Half-dose Groups Research Articles

Ultralow-dose [18F]FDG PET/CT imaging: demonstration of feasibility in dynamic and static images.

Validation of [18F]FDG PET/CT at ultralow-dose (0.37MBq/kg) and compared to imaging at half-dose (1.85MBq/kg). This prospective head-to-head intraindividual study compared dynamic and static parameters of ultralow-dose with half-dose [18F]FDG total-body PET/CT. In static imaging, the ultralow-dose groups of PET images were denoted ULD5, 60-65min; ULD8, 60-68min; ULD10, 60-70min; and ULD15, 60-75min. The half-dose group images were reconstructed to 60-61, 60-62, 60-63, and 60-75min, defined as LD1, LD2, LD3, and LD15, respectively. A 5-point Likert scale was used to subjectively evaluate the quality of static PET images, with a score greater than 3 considered to meet the requirements for clinical diagnosis. Thirty participants were included in this study, and in terms of kinetic indicators, no special differences were found between the two groups of normal organs and lesions. In static images, those in groups ULD8 and LD2 achieved scores of [Formula: see text] 3.0, meeting the requirements for clinical diagnosis. In static imaging, four lesions were missed in the LD1 group with a lesion detectability of 89.7% (35/39). In the meantime, lesions were not missed in the whole ultra-low dose group (ULD5, ULD8, ULD10, and ULD15) and half-dose groups (LD2 and LD3). Compared with half-dose imaging, ultralow-dose [18F]FDG total-body PET/CT imaging is clinically feasible, and there was no meaningful difference between the two groups of quantitative and qualitative analysis either dynamic or static images. Total-body PET/CT with ultralow-dose activity, the corresponding acquisition time of 8min provides acceptableimage quality and lesion detection. ClinicalTrials.gov identifier: ChiCTR2000036487 KEY POINTS: • A prospective single-center study showed that the total-body PET scanner allows ultralow-dose [18F]FDG imaging with acceptableimage quality and lesion detectability. • For the participant, radiation exposure can be reduced with ultralow-dose [18F]FDG total-body PET/CT imaging.

Immunogenicity and safety in healthy adults of full dose versus half doses of COVID-19 vaccine (ChAdOx1-S or BNT162b2) or full-dose CoronaVac administered as a booster dose after priming with CoronaVac: a randomised, observer-masked, controlled trial in Indonesia

Inactivated COVID-19 vaccines effectively prevent death, but their effectiveness for preventing infection or severe illness is known to decrease within 3-6 months following the second priming dose. Here we aimed to evaluate the immunogenicity and safety of three potential booster vaccines administered as a full-dose homologous booster or full-dose or half-dose heterologous boosters among individuals primed with CoronaVac. We did an observer and participant masked, randomised controlled trial study of healthy Indonesian adults from five recruitment sites in Bandung and Jakarta, Indonesia, aged 18 years and older who had previously received two doses of CoronaVac within 3 to less than 6 months or 6 to 9 months before the booster dose. Participants were randomly assigned (1:1:1:1:1) by means of stratified randomisation with random block size to a homologous booster with full-dose CoronaVac or heterologous boosters with ChAdOx1-S or BNT162b2 in full dose or half dose. The primary outcome was to evaluate the seropositive, seroconversion rate, and the geometric mean titres of IgG anti-spike-receptor binding domain and neutralising antibodies, 28 days after booster dose vaccination in the per-protocol population. Safety was assessed as a secondary outcome in all vaccinated booster participants by the incidence rate and intensity of adverse events within 24 h, 7 days, and 28 days after the booster dose. This study is registered with ina-registry.org, INA-GO0HLGB, and is complete. Between Nov 26 and Dec 16, 2021, 1015 people were screened, and 960 healthy adults were enrolled; 190-193 were included in each group. 28 days after receiving the booster, combining the 3 to less than 6 months and 6 to 9 months groups, the proportions of seroconversion rates in each vaccine group were ChAdOx1-S 75 (82%) of 92 to 87 (88%) of 99 for full dose and half dose, BNT162b2 92 (92%) of 100 to 90 (98%) of 92 for full dose and half dose, and CoronaVac in 38 (41%) of 92 to 65 (66%) of 98. All booster groups achieved 100% seropositivity 28 days after the booster dose. Participants in the 6 to 9 months priming group achieved higher titres compared with participants in the 3 to less than 6 months priming group. The geometric mean titres in participants in the 6 to 9 months priming group in each vaccine group were ChAdOx1-S 11258·69 (9562·43-13 255·85) and 7853·04 (6698·92-9206·00) for full dose and half dose, BNT162b2 19999·84 (17 720·58-22 572·25) and 17 017·62 (14 694·40-19 708·16) for full dose and half dose and CoronaVac 1440·55 (1172·81-1769·42) achieved higher titres compared with participants in the 3 to less than 6 months priming group which in each vaccine group were ChAdOx1-S 7730·39 (6401·87-9334·60) and 6684·34 (5678·94-7867·73) for full dose and half dose, BNT162b2 16594·08 (13 993·08-19 678·55) and 12 121·67 (9925·21-14 804·19) for full dose and half dose, and CoronaVac 1210·23 (976·49-1499·92). The median percentage inhibition for the surrogate virus neutralisation test against the delta B.1.617.2 and wild-type (WT) variant before the booster and 28 days after the booster dose was very high in all groups (p<0·001), all with greater than 90% inhibition against both delta and WT strains. No serious adverse events were associated with the vaccines. Within the heterologous booster groups, the adverse event rates in the half-dose groups were lower compared with the full-dose groups. Geometric mean titre values between participants in the 6 to 9 months priming group and the 3 to less than 6 months priming group before the booster dose and between half-dose and full-dose groups 28 days before the booster were not significantly different for half-dose ChAdOx1-S, full-dose BNT162b2, and CoronaVac and were significantly different for full-dose ChAdOx1-S and half-dose BNT162b2. Among individuals primed with CoronaVac, boosting with BNT162b2 (full dose or half dose) or ChAdOx1-S (full dose or half dose) produces substantially better immune responses than in those boosted with CoronaVac. Full-dose and half-dose boosting with either BNT162b2 or ChAdOx1-S produced similar responses. Heterologous booster with half-dose might be considered in adults primed with two doses of CoronaVac vaccine. Ministry of Health, Indonesia. For the Indonesian translation of the abstract see Supplementary Materials section.

Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial

Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome. We designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks' gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076. Between Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI -0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI -0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3-4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia. Because non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction. French Ministry of Health.

Half-dose versus full-dose 18 F-FDG total-body PET/CT in patients with colorectal cancer.

The purpose of this study was to investigate image quality and lesion detectability of half-dose (1.85 MBq/kg) 18 F-fluorodeoxyglucose (FDG) total-body positron emission tomography/computed tomography (PET/CT) for colorectal cancer, full-dose (3.7 MBq/kg) 18 F-FDG serving as a reference. Fifty patients confirmed to have colorectal cancer who underwent total-body PET/CT with half-dose 18 F-FDG were included. Another 50 colorectal cancer patients with 3.70 MBq/kg 18 F-FDG activity were selected for the full-dose group. PET images in the half-dose group were scanned for 15 min and split into 1-, 2-, 3-, 4- and 10-min duration groups, denoted G1, G2, G3, G4 and G10, respectively. In the full-dose group, PET scanning was performed for 5 min, reconstructed with the first 0.5, 1, 2 and 5 min intervals, defined as G0.5', G1', G2' and G5', respectively. Subjective image quality was assessed with 5-point Likert scales. Objective image quality parameters included maximum standardized uptake values (SUV max) , mean standardized uptake values (SUV mean )and signal-to-noise ratio (SNR) of the liver, blood pool and muscle and SUV max and tumor-to-background ratio (TBR) of lesions. In the two groups, the G3 and G2' images met clinical diagnosis requirements in terms of subjective image quality, with scores ≥3. There were no differences in terms of subjective and objective image quality between the groups (G1 and G0.5', G2 and G1', G4 and G2' and G10 and G5'). In the half-dose group, 56 colorectal lesions in 50 patients confirmed by surgical pathology were clearly visible in all groups. The number of FDG-avid lymph nodes was 37 in G1, 38 in G2 and 39 in the remaining half-dose groups. The number of missed metastatic liver lesions was 1 both in G1 and G2. Total-body PET/CT with half-dose was feasible for diagnosing and staging colorectal cancer compared with full-dose 18 F-FDG PET/CT. Moreover, for half-dose total-body PET/CT, a 3-min scan duration could maintain image quality and lesion detectability.

The optimal monoenergetic spectral image level of coronary computed tomography (CT) angiography on a dual-layer spectral detector CT with half-dose contrast media.

To investigate the optimal monoenergetic level of spectral reconstructions in coronary computed tomography angiography (coronary CTA) on a dual-layer spectral detector computed tomography (SDCT) with half-dose contrast media. Two hundred patients with suspected coronary artery disease (CAD) were enrolled in this prospective coronary CTA study and randomly divided into a routine-dose contrast media group and a half-dose contrast media group (each n=100). Coronary CTA was performed using SDCT with prospective electrocardiogram (ECG)-gated mode. A tube voltage of 120 kVp was used, along with an automated tube current modulation. A dose of iodixanol 270 mgI/mL of 0.8 and 0.4 mL/kg was administered to the routine and half-dose groups, respectively. For the routine-dose group, 120 kVp polychromatic images with a model-based iterative reconstruction (IMR) (Group A) were reconstructed. For the half-dose group, three monoenergetic levels of images were reconstructed (Group B, 45 keV; Group C, 50 keV; and Group D, 55 keV). Objective indicators [mean CT values; noise; signal-to-noise ratio (SNR); and contrast-to-noise ratio (CNR)] and subjective indicators (contrast, sharpness, subjective noise, and acceptability) in each group were compared. There were no significant differences in demographics or radiation dose (1.83±0.51 vs. 1.80±0.53 mSv, P=0.78) between the routine- and half-dose groups. The average iodine loads were 15.33±2.26 and 7.48±1.14 g, respectively. Mean CT values, SNR, CNR, and subjective contrast in Group C were higher than those in Group A (P<0.05), and there were no significant differences in other indicators between Group C and Group A (P>0.05). The objective and subjective noise in Group B were worse than those in Group A (P<0.05). The contrast, sharpness, and acceptability of Group D were all worse than those of Group A (P<0.05). Compared to routine polychromatic images, 50 keV monoenergetic images can provide equivalent or improved coronary image quality in coronary CTA performed on SDCT with half the amount of contrast media.

Half-dose olaparib reduction: Safe and efficient dose in multi-treated Mexican ovarian cancer patients.

e17101 Background: Ovarian cancer (OC) is the most common gynecological cancer worldwide, and in Mexico stands as the 2nd gynecological cancer-related death cause with 4,759 new cases yearly. PARP inhibitors in BRCA1/2 mutated patients offer disease control after response to chemotherapy with few side effects and minimal impact on quality of life. The primary objective of this study was to evaluate the clinical benefit of Olaparib half-dose reduction in multi-treated Mexican OC patients. Methods: Nineteen OC BRCA1/2 positive patients were enrolled (Nov 2016-Dec 2018), at the Instituto Nacional de Cancerología, Mexico. Eligible patients had received &gt; 2 previous platinum-based lines. Olaparib dose was 800 mg/day, as maintenance therapy after complete or partial response. Half-dose administration was allowed in grade 3 toxicity events. Median PFS curves were estimated by the Kaplan–Meier method. Results: The most common mutation in OC patients was BRCA1 (78.9%), four patients had founder mutation (Del9-12). Eleven patients (57.9%) received Olaparib in ≥4 lines. Nine patients required dose adjustment following hematological (42.1%) and gastrointestinal toxicity (5.2%). There was not statistical differences between complete-dose and half-dose administration groups. However patients with founder BRCA1 mutation did not require dose adjustment ( P= 0.033) and multi-treated (≥4 lines) patients were more susceptible to develop hematological toxicity ( P= 0.030). The median PFS was 12.02 months, patients HGSP histology had a better PFS compared with endometroid histology (14.8 Vs 5.19; P= 0.020). BRCA1 founder mutated patients had a better PFS compared with other BRCA mutations (NR Vs 11.30; P= 0.050). The median PFS in first, second and third or more recurrence was NR Vs 14.8 Vs 8.3; P= 0.050. We did not find statistical difference in the PFS in half-dose reduction compared with complete-dose groups (9.6 Vs NR; P= 0.221). Conclusions: We provide evidence that using Olaparib in first and second recurrence had better outcome compared with third or more recurrence. However the recommended dose exhibits a high toxicity profile; therefore half-dose reduction in multi-treated patients needs to be suggested in Olaparib OC guidelines as a safety and effective strategy.

The Comparison of Short-Term Therapeutic Effects of Acute Low-Tone Sensorineural Hearing Loss according to Steroid Capacity

Background and Objectives Acute low-tone sensorineural hearing loss refers to a condition wherein thresholds increase only at low frequencies in pure-tone audiometry. Systemic steroid treatment is commonly used for acute low-tone sensorineural hearing loss without vertigo, but there has been no established treatment in most clinical researches. The purpose of this study is to compare and analyze the short-term effects of high- and half-dose oral steroid therapy on patients suffering from acute low-tone sensorineural hearing loss without vertigo. Subjects and Method Forty-six patients diagnosed with acute low-tone sensorineural hearing loss were divided into two groups and treated with high-dose (24 patients) and half-dose (22 patients) steroids, respectively. A retrospective analysis was conducted on their medical records. Results There were no significant differences between the two groups in any of the following: age, sex ratio, duration of symptoms before treatment, pure-tone hearing thresholds, low frequency hearing thresholds and speech intelligibility. However, both groups showed significant differences in hearing thresholds before and after treatment. In addition, no significant difference was noted in the recovery and recurrence rate between the two groups. Conclusion According to the results of this study, there is no difference in treatment effect between the high- and half-dose groups. Therefore, half-dose steroids may be used as a treatment option for acute low tone sensorineural hearing loss. Key words: Low-tone ㆍ Sensorineural hearing loss ㆍ Steroid

The Transcendental Meditation Program's Impact on the Symptoms of Post-traumatic Stress Disorder of Veterans: An Uncontrolled Pilot Study.

Current treatments for post-traumatic stress disorder (PTSD) are only partially effective. This study evaluated whether an extensively researched stress reduction method, the Transcendental Meditation (TM) technique, can reduce the PTSD symptoms of veterans. Previous research suggested that TM practice can decrease veterans' PTSD symptoms. A one-group pretest-posttest design was used to evaluate the impact of TM practice on reducing PTSD symptoms. A convenience sample of 89 veterans completed PTSD Checklist-Civilian (PCL-5) questionnaires. Among those, 46 scored above 33, the threshold for provisional diagnosis of PTSD, and were included in this evaluation. The PCL-5 measured PTSD symptoms at baseline and 30 and 90 d after intervention. Regularity of TM practice was recorded. Paired sample t-tests were used to assess within-group changes from baseline to post-intervention periods. Analysis of variance was used to compare full-dose (two 20-min TM sessions per day) and half-dose (one 20-min TM session per day) groups. After 1 mo of TM practice, all 46 veterans responded; their PCL-5 average decreased from 51.52 in the pre-intervention period to a post-intervention mean of 23.43, a decline of 28.09 points (-54.5%); standard deviation: 14.57; confidence interval: 23.76-32.41; and effect size: -1.93; p < 0.0001. The median PTSD scores declined from 52.5 to 22.5, a decrease of 30 points (-57%), while 40 veterans (87%) had clinically significant declines (>10 points) in PTSD symptoms, and 37 (80%) dropped below the clinical level (<33). At the 90 d posttest, 31 of the 46 responded and three more dropped below the 33 threshold. Intent-to-treat analyses revealed clinically and statistically significant effects. A dose-response effect suggested a causal relationship. The full-dose group exhibited larger mean declines in PTSD symptoms than the half-dose group. Averages of the 46 veterans' responses to 20 PCL-5 questions exhibited significant (p < 0.0001) declines from the pre-intervention period to the 30-d post-intervention assessment. Results indicated that TM practice reduced PTSD symptoms without re-experiencing trauma. Because of the magnitude of these results and dose-response effect, regression to the mean, spontaneous remission of symptoms, and placebo effects are unlikely explanations for the results. Major limitations were absence of random assignment and lack of a control group. Participants chose to start and continue TM practice and to complete PCL-5 questionnaires. Those who self-selected to enter this study may not be representative of all veterans who have PTSD. Those who did not complete follow-up questionnaires at 90 d may or may not have had the same results as those who responded. The design and sampling method affect the generalizability of the results to wider populations. When taking into account these results and all previous research on the TM technique in reducing psychological and physiological stress, the convergence of evidence suggests that TM practice may offer a promising adjunct or alternative method for treating PTSD. Because of the widely recognized need to identify effective new approaches for treating PTSD, randomized research with control groups is warranted to further investigate the effectiveness of TM practice as a treatment for PTSD.

Optimization of hybrid iterative reconstruction level and evaluation of image quality and radiation dose for pediatric cardiac computed tomography angiography.

Hybrid iterative reconstruction can reduce image noise and produce better image quality compared with filtered back-projection (FBP), but few reports describe optimization of the iteration level. We optimized the iteration level of iDose4 and evaluated image quality for pediatric cardiac CT angiography. Children (n = 160) with congenital heart disease were enrolled and divided into full-dose (n = 84) and half-dose (n = 76) groups. Four series were reconstructed using FBP, and iDose4 levels 2, 4 and 6; we evaluated subjective quality of the series using a 5-grade scale and compared the series using a Kruskal-Wallis H test. For FBP and iDose4-optimal images, we compared contrast-to-noise ratios (CNR) and size-specific dose estimates (SSDE) using a Student's t-test. We also compared diagnostic-accuracy of each group using a Kruskal-Wallis H test. Mean scores for iDose4 level 4 were the best in both dose groups (all P < 0.05). CNR was improved in both groups with iDose4 level 4 as compared with FBP. Mean decrease in SSDE was 53% in the half-dose group. Diagnostic accuracy for the four datasets were in the range 92.6-96.2% (no statistical difference). iDose4 level 4 was optimal for both the full- and half-dose groups. Protocols with iDose4 level 4 allowed 53% reduction in SSDE without significantly affecting image quality and diagnostic accuracy.

The combination of Everolimus with Verapamil reduces ovarian weight and vascular permeability on ovarian hyperstimulation syndrome: a preclinical experimental randomized controlled study

The efficacy of pathways inhibition and the combined effect of Everolimus (mTOR inhibitor) and Verapamil (CYP3A inhibitor) in ovarian hyperstimulation syndrome (OHSS) need to be tested. Therefore, the impact of a leucotriene receptor antagonist, an anticoagulant, a GnRH antagonist as well as Everolimus plus Verapamil (at various doses and days of administration) on an OHSS rat model was tested. Sixty three female Wistar rats were randomly divided into seven groups. The control group received saline, while the OHSS group received rec-FSH for four consecutive days. The other five groups received rec-FSH for four days and Montelukast daily, Heparin daily, GnRH antagonist daily, Everolimus plus Verapamil in the last two days (half days group) and Everolimus plus Verapamil (half dose group) daily, respectively. All groups received also hCG at the fifth day. Significantly reduced ovarian weight was observed in the Everolimus plus Verapamil groups (half days and half-dose groups) and the Montelukast group compared to the OHSS group (p = 0.001 and p = 0.001, respectively). The vascular permeability was significantly reduced in the Everolimus plus Verapamil group (half dose group) and the GnRH antagonist group compared to the OHSS group (p < 0.001 and p = 0.011, respectively). However, estradiol and progesterone levels did not differ significantly between the groups. Studying the inhibition of different pathways, we concluded that the co-administration of Everolimus and Verapamil (at half dose) is beneficial for reducing ovarian weight and vascular permeability in an OHSS animal model.

Relapse in psoriasis with two different tapering regimens of methotrexate: a randomized open-label controlled study.

Background : Systemic therapy with methotrexate is a very useful modality in psoriasis, but relapses can occur soon after stopping it. Aim : To compare the relapse rates in psoriasis with two different tapering regimens of methotrexate after control is achieved. Methods : This was a randomized open-label controlled study, and patients of chronic plaque psoriasis with psoriasis area and severity index (PASI) >10 were included. Methotrexate 0.3 mg/kg weekly was given and the PASI calculated every 2 weeks. After achieving a 75% reduction in the PASI (PASI-75), patients were assigned randomly in to one of three groups. In the half-dose group, the dose of methotrexate was reduced to half and given weekly; in the 2-weekly group, the same dose was given at 2-week intervals; in the control group, methotrexate was stopped. Patients were followed up for 12 weeks. Results : Out of 141 registered patients, 81 were included: 27 in the half-dose group, 28 in the 2-weekly group, and 26 in the control group. After further exclusions due to adverse effects and loss to follow-up, the results were analysed for 16, 17 and 19 patients respectively in the 3 groups. There was statistically a highly significant difference in relapse rates between the half-dose and control groups (P < 0.001), and a significant difference between the 2-weekly and control groups (P = 0.001). Relapse rates in the half-dose and 2-weekly groups did not show a significant difference (P = 0.680). Many (35.8%) patients were excluded and only 52 (64.2%) completed the study. There appears to be no significant difference in the frequency of relapse in psoriasis whether methotrexate is tapered by halving the weekly dose or by doubling the interval between two doses, and both methods led to fewer relapses than abrupt cessation of the drug.

Bayesian estimation of cerebral perfusion using reduced-contrast-dose dynamic susceptibility contrast perfusion at 3T.

DSC perfusion has been increasingly used in conjunction with other contrast-enhanced MR applications and therefore there is need for contrast-dose reduction when feasible. The purpose of this study was to establish the feasibility of reduced-contrast-dose brain DSC perfusion by using a probabilistic Bayesian method and to compare the results with the commonly used singular value decomposition technique. Half-dose (0.05-mmol/kg) and full-dose (0.1-mmol/kg) DSC perfusion studies were prospectively performed in 20 patients (12 men; 34-70 years of age) by using a 3T MR imaging scanner and a gradient-EPI sequence (TR/TE, 1450/22 ms; flip angle, 90°). All DSC scans were processed with block circulant singular value decomposition and Bayesian probabilistic methods. SNR analysis was performed in both half-dose and full-dose groups. The CBF, CBV, and MTT maps from both full-dose and half-dose scans were evaluated qualitatively and quantitatively in both WM and GM on coregistered perfusion maps. Statistical analysis was performed by using a t test, regression, and Bland-Altman analysis. The SNR was significantly (P < .0001) lower in the half-dose group with 32% and 40% reduction in GM and WM, respectively. In the half-dose group, the image-quality scores were significantly higher in Bayesian-derived CBV (P = .02) and MTT (P = .004) maps in comparison with block circulant singular value decomposition. Quantitative values of CBF, CBV, and MTT in Bayesian-processed data were comparable and without a statistically significant difference between the half-dose and full-dose groups. The block circulant singular value decomposition-derived half-dose perfusion values were significantly different from those of the full-dose group both in GM (CBF, P < .001; CBV, P = .02; MTT, P = .02) and WM (CBF, P < .001; CBV, P = .003; MTT, P = .01). Reduced-contrast-dose (0.05-mmol/kg) DSC perfusion of the brain is feasible at 3T by using the Bayesian probabilistic method with quantitative results comparable with those of the full-dose protocol.

Effect of almond consumption on the serum fatty acid profile: a dose-response study.

Consumption of almonds has been shown to be associated with a decreased risk of CHD, which may be related to their fatty acid (FA) composition. However, the effect of almond consumption on the serum FA composition is not known. Therefore, in the present study, we investigated whether almond consumption would alter the serum FA profile and risk of CHD, as calculated using Framingham's 10-year risk score, in a dose-dependent manner in hyperlipidaemic individuals when compared with a higher-carbohydrate control group using dietary interventions incorporating almonds. A total of twenty-seven hyperlipidaemic individuals consumed three isoenergetic (mean 1770kJ/d) supplements during three 1-month dietary phases: (1) full-dose almonds (50-100g/d); (2) half-dose almonds with half-dose muffins; (3) full-dose muffins. Fasting blood samples were obtained at weeks 0 and 4 for the determination of FA concentrations. Almond intake (g/d) was found to be inversely associated with the estimated Framingham 10-year CHD risk score (P=0·026). In both the half-dose and full-dose almond groups, the proportions of oleic acid (OA) and MUFA in the TAG fraction (half-almond: OA P=0·003; MUFA P=0·004; full-almond: OA P<0·001; MUFA P<0·001) and in the NEFA fraction (half-almond: OA P=0·01; MUFA P=0·04; full-almond: OA P=0·12; MUFA P=0·06) increased. The estimated Framingham 10-year CHD risk score was inversely associated with the percentage change of OA (P=0·011) and MUFA (P=0·016) content in the TAG fraction. The proportions of MUFA in the TAG and NEFA fractions were positively associated with changes in HDL-cholesterol concentrations. Similarly, the estimated Framingham 10-year CHD risk score was inversely associated with the percentage change of OA (P=0·069) and MUFA content in the NEFA fraction (P=0·009). In conclusion, the results of the present study indicate that almond consumption increases OA and MUFA content in serum TAG and NEFA fractions, which are inversely associated with CHD lipid risk factors and overall estimated 10-year CHD risk.

Field practice study of half-dose sorafenib treatment on safety and efficacy for hepatocellular carcinoma: A propensity score analysis.

Patients with hepatocellular carcinoma (HCC) who receive an initial full dose of sorafenib (800 mg/day) often require a decreased dose (400 mg/day) or discontinuation of therapy because of severe adverse events. We conducted a retrospective analysis of patients with HCC to compare the safety and efficacy of full- to half-dose sorafenib. We reviewed the medical records of 218 consecutive patients with intermediate or advanced stage HCC who received half (n = 73) or full-dose sorafenib (n = 145) between 2009 and 2012 at four institutions. A propensity score-matching analysis was used to adjust for potential bias. Multivariate logistic regression analysis showed that increased age was an independent factor for the selection of initial half-dose sorafenib (odds ratio, 1.10; 95% confidence interval, 1.05-1.15; P < 0.001). Fifty-eight patients each in the half-dose and full-dose groups were selected for propensity score matching. The incidence of grade 3-4 severe adverse effects was lower in the half-dose group (47.4% vs 66.7%, P = 0.037). In contrast, the median progression-free survival (PFS) and overall survival (OS) rates were not significantly different (half-dose group, 3.8 and 10.2 months; full-dose group, 2.5 and 8.8 months; P = 0.143 and 0.911, respectively). Propensity score-matched analyses indicate that initial half-dose sorafenib treatment led to fewer severe adverse effects and a comparable survival benefit compared with a full dose in select patients with HCC, particularly for those of advanced age.

Primary Endpoint Results of the EVOLVE Trial: A Randomized Evaluation of a Novel Bioabsorbable Polymer-Coated, Everolimus-Eluting Coronary Stent

This study sought to compare the safety and efficacy of 2 dose formulations of SYNERGY, a novel bioabsorbable polymer everolimus-eluting stent (EES) (Boston Scientific Corp., Natick, Massachusetts) compared with the durable polymer PROMUS Element EES (Boston Scientific Corp.). Durable polymer coatings on drug-eluting stents have been associated with chronic inflammation and impaired healing. Bioabsorbable polymer-coated drug-delivery systems may reduce the risk of late adverse events, including stent thrombosis, and thus the need for prolonged dual-antiplatelet therapy. A total of 291 patients with a de novo lesion ≤28 mm in length, in a coronary artery of ≥2.25 to ≤3.5 mm diameter, were enrolled in the EVOLVE study, a prospective, randomized, single-blind, noninferiority trial. Patients were randomly assigned in a 1:1:1 ratio to PROMUS Element, SYNERGY, or SYNERGY half dose. The primary clinical endpoint was the 30-day rate of target lesion failure, defined as cardiac death or myocardial infarction related to the target vessel, or target lesion revascularization. The primary angiographic endpoint was 6-month in-stent late loss measured by quantitative coronary angiography. The 30-day primary clinical endpoint of target lesion failure occurred in 0%, 1.1%, and 3.1% of patients in the PROMUS Element, SYNERGY, and SYNERGY half dose groups, respectively. The 6-month in-stent late loss was 0.15 ± 0.34 mm for PROMUS Element, 0.10 ± 0.25 mm for SYNERGY, and 0.13 ± 0.26 mm for SYNERGY half dose (SYNERGY, difference -0.06, upper 95.2% confidence limit: 0.02, p for noninferiority <0.001; SYNERGY half dose, difference -0.03, upper 95.2% confidence limit: 0.05, p for noninferiority <0.001). Clinical event rates remained low and comparable between groups, with no stent thromboses in any group at 6 months. The EVOLVE trial confirms the effective delivery of everolimus by a unique directional bioabsorbable polymer system utilizing the SYNERGY stent. (A Prospective Randomized Multicenter Single-Blind Noninferiority Trial to Assess the Safety and Performance of the Evolution Everolimus-Eluting Monorail Coronary Stent System [Evolution Stent System] for the Treatment of a De Novo Atherosclerotic Lesion [EVOLVE]; NCT01135225).

Does low-dose botulinum toxin help the recovery of arm function when given early after stroke? A phase II randomized controlled pilot study to estimate effect size

Objective: Spasticity after stroke may be associated with worse functional outcome. Our study aim is to establish whether a low dose of botulinum toxin, given early post stroke before clinically evident spasticity warrants treatment, will improve recovery of arm function. Design: A double-blind randomized placebo-controlled trial. Setting: An acute stroke unit. Subjects: Individuals recruited within three weeks of stroke onset with severe arm function deficits. Interventions: Injections of quarter and half standard dose botulinum toxin A to the upper limb, with a control of normal saline injections. Main measures: Arm function, active and passive movement, and spasticity at elbow and wrist were recorded at baseline, and at 4, 8, 12 and 20 weeks post intervention. A pre-planned subgroup analysis included only subjects with no arm function at baseline (Action Research Arm Test score = 0). Results: Thirty subjects were recruited, and 21 completed all assessments. Arm function scores improved in all three groups between baseline and week 20. There was no benefit for active treatment over control in the whole group analysis. In the subgroup analysis the active groups improved when compared with the control group and effect sizes for improvement in this subgroup were 0.6 and 0.5 for the quarter dose and half dose groups respectively. Conclusions: Individuals with no arm function within three weeks of stroke may benefit functionally from botulinum toxin. Using the effect size of 0.5, further studies would need a minimum of 101 participants in each group to confirm this finding.

Safety and Immunogenicity of an AMA-1 Malaria Vaccine in Malian Adults: Results of a Phase 1 Randomized Controlled Trial

BackgroundThe objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria.Methodology/Principal FindingsA phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18–55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 µg/AS02A 0.25 mL or FMP2.1 50 µg/AS02A 0.5 mL) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively.Conclusion/SignificanceThe FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.Trial RegistrationClinicalTrials.gov NCT00308061

Dose-related effects of direct hemoperfusion using a cytokine adsorbent column for the treatment of experimental endotoxemia

To clarify the dose-related effects of direct hemoperfusion using a cytokine adsorbent column (CTR) on the mortality and inflammatory responses to endotoxin-induced shock in rats. Prospective and randomized study. University research laboratory. Male Wistar rats. Forty-eight rats were injected intravenously with Escherichia coli endotoxin (15 mg/kg over 2 min), and then were randomly allocated to one of the following four groups (n = 12 per group): control group, treated without CTR for 120 min; quarter-dose treatment group, treated with CTR 0.25 ml for 120 min; half-dose treatment group, treated with CTR 0.50 ml; and full-dose treatment group, treated with CTR 1.0 ml. Hemodynamics and arterial blood gases were recorded, and mortality and plasma cytokine concentrations were calculated for the 8-h observation period. The mortality rates 8 h after endotoxin injection were 92%, 58%, 42% and 17% for the control column, quarter-dose, half-dose, and full-dose CTR groups, respectively. The increases in plasma cytokine concentrations were smaller in the half-dose and full-dose CTR treatment groups than in the endotoxemic group. The present study showed that CTR treatment dose-dependently decreased the mortality rate and inhibited inflammatory responses in vivo.

Effectiveness of half-dose versus full-dose influenza vaccine in health care workers

A prospective, randomized, double-blind study comparing the effectiveness of half-dose versus full-dose trivalent inactivated influenza vaccine (TIV) in health care workers was conducted. The study was conducted at a 760-bed tertiary care community hospital. Study participants (n = 444) were hospital staff or employees over 18 years of age who were enrolled during a two-week period in October and November 2004. Participants were assigned to either full-dose (n = 222) or half-dose (n = 222) TIV. The participants completed a standardized questionnaire monthly from November 2004 through March 2005. The primary outcome was the incidence of influenza between the two groups; the secondary outcomes were self-reported days of work missed as a result of influenza and the proportion of participants in each group self-reporting signs and symptoms of influenza. Laboratory confirmation of influenza diagnosis was sought in participants reporting a clinical diagnosis by their physicians. Differences in the groups were analyzed with Fisher's exact test, with a < 0.05 considered significant. There was no difference between the full-dose and half-dose groups in the diagnosis of influenza (4% versus 7%, p = 0.198). Laboratory confirmation of an influenza diagnosis occurred in one participant who received full-dose TIV. Half-dose TIV demonstrated a similar effectiveness to full-dose TIV, measured by the number of diagnoses of influenza and symptom survey of participating health care workers. Administration of half-dose TIV is an acceptable strategy for maximizing the number of vaccinations in health care workers, but additional studies are needed to confirm the comparable immunogenicity and effectiveness between the two doses.