric emptying flow curves separated from carbon-labeled octanoic acid breath test results.

Recently, we developed the [13/14C]octanoic acid breath test to measure gastric emptying of solids. Although the method has been validated extensively, absorption, metabolism, and excretion of the label in the breath need to be corrected for. In this study a mathematical model was developed that allows for 1) separation of the global CO2 excretion after ingestion of the labeled test meal into the emptying rate of the labeled test meal from mouth to pylorus and the postgastric processing of absorption, metabolism, and excretion of the label, and 2) numerical calculation of the half-emptying time and lag phase of the emptied meal. The model was applied to the gastric emptying results obtained by simultaneous scintigraphic and breath test measurements. An excellent correlation was found between the gastric half-emptying time (r = 0.98) and lag phase (r = 0.85) determined scintigraphically and via breath test. There was also a good agreement between the two methods [mean values and confidence limits for differences: t1/2 = 10 min (-20 to 41) and tlag = -3 min (-39 to 34)]. Moreover, the separated gastric emptying curves, lacking the influence of postgastric processing of the label, showed real patterns of gastric outflow, which changes from moment to moment.

Lothian and Forth Valley Leg Ulcer Healing Trial, Part 2: Knitted Viscose Dressing versus a Hydrocellular Dressing in the Treatment of Chronic Leg Ulceration

Objective: To compare a new ‘advanced’ hydrocellular Polyurethane dressing (HPD) (Allevyn) with a traditional simple non-adherent knitted viscose dressing (KDV) (Tricotex) in the treatment of chronic venous leg ulcers. Design: A randomized trial of factorial design, with interaction testing, to allow the evaluation of two different therapeutic components (dressing and bandages) within a single trial. The treatment period was 12 weeks or until healing, whichever occurred sooner. Setting: The Leg Ulcer Clinics of Edinburgh and Falkirk and District Royal Infirmaries, Scotland. Patients: 132 patients with chronic venous leg ulcers were randomized, 66 to HPD and 66 to KVD. Principal exclusions were patients with diabetes, rheumatoid disease or Doppler ankle/brachial pressure indices of less than 0.8. There were 28 withdrawals (15 KVD, 13 HPD). These were considered as treatment failures. Interventions: Dressings and bandaging were applied by specialist leg ulcer nurses using standard techniques throughout, the bandaging being randomized to either elastic or non-elastic multilayer systems. Main outcome measure: The principal end-point was ulcer healing. Also monitored were healing rates, pain and the frequency of dressing changes. Results: Pain relief was significantly better in the HPD group ( p=0.01). Thirty-one (47%) of the HPD patients healed within 12 weeks compared with only 23 (35%) of the those treated with KVD (95% confidence limits for difference, −5% to +29%). The higest healing rates (61% for all ulcers and 74% for those less than 10 cm2) were observed in the subgroup in which HPD was used in combination with an elastic bandaging system. Conclusion: Patients treated with HPD did significantly better in terms of pain relief, although the higher healing rates observed in this group failed to reach significance at the 5% level.

Corrigenda: A Table of Exact Confidence Limits for Differences and Ratios of Two Proportions and Their Odds Ratios

Corrigenda: A Table of Exact Confidence Limits for Differences and Ratios of Two Proportions and Their Odds Ratios

Variability of relaxed expiratory volume and forced inspiratory volume.

Measurements of relaxed expiratory volume in one second (REV_1·0) and forced inspiratory volume in one second (FIV_1·0) were made on 50 subjects on two occasions to know the variability of these procedures in the individual subject. The mean coefficients of variation for REV_1·0 and FIV_1·0 were 6·74% and 8·92%, respectively. The 95% confidence limit of difference between highest readings obtained on two occasions for REV_1·0 and FIV_1·0 was 0·38 litre and 0·214 litre, respectively. These results compare favourably with similar data reported for other ventilatory tests. We feel that if a little time is spent teaching subjects to produce REVs, then reproducible results may be obtained.