Confidence Interval Of Mean Difference Research Articles

Intermittent preventive treatment for malaria in pregnancy and infant growth: a mediation analysis of a randomised trial

Intermittent preventive treatment for malaria in pregnancy (IPTp) can improve birth outcomes, but whether it confers benefits to postnatal growth is unclear. We investigated the effect of IPTp on infant growth in Uganda and its pathways of effects using causal mediation analyses. We analysed data from 633 infants born to mothers enrolled in a randomised trial of monthly IPTp with dihydroartemisinin-piperaquine (DP) vs. sulfadoxine-pyrimethamine (SP) (NCT02793622). Weight and length were measured from 0 to 12 months of age. Using generalised linear models, we estimated effects of DP vs. SP on gravidity-stratified mean length-for-age (LAZ) and weight-for-length Z-scores (WLZ). We investigated mediation by placental malaria, gestational weight change, maternal anaemia, maternal inflammation-related proteins, preterm birth, birth length, and birth weight. Mediation models adjusted for infant sex, gravidity, gestational age at enrolment, maternal age, maternal parasitaemia at enrolment, education, and wealth. SP increased mean LAZ by 0.18-0.28 Z from birth through age 4 months compared to DP, while DP increased mean WLZ by 0.11-0.28 Z from 2 to 8 months compared to SP among infants of multigravidae; at these ages, confidence intervals for mean differences excluded 0. We did not observe differences among primigravida. Mediators of SP included birth weight, birth length, maternal stem cell factor, and DNER. Mediators of DP included placental malaria and birth length, maternal IL-18, CDCP1, and CD6 at delivery. In high malaria transmission settings, this exploratory study suggests different IPTp regimens may influence infant growth among multigravidae, potentially through distinct pathways, in the exclusive breastfeeding period, when few other interventions are available. Stanford Center for Innovation in Global Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bill & Melinda Gates Foundation.

Peripheral warming for prevention of hypothermia in small dogs during soft tissue surgery: A randomized controlled trial

ObjectiveTo evaluate the effects of wrapping the extremities of small dogs with table leg covers to prevent hypothermia during anesthesia. Study designRandomized parallel-group study. AnimalsA total of 60 adult dogs with a body mass <15 kg anesthetized for soft tissue surgery. MethodsDogs were randomly assigned to one of two groups. The control group received routine intraoperative thermal support, while the limb-wrapping group had their peripheral limbs covered with table leg covers up to the mid-metacarpal/metatarsal region, in addition to routine thermal support. Rectal temperature during anesthesia was recorded and compared between the two groups. Data analyses were performed using Student’s t-test for rectal temperature, Fisher’s exact test for hypothermia incidence and analysis of covariance for the effect of limb-wrapping while taking other factors into account. ResultsThirty dogs were included per group. Rectal temperature did not differ between the groups at the time of intubation, but it was significantly higher in the limb-wrapping group (36.7 ± 1.0 °C) than in the control group (35.9 ± 0.8 °C) at the end of surgery (p = 0.003). The mean difference was 0.81 °C (95% confidence interval of mean difference 0.33–1.29 °C). The incidence of hypothermia (<37.0 °C) was significantly lower in the limb-wrapping group than in the control group (19/30 versus 28/30 dogs, respectively; p = 0.010). ConclusionsFor dogs with body masses <15 kg, limb-wrapping with table leg covers slowed the reduction in intraoperative rectal temperature. Limb-wrapping is inexpensive and easy to perform, making it a practical method for minimizing hypothermia during anesthesia in small dogs undergoing soft tissue surgery. Clinical relevancePeripheral warming with table leg covers has the potential to reduce hypothermia during soft tissue surgery in small dogs.

Design of experiments to evaluate pH and temperature parameters with different inoculums in domestic biodigester

The comprehensive management of organic urban solid waste is a concern due to its direct and indirect impact on the environment. Anaerobic Digestion (AD) has been recognized as an alternative and environmentally friendly technology for waste disposal, converting them into organic fertilizers and renewable energy. This research presents an experiment involving four reactors fed with household organic waste, three inoculated with canine, goat, and rabbit manure, and one without inoculum. The experiment was observed for 30 consecutive days to analyze the pH and temperature parameters involved in the AD process in domestic reactors. Statistical methodology, including one-way analysis of variance for assessing the effect of the type of inoculum, Tukey's simultaneous confidence intervals for mean differences, and 90 % confidence intervals for μ in temperature and manure, was utilized. Additionally, main effects analysis of the factors of average temperature and pH were conducted. The results of the one-factor experiment show that the type of inoculum does not significantly influence the variation in pH, while temperature remains relatively stable throughout the AD process. However, the analysis of main effects indicates that goat manure tends to stabilize the temperature with minimal variation, whereas variation is more heterogeneous in the other experiments.

Efficacy of SB12 (Eculizumab Biosimilar) in Asian and Non-Asian Patients with Paroxysmal Nocturnal Hemoglobinuria: Subgroup Analysis of a Global Phase III Randomized Controlled Trial

Background SB12 is a humanized monoclonal antibody biosimilar to reference eculizumab (ECU) which received marketing authorization in Europe in May 2023 after a comprehensive biosimilarity demonstration including non-clinical and clinical assessments. The pivotal SB12 Phase III study demonstrated equivalent clinical efficacy by evaluating lactate dehydrogenase (LDH) and comparable safety, pharmacokinetics, pharmacodynamics, and immunogenicity between SB12 and ECU in patients with paroxysmal nocturnal hemoglobinuria (PNH) (Jun Ho Jang et al., eJHaem 2022). Objective To analyze the efficacy of SB12 in Asian and non-Asian patients with PNH from the pivotal phase III study. Methods A total of 50 adult patients with a confirmed diagnosis of PNH and ≥ 1.5 upper limit of normal range (ULN) of LDH without previous exposure to a complement inhibitor (naïve) were randomized. All patients provided written informed consents and were randomized (1:1) to treatment sequence I (TS1: SB12 to ECU, n=25) or II (TS2: ECU to SB12, n=25), to receive 600 mg of SB12 or ECU intravenously every week for first 4 weeks (initial phase) and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter (maintenance phase). Patients were switched to ECU or SB12 at Week 26, and switched treatment was provided until Week 50. The primary endpoints included LDH level at Week 26 and time-adjusted area of under the effect curve (AUEC) of LDH from Week 14 to Week 26 and Week 40 to Week 52. Equivalence was declared for LDH level at Week 26 if the two-sided 95% confidence interval (CI) of the mean difference in between SB12 and ECU lied within the pre-defined equivalence margin of [−1.2 × ULN, 1.2 × ULN] = [−337.2, 337.2], where ULN = 281 U/L. In addition, equivalence was declared for time-adjusted AUEC of LDH if the two-sided 90% CI of the ratio of geometric means between SB12 and ECU lied within the pre-defined equivalence margin of [0.77, 1.29]. Secondary endpoints included the LDH profile over time. Overall, post-hoc analysis in Asian and Non-Asian (based on race) patients who received either ECU or SB12 during the study period was conducted for the aforementioned efficacy endpoints. Results Asian patients were 27 (54.0%) of total 50. Overall, 15 (60%) Asian patients and 10 (40%) Non-Asian patients were randomized to TS1 and 12 (48%) Asian patients and 13 (52%) Non-Asian patients were randomized to TS2. Baseline demographic and disease characteristic were comparable between the two treatment sequences, with no significant differences between the treatment sequences by race between Asian and Non-Asian patients. The 95% CI of mean difference in LDH level at Week 26 between SB12 and ECU in Asian (SB12 − ECU: -12.02, 95% CI [−126.87, 102.83]) and Non-Asian patients (SB12 − ECU: 76.12, 95% CI [−56.75, 208.99]) lied within the pre-defined equivalence margins (Table). The 90% CI of ratio of time-adjusted AUEC of LDH between SB12 and ECU in Asian patients (SB12/ECU: 1.01, 90% CI [0.92, 1.10]) lied within the pre-defined equivalence margin and was also comparable in Non-Asian patients (SB12/ECU: 1.15, 90% CI [0.90, 1.46]). The overall LDH profile during the study period was also comparable between Asian and Non-Asian patients. No patient developed anti-drug antibodies during the study period and no patient discontinued due to lack of efficacy. While the limited sample size suggests for caution, the comparable efficacy results by Asian and Non-Asian subgroups are also comparable to previously published results in the overall population (Jun Ho Jang et al., eJHaem 2022), with no significant differences identified. Conclusion SB12 showed comparable efficacy to ECU in complement-inhibitor naïve PNH patients in both Asian and Non-Asian subgroups. No patient developed anti-drug antibodies nor discontinued due to lack of efficacy during the study period.

Dysphagia in adult intensive care patients: Results of a prospective, multicentre binational point prevalence study

BackgroundDysphagia occurs in intensive care unit (ICU) patients. However, there is a lack of epidemiological data on the prevalence of dysphagia in adult ICU patients. ObjectivesThe objective of this study was to describe the prevalence of dysphagia in nonintubated adult patients in the ICU. MethodsA prospective, multicentre, binational, cross-sectional point prevalence study was conducted in 44 adult ICUs in Australia and New Zealand. Data were collected in June 2019 on documentation of dysphagia, oral intake, and ICU guidelines and training. Descriptive statistics were used to report demographic, admission, and swallowing data. Continuous variables are reported as means and standard deviations (SDs). Precisions of estimates were reported as 95% confidence intervals (CIs). ResultsOf the 451 eligible participants, 36 (7.9%) were documented as having dysphagia on the study day. In the dysphagia cohort, the mean age was 60.3 years (SD: 16.37) vs 59.6 years (SD: 17.1) and almost two-thirds were female (61.1% vs 40.1%). The most common admission source for those patients with dysphagia were from the emergency department (14/36, 38.9%), and seven of 36 (19.4%) had a primary diagnosis of trauma (odds ratio: 3.10, 95% CI 1.25 - 7.66). There were no statistical differences in Acute Physiology and Chronic Health Evaluation (APACHE II) scores between those with and without a dysphagia diagnosis. Patients with dysphagia were more likely to have a lower mean body weight of 73.3 kg vs 82.1 kg than patients not documented as having dysphagia (95% CI of mean difference: 0.43 to 17.07) and require respiratory support (odds ratio: 2.12, 95% 1.06 to 4.25). The majority of patients with dysphagia were prescribed modified food and fluids in the ICU. Less than half of ICUs surveyed reported unit-level guidelines, resources, or training for management of dysphagia. ConclusionsThe prevalence of documented dysphagia in adult ICU nonintubated patients was 7.9%. There were a higher proportion of females with dysphagia than previously reported. Approximately two-thirds of patients with dysphagia were prescribed oral intake, and the majority were receiving texture-modified food and fluids. Dysphagia management protocols, resources, and training are lacking across Australian and New Zealand ICUs.

Comparison of a New 5% Minoxidil Foam and Rogaine® in the Treatment of Androgenetic Alopecia in Chinese Men: A Randomized, Double‐Blind, Phase III, Equivalence Trial

Androgenetic alopecia (AGA) is a common cause of hair loss in adults. We aimed to compare the efficacy and safety of topical generic 5% new minoxidil foam (NMF) versus 5% minoxidil Rogaine® foam in male patients with AGA. A randomized, double‐blind, controlled, phase III, equivalence trial in 10 centers in China between December 25, 2019, and June 28, 2021, was performed. In total, 417 men patients (≥18 years) with AGA were randomized to receive 5% NMF (211 patients) or 5% Rogaine® foam (206 patients) 1 g two times daily for 24 weeks. The primary outcome was the changes in nonvellus target area hair counts (TAHC) from baseline to week 24. Equivalence was concluded if the 95% confidence interval (CI) for the treatment difference between the 5% NMF and Rogaine® groups was within (−8.00, 8.00). After 24 weeks of treatment, the mean difference in the change of nonvellus TAHC between the 5% NMF group and the Rogaine® group was −3.85 ± 1.62 hair/cm2 in full‐analysis set (FAS) and −3.96 ± 1.68 hair/cm2 in per‐protocol set (PPS), and the 95% CI of mean difference was (−7.03, −0.67) in FAS and (−7.26, −0.66) in PPS. No significant differences were found between the two groups in hair diameter, the ratio of terminal hair to vellus hair, the global photographic assessment by investigators, and adverse events (all P &gt; 0.05). 5% NMF is as effective as Rogaine® in increasing hair density and hair diameter in AGA patients and was found to be safe. This trial is registered with CTR20191708.

P829: A PHASE III RANDOMIZED CLINICAL TRIAL COMPARING SB12 (PROPOSED ECULIZUMAB BIOSIMILAR) WITH REFERENCE ECULIZUMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

Background: SB12, a proposed eculizumab biosimilar, is a humanized monoclonal antibody that blocks complement C5 cleavage, thereby inhibits terminal complement-mediated intravascular hemolysis. Aims: The randomized, double-blind, multicenter, cross-over study was aimed to demonstrate comparable clinical efficacy by evaluating the lactate dehydrogenase (LDH), safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of SB12 and reference eculizumab (ECU) in paroxysmal nocturnal hemoglobinuria (PNH) patients (NCT04058158). Methods: A total of 50 patients aged ≥ 18 years with a confirmed diagnosis of PNH and ≥ 1.5 upper limit of normal range (ULN) of LDH without previous exposure to a complement inhibitor were included. All patients provided written informed consents and were randomized (1:1) to treatment sequence I (TS1: SB12 to ECU, n=25) or II (TS2: ECU to SB12, n=25). Patient received 600 mg of SB12 (TS1) or ECU (TS2) intravenously every week for first 4 weeks (initial phase) and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter (maintenance phase). The treatment was switched to ECU (TS1) or SB12 (TS2) at Week 26, and switched treatment was provided until Week 50. Primary endpoints were LDH level at Week 26 and time-adjusted area of under the effect curve (AUEC) of LDH from Week 14 to Week 26 and Week 40 to Week 52. Equivalence was declared for LDH level at Week 26 if the two-sided 95% confidence interval (CI) of the mean difference in between SB12 and ECU lied within the pre-defined equivalence margin of [−1.2 × ULN, 1.2 × ULN] = [−337.2, 337.2], where ULN = 281 U/L. Equivalence was declared for time-adjusted AUEC of LDH if the two-sided 90% CI of the ratio of geometric means between SB12 and ECU lied within the pre-defined equivalence margin of [0.77, 1.29]. Secondary endpoints were LDH profile over time and number of units of packed red blood cells (pRBCs) transfused throughout the study period, safety, PK, PD, and immunogenicity. Results: Of the 50 randomized patients, 49 patients received the study treatment and 46 patients completed the study. Baseline demographic and disease characteristic were comparable between the two treatment sequences. The 95% CI of mean difference in LDH level at Week 26 between SB12 and ECU (SB12 − ECU: 34.48, 95% CI [−47.66, 116.62]) lied within the pre-defined equivalence margin. The 90% CI of ratio of time-adjusted AUEC of LDH between SB12 and ECU (SB12/ECU: 1.08, 90% CI [0.95, 1.23]) lied within the pre-defined equivalence margin. The overall LDH profile during the study period was also comparable. The mean number of units of pRBCs transfused during Period 1 (TS1: 1.1 U; TS2: 0.9 U, respectively) and Period 2 (TS1: 1.1 U; TS2: 1.0 U, respectively) was comparable. Treatment-emergent adverse events (TEAEs) was reported in 72.3% for SB12 and 68.1% in ECU. Three patients in SB12 and 2 patients in ECU had serious TEAEs. None of three serious TEAEs reported in SB12 were related to the treatment. Two of three TEAEs (cellulitis; infusion site hypersensitivity) reported in ECU were treatment-related, and 1 death due to major adverse vascular event (portal vein thrombosis) not related to the treatment was reported in ECU. The mean eculizumab serum trough concentrations and the mean terminal complement activities in both treatment sequences were comparable. No patient developed anti-drug antibodies during the study period. Image:Summary/Conclusion: SB12 showed clinical equivalence to ECU measured by LDH. SB12 and ECU were comparable in terms of safety, PK, PD, and immunogenicity.

A randomized trial of non-fasting vs. fasting for cardiac implantable electronic device procedures (Fast-CIED Study).

Data on safety and efficacy of a non-fasting strategy in minimal invasive cardiac procedures are lacking. We assessed a non-fasting strategy compared with a fasting strategy regarding patient's well-being and safety in elective cardiac implantable electronic device (CIED) procedures. In this randomized, single-blinded clinical trial, 201 patients (non-fasting = 100, fasting = 101) with a mean age of 72.0 ± 11.6 years (66.7% male) were assigned to a non-fasting strategy (solids/fluids allowed up to 1 h) or a fasting strategy (at least 6 h no solids and 2 h no fluids) before the procedure and analysed on an intention-to-treat basis. The co-primary outcomes were patients' well-being scores (based on numeric rating scale, 0-10) and incidence of intra-procedural food-related adverse events, including vomiting, perioperative pulmonary aspiration, and emergency intubation. Renal, haematological, and metabolic blood parameters and 30-day follow-up data were gathered. The summed pre-procedural patients' well-being score was significantly lower in the non-fasting group [non-fasting: 13.1 ± 9.6 vs. fasting: 16.5 ± 11.4, 95% confidence interval (CI) of mean difference (MD) -6.35 to -0.46, P = 0.029], which was mainly driven by significantly lower scores for hunger and tiredness in the non-fasting group (non-fasting vs. fasting; hunger: 0.9 ± 1.9 vs. 3.1 ± 3.2, 95% CI of MD -2.86 to -1.42, P < 0.001; tiredness: 1.6 ± 2.3 vs. 2.6 ± 2.7, 95% CI of MD -1.68 to -0.29, P = 0.023). No intra-procedural food-related adverse events were observed. Relevant blood parameters and 30-day follow-up did not show significant differences. These results showed that a non-fasting strategy is beneficial to a fasting one regarding patient's well-being and comparable in terms of safety for CIED procedures (NCT04389697).

Improved neonatal brain MRI segmentation by interpolation of motion corrupted slices.

Background and PurposeTo apply and evaluate an intensity‐based interpolation technique, enabling segmentation of motion‐affected neonatal brain MRI.MethodsModerate‐late preterm infants were enrolled in a prospective cohort study (Brain Imaging in Moderate‐late Preterm infants “BIMP‐study”) between August 2017 and November 2019. T2‐weighted MRI was performed around term equivalent age on a 3T MRI. Scans without motion (n = 27 [24%], control group) and with moderate‐severe motion (n = 33 [29%]) were included. Motion‐affected slices were re‐estimated using intensity‐based shape‐preserving cubic spline interpolation, and automatically segmented in eight structures. Quality of interpolation and segmentation was visually assessed for errors after interpolation. Reliability was tested using interpolated control group scans (18/54 axial slices). Structural similarity index (SSIM) was used to compare T2‐weighted scans, and Sørensen‐Dice was used to compare segmentation before and after interpolation. Finally, volumes of brain structures of the control group were used assessing sensitivity (absolute mean fraction difference) and bias (confidence interval of mean difference).ResultsVisually, segmentation of 25 scans (22%) with motion artifacts improved with interpolation, while segmentation of eight scans (7%) with adjacent motion‐affected slices did not improve. Average SSIM was .895 and Sørensen‐Dice coefficients ranged between .87 and .97. Absolute mean fraction difference was ≤0.17 for less than or equal to five interpolated slices. Confidence intervals revealed a small bias for cortical gray matter (0.14‐3.07 cm3), cerebrospinal fluid (0.39‐1.65 cm3), deep gray matter (0.74‐1.01 cm3), and brainstem volumes (0.07‐0.28 cm3) and a negative bias in white matter volumes (–4.47 to –1.65 cm3).ConclusionAccording to qualitative and quantitative assessment, intensity‐based interpolation reduced the percentage of discarded scans from 29% to 7%.

Agreement between corneal diameter measurements obtained with an optical biometer and a Placido-based topographer.

The purpose of this study was to compare the white-to-white distance measurements of two devices (IOL Master 500 and Atlas corneal topographer) commonly used in clinical practice to determine if they were interchangeable. Providing information on instrument interchangeability could eliminate several unnecessary tests and consequently reduce the economic burden for the patient and society. In this prospective, comparative case series, the white-to-white distance was measured by independent examiners using the Atlas topographer (Carl Zeiss Meditec) and the IOL Master 500 (Carl Zeiss Meditec). One eye each of 184 patients was tested. Statistical analyses were performed using a paired t-test, Pearson correlation analysis, and Bland-Altman analysis to compare the measurement methods. The mean white-to-white distance measurements with the Atlas topographer and the IOL Master 500 were 12.20 ± 0.44 mm and 12.12 ± 0.41 mm, respectively (p<0.001). The mean white-to-white difference between the two devices was 0.07 mm (95% confidence interval of mean difference: 0.04-0.11 mm). The Pearson correlation coefficient between the two devices was 0.85 (p<0.0001). The 95% limits of agreement between the two devices were -0.38 mm to 0.53 mm. The Atlas topographer and IOL Master 500 can be used interchangeably with respect to white-to-white distance measurements, as the range of differences is unlikely to affect clinical practice and decision making.

Effects of Rhythmic Interventions on Cognitive Abilities in Parkinson’s Disease

Objective: The objective of this study is to compare 2 different rhythmic, high-intensive interventions, that is, rhythmic speech-language therapy (rSLT) versus rhythmic balance-mobility training (rBMT), against a no-therapy (NT) condition in patients with Parkinson’s disease and against healthy controls (HCs) with regard to the change in or enhancement of cognitive abilities. Methods: The 4 groups (rSLT: N = 16; rBMT: N = 10; NT: N = 18; and HC: N = 17) were matched for age, sex, and educational level and were tested in 6 cognitive domains: working memory, executive function, visuo-construction, episodic memory, attention, and word retrieval. Assessments took place at baseline, at 4 weeks (T1), and at 6 months (T2). Rhythmic interventions were provided 3 times per week for 4 weeks in total. To analyze true intervention effects between groups and across time, statistical analyses included reliable change index. Intergroup differences were assessed with multivariate assessment of variance, while differences within groups were assessed with 95% confidence intervals of mean difference. Results: The rSLT improved working memory and word retrieval (p < 0.05), possibly a beneficial transfer effect of the training method per se. In contrast, the NT group worsened in phonemic and semantic shifting (p < 0.01). Observed improvements in flexibility and in episodic memory in the HC may be linked to training effects of retesting. Conclusions: Rhythmic cues are resistant to neurodegeneration and have a strong motivating factor. As thus, these may facilitate high-intensive and demanding training. Although both trainings were superior to NT, the improvement of cognitive abilities depends on the specific training method. Further, therapy may be more effective when delivered by a therapist rather than by an impersonal computer program.

Simultaneous confidence intervals for mean differences of multiple zero-inflated gamma distributions with applications to precipitation

Changes in precipitation over different periods or regions are important because they have significant effects on many aspects of everyday life. Comparison of multiple forms of precipitation between several periods or regions may therefore be helpful as an aid to decision-making. Precipitation data have generally been assumed to follow a gamma distribution. However, since some dry days have zero precipitation, a zero-inflated gamma distribution is more appropriate for fitting the data. In this article, we consider three fiducial methods (one accurate method and two approximate) to construct simultaneous confidence intervals for mean differences of multiple zero-inflated gamma distributions. Our simulation studies show that the exact method gives more accurate results than the two approximate ones, and it is applicable to various situations. However, the two approximate methods are much faster than the exact one. Also, they provide satisfactory results when the shape parameters are large. Real data on three-year daily precipitations for Waterloo in Canada are used to illustrate the three methods.

The automated processing algorithm to correct the test result of serum neuron-specific enolase affected by specimen hemolysis.

IntroductionSerum neuron‐specific enolase (NSE) is an important tumor marker for small cell lung cancer and neuroblastoma. However, the test of serum NSE compromised by specimen hemolysis is presented as a falsely higher result, which seriously disturbs clinical decision. This study aimed to establish a solution integrated with laboratory information system to clear the bias from hemolysis on serum NSE test.MethodsThe reference range of serum hemolysis index (HI) was first established, and specimen hemolysis rate was compared between HI test and visual observation. NSE concentration in serum pool with normal HI was spiked with serial diluted lysates from red blood cells to deduce individual corrective equation. The agreement between individual corrective equation and original NSE test was assayed by Bland and Altman plots.ResultsThe high HI existed in 32.6% of specimens from patients. The NSE median of hemolyzed specimens was significant higher than the baseline (p = 0.038), while the corrected NSE median had no difference compared with the baseline (p = 0.757). The mean difference of corrected NSE and initial NSE was 1.92%, the SD of difference was 5.23%, and furthermore, the difference was independent of tendency of HI (Spearman r = −0.069, p = 0.640). The 95% confidence interval of mean difference (from −8.33% to 12.17%) was less than the acceptable bias range (±20%).ConclusionThe agreement between individual correction equation and NSE assay was satisfied. Our automated processing algorithm for serum NSE could provide efficient management of posttest data and correct positive bias from specimen hemolysis.

Empirical likelihood for mean difference between two samples with missing data

In this paper, we consider the empirical likelihood confidence intervals for mean difference under the assumption of missing at random (MAR). We prove that the empirical log-likelihood ratio of mean difference converges to a standard chi-squared distribution. We conduct simulation study to compare the proposed empirical likelihood with the normal approximation method in terms of the coverage accuracies and average lengths of confidence intervals. By Monte Carlo simulations, we verify that the proposed method performs well.

Assessing variability and uncertainty in orthopedic randomized controlled trials

Background and purpose — Low statistical power remains endemic in clinical medicine including orthopedics and manifests as high uncertainty and wide confidence intervals (CI). We evaluated the reporting and correspondence between power calculation and observed data on key parameters of variability and uncertainty in orthopedic randomized controlled trials (RCTs).Material and methods — RCTs with 1:1 allocation published in 8 major orthopedic journals between 2016 and 2017 with one continuous primary outcome were included in the review. The components of power calculation and observed standard deviation (SD), mean difference (MD), and confidence interval (CI) of MD between groups were assessed for primary outcome.Results — 160 RCTs were included, of which 93 (58%) and 138 (86%) studies reported the estimated SD and MD in the power calculation, respectively. The median ratio of the estimated SD and SDs observed in the data was 1.0 (IQR –0.76 to 1.32) for 69 (43%) studies. Only 31 of 138 studies reported the CI of MD in primary outcome. In 42% of the negative studies, the estimated MD was included in the CI of the observed MD.Interpretation — The key parameters of data variability, both in power analyses and in final study results, were poorly reported. Low power in orthopedics may result from too high an estimated effect size due to an overoptimistic estimate of MD between study groups. In almost half of the studies, overlap of the CI of the observed MD and estimated MD suggested that the reported results of these studies were inconclusive.

Evaluation of the MC-Media Pad® Rapid Aerobic CountDevice for the Enumeration of Total Aerobic Counts in a Variety of Foods: Collaborative Study, FirstAction Official MethodSM 2019.02.

The MC-Media Pad® Rapid Aerobic Count (RAC) is a ready-to-use culture device combining a test pad coated with medium and water absorption polymers that are designed for the rapid quantification of total aerobic bacteria in food products. The MC-Media Pad RAC was compared to the U.S. Department of Agriculture Food Safety and Inspection Service Microbiology Laboratory Guidebook, Chapter 3.02: Quantitative Analysis of Bacteria in Foods as Sanitary Indicators for raw ground pork and the Standard Methods for the Examination of Dairy Products, Chapter 6: Microbial Count Methods for yogurt drink. The candidate method was evaluated against the reference methods using a paired study design in a multi-collaborator study, following the current AOAC INTERNATIONAL Official Methods of AnalysisSM Appendix J guidelines. Three target contamination levels (low, medium, and high) were evaluated. MC-Media Pad RAC devices were enumerated after 24 and 48 h of incubation. Plate counts obtained by both methods were log10-transformed and the difference of means (including 95% confidence intervals), repeatability SD, and reproducibility SD were determined for each contamination level. All 95% confidence intervals for mean difference fell easily within ±0.10, the performance requirement being ±0.5. The MC-Media Pad RAC (for both 24 and 48 h) and both reference methods for each contamination level were therefore shown to be equivalent, with 97.5% confidence. The new method offers a convenient alternative to the reference methods for detection of aerobic plate count in food products, yielding reliable and comparable results in 24 or 48 h compared to 48 h for the reference methods.

Vitamin K2 Status and Arterial Stiffness Among Untreated Migraine Patients: A Case-Control Study.

We aimed to examine arterial stiffness and vitamin K2 status in migraine subjects by comparison to controls. Migraine is a primary headache disorder that has been associated with an increased risk of cardiovascular events. Mechanisms underlying this increased risk, however, remain unclear. Vitamin K2 deficiency emerged as a cardiovascular risk factor, but vitamin K2 status has never been explored in migraine subjects. This is a case-control, single-center, observational study that includes a cohort of subjects with migraine and their age- and sex-matched controls. Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Dephosphorylated-uncarboxylated matrix-Gla-protein (dp-ucMGP) was used as a marker for vitamin K2 status. A propensity-matched scoring method was used. A total of 146 patients (73 matched pairs) were included in this study, of whom 89% were women with a mean age of 31.9±8.4years. Compared with controls, migraine patients had statistically significantly higher mean cfPWV (7.2±1.1 vs 6.4±0.8m/s, 95% confidence interval (CI) of mean difference [0.45, 1.08], P<.001), as well as higher dp-ucMGP (454.3±116.7pmol/L vs 379.8±126.6pmol/L, 95% CI of mean difference [34.63, 114.31], P<.001). Higher cfPWV was associated with higher dp-ucMGP concentrations only in the migraine with aura (MWA) group. Moreover, migraine subjects had a higher frequency of vitamin K2 deficiency (dp-ucMGP≥500pmol/L) compared to controls, but this association was not statistically significant (23/73 [31.5%] vs 16/73 [21.9%], P=.193). Individuals with migraine have worse indices of arterial stiffness as compared with their age- and sex-matched control subjects. This increase in arterial stiffness is associated with an increase in markers of vitamin K2 deficiency in the MWA group.

Exploration of associations between the FTO rs9939609 genotype, fasting and postprandial appetite-related hormones and perceived appetite in healthy men and women

BackgroundThe fat mass and obesity-associated gene (FTO) rs9939609 A-allele has been associated with obesity risk. Although the exact mechanisms involved remain unknown, the FTO rs9939609 A-allele has been associated with an impaired postprandial suppression of appetite. ObjectivesTo explore the influence of FTO rs9939609 genotype on fasting and postprandial appetite-related hormones and perceived appetite in a heterogeneous sample of men and women. Design112 healthy men and women aged 18-50-years-old completed three laboratory visits for the assessment of FTO rs9939609 genotype, body composition, aerobic fitness, resting metabolic rate, visceral adipose tissue, liver fat, fasting leptin, and fasting and postprandial acylated ghrelin, total PYY, insulin, glucose and perceived appetite. Participants wore accelerometers for seven consecutive days for the assessment of physical activity and sedentary behaviour. Multivariable general linear models quantified differences between FTO rs9939609 groups for fasting and postprandial appetite outcomes, with and without the addition of a priori selected physiological and behavioural covariates. Sex-specific univariable Pearson's correlation coefficients were quantified between the appetite-related outcomes and individual characteristics. Results95% confidence intervals for mean differences between FTO rs9939609 groups overlapped zero in unadjusted and adjusted general linear models for all fasting (P ≥ 0.28) and postprandial (P ≥ 0.19) appetite-related outcomes. Eta2 values for explained variance attributable to FTO rs9939609 were <5% for all outcomes. An exploratory correlation matrix indicated that associations between fasting and postprandial acylated ghrelin, total PYY and general or abdominal adiposity were also small (r = −0.23 to 0.15, P ≥ 0.09). Fasting leptin, glucose and insulin and postprandial insulin concentrations were associated with adiposity outcomes (r = 0.29 to 0.81, P ≤ 0.033). ConclusionsAssociations between the FTO rs9939609 genotype and fasting or postprandial appetite-related outcomes were weak in healthy men and women.

Effects Of Running Biomechanics On The Occurrence Of Iliotibial Band Syndrome- A Prospective Study

Iliotibial band syndrome (ITBS) is the second most common running injury, accounts for 1.6%-12% of all running-related injuries. The exact etiology of ITBS is unclear, but gait and posture are considered one of the factors. Most of studies on ITBS were retrospective cross-sectional in design and could not elaborate on the pathogenesis of ITBS. PURPOSE: This prospective study aimed to determine the gait characteristics that easily induce ITBS and explore the posture changes after the occurrence of ITBS. METHODS: 15 ITBS-stricken runners (I group) and matched 15 healthy runners (C group). All participants underwent two gait trials, namely, before the first day of running (trial1) and after 8-week running (trial2). An eight-camera motion capture system was used to collect kinematic data. Sub-group comparisons were assessed via respective 95% confidence intervals of mean difference. RESULTS: In trial2, the ITBS group exhibited greater peak anterior pelvic tilt and hip flexion angle than the control group(Fig1a). The ITBS group showed increased peak trunk inclination angle , whereas the control group demonstrated lower peak hip flexion (Fig1b)and peak hip adduction than those at trial1(Fig1c).Fig 1: Comparison of joint activity between the two groups■■ Represent significant differences between the two groups in trial 2. ▲▲ Significant differences in the control group compared with trial 1. Abbreviation: t1: trial1; t2: trial2 ; LTD=left foot touch down; LTO=left foot take off; RTD=right foot touch down; RTO= right foot take off; CONCLUSION: Decreasing the peak hip flexion and peak hip adduction angle may be a reasonable strategy to avoid the occurrence of ITBS. Occurrence of ITBS may be due to the lack of timely gait adjustment. The posture of excessive trunk inclination and anterior pelvic tilt may be a risk factor in the development of ITBS during running. This work was supported by the Project of Shandong Science & Technology Department (2017G006044).

Impact of self-instruction manual-based training of family caregivers of neurosurgery patients on their knowledge and care practices - A randomized controlled trial.

Background:Family caregivers of operated neurosurgery patients function as informal extensions of the health system. But they are untrained and unprepared for their new role. It has been felt that their problems related to care provision can be resolved by appropriate training.Aim:This study aimed to compare the impact of self-instruction manual-based training of family caregivers of operated neurosurgery patients on their knowledge regarding care provision and care practices.Setting:Tertiary care hospital setting located in North India.Design:Randomized controlled trial.Materials and Methods:A randomized controlled trial was done among the operated neurosurgery patients and their caregiver dyads (n = 90). They were randomly allocated to receive either self-instruction manual and one-to-one training (TP1) or self-instruction manual only (TP2). Block randomization method was used. Sequentially numbered sealed envelope was used for allocation concealment. Monthly follow-up was done for 3 months. The primary outcome measure was knowledge gain of the caregivers.Statistical Analysis Used:Chi-square test, Student's t-test, paired t-test, repeated measures analysis of variance, and Bonferroni's correction were used.Results:The attrition rate was 15.5%. Intention-to-treat analysis was followed. Caregivers in the TP1 group had significant knowledge gain (95% confidence interval of mean difference 9.4–14.5, P < 0.05). The number of caregivers who had followed correct caregiving practices was significantly more in the TP1 group.Conclusion:Training of caregivers by providing information along with one-to-one training is an effective strategy for improving the knowledge and skills of caregivers regarding care provision of the operated neurosurgery patients.