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Background: Early childhood caries (ECC) remain a serious oral health problem on a global scale. Risk-based caries management (RBCM) implemented in some parts of the world has been effective in preventing ECC. However, there is a lack of prospective research on the application of RBCM among Chinese children, and little is known about its effectiveness. The purpose of this study was to evaluate the effectiveness of RBCM in preventing caries among children aged 3–5 years in Wanzhou District, Chongqing Municipality, China. Methods: Three- to five-year-old children from four kindergartens in Wanzhou were randomly selected for baseline dental examination and caries risk assessment (CRA) and randomly assigned to the experimental group (EG) or the control group (CG) according to the kindergarten. The EG received caries prevention measures of different intensities based on the child's caries risk level. The CG received full-mouth fluoride twice a year according to standard prevention, regardless of their caries risk. One year later, another dental examination and CRA were conducted, to observe changes in the decayed, missing, and filled teeth (dmft) index and caries risk, and to analyze potential factors that may affect the incidence of new caries. Results: Complete data were collected from 291 children (EG, N = 140, 84.8%; CG, N = 181, 83.4%). A total of 25.7% of the EG and 50.3% of the CG children developed new caries, with newly added dmft scores of 0.54 ± 1.12 and 1.32 ± 1.72, respectively (P < 0.05). Multivariate logistic regression indicated that children living in rural areas, assigned to the CG, and rated as high-risk at baseline were more likely to develop new caries (P < 0.05). The proportion of children with an increased caries risk in the EG was significantly lower than that in the CG (P < 0.05). Conclusions: RBCM effectively prevented new caries in 3- to 5-year-old Wanzhou children and reduced the proportion of children at increased risk of caries. It is an effective approach for preventing ECC. Clinical trial registration: This trial was registered in the Chinese Clinical Trials Register. The registration number was ChiCTR230067551 (11/01/2023). [ABSTRACT FROM AUTHOR]

Aims and objectives: To compare the safety of replacing peripheral intravenous catheter as clinically indicated versus routine replacement on patient outcomes in the Chinese context. Background: Some evidence from developed countries recommend replacing peripheral intravenous catheter as clinically indicated; however, there is limited evidence from developing countries. Design: A multisite randomised controlled trial. Methods: The 3050 participants from three hospitals in China were randomly assigned to clinically indicated or routine replacement groups. Patients in the clinically indicated group had the catheters kept in situ until any of the following clinical signs appeared: phlebitis, infiltration, occlusion, displacement, local infection and diagnosed catheter‐related bloodstream infection. Patients in the routine replacement group had their peripheral intravenous catheters replaced every 96 hours. The outcomes of phlebitis, infiltration, occlusion, displacement; catheter‐related bloodstream infection, all‐cause bloodstream infection, and local infection were compared. CONSORT checklist was used to guide the reporting of this RCT. Results: The risk of phlebitis, phlebitis per 1000 catheter days, occlusion, dislodgement, all bloodstream infections, local infection and mortality between the two groups were not significantly different. The risk of infiltration was increased in the clinically indicated group (HR 1.29). There was no catheter‐related bloodstream infection reported in either group. Patients' first peripheral intravenous catheter dwelling time and cumulative indwelling time of all peripheral intravenous catheters in the clinically indicated group were significantly longer than the routine replacement group. There was no statistical significant difference in survival times from phlebitis between the two groups. Conclusions: In the Chinese context, removing peripheral catheters as clinical indicated did not increase the risk of phlebitis, occlusion, catheter displacement and catheter infection; however, there was an increased infiltration incidence. Relevance to clinical practice: In developing countries, removing peripheral catheters as clinical indicated is feasible, but more frequent observations of infiltration are highly recommended. [ABSTRACT FROM AUTHOR]

Background Exercise therapy is a key intervention in the management of knee osteoarthritis (KOA) and recommended in international guidelines on KOA management. An effective home-exercise programme for frail older adults with KOA was successful in achieving high adherence. This randomised controlled trial was to compare the adherence to the exercise and lasting effects of follow-up 3 months. Methods Sixty-eight participants in the original Wuqinxi (WQX) exercise study were community dwelling older adults (age = 70.95 ± 9.85 years) with KOA were categorised into 34 controls group, 34 WQX group adherers. The Western Ontario and Mc Master Universities Osteoarthritis Index questionnaire score (WOMAC) pain and Berg Balance Scale, Timed Up and Go Test, 6-min Walk Test, 30-s chair stand test, isokinetic muscle strength testing of knee flexion and extension measured at pre-test and post-test of the intervention period and follow-up for two groups. Results The WQX group maintained or improved in all nine measures from post-test to follow-up, whereas the control group significantly declined in WOMAC pain, Knee extensor strength and Knee flexor strength. Conclusion The WQX programme was an effective home-exercise programme that achieves high adherence in older adults with KOA who lived in these communities. [ABSTRACT FROM AUTHOR]

Objectives: To reduce all-cause maternal and perinatal mortality and major morbidity through Lady Health Worker (LHW)-facilitated community engagement and early diagnosis, stabilization and referral of women with preeclampsia, an important contributor to adverse maternal and perinatal outcomes given delays in early detection and initial management.Study Design: In the Pakistan Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomized controlled trial (NCT01911494), LHWs engaged the community, recruited pregnant women from 20 union councils (clusters), undertook mobile health-guided clinical assessment for preeclampsia, and referral to facilities after stabilization.Main Outcome Measures: The primary outcome was a composite of maternal, fetal and newborn mortality and major morbidity.Findings: We recruited 39,446 women in intervention (N = 20,264) and control clusters (N = 19,182) with minimal loss to follow-up (3∙7% vs. 4∙5%, respectively). The primary outcome did not differ between intervention (26·6%) and control (21·9%) clusters (adjusted odds ratio, aOR, 1∙20 [95% confidence interval 0∙84-1∙72]; p = 0∙31). There was reduction in stillbirths (0·89 [0·81-0·99]; p = 0·03), but no impact on maternal death (1·08 [0·69, 1·71]; p = 0·74) or morbidity (1·12 [0·57, 2·16]; p = 0·77); early (0·95 [0·82-1·09]; p = 0·46) or late neonatal deaths (1·23 [0·97-1·55]; p = 0·09); or neonatal morbidity (1·22 [0·77, 1·96]; p = 0·40). Improvements in outcome rates were observed with 4-7 (p = 0·015) and ≥8 (p < 0·001) (vs. 0) CLIP contacts.Interpretation: The CLIP intervention was well accepted by the community and implemented by LHWs. Lack of effects on adverse outcomes could relate to quality care for mothers with pre-eclampsia in health facilities. Future strategies for community outreach must also be accompanied by health facility strengthening.Funding: The University of British Columbia (PRE-EMPT), a grantee of the Bill & Melinda Gates Foundation (OPP1017337). [ABSTRACT FROM AUTHOR]

Objectives: Pregnancy hypertension is the third leading cause of maternal mortality in Mozambique and contributes significantly to fetal and neonatal mortality. The objective of this trial was to assess whether task-sharing care might reduce adverse pregnancy outcomes related to delays in triage, transport, and treatment.Study Design: The Mozambique Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised controlled trial (NCT01911494) recruited pregnant women in 12 administrative posts (clusters) in Maputo and Gaza Provinces. The CLIP intervention (6 clusters) consisted of community engagement, community health worker-provided mobile health-guided clinical assessment, initial treatment, and referral to facility either urgently (<4hrs) or non-urgently (<24hrs), dependent on algorithm-defined risk. Treatment effect was estimated by multi-level logistic regression modelling, adjusted for prognostically-significant baseline variables. Predefined secondary analyses included safety and evaluation of the intensity of CLIP contacts.Main Outcome Measures: 20% reduction in composite of maternal, fetal, and newborn mortality and major morbidity.Results: 15,013 women (15,123 pregnancies) were recruited in intervention (N = 7930; 2·0% loss to follow-up (LTFU)) and control (N = 7190; 2·8% LTFU) clusters. The primary outcome did not differ between intervention and control clusters (adjusted odds ratio (aOR) 1·31, 95% confidence interval (CI) [0·70, 2·48]; p = 0·40). Compared with intervention arm women without CLIP contacts, those with ≥8 contacts experienced fewer primary outcomes (aOR 0·79 (95% CI 0·63, 0·99); p = 0·041), primarily due to improved maternal outcomes (aOR 0·72 (95% CI 0·53, 0·97); p = 0·033).Interpretation: As generally implemented, the CLIP intervention did not improve pregnancy outcomes; community implementation of the WHO eight contact model may be beneficial.Funding: The University of British Columbia (PRE-EMPT), a grantee of the Bill & Melinda Gates Foundation (OPP1017337). [ABSTRACT FROM AUTHOR]

Objectives: Pregnancy hypertension is associated with 7.1% of maternal deaths in India. The objective of this trial was to assess whether task-sharing care might reduce adverse pregnancy outcomes related to delays in triage, transport, and treatment.Study Design: The Indian Community-Level Interventions for Pre-eclampsia (CLIP) open-label cluster randomised controlled trial (NCT01911494) recruited pregnant women in 12 clusters (initial four-cluster internal pilot) in Belagavi and Bagalkote, Karnataka. The CLIP intervention (6 clusters) consisted of community engagement, community health workers (CHW) provided mobile health (mHeath)-guided clinical assessment, initial treatment, and referral to facility either urgently (<4 h) or non-urgently (<24 h), dependent on algorithm-defined risk. Treatment effect was estimated by multi-level logistic regression modelling, adjusted for prognostically-significant baseline variables. Predefined secondary analyses included safety and evaluation of the intensity of mHealth-guided CHW-provided contacts.Main Outcome Measures: 20% reduction in composite of maternal, fetal, and newborn mortality and major morbidity.Results: All 14,783 recruited pregnancies (7839 intervention, 6944 control) were followed-up. The primary outcome did not differ between intervention and control arms (adjusted odds ratio (aOR) 0.92 [95% confidence interval 0.74, 1.15]; p = 0.47; intraclass correlation coefficient 0.013). There were no intervention-related safety concerns following administration of either methyldopa or MgSO4, and 401 facility referrals. Compared with intervention arm women without CLIP contacts, those with ≥8 contacts suffered fewer stillbirths (aOR 0.19 [0.10, 0.35]; p < 0.001), at the probable expense of survivable neonatal morbidity (aOR 1.39 [0.97, 1.99]; p = 0.072).Conclusions: As implemented, solely community-level interventions focussed on pre-eclampsia did not improve outcomes in northwest Karnataka. [ABSTRACT FROM AUTHOR]

Study Design: A prospective and controlled study of dexmedetomidine added to preemptive ropivacaine infiltration in lumbar fusion surgery.Objective: Assessment of dexmedetomidine added to preemptive ropivacaine infiltration for the relief of postoperative pain after lumbar fusion surgery.Summary Of Background Data: Single local anesthetic preemptive wound infiltration for the relief of postoperative pain does not translate into major or consistent clinical benefits after lumbar fusion surgery. Dexmedetomidine added to local anesthetics prolonged the duration of blockade and enhanced the analgesic in peripheral nerve block. The effect of dexmedetomidine added to preemptive ropivacaine infiltration in lumbar fusion surgery for the relief of postoperative pain has yet not been studied.Methods: Fifty-seven patients with elective posterior lumbar fusion were randomly divided into two groups. Five minutes before incision, the skin and subcutaneous tissues were injected with 20 mL 0.5% ropivacaine in group R (n = 28) and 20 mL 0.5% ropivacaine and 1 ug/kg of dexmedetomidine in group RD (n = 29) in two divided doses (i.e., 10 mL per side of the incision line). After the operation, all patients received intravenous morphine for analgesia. The total morphine consumption, the time of first analgesic demand, numbers of PCA analgesia, Visual Analog Scale, and postoperative adverse effects were collected.Results: In group RD, cumulative morphine dose and numbers of PCA analgesia in group RD were significantly reduced, the time of first analgesic demand was significantly delayed compared to the group R. Visual Analog Scale in group RD showed a marked reduction at 8 hours, 12 hours, 16 hours after operation and less patients in group RD experienced postoperative nausea or vomiting compared to the group R.Conclusion: The addition of dexmedetomidine to preemptive ropivacaine wound infiltration provided a superior analgesic effect, reduced postoperative morphine consumption, and prolonged the time of the first analgesic demand with no serious side effects.Level Of Evidence: 2. [ABSTRACT FROM AUTHOR]

Objective: To determine the prophylactic efficacy of short-term intensive preoperative inspiratory muscle training on the incidence of postoperative pulmonary complications in patients scheduled for cardiac surgery. Design: Single-blind, randomized controlled pilot study. Setting: TEDA International Cardiovascular Hospital, China. Subjects: In total, 197 subjects aged ⩾50 years scheduled for cardiac surgery were selected. Intervention: The intervention group (n = 98) received five days of preoperative inspiratory muscle training on top of the usual care received by the patients in the control group (n = 99). Main measures: The primary outcome variable was the occurrence of postoperative pulmonary complications. The secondary outcome variables were inspiratory muscle strength, lung function and length of hospitalization. Results: After cardiac surgery, a total of 10 (10.2%) of the 98 patients in the intervention group and 27 (27.3%) of 99 patients in the control group had postoperative pulmonary complications (risk ratio, 0.23; 95% confidence interval (CI), 0.09–0.58, P = 0.002). The study revealed that, compared with the control group, the intervention group had a significant increase in inspiratory muscle strength (by 10.48 cm H2O, P < 0.001), forced expiratory volume in the first second of expiration (FEV1) %predicted (by 3.75%, P = 0.030), forced vital capacity (FVC) %predicted (by 4.15%, P = 0.008) and maximal voluntary ventilation (MVV) %predicted (by 6.44%, P = 0.034). Length of hospital stay was 7.51 (2.83) days in the intervention group and 9.38 (3.10) days in the control group (P = 0.039). Conclusion: A five-day intensive pattern of preoperative inspiratory muscle training reduced the incidence of postoperative pulmonary complications and duration of postoperative hospitalization in patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

Object: To assess the effect of auricular points treatment combined with acupoints application on patient with constipation after lung cancer surgery.Methods: Design and participants: This is a single-center randomized controlled trial. Totally 341 after lung cancer surgery patients were randomly assigned into the experimental group (n = 174) and the control group (n = 167). The control group received routine nursing care, which was included psychological support, diet instruction, and post-operative activities guidance. The experimental group received auricular points treatment combined with acupoints application therapy in addition to the routine nursing care. All the patients had defecation within 3 days after operation. The characteristics of the stool were recorded, and the progress and performance of the incidence of constipation was recorded in two groups.Results: The incidence of constipation in the control group was higher than that in the experimental group (P < 0.001). Moreover, the stool characteristics of experimental group were better than it in the control group by rank-sum test (P = 0.047).Conclusion: On the basis of routine measures to prevent constipation after lung cancer surgery, auricular point sticking combined with acupoint application therapy can effectively decrease the incidence of postoperative constipation. [ABSTRACT FROM AUTHOR]

Study Question: Do oral contraceptives (OCs) and progestins impact live birth rate of IVF when used for cycle scheduling in women with polycystic ovary syndrome (PCOS)?Summary Answer: OCs used for scheduling IVF cycle were associated with lowered rates of pregnancy and live birth after fresh embryo transfer, whereas progestins used for this purpose yield higher rates of pregnancy and live birth than OCs.What Is Known Already: Due to oligo-menorrhea in PCOS, OCs and progestin are extensively used to schedule the start of an IVF cycle in women with PCOS. Little is known about the effect of such pretreatments on outcomes, especially, the rate of live birth.Study Design, Size, Duration: This was a nested cohort study and secondary analysis of a multicenter randomized trial, which was designed to compare live birth rate after fresh embryo transfer vs frozen embryo transfer (FET) in women with PCOS (Frefro-PCOS). A total of 1508 women were enrolled from 14 centers between June 2013 and May 2014.Participants/materials, Setting, Methods: At the discretion of local investigators, subjects were instructed to wait for spontaneous menses (Control group, n = 323), or were prescribed progestins (P group, n = 283) or OCs (OCs group, n = 902) to induce menstruation prior to the start of ovarian stimulation. GnRH antagonist protocol was initiated at Day 2 or 3 of induced or spontaneous menses cycle. The rates of pregnancy, pregnancy loss and live birth after either fresh embryo transfer or FET were compared among these three groups.Main Results and the Role Of Chance: With fresh embryo transfer, women with OC-induced menses had lower rates of clinical pregnancy (48.8% vs 63.6%, relative rate (RR): 0.77, 95% CI: 0.66-0.89) and live birth (36.1% vs 48.1%, RR: 0.75, 95% CI: 0.61-0.92) than women with spontaneous menses. With freeze-all and deferred FET, women with OC-induced menses had a similar pregnancy rate but a higher pregnancy loss rate (27.7% vs 13.0%, RR: 2.13, 95% CI: 1.28-3.52) after FET than women with spontaneous menses. The live birth rate after FET in women with OC-induced menses, progestin-induced menses and spontaneous menses was 49.4%, 50.7% and 60.2%, respectively (P = 0.06). Progestin-induced menses was associated with similar rates of pregnancy, pregnancy loss and live birth after transfer of either fresh or frozen embryos compared with spontaneous menses. Multivariate logistic regression analysis showed that OCs used for menses induction was associated with lower rate of live birth.Limitations, Reasons For Caution: The methods for menses induction were not assigned randomly, thus selection bias was highly likely because of the study design and significant differences that were observed in the baseline characteristics of the women in the different groups. The mean BMI in this study population was relatively normal; the applicability of this result to obese PCOS women needs to be evaluated in further study.Wider Implications Of the Findings: Our results suggest that either waiting for a spontaneous menses or using progestin is a better option than using OCs to induce menses in women with PCOS prior to ovarian stimulation using GnRH antagonist protocol for IVF. Further randomized controlled studies are needed to confirm our findings.Study Funding/competing Interests: This study was funded by National Basic Research Program of China (973 Program) (2012CB944700), the State Key Program of National Natural Science Foundation of China (81430029), National Natural Science Foundation of China (81471428) and Thousand Talents Program (Drs Legro and Zhang H). Dr Legro reports receiving consulting fees from Euroscreen, Kindex, Bayer and Millendo Pharmaceuticals and research funding from Ferring. Others report no disclosures.Trial Registration Number: Frefro-PCOS was registered at Clinicaltrials.gov: NCT01841528. [ABSTRACT FROM AUTHOR]

Background: Catheter-related bladder discomfort (CRBD) is a common distressing symptom complex during the postoperative period, especially after urologic procedures with a relatively greater size urinary catheter. In this study, we will enroll male patients undergoing elective prostate surgery with urinary catheterization under general anesthesia, and we will compare the efficacy of pudendal nerve block (PNB) and intravenous tramadol in CRBD prevention.Methods/design: This trial is a prospective, randomized controlled trial that will test the superiority of bilateral PNB with 0.33 % ropivacaine compared with intravenous tramadol 1.5 mg/kg for CRBD prevention. A total of 94 male patients undergoing elective prostate surgery with urinary catheterization after anesthesia induction will be randomized to receive either bilateral PNB with 0.33 % ropivacaine (the PNB group) or intravenous tramadol 1.5 mg/kg (the tramadol group) after the completion of surgery. The primary outcome is the incidence of CRBD. The most important secondary outcome is the severity of postoperative CRBD, and other secondary outcomes include Numeric Rating Scale (NRS) score for postoperative pain; incidence of postoperative side effects such as postoperative nausea/vomiting, sedation, dizziness, and dry mouth; postoperative requirement for tramadol as a rescue treatment for CRBD and sufentanil as a rescue analgesic for postoperative pain; and NRS score for acceptance of an indwelling urinary catheter.Discussion: This trial is planned to test the superiority of PNB with 0.33 % ropivacaine compared with intravenous tramadol 1.5 mg/kg. It may provide a basis for a new clinical practice for the prevention of CRBD.Trial Registration: ClinicalTrials.gov identifier NCT02683070 . Registered on 11 February 2016. [ABSTRACT FROM AUTHOR]

Background: Patients diagnosed with cervical cancer in the last 2 decades were mainly young females. Human papillomavirus (HPV) vaccination is the most radical way to prevent HPV infection and cervical cancer. However, most female college students in mainland China have not yet been vaccinated, and their relevant knowledge is limited. Theory-based education delivered via the internet is a potentially accessible and useful way to promote HPV vaccination among this population.Objective: This 3-month follow-up study intended to identify the feasibility and efficacy of an information-motivation-behavioral skills (IMB) model-based online intervention for promoting awareness and willingness regarding HPV vaccination among female college students.Methods: A 7-day online HPV education program for female college students in mainland China was developed using a cluster randomized trial design. Recruitment and questionnaire surveys were performed online without face-to-face contact. SPSS 23.0 was used for statistical analysis. The chi-square test and t test were used to compare differences in qualitative and continuous variables between intervention and control groups. The generalized estimating equation was used to test the effectiveness of the intervention with a consideration of the time factor.Results: Among 3867 participants, 102 had been vaccinated against HPV before the study (vaccination rate of 2.6%). A total of 3484 participants were followed up after the baseline survey, with no statistical difference in the loss rate between the intervention and control groups during the intervention and follow-up periods. At different follow-up time points, HPV-related knowledge, and the motivation, behavioral skills, and willingness regarding HPV vaccination were higher in the intervention group than in the control group. HPV-related knowledge was statistically different between the 2 groups, while the motivation, behavioral skills, and willingness regarding HPV vaccination only showed statistical differences right after the intervention, reaching a peak right after the intervention and then gradually reducing over time. Furthermore, there was no statistical difference in the HPV vaccination rate between the 2 groups.Conclusions: IMB model-based online education could be a promising way to increase the HPV vaccination rate and reduce the burden of HPV infection and cervical cancer among high-risk female college students in China.Trial Registration: Chinese Clinical Trial Registry ChiCTR1900025476; http://www.chictr.org.cn/showprojen.aspx? proj=42672.International Registered Report Identifier (irrid): RR2-DOI:10.1186/s12889-019-7903-x. [ABSTRACT FROM AUTHOR]

Background: We examined clinical outcomes in a population-based cohort of EGFR mutant advanced NSCLC patients, exploring the potential role of factors including tumour EGFR mutation fraction and cellularity in predicting outcomes.Methods: A cohort of patients with EGFR mutant advanced NSCLC was identified (N =2 93); clinical outcomes, pathologic and treatment details were collected. Tumour response was determined from radiology and clinical notes. Association between demographic and pathologic variables EGFR TKI response, time to treatment failure (TTF) and overall survival (OS) was examined using logistic regression and proportional hazards regression. EGFR TKI response rates were summarised by percent mutation fraction to explore their association.Results: Higher mutation fraction was associated with greater EGFR TKI response rate (odds ratio 1.58, 95% CI = 1.21-2.07, P = 0.0008), longer TTF (hazard ratio 0.80, 95% CI = 0.68-0.92, P = 0.003) and better OS (hazard ratio 0.81, 95% CI = 0.67-0.99, P = 0.04). However, even in patients with ⩽ 5% mutation fraction, response rate was 34%. Females had longer TTF (P = 0.02).Conclusions: EGFR mutation fraction in tumour samples was significantly associated with response, TTF and OS. Despite this, no lower level of mutation fraction was detected for which EGFR TKI should be withheld in those with activating EGFR mutations. [ABSTRACT FROM AUTHOR]

Introduction: The anti-IgE therapy omalizumab is currently licensed for the treatment of moderate to severe allergic asthma and chronic idiopathic urticaria. Owing to limitations in the use of omalizumab, a need exists for optimized anti-IgE therapies to broaden clinical indications and patient populations, and to improve dosing schedules. The objective of this phase I, randomized, placebo/omalizumab-controlled, first-in-human, dose-escalation study was to evaluate the pharmacokinetics, pharmacodynamics, and safety of the high-affinity, anti-IgE therapy MEDI4212 in non-Japanese and Japanese subjects with atopy and/or diagnostic IgE ≥ 30 IU/mL.Methods: Subjects with atopy and/or baseline IgE ≥ 30 IU/mL were randomized to a single dose of subcutaneous (5, 15, 60, 150, or 300 mg) or intravenous (300 mg) MEDI4212, subcutaneous omalizumab, or placebo. Following administration, pharmacokinetic, pharmacodynamic [IgE (free and total), and cellular FcεRI expression], and safety assessments were made.Results: MEDI4212 rapidly suppressed free serum IgE to a greater extent than omalizumab; however, recovery of free IgE to baseline in MEDI4212-dosed subjects was rapid when compared with the slow and gradual recovery seen in omalizumab-dosed individuals. The loss of IgE suppression corresponded with a rapid decrease of serum MEDI4212. FcεRI expression on dendritic cells and basophils was reduced following MEDI4212 dosing. MEDI4212 was well tolerated by subjects; adverse events were generally of low severity and no subjects discontinued due to adverse events.Conclusions: The increased potency of MEDI4212 may be of clinical interest for individuals with high-diagnostic IgE levels where more extensive IgE suppression is required for clinical response. However, the modest duration of free IgE suppression below the target concentration noted with MEDI4212 in this study suggests limited potential for dosing schedule advantages over omalizumab.Funding: MedImmune.Trial Registration: ClinicalTrials.gov identifier, NCT01544348. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the population pharmacokinetics (PKs) of subcutaneous (SC) and intravenous (IV) trastuzumab in early breast cancer (EBC), assess the impact of covariates on trastuzumab PK, and evaluate fixed (nonweight-based) dosing for the SC regimen administrated via handheld syringe.Methods: Serum trastuzumab concentrations from 595 patients with HER2-positive EBC in the HannaH study (fixed 600 mg SC trastuzumab or weight-based IV trastuzumab) were analyzed using nonlinear mixed-effects modeling. Multiple logistic regression was used to assess the exposure-response relationships between PK, efficacy [pathologic complete response (pCR)], and safety [grade ≥3 adverse events (AEs)].Results: Trastuzumab PK was described by a two-compartment model with parallel linear and nonlinear elimination and first-order SC absorption, with a bioavailability of 77 %. Estimated total clearance (CL) values were 0.18-0.22 L/day for steady-state trough/peak concentrations of 75-148 µg/mL; the estimate for central volume of distribution was 2.9 L. Body weight and alanine transaminase, while showing significant effects on PK, only explained 8% of the variability in CL. Exposure-response analyses showed no relationship between PK, pCR, and grade ≥3 AEs for either regimen.Conclusion: A fixed 600 mg SC dose of trastuzumab provides the desired exposure, with steady-state trough concentrations (35-123 μg/mL for the 5th-95th percentiles) above the historical target concentration of 20 μg/mL for efficacy. Fixed dosing is further supported by lack of an exposure-response relationship between PK, pCR, and grade ≥3 AEs. No dose adjustment per patient factors is required within the ranges studied. [ABSTRACT FROM AUTHOR]

Background: Catheter-related bladder discomfort (CRBD) is common in male patients under general anesthesia, and it may cause patient agitation and exacerbated postoperative pain. In this study, we will enroll male patients undergoing elective surgery with urinary catheterization after anesthetic induction and compare the efficacy of a dorsal penile nerve block (DPNB) and intravenous tramadol for the prevention of CRBD.Methods/design: This trial is a prospective, open-label, randomized controlled trial that will test the superiority of a dorsal penile nerve block with 0.33% ropivacaine to the use of intravenous tramadol 1.5 mg/kg for CRBD prevention. A total of 60 male patients undergoing elective surgery with urinary catheterization after anesthetic induction will be randomized to receive either DPNB with 0.33% ropivacaine (DPNB group) or intravenous tramadol 1.5 mg/kg (TRAM group) after the completion of surgery but before extubation. The primary outcome is the incidence and severity of CRBD. Secondary outcomes include Visual Analog Score (VAS) for postoperative pain, number of patients requiring sulfentanil after operation, acceptance of an indwelling urinary catheter after extraction of the catheter, and postoperative side effects, which include postoperative nausea/vomiting (PONV), vertigo, sedation, drowsiness, and dry mouth.Discussion: For CRBD prevention, this trial is planned to test the superiority of a dorsal penile nerve block with 0.33% ropivacaine to the use of intravenous tramadol 1.5 mg/kg. The results will provide new insight into the mechanism of CRBD and new clinical practice for the prevention of CRBD.Trial Registration: The registration number is NCT01721031, which was assigned by the National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov) on 27 October 27. [ABSTRACT FROM AUTHOR]

Background: Animal and human studies have revealed reciprocal association between exercise and gut-brain axis. However, the clinical evidence from randomized controlled trials (RCT) are still limited to directly assess the effects of aerobic exercise on gut microbiota. To fill this gap, we conducted this 12-week RCT in both groups of adolescents with and without sub-threshold mood symptoms.Methods: A total of 224 adolescents were randomized to the aerobic exercise intervention or psychoeducation-controlled arm. 49 adolescents with subthreshold symptoms and 142 clinically-well adolescents provided the sample for microbiota assessed by metagenomic sequencing. Aerobic exercise of running at the moderate-intensity for 30 min per day, 5 days a week, were conducted for 12 weeks.Results: Adolescents with subthreshold symptoms had significantly lower beta diversity than clinically-well adolescents in both the exercise intervention and psychoeducation-controlled arms (p<0.05). After intervention, no difference in gut microbiota diversity, phylum, genus, species level abundancies or gut microbial functions were found in both of the symptomatic or non-symptomatic groups. Metagenome-wide association study analysis showed no significant difference in metagenomic linkage groups.Limitations: The sample size is relatively small. The exercise intensity we employed may be insufficient to result in observable effects on intestinal microbiota.Conclusion: We conclude that a 12-week moderate-intensity aerobic exercise intervention showed no significant beneficial effect on the gut microbiota in clinically-well adolescents as well as in adolescents with subthreshold symptoms. The beta diversity of gut microbiota in adolescents with subthreshold mood syndromes may be impaired when compared with clinically-well adolescents. [ABSTRACT FROM AUTHOR]

Background: Ivabradine has potent actions in reducing heart rate and improving clinical outcomes of chronic heart failure with reduced ejection fraction (HFrEF). At present, only the short-acting formulation of ivabradine is available that needs to be administered twice daily.Objectives: This study sought to evaluate the role of ivabradine hemisulfate sustained release (SR), a novel long-acting formulation of ivabradine dosed once daily, in stable patients with HFrEF.Methods: Patients with stabilized HFrEF in New York Heart Association functional class II-IV were enrolled and randomized to receive placebo or ivabradine SR in addition to standard medications. The primary endpoint was the change of left ventricular (LV) end-systolic volume index from baseline to week 32.Results: We randomly assigned 181 patients to placebo and 179 patients to ivabradine SR. After 32 weeks, a significant improvement of LV end-systolic volume index from baseline was observed in both arms with a greater effect in the ivabradine SR arm. Ivabradine SR therapy also exhibited superiority in improving LV end-diastolic volume index, LV ejection fraction, resting heart rate, the Kansas City Cardiomyopathy Questionnaire score, and hospital admission for heart failure worsening and cardiovascular disease in comparison to placebo. Overall adverse events showed no difference between the treatment arms. There were fewer occurrences of worsening heart failure in the ivabradine SR arm.Conclusions: The present study demonstrates that ivabradine SR once daily in addition to optimum standard therapy improved heart function in patients with HFrEF. (Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets [FIRST]; NCT02188082). [ABSTRACT FROM AUTHOR]

Background: This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study.Methods: This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389.Findings: 603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2-749·2) and 571·0 (467·6-697·3), with seroconversion rates at 96% (95% CI 93-98) and 97% (92-99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8-22·7) and 18·3 (14·4-23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85-93) of 253 and 113 (88%, 81-92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented.Interpretation: The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation.Funding: National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics. [ABSTRACT FROM AUTHOR]

Objectives: Although patients with primary and metastatic brain tumors and their partners are at risk of experiencing high symptom burden, they are often excluded from psychosocial intervention studies. Thus, we sought to examine the feasibility and preliminary efficacy of a couple-based meditation (CBM) program targeting symptom and well-being outcomes.Methods: Couples completed baseline measures assessing symptom and well-being outcomes and were randomized to the CBM or a usual care control group. Couples in the CBM groups attended four weekly (60 minutes each) therapist-led sessions that were delivered via FaceTime (Apple Inc, Cupertino, CA). The CBM program focused on cultivating mindfulness, compassion, gratitude and purpose, and integrated emotional disclosure exercises. Both groups were reassessed six and 12 weeks after baseline.Results: We approached 60 eligible dyads, of which 37 (62%) consented, 35 (95%) were randomized, and 22 (63%) completed all assessments. Couples in the CBM group attended a mean of 3.33 sessions (SD 1.09). For patients, significant group differences in favor of the CBM group were found for cognitive (d = 1.05) and general disease symptoms (d = 0.93), and relationship well-being (d = 0.68) and compassion (d = 0.96). No significant group differences were revealed for partners.Conclusion: It seems to be feasible, acceptable, and possibly efficacious to deliver a dyadic intervention via FaceTime to brain tumor couples. Although both patients and partners in the CBM group rated the intervention as beneficial, significant group differences with medium-to-large effect sizes were only found for patients. [ABSTRACT FROM AUTHOR]

Keywords: canagliflozin; chronic kidney disease; diabetes mellitus, type 2; SGLT2 inhibitors EN canagliflozin chronic kidney disease diabetes mellitus, type 2 SGLT2 inhibitors 407 410 4 04/20/20 20200204 NES 200204 Traditional management of diabetes mellitus has focused on glycemic control, beginning with lifestyle changes, followed by metformin, and then other classes of antiglycemic agents.[1] Sodium glucose co-transporter 2 inhibitors reduce cardiovascular events, including cardiovascular death, myocardial infarction, and heart failure, and slow the progression of renal dysfunction, including prevention of end-stage kidney disease.[2],[3] Because initial clinical trials included mostly patients with baseline HbA1c >7%, current guidelines have recommended this class of drugs as an add-on therapy for patients whose HbA1c is not at goal, typically >=7%.[1] We hypothesized that there would be similar benefits on cardiovascular and renal end points regardless of baseline HbA1c, including those with HbA1c <7%. We found that canagliflozin reduced the risk of both cardiovascular and renal events in patients with type 2 diabetes mellitus and chronic kidney disease without a significant interaction across the spectrum of baseline HbA1c values, which included patients with baseline HbA1c between 6.5% and 7%, suggesting that treatment of patients with chronic kidney disease or atherosclerotic cardiovascular disease is warranted, even if their diabetes mellitus is "well controlled.". [Extracted from the article]

Background: After brain metastasis resection, whole brain radiotherapy decreases local recurrence, but might cause cognitive decline. We did this study to determine if stereotactic radiosurgery (SRS) to the surgical cavity improved time to local recurrence compared with that for surgical resection alone.Methods: In this randomised, controlled, phase 3 trial, we recruited patients at a single tertiary cancer centre in the USA. Eligible patients were older than 3 years, had a Karnofsky Performance Score of 70 or higher, were able to have an MRI scan, and had a complete resection of one to three brain metastases (with a maximum diameter of the resection cavity ≤4 cm). Patients were randomly assigned (1:1) with a block size of four to either SRS of the resection cavity (within 30 days of surgery) or observation. Patients were stratified by histology of the primary tumour, metastatic tumour size, and number of metastases. The primary endpoint was time to local recurrence in the resection cavity, assessed by blinded central review of brain MRI scans by the study neuroradiologist in the modified intention-to-treat population that analysed patients by randomised allocation but excluded patients found ineligible after randomisation. Participants and other members of the treatment team (excluding the neuroradiologist) were not masked to treatment allocation. The trial is registered with ClinicalTrials.gov, number NCT00950001, and is closed to new participants.Findings: Between Aug 13, 2009, and Feb 16, 2016, 132 patients were randomly assigned to the observation group (n=68) or SRS group (n=64), with 128 patients available for analysis; four patients were ineligible (three from the SRS group and one from the observation group). Median follow-up was 11·1 months (IQR 4·8-20·4). 12-month freedom from local recurrence was 43% (95% CI 31-59) in the observation group and 72% (60-87) in the SRS group (hazard ratio 0·46 [95% CI 0·24-0·88]; p=0·015). There were no adverse events or treatment-related deaths in either group.Interpretation: SRS of the surgical cavity in patients who have had complete resection of one, two, or three brain metastases significantly lowers local recurrence compared with that noted for observation alone. Thus, the use of SRS after brain metastasis resection could be an alternative to whole-brain radiotherapy.Funding: National Institutes of Health. [ABSTRACT FROM AUTHOR]

Introduction: Split-thickness skin graft (STSG) donor site dressing has been controversial until now. Our study aimed to assess the patient comfort and wound-healing efficacy with the application of thin split-thickness skin grafts regrafting on STSG donor sites.Methods: One hundred ninety-two consecutive patients undergoing split-thickness skin grafting were included in the study, and the participants were randomly divided into the following three groups: group A was regrafted with thin STSGs and groups B and C were covered with occlusive hydrocellular dressing and paraffin gauze, respectively. The participants were compared according to the epithelialization time, pain and scar formation.Results: The average time of epithelialization was 6.2 ± 1.1 days in group A, 11.1 ± 2.1 days in group B and 13.5 ± 2.5 days in group C. The pain scores on days 2 and 5 after operation were 2.3 ± 0.8 and 1.9 ± 0.8 in group A, 2.5 ± 1.1 and 3.9 ± 1.3 in group B, and 3.8 ± 1.4 and 5.9 ± 2.1 in group C. The scar scores at half a year and one year after operation were 4.3 ± 0.6 and 2.50 ± 0.6 in group A, 7.4 ± 0.6 and 6.2 ± 0.6 in group B, and 11.8 ± 0.4 and 10.9 ± 1.0 in group C, separately. The difference in the three groups was significant.Conclusion: Utilizing thin STSGs regrafting on donor sites could significantly shorten the epithelialization time, reduce pain and prevent hyperplastic scar formulation. [ABSTRACT FROM AUTHOR]

Aims: To explore associations between adverse pregnancy outcomes and risk of postpartum diabetes and prediabetes among Chinese women with gestational diabetes mellitus (GDM).Methods: A total of 507 women with GDM who participated in a randomized controlled trial were successfully followed up at a median of 9.1  (interquartile range: 7.7-11.3) weeks after delivery and underwent a 75 g 2-h oral glucose tolerance test. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Group's criteria. Postpartum diabetes and prediabetes were defined by the World Health Organization's. Generalized logit model was used to obtain odds ratios (OR) and 95% confidence interval (CI) of adverse pregnancy outcomes for postpartum diabetes, prediabetes and abnormal glucose regulation (AGR).Results: Of 507 women with GDM, 3.7% (19) women developed postpartum diabetes, 35.1% (178) women developed postpartum prediabetes. Preterm birth was associated with increased risk of postpartum prediabetes and AGR (adjusted OR: 3.24, 95%CI: 1.48-7.07 & 3.16, 1.46-6.85). Low birth weight was associated with the risk of postpartum prediabetes, diabetes and AGR (adjusted OR: 2.78, 95%CI: 1.13-6.86; 5.21, 1.13-24.02 & 2.99, 1.24-7.21).Conclusions: Preterm birth and low birth weight were predictive of postpartum prediabetes, diabetes or AGR in Chinese women with GDM. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to investigate the potential wide application of beta tricalcium phosphate (β-TCP) only for bone defects as compared to allograft. 95 patients with a solitary bone cyst were randomly assigned to the treatment. A new radiographic scoring system was employed to calculate the biodegradation of bone graft and to evaluate the influence of multiple factors. At an average of 28.43months after surgery, a radiographic semi-quantitative analysis revealed that the degradation rates of β-TCP and the allograft were comparable (p >0.05). Age, complication, packing methods and granule diameters have a significant influence on β-TCP degradation. The loose packing method and 3–5mm granule size should be employed in clinical practice. A histological analysis of biopsy showed that β-TCP supported the growth of fibrous tissue, vascular tissue, as well as bone tissue into the implants. The results proved that single β-TCP is an advantageous alternative to allografts for lacunar bone defect repair and would well guide the design and clinical application of the β-TCP. [Copyright &y& Elsevier]