Search

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]

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: 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]

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: 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]

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]

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]

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: 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: 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]