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101.
《Vaccine》2022,40(24):3320-3329
BackgroundCurrently, booster dose is needed after 2 doses of non-live COVID-19 vaccine. With limited resources and shortage of COVID-19 vaccines, intradermal(ID) administration might be a potential dose-sparing strategy.ObjectiveTo determine immunologic response and reactogenicity of ID ChAdOx1 nCoV-19 vaccine (AZD1222,Oxford/AstraZeneca) as a booster dose after completion of 2-dose CoronaVac(SV) in healthy adult.MethodsThis is a prospective cohort study of adult aged 18–59 years who received 2-dose SV at 14–35 days apart for more than 2 months. Participants received ID AZD1222 at fractional low dose(1×1010 viral particles,0.1 ml). Antibody responses were evaluated by surrogate virus neutralization test(sVNT) against delta variant and wild type, and anti-spike-receptor-binding-domain immunoglobulin G(anti-S-RBD IgG) at prior, day14, 28, 90, and 180 post booster. Solicited reactogenicity was collected for 7 days post-booster. Primary endpoint was the differences of sVNT against delta strain ≥ 80% inhibition at day14 and 90 compared with the parallel cohort study of 0.5-ml intramuscular(IM) route.ResultsFrom August2021, 100 adults with median age of 46 years(IQR 41–52) participated. Prior to booster, geometric mean(GM) of sVNT against delta strain was 22.4% inhibition(95 %CI 18.7–26.9) and of anti-S-RBD IgG was 109.3 BAU/ml(95.4–125.1). Post ID booster, GMs of sVNT against delta strain were 95.5% inhibition (95%CI 94.2–96.8) at day14, 73.1% inhibition (66.7–80.2) at day90, and 22.7% inhibition (14.9–34.6) at day180. The differences of proportion of participants achieving sVNT against delta strain ≥ 80% inhibition in ID recipients versus IM were + 4.2% (95 %CI -2.0to10.5) at day14, and ?37.3%(-54.2to-20.3) at day90. Anti-S-RBD IgG GMs were 2037.1 BAU/ml (95%CI 1770.9–2343.2) at day14 and 744.6 BAU/ml(650.1–852.9) at day90, respectively. Geometric mean ratios(GMRs) of anti-S-RBD IgG were 0.99(0.83–1.20) at day14, and 0.82(0.66–1.02) at day90. Only 18% reported feverish, compared with 37% of IM (p = 0.003). Common reactogenicity was erythema at injection site(53%) while 7% reported blister.ConclusionLow-dose ID AZD1222 booster enhanced lower neutralizing antibodies at 3 months compared with IM route. Less systemic reactogenicity occurred, but higher local reactogenicity.  相似文献   
102.
103.
《Brain stimulation》2019,12(6):1526-1536
BackgroundEvidence suggests that repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, alters resting brain activity. Despite anecdotal evidence that rTMS effects wear off, there are no reports of longitudinal studies, even in humans, mapping the therapeutic duration of rTMS effects.ObjectiveHere, we investigated the longitudinal effects of repeated low-intensity rTMS (LI-rTMS) on healthy rodent resting-state networks (RSNs) using resting-state functional MRI (rs-fMRI) and on sensorimotor cortical neurometabolite levels using proton magnetic resonance spectroscopy (MRS).MethodsSprague-Dawley rats received 10 min LI-rTMS daily for 15 days (10 Hz or 1 Hz stimulation, n = 9 per group). MRI data were acquired at baseline, after seven days and after 14 days of daily stimulation and at two more timepoints up to three weeks post-cessation of daily stimulation.Results10 Hz stimulation increased RSN connectivity and GABA, glutamine, and glutamate levels. 1 Hz stimulation had opposite but subtler effects, resulting in decreased RSN connectivity and glutamine levels. The induced changes decreased to baseline levels within seven days following stimulation cessation in the 10 Hz group but were sustained for at least 14 days in the 1 Hz group.ConclusionOverall, our study provides evidence of long-term frequency-specific effects of LI-rTMS. Additionally, the transient connectivity changes following 10 Hz stimulation suggest that current treatment protocols involving this frequency may require ongoing “top-up” stimulation sessions to maintain therapeutic effects.  相似文献   
104.
105.

Background

Although it is known that women do not participate in trials as frequently as men, there are limited recent data examining how women recruitment has changed over time.

Methods

We conducted MEDLINE search using a validated strategy for randomized trials published in New England Journal of Medicine, Lancet, and Journal of the American Medical Association between 1986 and 2015, and included trials evaluating pharmacologic or nonpharmacologic therapies. We abstracted data on demographics, intervention type, clinical indication, and trial design characteristics, and examined their relationships with women enrollment.

Results

In total, 598 trials met inclusion criteria. Women enrollment increased significantly over time (21% between 1986 and 1990 to 33% between 2011 and 2015; Pfor trend < 0.001) and did not differ by journal or funding source. Women enrollment varied with clinical indication, comprising 37% for non–coronary artery disease vascular trials, 30% for coronary artery disease trials, 28% for heart failure trials, and 28% for arrhythmia trials (P < 0.001), which were all significantly lower than the expected proportion in disease populations (P < 0.001). Women enrollment varied with trial type (31%, 29%, and 26% for pharmacologic, device, and procedural trials, respectively; P = 0.001). These findings were corroborated using multivariable analysis. We found significant positive correlations between women enrolled, and mean age and total number of participants. Fewer women were enrolled in trials reporting statistically significant results than those who did not (P = 0.001).

Conclusions

Although enrollment of women has increased over time, it remains lower than the relative proportion in the disease population. Future studies should elucidate the reasons for persistent under-representation of women in clinical trials.  相似文献   
106.
107.
108.

Background

The STOP-BANG questionnaire screens for obstructive sleep apnoea (OSA) in surgical patients. In prior research, the association of STOP-BANG scores with comorbidities and outcomes was inconsistent. The objective of this study was to evaluate the validity of the STOP-BANG score.

Methods

We conducted a retrospective cohort study of patients undergoing major elective noncardiac surgery at the University Health Network (Toronto, ON, Canada) between 2011 and 2015. Cross-sectional construct validity was evaluated based on proportions with diagnosed OSA across STOP-BANG strata. Concurrent construct validity was assessed based on the correlation of STOP-BANG with ASA Physical Status (ASA-PS), the Revised Cardiac Risk Index, and the Charlson Comorbidity Index. Predictive validity was assessed based on the adjusted associations of STOP-BANG risk with 30-day mortality (logistic regression), cardiac complications (logistic regression), and length-of-stay (negative binomial regression).

Results

Of 26 068 patients in the cohort, 58% were in the low-risk STOP-BANG stratum, 23% in the intermediate-risk stratum, and 19% in the high-risk stratum. The proportion with previously diagnosed OSA was 4% (n=615) in the low-risk stratum, 12% (n=740) in the intermediate-risk stratum, and 44% (n=2142) in the high-risk stratum. The correlations of STOP-BANG with ASA-PS (Spearman ρ=0.28), Revised Cardiac Risk Index (ρ=0.24), and Charlson Comorbidity Index (ρ=0.10) were weak, albeit statistically significant (P<0.001). After risk-adjustment, STOP-BANG risk strata were not associated with 30-day mortality, cardiac complications, or length-of-stay.

Conclusions

The STOP-BANG questionnaire has modest construct validity but did not predict postoperative mortality, hospital length-of-stay, or cardiac complications.  相似文献   
109.
IntroductionThere is a growing interest in physical activity in relation to recovery after surgery. One important aspect of measuring recovery after surgical procedures is postoperative complications. The aim of this study was to determine if there is an association between the preoperative level of habitual physical activity and postoperative complications in patients undergoing elective surgery for colorectal cancer.Materials and methods115 patients scheduled for elective surgery due to colorectal cancer between February 2014 and September 2015 answered a questionnaire regarding physical activity and other baseline variables. Physical activity was assessed using the Saltin-Grimby physical activity level scale. Complications within 30 days after surgery were classified according to Clavien-Dindo, and the Comprehensive Complications Index (CCI) was calculated. Primary outcome was difference in CCI and key secondary outcome was risk for CCI ≥20.ResultsPhysically inactive individuals had a CCI that was 12 points higher than individuals with light activity (p = 0.002) and 17 points higher than regularly active individuals (p = 0.0004). Inactive individuals had a relative risk for a CCI ≥20 that was 65% higher than for individuals reporting light activity (95% confidence interval (CI) for relative risk (RR) = 1.1–2.5) and 338% higher than for regularly active individuals (95% CI for RR = 2.1–9.4).ConclusionSelf-assessed level of habitual physical activity before colorectal cancer surgery was associated with fewer postoperative complications measured with CCI, in a dose-response relationship.  相似文献   
110.

Objective

This study assessed whether immediate postpartum insertion of levonorgestrel contraceptive implants is associated with a difference in infant growth from birth to 6 months, onset of lactogenesis, or breastfeeding continuation at 3 and 6 months postpartum compared to delayed insertion at 6 to 8 weeks postpartum.

Study design

We conducted a randomized trial of women in Uganda who desired contraceptive implants postpartum. We randomly assigned participants to receive either immediate (within 5 days of delivery) or delayed (6 to 8 weeks postpartum) insertion of a two-rod levonorgestrel contraceptive implant system. This is a prespecified secondary analysis evaluating breastfeeding outcomes. The primary outcome of this secondary analysis was change in infant weight; infants were weighed and measured at birth and 6 months. We used a validated questionnaire to assess onset of lactogenesis daily in person while participants were in the hospital, and then daily by phone after they left the hospital, until lactogenesis was documented. We used interviewer-administered questionnaires to assess breastfeeding continuation and concerns at 3 months and 6 months postpartum.

Results

Among the 96 women randomized to the immediate group and the 87 women to the delayed group, the mean change in infant weight from birth to 6 months was similar between groups: 4632?g in the immediate group and 4407?g in the delayed group (p=.26). Among the 97 women who had not experienced lactogenesis prior to randomization, the median time to onset of lactogenesis did not differ significantly between the immediate and delayed groups (65?h versus 63?h; p=.84). Similar proportions of women in the immediate and delayed groups reported exclusive breastfeeding at 3 months (74% versus 71%; p=.74) and 6 months (48% versus 52%; p=.58).

Conclusion

We found no association between the timing of postpartum initiation of levonorgestrel contraceptive implants and change in infant growth from birth to 6 months, onset of lactogenesis, or breastfeeding continuation at 3 or 6 months postpartum.

Implications

This study provides evidence that immediate postpartum initiation of contraception implants does not have a deleterious effect on infant growth or initiation or continuation of breastfeeding.  相似文献   
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