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Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Nocturnal Blood Pressure Is Reduced by a Mandibular Advancement Device for Sleep Apnea in Women: Findings From Secondary Analyses of a Randomized Trial.Background:Obstructive sleep apnea is associated with high blood pressure. The magnitude of blood pressure effects from sleep apnea treatment is unclear. We aimed to determine the effect of mandibular advancement device therapy on ambulatory nighttime and daytime blood pressure in women and men with daytime sleepiness and snoring or mild to moderate sleep apnea (apnea-hypopnea index, <30).Methods and results:In this 4-month, double-blind, randomized controlled trial comprising 96 untreated patients, 27 women and 58 men, aged 31 to 70 years, completed the study. The active group received individually made adjustable mandibular advancement devices, and the control group was given individually made sham devices, to be used during sleep. Polysomnographic sleep recordings and ambulatory 24-hour blood pressure measurements were performed at baseline and at follow-up. In women with mandibular advancement devices, the mean nighttime systolic blood pressure was 10.8 mm Hg (95% confidence interval, 4.0-17.7 mm Hg; P=0.004) lower than in the women in the sham group, adjusted for baseline blood pressure, age, body mass index, and the apnea-hypopnea index. The mean nighttime adjusted diastolic blood pressure was 6.6 mm Hg (95% confidence interval, 2.7-10.4 mm Hg; P=0.002) lower in the mandibular advancement device group. In men, there were no significant differences in blood pressure at night or during the daytime between the intervention groups.Conclusions:A mandibular advancement device for obstructive sleep apnea reduces nocturnal blood pressure in women.Clinical trial registration:URL: https://www.clinicaltrials.gov. Unique identifier: NCT00477009.

Primary Outcome Measures is Sleep apnea and sleep measured by polysomnography; Extracted Interventionsis is Mandibular repositioning appliance, adjustable; Conditions is Sleep Apnea Syndromes|Snoring|Disorders of Excessive Somnolence ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Intranasal carbetocin reduces hyperphagia in individuals with Prader-Willi syndrome.Background:Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder of life-threatening hyperphagia, obesity, intellectual deficits, compulsivity, and other behavioral problems. The efficacy and safety of i.n. carbetocin, an oxytocin analog, was evaluated in a prospective, randomized, double-blinded trial in adolescents with PWS.Methods:Eligible patients aged 10-18 years with genetically confirmed PWS were randomized (1:1) to i.n. carbetocin or placebo 3 times daily for 14 days. The primary efficacy endpoint was change in parent/caregiver-rated Hyperphagia in PWS Questionnaire-Responsiveness (HPWSQ-R) total score. Secondary efficacy endpoints included HPWSQ-R behavior, drive, and severity domains; clinician-rated HPWSQ; Children's Yale-Brown Obsessive-Compulsive Severity Scale; food domain of the Reiss Profile; and Clinical Global Impression-Improvement scale. Endpoints were assessed using analysis of covariance. Relationship between primary and secondary endpoints was assessed using Pearson correlation coefficients. Safety was assessed throughout the study.Results:Demographics and clinical characteristics were similar between treatment groups (carbetocin, n = 17; placebo, n = 20). Patients receiving carbetocin had statistically significant reductions in HPWSQ-R total score at study end (-15.6) versus patients receiving placebo (-8.9; P = 0.029); several secondary efficacy endpoints also demonstrated significant differences (P < 0.05). Treatment effects for the primary and secondary endpoints were highly correlated (P ≤ 0.0001). Incidence of adverse events (AEs) was similar between treatment groups.Conclusion:I.n. carbetocin was well tolerated and improved hyperphagia and behavioral symptoms of PWS.Trial registration:ClinicalTrials.gov: NCT01968187FUNDING. The study was funded by Ferring Pharmaceuticals. Recruitment was aided by ongoing work in PWS performed through Eunice Kennedy Shriver National Institute of Child Health and Human Development grant U54 HD083211.

Primary Outcome Measures is Change in total hyperphagia score as measured by a Hyperphagia for Prader-Willi Syndrome Questionnaire; Extracted Interventionsis is FE 992097 Placebo; Conditions is Hyperphagia in Prader-Willi Syndrome ;Sex is ALL ;Age is CHILD, ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss.Background:Cisplatin chemotherapy and surgery are effective treatments for children with standard-risk hepatoblastoma but may cause considerable and irreversible hearing loss. This trial compared cisplatin with cisplatin plus delayed administration of sodium thiosulfate, aiming to reduce the incidence and severity of cisplatin-related ototoxic effects without jeopardizing overall and event-free survival.Methods:We randomly assigned children older than 1 month and younger than 18 years of age who had standard-risk hepatoblastoma (≤3 involved liver sectors, no metastatic disease, and an alpha-fetoprotein level of >100 ng per milliliter) to receive cisplatin alone (at a dose of 80 mg per square meter of body-surface area, administered over a period of 6 hours) or cisplatin plus sodium thiosulfate (at a dose of 20 g per square meter, administered intravenously over a 15-minute period, 6 hours after the discontinuation of cisplatin) for four preoperative and two postoperative courses. The primary end point was the absolute hearing threshold, as measured by pure-tone audiometry, at a minimum age of 3.5 years. Hearing loss was assessed according to the Brock grade (on a scale from 0 to 4, with higher grades indicating greater hearing loss). The main secondary end points were overall survival and event-free survival at 3 years.Results:A total of 109 children were randomly assigned to receive cisplatin plus sodium thiosulfate (57 children) or cisplatin alone (52) and could be evaluated. Sodium thiosulfate was associated with few high-grade toxic effects. The absolute hearing threshold was assessed in 101 children. Hearing loss of grade 1 or higher occurred in 18 of 55 children (33%) in the cisplatin-sodium thiosulfate group, as compared with 29 of 46 (63%) in the cisplatin-alone group, indicating a 48% lower incidence of hearing loss in the cisplatin-sodium thiosulfate group (relative risk, 0.52; 95% confidence interval [CI], 0.33 to 0.81; P=0.002). At a median of 52 months of follow-up, the 3-year rates of event-free survival were 82% (95% CI, 69 to 90) in the cisplatin-sodium thiosulfate group and 79% (95% CI, 65 to 88) in the cisplatin-alone group, and the 3-year rates of overall survival were 98% (95% CI, 88 to 100) and 92% (95% CI, 81 to 97), respectively.Conclusions:The addition of sodium thiosulfate, administered 6 hours after cisplatin chemotherapy, resulted in a lower incidence of cisplatin-induced hearing loss among children with standard-risk hepatoblastoma, without jeopardizing overall or event-free survival. (Funded by Cancer Research UK and others; SIOPEL 6 ClinicalTrials.gov number, NCT00652132 ; EudraCT number, 2007-002402-21 .).

Primary Outcome Measures is Rate of Brock grade ≥ 1 hearing loss; Extracted Interventionsis is cisplatin sodium thiosulfate; Conditions is Liver Cancer|Ototoxicity ;Sex is ALL ;Age is CHILD, ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.A potential therapeutic role for angiotensin-converting enzyme 2 in human pulmonary arterial hypertension.Pulmonary arterial hypertension (PAH) is a deadly disease with no cure. Alternate conversion of angiotensin II (AngII) to angiotensin-(1-7) (Ang-(1-7)) by angiotensin-converting enzyme 2 (ACE2) resulting in Mas receptor (Mas1) activation improves rodent models of PAH. Effects of recombinant human (rh) ACE2 in human PAH are unknown. Our objective was to determine the effects of rhACE2 in PAH.We defined the molecular effects of Mas1 activation using porcine pulmonary arteries, measured AngII/Ang-(1-7) levels in human PAH and conducted a phase IIa, open-label pilot study of a single infusion of rhACE2 (GSK2586881, 0.2 or 0.4 mg·kg-1 intravenously).Superoxide dismutase 2 (SOD2) and inflammatory gene expression were identified as markers of Mas1 activation. After confirming reduced plasma ACE2 activity in human PAH, five patients were enrolled in the trial. GSK2586881 was well tolerated with significant improvement in cardiac output and pulmonary vascular resistance. GSK2586881 infusion was associated with reduced plasma markers of inflammation within 2-4 h and increased SOD2 plasma protein at 2 weeks.PAH is characterised by reduced ACE2 activity. Augmentation of ACE2 in a pilot study was well tolerated, associated with improved pulmonary haemodynamics and reduced markers of oxidant and inflammatory mediators. Targeting this pathway may be beneficial in human PAH.

Primary Outcome Measures is Ratio of sex hormone metabolites; Extracted Interventionsis is nan; Conditions is Idiopathic Pulmonary Arterial Hypertension|Heritable Pulmonary Arterial Hypertension|Scleroderma Associated Pulmonary Arterial Hypertension|Appetite Suppressant Associate PAH ;Sex is ALL ;Age is CHILD, ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML.Background:Mutations in the gene encoding isocitrate dehydrogenase 1 ( IDH1) occur in 6 to 10% of patients with acute myeloid leukemia (AML). Ivosidenib (AG-120) is an oral, targeted, small-molecule inhibitor of mutant IDH1.Methods:We conducted a phase 1 dose-escalation and dose-expansion study of ivosidenib monotherapy in IDH1-mutated AML. Safety and efficacy were assessed in all treated patients. The primary efficacy population included patients with relapsed or refractory AML receiving 500 mg of ivosidenib daily with at least 6 months of follow-up.Results:Overall, 258 patients received ivosidenib and had safety outcomes assessed. Among patients with relapsed or refractory AML (179 patients), treatment-related adverse events of grade 3 or higher that occurred in at least 3 patients were prolongation of the QT interval (in 7.8% of the patients), the IDH differentiation syndrome (in 3.9%), anemia (in 2.2%), thrombocytopenia or a decrease in the platelet count (in 3.4%), and leukocytosis (in 1.7%). In the primary efficacy population (125 patients), the rate of complete remission or complete remission with partial hematologic recovery was 30.4% (95% confidence interval [CI], 22.5 to 39.3), the rate of complete remission was 21.6% (95% CI, 14.7 to 29.8), and the overall response rate was 41.6% (95% CI, 32.9 to 50.8). The median durations of these responses were 8.2 months (95% CI, 5.5 to 12.0), 9.3 months (95% CI, 5.6 to 18.3), and 6.5 months (95% CI, 4.6 to 9.3), respectively. Transfusion independence was attained in 29 of 84 patients (35%), and patients who had a response had fewer infections and febrile neutropenia episodes than those who did not have a response. Among 34 patients who had a complete remission or complete remission with partial hematologic recovery, 7 (21%) had no residual detectable IDH1 mutations on digital polymerase-chain-reaction assay. No preexisting co-occurring single gene mutation predicted clinical response or resistance to treatment.Conclusions:In patients with advanced IDH1-mutated relapsed or refractory AML, ivosidenib at a dose of 500 mg daily was associated with a low frequency of grade 3 or higher treatment-related adverse events and with transfusion independence, durable remissions, and molecular remissions in some patients with complete remission. (Funded by Agios Pharmaceuticals; ClinicalTrials.gov number, NCT02074839 .).

Primary Outcome Measures is Safety/tolerability: incidence of adverse events.; Extracted Interventionsis is AG-120; Conditions is Relapsed or Refractory Acute Myeloid Leukemia (AML)|Untreated AML|Other IDH1-mutated Positive Hematologic Malignancies|Myelodysplastic Syndromes ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström's Macroglobulinemia.Background:Single-agent ibrutinib has shown substantial activity in patients with relapsed Waldenström's macroglobulinemia, a rare form of B-cell lymphoma. We evaluated the effect of adding ibrutinib to rituximab in patients with this disease, both in those who had not received previous treatment and in those with disease recurrence.Methods:We randomly assigned 150 symptomatic patients to receive ibrutinib plus rituximab or placebo plus rituximab. The primary end point was progression-free survival, as assessed by an independent review committee. Key secondary end points were response rates, sustained hematologic improvement from baseline, and safety. The mutational status of MYD88 and CXCR4 was assessed in bone marrow samples.Results:At 30 months, the progression-free survival rate was 82% with ibrutinib-rituximab versus 28% with placebo-rituximab (hazard ratio for progression or death, 0.20; P<0.001). The benefit in the ibrutinib-rituximab group over that in the placebo-rituximab group was independent of the MYD88 or CXCR4 genotype. The rate of major response was higher with ibrutinib-rituximab than with placebo-rituximab (72% vs. 32%, P<0.001). More patients had sustained increases in hemoglobin level with ibrutinib-rituximab than with placebo-rituximab (73% vs. 41%, P<0.001). The most common adverse events of any grade with ibrutinib-rituximab included infusion-related reactions, diarrhea, arthralgia, and nausea. Events of grade 3 or higher that occurred more frequently with ibrutinib-rituximab than with placebo-rituximab included atrial fibrillation (12% vs. 1%) and hypertension (13% vs. 4%); those that occurred less frequently included infusion reactions (1% vs. 16%) and any grade of IgM flare (8% vs. 47%). The major hemorrhage rate was the same in the two trial groups (4%).Conclusions:Among patients with Waldenström's macroglobulinemia, the use of ibrutinib-rituximab resulted in significantly higher rates of progression-free survival than the use of placebo-rituximab, both among those who had received no previous treatment and among those with disease recurrence. Atrial fibrillation and hypertension were more common with ibrutinib-rituximab, whereas infusion reactions and IgM flare were more common with placebo-rituximab. (Funded by Pharmacyclics and Janssen Research and Development; ClinicalTrials.gov number, NCT02165397 .).

Primary Outcome Measures is Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 54; Extracted Interventionsis is Ibrutinib Placebo Rituximab; Conditions is Waldenström's Macroglobulinemia ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.A Randomized Trial of a Family-Support Intervention in Intensive Care Units.Background:Surrogate decision makers for incapacitated, critically ill patients often struggle with decisions related to goals of care. Such decisions cause psychological distress in surrogates and may lead to treatment that does not align with patients' preferences.Methods:We conducted a stepped-wedge, cluster-randomized trial involving patients with a high risk of death and their surrogates in five intensive care units (ICUs) to compare a multicomponent family-support intervention delivered by the interprofessional ICU team with usual care. The primary outcome was the surrogates' mean score on the Hospital Anxiety and Depression Scale (HADS) at 6 months (scores range from 0 to 42, with higher scores indicating worse symptoms). Prespecified secondary outcomes were the surrogates' mean scores on the Impact of Event Scale (IES; scores range from 0 to 88, with higher scores indicating worse symptoms), the Quality of Communication (QOC) scale (scores range from 0 to 100, with higher scores indicating better clinician-family communication), and a modified Patient Perception of Patient Centeredness (PPPC) scale (scores range from 1 to 4, with lower scores indicating more patient- and family-centered care), as well as the mean length of ICU stay.Results:A total of 1420 patients were enrolled in the trial. There was no significant difference between the intervention group and the control group in the surrogates' mean HADS score at 6 months (11.7 and 12.0, respectively; beta coefficient, -0.34; 95% confidence interval [CI], -1.67 to 0.99; P=0.61) or mean IES score (21.2 and 20.3; beta coefficient, 0.90; 95% CI, -1.66 to 3.47; P=0.49). The surrogates' mean QOC score was better in the intervention group than in the control group (69.1 vs. 62.7; beta coefficient, 6.39; 95% CI, 2.57 to 10.20; P=0.001), as was the mean modified PPPC score (1.7 vs. 1.8; beta coefficient, -0.15; 95% CI, -0.26 to -0.04; P=0.006). The mean length of stay in the ICU was shorter in the intervention group than in the control group (6.7 days vs. 7.4 days; incidence rate ratio, 0.90; 95% CI, 0.81 to 1.00; P=0.045), a finding mediated by the shortened mean length of stay in the ICU among patients who died (4.4 days vs. 6.8 days; incidence rate ratio, 0.64; 95% CI, 0.52 to 0.78; P<0.001).Conclusions:Among critically ill patients and their surrogates, a family-support intervention delivered by the interprofessional ICU team did not significantly affect the surrogates' burden of psychological symptoms, but the surrogates' ratings of the quality of communication and the patient- and family-centeredness of care were better and the length of stay in the ICU was shorter with the intervention than with usual care. (Funded by the UPMC Health System and the Greenwall Foundation; PARTNER ClinicalTrials.gov number, NCT01844492 .).

Primary Outcome Measures is Hospital Anxiety and Depression Scale; Extracted Interventionsis is The PARTNER Intervention ICU Usual Care Control; Conditions is Anxiety|Depression ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Indacaterol/glycopyrronium versus salmeterol/fluticasone in the prevention of clinically important deterioration in COPD: results from the FLAME study.Background:Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening. This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study.Methods:CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1) or ≥ 4-unit increase in St. George's Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation. Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID-) at Week 12.Results:IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67-0.78]; P < 0.0001), and reduced the incidences of CID versus SFC. Additionally, IND/GLY delayed the time to CID in all patient subgroups. After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID- patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID- patients (P < 0.0001). CID+ patients had a comparable change in the SGRQ total score versus CID- patients.Conclusions:IND/GLY reduced the risk of CID versus SFC. CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year.Trial registration:Clinicaltrials.gov NCT01782326 .

Primary Outcome Measures is Rate of COPD Exacerbations; Extracted Interventionsis is QVA149 Long acting B2 agonist (LABA) and inhaled corticosteroid (ICS); Conditions is Chronic Obstructive Pulmonary Disease (COPD) ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Comparison of the effects of photodynamic therapy, intravitreal ranibizumab and combination for polypoidal choroidal vasculopathy under 1 + PRN regimen.Background:The optimal treatment for polypoidal choroidal vasculopathy (PCV) is still under debate. Little knowledge is known about the treatment effect of "1+pro re nata(PRN)" treatment regimen for PCV. The aim of this study was to compare the outcomes of photodynamic therapy (PDT), intravitreal ranibizumab injection (IVR) and combination therapy under the "1 + PRN" treatment regimen for PCV.Methods:Fifty-seven eyes of 57 patients completed the 12 months' follow-up in this prospective study. The patients in the PDT arm(n = 23), ranibizumab arm(n = 18), or combination arm(n = 16) underwent a session of PDT, IVR or combination of both at baseline followed by additional IVR as needed. Mean change of logarithm of the minimal angle of resolution (logMAR) visual acuity (VA), central foveal thickness (CFT) and the regression rate of polyps were evaluated. Cost-benefit analysis was also performed.Results:At Month 12, the mean logMAR VA improved from 0.90 ± 0.52 to 0.75 ± 0.57 in the PDT group (P < 0.05), from 0.96 ± 0.58 to 0.77 ± 0.41 in the IVR group (P < 0.05), and from 0.94 ± 0.55 to 0.72 ± 0.44 in the combination group (P < 0.05), respectively. The CFT decreased from 478.04 ± 156.70 μm, 527.5 ± 195.90 μm, and 522.63 ± 288.40 μm at the baseline to 366.43 ± 148.28 μm, 373.17 ± 134.88 μm and 328.44 ± 103.25 in the PDT group (P < 0.05), IVR group (P < 0.01), and the combination group (P < 0.05), respectively. However, no statistical difference was found between groups (P > 0.05). PDT treatment (60.87%) was superior to the IVR therapy (22.22%) in achieving complete regression of polyps (P < 0.05). Cost-benefit analysis showed that IVR treatment cost the least money for improving per 0.1logMAR units and the combination therapy demanded the least money for reducing per 100 μm of CFT.Conclusions:PDT, IVR and the combination therapy have similar efficacy in the VA improvement as well as the reduction of CFT under the "1 + PRN" treatment regimen.Trial registration:Current Controlled Trials NCT03459144 . Registered retrospectively on March 2, 2018.

Primary Outcome Measures is Best corrected visual acuity; Extracted Interventionsis is verteporfin verteporfin and ranibizumab; Conditions is Polypoidal Choroidal Vasculopathy ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.The role of Gabapentin oral solution in decreasing desflurane associated emergence agitation and delirium in children after stabismus surgery, a prospective randomized double-blind study.Background:Short acting inhalational anesthetic (Desflurane) produces emergence agitation (EA) in pediatrics with an incidence up to 80%. The aim of the present study was to examine the role of Gabapentin oral solution in attenuating desflurane associated EA in children after strabismus surgery under general anesthesia.Methods:Seventy patients, 2-6 years old, scheduled for strabismus surgery were randomly allocated into two groups (35 each); Control group (c): received 5 ml of oral strawberry juice (placebo) and Gabapentin group (G) received 5 mg/Kg gabapentin oral solution in 5 ml strawberry juice, 1 h before anesthesia. Patient separation, cooperation, emergence incidence and emergence severity were assessed. Also time to extubation and time to emergence, duration of PACU stay, PONV and number of patients required meperidine postoperatively were recorded.Results:Duration to extubation and duration to emergence were statistically prolonged in gabapentin group compared to the control group. The incidence of EA and its severity were reduced in gabapentin group with more tendencies to be asleep and less attentive. More patients in the control group required postoperative meperidine to reduce crying and agitation.Conclusion:Oral gabapentin 5 mg/kg reduced the incidence and severity scoring of emergence agitation (by 20%) with more tendencies for sleeping with preserved response to stimuli in PACU.Trial registration:Number: NCT03347916 , date: November 17, 2017, retrospectively.

Primary Outcome Measures is emergence agitation incidence and scores; Extracted Interventionsis is Strawberry juice as (placebo) Gabapentin Oral Solution [Neurontin]; Conditions is Emergence Agitation After Desflurane Anesthesia ;Sex is ALL ;Age is CHILD

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Propofol attenuates the increase of sonographic optic nerve sheath diameter during robot-assisted laparoscopic prostatectomy: a randomized clinical trial.Background:Robot-assisted laparoscopic prostatectomy (RALP) requires pneumoperitoneum and the Trendelenburg position to optimize surgical exposure, which can increase intracranial pressure (ICP). Anesthetic agents also influence ICP. We compared the effects of propofol and sevoflurane on sonographic optic nerve sheath diameter (ONSD) as a surrogate for ICP in prostate cancer patients who underwent RALP.Methods:Thirty-six patients were randomly allocated to groups receiving propofol (propofol group, n = 18) or sevoflurane (sevoflurane group, n = 18) anesthesia. The ONSD was measured 10 min after induction of anesthesia in the supine position (T1); 5 min (T2), 30 min (T3), and 60 min (T4) after establishing pneumoperitoneum and the Trendelenburg position; and at the end of surgery after desufflation in the supine position (T5). Respiratory and hemodynamic variables were also evaluated.Results:The ONSD was significantly different between the propofol group and the sevoflurane group at T4 (5.27 ± 0.35 mm vs. 5.57 ± 0.28 mm, P = 0.007), but not at other time points. The ONSDs at T2, T3, T4, and T5 were significantly greater than at T1 in both groups (all P < 0.001). Arterial carbon dioxide partial pressure, arterial oxygen partial pressure, peak airway pressure, plateau airway pressure, systolic blood pressure, pulse pressure variation, body temperature and regional cerebral oxygen saturation, except heart rate, were not significantly different between the two groups.Conclusions:The ONSD was significantly lower during propofol anesthesia than during sevoflurane anesthesia 60 min after pneumoperitoneum and the Trendelenburg position, suggesting that propofol anesthesia may help minimize ICP changes in robotic prostatectomy patients.Trial registration:Clinicaltrials.gov identifier: NCT03271502 . Registered August 31, 2017.

Primary Outcome Measures is Difference in optic nerve sheath diameter; Extracted Interventionsis is Total intravenous anesthesia Inhalation anesthesia; Conditions is Prostate Cancer ;Sex is MALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Phase Ia study of the indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor navoximod (GDC-0919) in patients with recurrent advanced solid tumors.Background:Indoleamine-2,3-dioxygenase 1 (IDO1) catalyzes the oxidation of tryptophan into kynurenine and is partially responsible for acquired immune tolerance associated with cancer. The IDO1 small molecule inhibitor navoximod (GDC-0919, NLG-919) is active as a combination therapy in multiple tumor models.Methods:This open-label Phase Ia study assessed safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of navoximod in patients with recurrent/advanced solid tumors, administered as 50-800 mg BID on a 21/28 day and at 600 mg on a 28/28 day schedule. Plasma kynurenine and tryptophan were longitudinally evaluated and tumor assessments were performed.Results:Patients (n = 22) received a median of 3 cycles of navoximod. No maximum tolerated dose was reached. One dose-limiting toxicity of Grade 4 lower gastrointestinal hemorrhage was reported. Adverse events (AEs) regardless of causality in ≥20% of patients included fatigue (59%), cough, decreased appetite, and pruritus (41% each), nausea (36%), and vomiting (27%). Grade ≥ 3 AEs occurred in 14/22 patients (64%), and were related to navoximod in two patients (9%). Navoximod was rapidly absorbed (Tmax ~ 1 h) and exhibited dose-proportional increases in exposure, with a half-life (t1/2 ~ 11 h) supportive of BID dosing. Navoximod transiently decreased plasma kynurenine from baseline levels with kinetics consistent with its half-life. Of efficacy-evaluable patients, 8 (36%) had stable disease and 10 (46%) had progressive disease.Conclusions:Navoximod was well-tolerated at doses up to 800 mg BID decreasing plasma kynurenine levels consistent with its half-life. Stable disease responses were observed.Trial registration:ClinicalTrials.gov identifier: NCT02048709 .

Primary Outcome Measures is Percentage of patients with dose-limiting toxicities; Extracted Interventionsis is GDC-0919; Conditions is Solid Tumor ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.nan

Primary Outcome Measures is Medication adherence measured by Chinese version of the 8-item Morisky medication adherence scale (C-MMAC-8); Extracted Interventionsis is APP intervention; Conditions is Coronary Artery Bypass Grafting|Medication Adherence|Mobile Applications ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Relapse After Antipsychotic Discontinuation in Schizophrenia as a Withdrawal Phenomenon vs Illness Recurrence: A Post Hoc Analysis of a Randomized Placebo-Controlled Study.Background:It has been proposed that relapse rates after antipsychotic discontinuation may be artificially inflated and that some of these symptom recurrences may be due to rebound or withdrawal phenomena rather than due to illness recurrence.Methods:Post hoc analysis of data from a relapse-prevention study (conducted from March 2005 to February 2007) of paliperidone palmitate once-monthly (PP1M) versus placebo was conducted to compare the nature of operationally defined relapse events in schizophrenia patients (diagnosed by DSM-IV criteria) experiencing relapses after randomization to placebo (n = 97) with those in patients receiving maintenance PP1M treatment (n = 36). These 2 groups were compared for onset and severity of recurrence symptoms, symptom profiles at relapse, and postrelapse treatment response. Psychological and physiological signs of discontinuation and signs of antipsychotic tolerance, dyskinesia, and prolactin elevation that might indicate dopamine receptor supersensitivity were compared.Results:Both groups were similar in terms of relapse symptom profiles, onset and severity of relapse symptoms, and postrelapse treatment response. The Positive and Negative Syndrome Scale total score (mean ± SD) for placebo versus maintenance treatment group at baseline was 54.5 ± 11.74 vs 54.1 ± 11.64 and at relapse was 75.6 ± 16.79 vs 75.2 ± 17.23 (P = .9). No elevated blood pressure or heart rate, dyskinesia, antipsychotic tolerance, or elevated prolactin in the patients relapsing after antipsychotic discontinuation was noted.Conclusions:Findings suggest that relapses after treatment discontinuation reflect recurrence of the underlying illness and may be consistent with a hypothesis of direct relationship between dopamine and psychosis. No evidence was obtained for withdrawal-related phenomena contributing to the high relapse rates after treatment discontinuation.Trial registration:ClinicalTrials.gov identifier: NCT00111189.

Primary Outcome Measures is The primary efficacy criteria for this study is the time from randomization to the first recurrence event during the double-blind recurrence prevention period; Extracted Interventionsis is Placebo Paliperidone Palmitate; Conditions is Schizophrenia ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Clinical Predictors of Extrapyramidal Symptoms Associated With Aripiprazole Augmentation for the Treatment of Late-Life Depression in a Randomized Controlled Trial.Objective:Augmentation with aripiprazole is an effective pharmacotherapy for treatment-resistant late-life depression (LLD). However, aripiprazole can cause extrapyramidal symptoms (EPS) such as akathisia and parkinsonism; these symptoms are distressing and can contribute to treatment discontinuation. We investigated the clinical trajectories and predictors of akathisia and parkinsonism in older patients receiving aripiprazole augmentation for treatment-resistant LLD.Methods:Between 2009 and 2013, depressed older adults who did not remit with venlafaxine were randomized to aripiprazole or placebo in a 12-week trial. Participants were 60 years or older and met DSM-IV-TR criteria for major depressive episode with at least moderate symptoms. The presence of akathisia and parkinsonism was measured at each visit using the Barnes Akathisia Scale (BAS) and Simpson-Angus Scale (SAS), respectively. In an exploratory analysis, we examined a broad set of potential clinical predictors and correlates: age, sex, ethnicity, weight, medical comorbidity, baseline anxiety severity, depression severity, concomitant medications including rescue medications, and aripiprazole dosage.Results:Twenty-four (26.7%) of 90 participants randomized to aripiprazole and who had akathisia scores available developed akathisia compared to 11 (12.2%) of 90 randomized to placebo. Greater depression severity was the main predictor of treatment-emergent akathisia. Most participants who developed akathisia improved over time, especially with reductions in dosage. Fifteen (16.5%) of 91 participants taking aripiprazole and who had parkinsonism scores available developed parkinsonism, but no clinical predictors or correlates were identified.Conclusions:Akathisia is a common side effect of aripiprazole, but it is typically mild and responds to dose reduction. Patients with greater baseline depression may warrant closer monitoring for akathisia. More research is needed to understand the course and predictors of treatment-emergent EPS with antipsychotic augmentation for treatment-resistant LLD.Trial registration:ClinicalTrials.gov identifier: NCT00892047.

Primary Outcome Measures is Percentage of Subjects Who Met Criteria for Remission Based on the Montgomery-Asberg Depression Rating Scale (MADRS); Extracted Interventionsis is venlafaxine XR plus aripiprazole venlafaxine plus placebo; Conditions is Depression ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Comparison of prostatic artery embolisation (PAE) versus transurethral resection of the prostate (TURP) for benign prostatic hyperplasia: randomised, open label, non-inferiority trial.Objective:To compare prostatic artery embolisation (PAE) with transurethral resection of the prostate (TURP) in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia in terms of patient reported and functional outcomes.Design:Randomised, open label, non-inferiority trial.Setting:Urology and radiology departments of a Swiss tertiary care centre.Participants:103 patients aged ≥40 years with refractory lower urinary tract symptoms secondary to benign prostatic hyperplasia were randomised between 11 February 2014 and 24 May 2017; 48 and 51 patients reached the primary endpoint 12 weeks after PAE and TURP, respectively.Interventions:PAE performed with 250-400 μm microspheres under local anaesthesia versus monopolar TURP performed under spinal or general anaesthesia.Main outcomes and measures:Primary outcome was change in international prostate symptoms score (IPSS) from baseline to 12 weeks after surgery; a difference of less than 3 points between treatments was defined as non-inferiority for PAE and tested with a one sided t test. Secondary outcomes included further questionnaires, functional measures, magnetic resonance imaging findings, and adverse events; changes from baseline to 12 weeks were compared between treatments with two sided tests for superiority.Results:Mean reduction in IPSS from baseline to 12 weeks was -9.23 points after PAE and -10.77 points after TURP. Although the difference was less than 3 points (1.54 points in favour of TURP (95% confidence interval -1.45 to 4.52)), non-inferiority of PAE could not be shown (P=0.17). None of the patient reported secondary outcomes differed significantly between treatments when tested for superiority; IPSS also did not differ significantly (P=0.31). At 12 weeks, PAE was less effective than TURP regarding changes in maximum rate of urinary flow (5.19 v 15.34 mL/s; difference 10.15 (95% confidence interval -14.67 to -5.63); P<0.001), postvoid residual urine (-86.36 v -199.98 mL; 113.62 (39.25 to 187.98); P=0.003), prostate volume (-12.17 v -30.27 mL; 18.11 (10.11 to 26.10); P<0.001), and desobstructive effectiveness according to pressure flow studies (56% v 93% shift towards less obstructive category; P=0.003). Fewer adverse events occurred after PAE than after TURP (36 v 70 events; P=0.003).Conclusions:The improvement in lower urinary tract symptoms secondary to benign prostatic hyperplasia seen 12 weeks after PAE is close to that after TURP. PAE is associated with fewer complications than TURP but has disadvantages regarding functional outcomes, which should be considered when selecting patients. Further comparative study findings, including longer follow-up, should be evaluated before PAE can be considered as a routine treatment.Trial registration:Clinicaltrials.gov NCT02054013.

Primary Outcome Measures is Changes in the International Prostate Symptom Score; Extracted Interventionsis is Prostatic artery embolization monopolar transurethral prostatectomy; Conditions is Benign Prostatic Hyperplasia ;Sex is MALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Multicomponent mHealth Intervention for Large, Sustained Change in Multiple Diet and Activity Risk Behaviors: The Make Better Choices 2 Randomized Controlled Trial.Background:Prevalent co-occurring poor diet and physical inactivity convey chronic disease risk to the population. Large magnitude behavior change can improve behaviors to recommended levels, but multiple behavior change interventions produce small, poorly maintained effects.Objective:The Make Better Choices 2 trial tested whether a multicomponent intervention integrating mHealth, modest incentives, and remote coaching could sustainably improve diet and activity.Methods:Between 2012 and 2014, the 9-month randomized controlled trial enrolled 212 Chicago area adults with low fruit and vegetable and high saturated fat intakes, low moderate to vigorous physical activity (MVPA) and high sedentary leisure screen time. Participants were recruited by advertisements to an open-access website, screened, and randomly assigned to either of two active interventions targeting MVPA simultaneously with, or sequentially after other diet and activity targets (N=84 per intervention) or a stress and sleep contact control intervention (N=44). They used a smartphone app and accelerometer to track targeted behaviors and received personalized remote coaching from trained paraprofessionals. Perfect behavioral adherence was rewarded with an incentive of US $5 per week for 12 weeks. Diet and activity behaviors were measured at baseline, 3, 6, and 9 months; primary outcome was 9-month diet and activity composite improvement.Results:Both simultaneous and sequential interventions produced large, sustained improvements exceeding control (P<.001), and brought all diet and activity behaviors to guideline levels. At 9 months, the interventions increased fruits and vegetables by 6.5 servings per day (95% CI 6.1-6.8), increased MVPA by 24.7 minutes per day (95% CI 20.0-29.5), decreased sedentary leisure by 170.5 minutes per day (95% CI -183.5 to -157.5), and decreased saturated fat intake by 3.6% (95% CI -4.1 to -3.1). Retention through 9-month follow-up was 82.1%. Self-monitoring decreased from 96.3% of days at baseline to 72.3% at 3 months, 63.5% at 6 months, and 54.6% at 9 months (P<.001). Neither attrition nor decline in self-monitoring differed across intervention groups.Conclusions:Multicomponent mHealth diet and activity intervention involving connected coaching and modest initial performance incentives holds potential to reduce chronic disease risk.Trial registration:ClinicalTrials.gov NCT01249989; https://clinicaltrials.gov/ct2/show/NCT01249989 (Archived by WebCite at https://clinicaltrials.gov/ct2/show/NCT01249989).

Primary Outcome Measures is Change in Fruit/Vegetable Serving Intake; Extracted Interventionsis is Sequential MBC Condition Simultaneous MBC Condition Stress Management; Conditions is Health Behavior ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Early initiation of a strength training based rehabilitation after lumbar spine fusion improves core muscle strength: a randomized controlled trial.Background:To analyze the safety and effects of early initiation of rehabilitation including objective measurement outcomes after lumbar spine fusion based on principles of strength training.Methods:The study recruited 27 patients, aged 45 to 70 years, who had undergone lumbar spine fusion. The method of concealed random allocation without blocking was used to form two groups. The strength training group started rehabilitation 3 weeks after surgery. Patients exercised twice weekly over 9 weeks focusing on muscle activation of lumbopelvic stabilization muscles. The control group followed a standard postoperative protocol, where no exercises were performed at that stage of rehabilitation. Functional outcomes and plain radiographs were evaluated at 3 weeks and subsequently at 3 and 18 months after the surgery.Results:No hardware loosening of failure was observed in the training group. Both groups improved their walking speed after 3 months (p < 0.01), although improvement in the training group was significantly greater than in the control group (p < 0.01). Moreover, the training group significantly improved after the training period in all isometric trunk muscles measurements (p < 0.03), standing reach height (p < 0.02), and pre-activation pattern (p < 0.05). After 18 months, no training effects were observed.Conclusions:The study showed that early initiation of a postoperative rehabilitation program based on principles of strength training is safe, 3 weeks after lumbar spine fusion, and enable earlier functional recovery than standard rehabilitation protocol.Trial registration:The study is registered at the US National Institutes of Health ( ClinicalTrials.gov ) NCT03349580 . The date of registration: November 21, 2017 - Retrospectively registered.

Primary Outcome Measures is Change of isometric trunk muscle strength; Extracted Interventionsis is The training group; Conditions is Lumbar Spine Fusion ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Randomized controlled trial of robot-assisted gait training with dorsiflexion assistance on chronic stroke patients wearing ankle-foot-orthosis.Background:Robot-assisted ankle-foot-orthosis (AFO) can provide immediate powered ankle assistance in post-stroke gait training. Our research team has developed a novel lightweight portable robot-assisted AFO which is capable of detecting walking intentions using sensor feedback of wearer's gait pattern. This study aims to investigate the therapeutic effects of robot-assisted gait training with ankle dorsiflexion assistance.Methods:This was a double-blinded randomized controlled trial. Nineteen chronic stroke patients with motor impairment at ankle participated in 20-session robot-assisted gait training for about five weeks, with 30-min over-ground walking and stair ambulation practices. Robot-assisted AFO either provided active powered ankle assistance during swing phase in Robotic Group (n = 9), or torque impedance at ankle joint as passive AFO in Sham Group (n = 10). Functional assessments were performed before and after the 20-session gait training with 3-month Follow-up. Primary outcome measure was gait independency assessed by Functional Ambulatory Category (FAC). Secondary outcome measures were clinical scores including Fugl-Meyer Assessment (FMA), Modified Ashworth Scale (MAS), Berg Balance Scale (BBS), Timed 10-Meter Walk Test (10MWT), Six-minute Walk Test (SMWT), supplemented by gait analysis. All outcome measures were performed in unassisted gait after patients had taken off the robot-assisted AFO. Repeated-measures analysis of covariance was conducted to test the group differences referenced to clinical scores before training.Results:After 20-session robot-assisted gait training with ankle dorsiflexion assistance, the active ankle assistance in Robotic Group induced changes in gait pattern with improved gait independency (all patients FAC ≥ 5 post-training and 3-month follow-up), motor recovery, walking speed, and greater confidence in affected side loading response (vertical ground reaction force + 1.49 N/kg, peak braking force + 0.24 N/kg) with heel strike instead of flat foot touch-down at initial contact (foot tilting + 1.91°). Sham Group reported reduction in affected leg range of motion (ankle dorsiflexion - 2.36° and knee flexion - 8.48°) during swing.Conclusions:Robot-assisted gait training with ankle dorsiflexion assistance could improve gait independency and help stroke patients developing confidence in weight acceptance, but future development of robot-assisted AFO should consider more lightweight and custom-fit design.Trial registration:ClinicalTrials.gov NCT02471248 . Registered 15 June 2015 retrospectively registered.

Primary Outcome Measures is 6-minute Walk Test; Extracted Interventionsis is Ankle Robot with Power Assistance Sham; Conditions is Stroke ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Item distribution and inter-rater reliability of the German version of the quality of life in Alzheimer's disease scale (QoL-AD) proxy for people with dementia living in nursing homes.Background:The Quality of Life in Alzheimer's disease scale (QoL-AD) is a widely used Health Related Quality of Life (HRQoL) instrument. However, studies investigating the instrument's inter-rater reliability (IRR) are missing. This study aimed to determine the item distribution and IRR of the German proxy version of the QoL-AD (13 Items) and a nursing home-specific instrument version (QoL-AD NH, 15 Items).Methods:The instruments were applied to 73 people with dementia living in eight nursing homes in Germany. Individuals with dementia were assessed two times by blinded proxy raters. The IRR analyses were based on methodological criteria of the quality appraisal tool for studies of diagnostic reliability (QAREL), the COSMIN group and the single-measure Intra-Class Correlation Coefficient (ICC) for absolute agreement ≥0.70.Results:All items for both instrument versions demonstrated acceptable item difficulty, with the exception of one item (QoL-AD proxy). The IRR was moderate for the QoL-AD (ICC: 0.65) and insufficient for the QoL-AD NH (ICC: 0.18). The additional computation of the average measure ICC for two proxy-raters demonstrated a strong IRR (ICC: 0.79) for the QoL-AD and a weak IRR for the QoL-AD NH (ICC: 0.31). The detailed analysis of the IRR for each item underpinned the need for the further development of both instruments.Conclusions:The unsatisfactory IRRs for both instruments highlight the need for the development of a user guide including general instructions for instrument application as well as definitions and examples reflecting item meaning. Priority should be given to the development of reliable proxy-person versions of both instruments.Trial registration:ClinicalTrials.gov: NCT02295462 , Date of registration: 11-20-2014.

Primary Outcome Measures is Proportion of residents receiving at least one antipsychotic medication after 12 months; Extracted Interventionsis is Person-centered Care Optimised Treatment; Conditions is Dementia ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Anticoagulation and Antiplatelet Strategies After On-X Mechanical Aortic Valve Replacement.Background:The burden oral anticoagulation is a limitation of mechanical valve prostheses.Objectives:The aim of this study was to test whether patients could be safely managed with dual-antiplatelet therapy (DAPT) (aspirin 325 mg and clopidogrel 75 mg) or lower warfarin after On-X mechanical aortic valve replacement (mAVR).Methods:PROACT (Prospective Randomized On-X Anticoagulation Trial) (n = 576) is a multicenter (41 sites) noninferiority trial. From June 2006 through February 2014, 201 patients ≥18 years of age without thromboembolic risk factors undergoing mAVR were randomized to receive DAPT (n = 99) or standard warfarin plus aspirin (n = 102) 3 months after mAVR (low-risk arm). From June 2006 through October 2009, 375 patients with 1 or more thromboembolic risk factors were also randomized to lower intensity warfarin plus aspirin (international normalized ratio 1.5 to 2.0; n = 185) or standard warfarin plus aspirin (international normalized ratio 2.0 to 3.0; n = 190) 3 months after mAVR (high-risk arm).Results:The low-risk arm was terminated for excess cerebral thromboembolic events (3.12% per patient-year vs. 0.29% per patient-year, p = 0.02) in the DAPT group at up to 8.8-year follow-up (631.6 patient-years), with no differences in bleeding or all-cause mortality. High-risk arm patients experienced significantly lower major (1.59% per patient-year vs. 3.94% per patient-year, p = 0.002) and minor (1.27% per patient-year vs. 3.49% per patient-year, p = 0.002) bleeding up to 8.7-year follow-up (2,035.2 patient-years), with no differences in thromboembolism (0.42% per patient-year vs. 0.09% per patient-year, p = 0.20) and all-cause mortality.Conclusions:DAPT was associated with higher rates of thromboembolism and valve thrombosis compared with control in the low-risk arm. International normalized ratios were safely maintained at 1.5 to 2.0 in high-risk patients, without differences in mortality or thromboembolic complications. (Randomized On-X Anticoagulation Trial [PROACT]; NCT00291525).

Primary Outcome Measures is Thromboembolism; Extracted Interventionsis is On-X valve using reduced anticoagulation On-X Valve with Standard warfarin Therapy; Conditions is Heart Valve Disease ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Impact of Primary Care Intensive Management on High-Risk Veterans' Costs and Utilization: A Randomized Quality Improvement Trial.Background:Primary care models that offer comprehensive, accessible care to all patients may provide insufficient resources to meet the needs of patients with complex conditions who have the greatest risk for hospitalization.Objective:To assess whether augmenting usual primary care with team-based intensive management lowers utilization and costs for high-risk patients.Design:Randomized quality improvement trial. (ClinicalTrials.gov: NCT03100526).Setting:5 U.S. Department of Veterans Affairs (VA) medical centers.Patients:Primary care patients at high risk for hospitalization who had a recent acute care episode.Intervention:Locally tailored intensive management programs providing care coordination, goals assessment, health coaching, medication reconciliation, and home visits through an interdisciplinary team, including a physician or nurse practitioner, a nurse, and psychosocial experts.Measurements:Utilization and costs (including intensive management program expenses) 12 months before and after randomization.Results:2210 patients were randomly assigned, 1105 to intensive management and 1105 to usual care. Patients had a mean age of 63 years and an average of 7 chronic conditions; 90% were men. Of the patients assigned to intensive management, 487 (44%) received intensive outpatient care (that is, ≥3 encounters in person or by telephone) and 204 (18%) received limited intervention. From the pre- to postrandomization periods, mean inpatient costs decreased more for the intensive management than the usual care group (-$2164 [95% CI, -$7916 to $3587]). Outpatient costs increased more for the intensive management than the usual care group ($2636 [CI, $524 to $4748]), driven by greater use of primary care, home care, telephone care, and telehealth. Mean total costs were similar in the 2 groups before and after randomization.Limitations:Sites took up to several months to contact eligible patients, limiting the time between treatment and outcome assessment. Only VA costs were assessed.Conclusion:High-risk patients with access to an intensive management program received more outpatient care with no increase in total costs.Primary funding source:Veterans Health Administration Primary Care Services.

Primary Outcome Measures is VA health care cost; Extracted Interventionsis is PACT Intensive Management; Conditions is Primary Health Care|Health Care Costs ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Increased cholesterol absorption rather than synthesis is involved in boosted protease inhibitor-associated hypercholesterolaemia.Objective:The aim of this study was to compare the differential effects of first-line efavirenz (EFV)-based vs. boosted lopinavir-based antiretroviral regimens on cholesterol metabolism.Design:Multicentre, open-label, randomized clinical trial.Methods:Forty-nine naive HIV-infected patients were randomized (1 : 1) to receive either ritonavir-boosted lopinavir (LPV/r) or EFV both in combination with tenofovir and emtricitabine (ClinicalTrials.gov: NCT00759070). Lipid profile and serum phytosterols and cholesterol precursors were determined at baseline and after 16 weeks.Results:After 16 weeks of intervention, total and non-HDL cholesterol as well as triglyceride levels significantly increased in the LPV/r-group (+1.0 ± 0.8; +0.8 ± 0.7 and +0.8 ± 1.5 mmol/l, respectively), but not in the EFV-group (+0.4 ± 0.7; +0.4 ± 0.6 and 0.2 ± 0.5 mmol/l, respectively). Markers of cholesterol absorption (campesterol-to-cholesterol and sitosterol-to-cholesterol ratios) significantly increased in the LPV/r-group, but not in the EFV-group, whereas there were no changes in either group of the lathosterol-to-cholesterol ratio, a marker of cholesterol synthesis.Conclusion:Treatment with an LPV/r-based therapy increased total cholesterol relative to EFV-based therapy. Our data suggest that absorption rather than synthesis is the mechanism involved in LPV/r-associated increased total cholesterol.

Primary Outcome Measures is Changes in total cholesterol and HDL and LDL fractions; Extracted Interventionsis is Tenofovir + emtricitabine + efavirenz Tenofovir + emtricitabine + lopinavir/ritonavir; Conditions is HIV Infections ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.A phase IIa proof-of-concept, placebo-controlled, randomized, double-blind, crossover, single-dose clinical trial of a new class of bronchodilator for acute asthma.Background:This study evaluates a novel bronchodilator, S1226, for its efficacy in reversing allergen-induced bronchoconstriction in subjects with mild, allergic asthma. S1226 is a new class of bronchodilator that is an aerosol/vapor/gas mixture combining pharmacological and biophysical principles for a novel mode of action. It contains a potent bronchodilator gas (carbon dioxide or CO2) and nebulized perflubron (a synthetic surfactant possessing mucolytic properties). It has demonstrated rapid reversal of allergen-induced bronchoconstriction in an ovine study model.Methods:This was a phase IIa proof-of-concept, placebo-controlled, randomized, double-blind, crossover single-dose clinical trial to evaluate the safety, tolerability, and efficacy of S1226 (8% CO2) administered by nebulization following an allergen-induced early asthmatic response in 12 subjects with mild, allergic asthma. Primary safety endpoints were adverse events, vital signs, pulse oximetry, and spirometry. Efficacy endpoints included bronchodilator response (measured as the forced expiratory volume in 1 s or FEV1) over time, the area under the curve of FEV1 for the early asthmatic response over time, and achievement of responder status, defined as a 12% improvement after the allergen challenge.Results:No significant safety issues were observed. All adverse events were non-serious, mild, and transient. There was a statistically significant decrease in peripheral blood oxygenation levels over time in the placebo group following allergen inhalation, whereas blood oxygenation was maintained at normal levels in the S1226-treated subjects (P = 0.028). This effect was greatest 5 min after start of treatment (P < 0.001). The recovery rate was faster but not significantly so (P = 0.272) for S1226 compared to the placebo at earlier time points (5, 10, and 15 min), as assessed by ≥12% reversal of FEV1. The recovery of FEV1 over time was significantly greater (P = 0.04) with S1226 compared to the placebo.Conclusions:S1226 was safe, tolerated well, and provided bronchodilation and improved blood oxygenation in subjects with mild atopic asthma following allergen-induced bronchoconstriction. Additional studies to optimize the therapeutic response are indicated.Trial registration:ClinicalTrials.gov, NCT02334553 . Registered on 12 November 2014.

Primary Outcome Measures is The number of treatment emergent adverse events (AEs).; Extracted Interventionsis is S1226(8%) Placebo; Conditions is Asthma ;Sex is ALL ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.How to address the challenges of evaluating treatment benefits-risks in rare diseases? A convergent mixed methods approach applied within a Merkel cell carcinoma phase 2 clinical trial.Background:Demonstrating treatment benefits within clinical trials in the context of rare diseases is often methodologically and practically challenging. Mixed methods research offers an approach to overcome these challenges by combining quantitative and qualitative data, thus providing a better understanding of the research question. A convergent mixed methods design in the context of Merkel cell carcinoma, a rare skin cancer, was used during the JAVELIN Merkel 200 trial (NCT02155647).Methods:Nine patients receiving avelumab in the JAVELIN Merkel 200 trial were interviewed at baseline prior to receiving study treatment, and at 13 weeks and 25 weeks after first avelumab administration. Key concepts of interest identified from the baseline interviews were physical functioning, fatigue/energy, and pain. Patient perceptions of the overall change in their cancer-related health status since starting study treatment were also recorded. During qualitative analysis, at each time-point, each concept of interest was assigned a category describing the trend in change (e.g. newly emerged, no change/stable, improved, worsened, ceased/disappeared). In parallel, patients' tumour status was determined by the clinical overall response status as per the clinical trial protocol.Results:A high concordance between patient-reported qualitative data and assessed tumour response was observed. All eight patients who clinically improved had perceived a subjective improvement in their disease since the beginning of the study; the single patient whose disease worsened had a perceived deterioration. Patient perceived benefit in physical functioning, fatigue/energy and pain was subsequent to the measured change in clinical status as assessed by tumour response. This suggests that patient-reported assessment should be examined over the long term in order to optimally capture meaningful treatment effect.Conclusion:Embedding qualitative research in clinical trials to complement the quantitative data is an innovative approach to characterise meaningful treatment effect. This application of mixed methods research has the potential to overcome the hurdles associated with clinical outcomes assessment in rare diseases.

Primary Outcome Measures is Part A: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1; Extracted Interventionsis is Avelumab; Conditions is Carcinoma, Merkel Cell ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Comparative impact of two continuing education activities targeted at COPD educators on educational outcomes: protocol for a non-randomized controlled study using mixed methods.Background:Therapeutic patient education (TPE) improves quality of life and reduces health care utilization among patients with chronic obstructive pulmonary disease (COPD). However, benefits from TPE might depend on the performance of the educators and training is needed to ensure the effective delivery of TPE interventions. Based on the framework by Moore et al. (J Contin Educ Health Prof 29:1-15, 2009), we will compare the impact of two continuing education (CE) activities on TPE in regard to the following educational outcomes: (1) learning, (2) self-report of competence, (3) performance of the educators, and (4) outcomes of COPD patients who will meet the newly trained educators for TPE.Methods:We will conduct a non-randomized controlled study using mixed methods. Educators will first participate in a CE activity on TPE that will include a role-playing simulation (experimental group) or in a lecture on TPE (comparison group) and then will perform TPE in COPD patients. Among educators, we will assess: (1) learning, by measuring knowledge about TPE, and (2) self-report of competence using self-administered questionnaires before and after the activity. Then, after the CE activity, we will assess (3) educators' performance levels in delivering TPE by rating a videotaped TPE intervention. In COPD patients who will meet the newly trained educators for TPE after either CE activity, we will assess (4) quality of life and resource utilization using interviewer-administered questionnaires, before and after TPE. Statistical analyses will compare the experimental group against the comparison group using multivariate models. Using a semi-structured interview guide, we will conduct interviews with educators and perform content analysis. Results will be integrated in order that qualitative results further explain the quantitative ones.Discussion:To the best of our knowledge, this is the first controlled mixed methods study to compare the impact of two CE activities on TPE in regard to four educational outcomes. We believe this study will serve as a model for evaluating CE activities on TPE. Results from this study could increase educators' performance levels in delivering effective TPE interventions, and, in turn, COPD patient outcomes.Trial registration:The study was registered on https://clinicaltrials.gov/ ( NCT02870998 ) on March 15, 2016.

Primary Outcome Measures is Performance; Extracted Interventionsis is Active learning Passive learning; Conditions is Lung Diseases, Obstructive ;Sex is ALL ;Age is CHILD, ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Motivational interviewing in long-term sickness absence: study protocol of a randomized controlled trial followed by qualitative and economic studies.Background:Motivational interviewing (MI), mainly used and shown effective in health care (substance abuse, smoking cessation, increasing exercise and other life style changes), is a collaborative conversation (style) about change that could be useful for individuals having problems related to return to work (RTW). The aim of this paper is to describe the design of a randomized controlled trial evaluating the effect of MI on RTW among sick listed persons compared to usual care, in a social security setting.Methods:The study is a randomized controlled trial with parallel group design. Individuals between 18 and 60 years who have been sick listed for more than 7 weeks, with a current sick leave status of 50-100%, are identified in the Norwegian National Social Security System and invited to participate in the study. Exclusion criteria are no employment and pregnancy. Included participants are randomly assigned to the MI intervention or one of two control groups. The MI intervention consists of two MI sessions offered by caseworkers at the Norwegian Labor and Welfare Service (NAV), while the comparative arms consist of a usual care group and a group that receives two extra sessions without MI content (to control for attentional bias). The primary outcome measure is the total number of sickness absence days during 12 months after inclusion, obtained from national registers. Secondary outcomes include time until full sustainable return to work, health-related quality of life and mental health status. In addition, a health economic evaluation, a feasibility/process evaluation and qualitative studies will be performed as part of the study.Discussion:A previous study has suggested an effect of MI on RTW for sick listed workers with musculoskeletal complaints. The present study will evaluate the effect of MI for all sick listed workers, regardless of diagnosis. The knowledge from this study will potentially be important for policy makers, clinicians and other professionals` practical work.Trial registration:ClinicalTrials.gov: NCT03212118 (registered July 11, 2017).

Primary Outcome Measures is Total number of sickness absence days during the year after enrollment in the study (i.e. after randomization); Extracted Interventionsis is Treatment as usual (TAU-0) Structured talks (TAU-2) motivational interviewing (MI); Conditions is Sick Leave ;Sex is ALL ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Safety and immunogenicity of a Vi-DT typhoid conjugate vaccine: Phase I trial in Healthy Filipino adults and children.Background:Typhoid fever remains a major public health problem in low- and middle-income countries where children aged 2-14 years bear the greatest burden. Vi polysaccharide is poorly immunogenic in children <2 years of age, and protection in adults is modest. The limitations of Vi polysaccharide vaccines can be overcome by conjugation of the Vi to a carrier protein. A typhoid conjugate vaccine composed of Vi polysaccharide conjugated to diphtheria toxoid (Vi-DT) has been developed. The Phase I study results are presented here.Methods:This was a randomized, observer-blinded Phase I study to assess the safety and immunogenicity of Vi-DT compared to Vi polysaccharide vaccine, conducted in Manila, Philippines. Participants enrolled in an age de-escalation manner (18-45, 6-17 and 2-5 years) were randomized between Test (Vi-DT, 25 µg) administered at 0 and 4 weeks and Comparator (Vi polysaccharide, Typhim Vi® and Vaxigrip®, Sanofi Pasteur) vaccines.Results:A total of 144 participants were enrolled (48 by age strata, 24 in Test and Comparator groups each). No serious adverse event was reported in either group. Solicited and unsolicited adverse events were mild or moderate in both groups with the exception of a 4-year old girl in Test group with grade 3 fever which resolved without sequelae. All participants in Test group seroconverted after first and second doses of Vi-DT while the proportions in the Comparator group were 97.1% and 97.2%, after first dose of Typhim Vi® and second dose of Vaxigrip®, respectively. Vi-DT showed 4-fold higher Geometric Mean Titers (GMT) compared to Typhim Vi® (adjusted for age strata, p < 0.001). No further increase of GMT was detected after the second dose of Vi-DT. Anti-DT IgG seroresponse rates were 81.2% and 84.5% post first and second Vi-DT doses, respectively.Conclusions:Vi-DT vaccine was safe, well-tolerated and immunogenic in participants aged 2-45 years. ClinicalTrials.gov registration number: NCT02645032.

Primary Outcome Measures is Safety endpoints for solicited adverse events (reactogenicity) and serious adverse events; Extracted Interventionsis is Vi-DT Typhim Vi® VAXIGRIP®; Conditions is Typhoid ;Sex is ALL ;Age is CHILD, ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Quality of life in the GLARIUS trial randomizing bevacizumab/irinotecan versus temozolomide in newly diagnosed, MGMT-nonmethylated glioblastoma.Background:The GLARIUS trial, which investigated the efficacy of bevacizumab (BEV)/irinotecan (IRI) compared with standard temozolomide in the first-line therapy of O6-methylguanine-DNA methyltransferase (MGMT)-nonmethylated glioblastoma, showed that progression-free survival was significantly prolonged by BEV/IRI, while overall survival was similar in both arms. The present report focuses on quality of life (QoL) and Karnofsky performance score (KPS) during the whole course of the disease.Methods:Patients (n = 170) received standard radiotherapy and were randomized (2:1) for BEV/IRI or standard temozolomide. At least every 3 months KPS was determined and QoL was measured using the European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life and 20-item Brain Neoplasm questionnaires. A generalized estimating equation (GEE) model evaluated differences in the course of QoL and KPS over time. Also, the time to first deterioration and the time to postprogression deterioration were analyzed separately.Results:In all dimensions of QoL and KPS, GEE analyses and time to first deterioration analyses did not detect significant differences between the treatment arms. At progression, 82% of patients receiving second-line therapy in the standard arm received BEV second-line therapy. For the dimensions of motor dysfunction and headaches, time to postprogression deterioration was prolonged in the standard arm receiving crossover second-line BEV in the vast majority of patients at the time of evaluation.Conclusions:GLARIUS did not find indications for a BEV-induced detrimental effect on QoL in first-line therapy of MGMT-nonmethylated GBM patients. Moreover, GLARIUS provided some indirect corroborative data supporting the notion that BEV may have beneficial effects upon QoL in relapsed GBM.

Primary Outcome Measures is Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months; Extracted Interventionsis is bevacizumab [Avastin] irinotecan temozolomide; Conditions is Glioblastoma Multiforme ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial.Background:Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue.Methods:We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008-000625-19, and ClinicalTrials.gov, number NCT01288794.Findings:From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40-0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3-4 non-liver related adverse events.Interpretation:In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis.Funding:Italian Medicine Agency.

Primary Outcome Measures is Mortality; Extracted Interventionsis is Diuretics plus human albumin Diuretics (standard medical treatment); Conditions is Liver Cirrhosis|Ascites ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Additional hepatic 166Ho-radioembolization in patients with neuroendocrine tumours treated with 177Lu-DOTATATE; a single center, interventional, non-randomized, non-comparative, open label, phase II study (HEPAR PLUS trial).Background:Neuroendocrine tumours (NET) consist of a heterogeneous group of neoplasms with various organs of origin. At diagnosis 21% of the patients with a Grade 1 NET and 30% with a Grade 2 NET have distant metastases. Treatment with peptide receptor radionuclide therapy (PRRT) shows a high objective response rate and long median survival after treatment. However, complete remission is almost never achieved. The liver is the most commonly affected organ in metastatic disease and is the most incriminating factor for patient survival. Additional treatment of liver disease after PRRT may improve outcome in NET patients. Radioembolization is an established therapy for liver metastasis. To investigate this hypothesis, a phase 2 study was initiated to assess effectiveness and toxicity of holmium-166 radioembolization (166Ho-RE) after PRRT with lutetium-177 (177Lu)-DOTATATE.Methods:The HEPAR PLUS trial ("Holmium Embolization Particles for Arterial Radiotherapy Plus 177 Lu-DOTATATE in Salvage NET patients") is a single centre, interventional, non-randomized, non-comparative, open label study. In this phase 2 study 30-48 patients with > 3 measurable liver metastases according to RECIST 1.1 will receive additional 166Ho-RE within 20 weeks after the 4th and last cycle of PRRT with 7.4 GBq 177Lu-DOTATATE. Primary objectives are to assess tumour response, complete and partial response according to RECIST 1.1, and toxicity, based on CTCAE v4.03, 3 months after 166Ho-RE. Secondary endpoints include biochemical response, quality of life, biodistribution and dosimetry.Discussion:This is the first prospective study to combine PRRT with 177Lu-DOTATATE and additional 166Ho-RE in metastatic NET. A radiation boost on intrahepatic disease using 166Ho-RE may lead to an improved response rate without significant additional side-effects.Trial registration:Clinicaltrials.gov NCT02067988 , 13 February 2014. Protocol version: 6, 30 november 2016.

Primary Outcome Measures is Response (RECIST 1.1 Partial plus complete); Extracted Interventionsis is Holmium-166 microspheres hepatic radioembolization.; Conditions is Neuroendocrine Tumors ;Sex is ALL ;Age is CHILD, ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.TOPical Imiquimod treatment of residual or recurrent cervical intraepithelial neoplasia (TOPIC-2 trial): a study protocol for a randomized controlled trial.Background:Cervical dysplasia (cervical intraepithelial neoplasia (CIN)) is caused by Human Papillomavirus (HPV) and is most common in women of reproductive age. Current treatment of moderate to severe CIN is surgical. This procedure has potential complications, such as haemorrhage, infection and preterm birth in subsequent pregnancies. Moreover, 15% of women treated for high grade CIN develop residual/recurrent CIN or cervical cancer after surgical excision. Finally, 75-100% of patients with a residual and recurrent CIN 2-3 lesion are still HPV positive. They could possibly benefit from an alternative medical treatment, which aims to eliminate HPV. The primary study objective is to evaluate the effectivity of imiquimod 5% cream compared to treatment with Large Loop Excision of the Transformation Zone (LLETZ) for recurrent/residual CIN.Methods/design:This study is a multicentre, non-inferiority randomized single blinded study. The study population consists of female patients with histological proven residual/recurrent CIN after previous surgical treatment. Four hundred thirty-three patients will be included in the Netherlands. The first 35 patients will be included in a pilot study to prove non-futility. Included patients will be randomized to receive either 5% imiquimod cream or LLETZ treatment. Imiquimod will be inserted three times a week intravaginally for a period of 16 weeks using a vaginal applicator. Ten weeks after the end of imiquimod treatment a biopsy will be taken for treatment response. In case of progressive or stable disease a LLETZ will be performed. At 12 and 24 months after the start of treatment cytology will be taken for follow up. The LLETZ group will be treated according to the current guidelines. Throughout the study, HPV typing and quality of life will be tested.Discussion:Repeated LLETZ in women with residual/recurrent CIN lesions has complications. We would like to possibly offer alternative treatment in a selected group to avoid these risks. Moreover, we monitor treatment efficacy, side effects and long-term recurrence rates.Trial registration:Medical Ethical Committee approval number: NL 53792.078.15. Affiliation: Erasmus Medical Center. Registration number ClinicalTrials.gov : NCT02669459 , date of registration: 27th January 2016.

Primary Outcome Measures is Reduction to normal cytology; Extracted Interventionsis is Imiquimod LLETZ; Conditions is Cervical Intraepithelial Neoplasia ;Sex is FEMALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.nan

Primary Outcome Measures is Number of Participants With Death (Both on and Off Treatment) Due to Any Cause; Extracted Interventionsis is fluticasone furoate/vilanterol fluticasone furoate vilanterol Placebo; Conditions is Pulmonary Disease, Chronic Obstructive ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Bortezomib and high-dose melphalan conditioning regimen in frontline multiple myeloma: an IFM randomized phase 3 study.High-dose melphalan (HDM) and transplantation are recommended for eligible patients with multiple myeloma. No other conditioning regimen has proven to be more effective and/or safer. We previously reported in a phase 2 study that bortezomib can safely and effectively be combined with HDM (Bor-HDM), with a 32% complete response (CR) rate after transplantation. These data supported a randomized phase 3 trial. Randomization was stratified according to risk and response to induction: 300 patients were enrolled, and 154 were allocated to the experimental arm (ie, arm A) with bortezomib (1 mg/m2 intravenously [IV]) on days -6, -3, +1, and +4 and melphalan (200 mg/m2 IV) on day -2. The control arm (ie, arm B) consisted of HDM alone (200 mg/m2 IV). There were no differences in stringent CR + CR rates at day 60 posttransplant (primary end point): 22.1% in arm A vs 20.5% in arm B (P = .844). There were also no differences in undetectable minimum residual disease rates: 41.3% vs 39.4% (P = .864). Median progression-free survival was 34.0 months for arm A vs 29.6 months for arm B (adjusted HR, 0.82; 95% CI, 0.61-1.13; P = .244). The estimated 3-year overall survival was 89.5% in both arms (hazard ratio, 1.28; 95% CI, 0.62-2.64; P = .374). Sixty-nine serious adverse events occurred in 18.7% of Bor-HDM-treated patients (vs 13.1% in HDM-treated patients). The proportion of grade 3/4 AEs was similar within the 2 groups (72.0% vs 73.1%), mainly (as expected) blood and gastrointestinal disorders; 4% of patients reported grade 3/4 or painful peripheral neuropathy in arm A (vs 1.5% in arm B). In this randomized phase 3 study, a conditioning regimen with Bor-HDM did not improve efficacy end points or outcomes compared with HDM alone. The original trial was registered at www.clinicaltrials.gov as #NCT02197221.

Primary Outcome Measures is Complete Response rates (according to IMWG 2011 criteria); Extracted Interventionsis is Bortezomib-Melphalan Melphalan; Conditions is Multiple Myeloma ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis.Background:The Phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control; randomized 2:1 to olaparib or control) in men with homologous recombination repair gene alterations and metastatic castration-resistant prostate cancer whose disease progressed on prior next-generation hormonal agent.Methods:We present efficacy and safety data from an exploratory post hoc analysis of olaparib in the PROfound Asian subset. Analyses were not planned, alpha controlled or powered. Of 101 Asian patients enrolled in Japan (n=57), South Korea (n=29) and Taiwan (n=15), 66 and 35 patients received olaparib and control, respectively.Results:Radiographic progression-free survival (rPFS) and overall survival (OS) favored olaparib versus control in Cohort A [rPFS 7.2 vs. 4.5 months, HR 0.58, 95% CI 0.29-1.21, P = 0.14 (nominal); OS 23.4 vs. 17.8 months, HR 0.81, 95% CI 0.40-1.74, P = 0.57 (nominal)] and Cohorts A+B [rPFS 5.8 vs. 3.5 months, HR 0.69, 95% CI 0.42-1.16, P = 0.13 (nominal); OS 18.6 vs. 16.2 months, HR 0.96, 95% CI 0.56-1.70, P = 0.9 (nominal)]. Olaparib showed greatest improvement in patients harboring BRCA alterations [rPFS 9.3 vs. 3.5 months, HR 0.17, 95% CI 0.06-0.49, P = 0.0003 (nominal); OS 26.8 vs. 14.3 months, HR 0.62, 95% CI 0.24-1.79, P = 0.34 (nominal)]. Safety data were consistent with the known profile of olaparib, with no new safety signals identified.Conclusion:In PROfound, there was a statistically significant improvement in outcomes reported in the global population of patients with metastatic castration-resistant prostate cancer and alterations in homologous recombination repair genes whose disease progressed on prior next-generation hormonal agent compared with control. For the subset of Asian patients reported here, exploratory analysis suggested that there was also an improvement in outcomes versus control. The safety and tolerability of olaparib in Asian patients were similar to that of the PROfound global population.Clinical trial number:ClinicalTrials.gov NCT02987543.

Primary Outcome Measures is Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A Only; Extracted Interventionsis is olaparib enzalutamide abiraterone acetate abiraterone acetate enzalutamide; Conditions is Metastatic Castration-resistant Prostate Cancer ;Sex is MALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Different Doses, Forms, and Frequencies of Zinc Supplementation for the Prevention of Diarrhea and Promotion of Linear Growth among Young Bangladeshi Children: A Six-Arm, Randomized, Community-Based Efficacy Trial.Background:Children in resource-limited settings remain vulnerable to zinc deficiency and its consequences.Objectives:To evaluate the effects of different doses, durations, and frequencies of zinc supplementation on the incidence of diarrhea and change in linear growth among young children.Methods:We conducted a randomized, partially double-blind, controlled, 6-arm, community-based efficacy trial in Dhaka, Bangladesh. Children aged 9-11 mo were randomly assigned to receive 1 of the following interventions for 24 wk: 1) standard micronutrient powder (MNP) containing 4.1 mg zinc and 10 mg iron, daily; 2) high-zinc (10 mg), low-iron (6 mg) (HiZn LoFe) MNP, daily; 3) HiZn (10 mg) LoFe (6 mg)/HiZn (10 mg), no-iron MNPs on alternating days; 4) dispersible zinc tablet (10 mg), daily; 5) dispersible zinc tablet (10 mg), daily for 2 wk at enrollment and 12 wk; 6) placebo powder, daily. Primary outcomes were incidence of diarrhea and change in length-for-age z-score (LAZ) over the 24-wk intervention period. Home visits were conducted twice weekly to assess diarrhea and other morbidity. Incidence and prevalence outcomes were compared among groups with Poisson regression; continuous outcomes were compared using ANCOVA.Results:A total of 2886 children were enrolled between February 2018 and July 2019. The mean incidence and prevalence of diarrhea among all participants was 1.21 episodes per 100 d and 3.76 d per 100 d, respectively. There were no differences in the incidence or prevalence of diarrhea across intervention groups. The decline in LAZ was slightly smaller among children in the daily HiZn LoFe MNP group compared with the placebo powder group (P < 0.05).Conclusions:The dose of zinc in MNPs as well as the duration and frequency of supplementation evaluated in this trial were not effective in reducing diarrhea; however, the daily HiZn LoFe MNP formulation offered modest improvements in linear growth among young children. This trial was registered at clinicaltrials.gov as NCT03406793.

Primary Outcome Measures is Incidence of diarrhea; Extracted Interventionsis is Standard MNP High zinc, low iron MNP High zinc, low/no iron on alternating days Dispersible zinc supplement Intermittent zinc supplement Placebo powder; Conditions is Diarrhea|Stunting ;Sex is ALL ;Age is CHILD

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Higher Extrusion Temperature Induces Greater Formation of Less Digestible Type V and Retrograded Starch in Iron-Fortified Rice Grains But Does Not Affect Iron Bioavailability: Stable Isotope Studies in Young Women.Background:Hot extrusion is widely used to produce iron-fortified rice, but heating may increase resistant starch and thereby decrease iron bioavailability. Cold-extruded iron-fortified rice may have higher bioavailability but has higher iron losses during cooking. Thus, warm extrusion could have nutritional benefits, but this has not been tested. Whether the addition of citric acid (CA) and trisodium citrate (TSC) counteracts any detrimental effect of high-extrusion temperature on iron bioavailability is unclear.Objectives:Our aim was to assess the effects of varying processing temperatures on the starch microstructure of extruded iron-fortified rice and resulting iron solubility and iron bioavailability.Methods:We produced extruded iron-fortified rice grains at cold, warm, and hot temperatures (40°C, 70°C, and 90°C), with and without CA/TSC at a molar ratio of iron to CA/TSC of 1:0.3:5.5. We characterized starch microstructure using small- and wide-angle X-ray scattering and differential scanning calorimetry, assessed color over 6 mo, and measured in vitro iron solubility. In standardized rice and vegetable test meals consumed by young women (n = 22; mean age: 23 y; geometric mean plasma ferritin: 29.3 μg/L), we measured iron absorption from the fortified rice grains intrinsically labeled with 57ferric pyrophosphate (57FePP), compared with ferrous sulfate (58FeSO4) solution added extrinsically to the meals.Results:Warm and hot extrusion altered starch morphology from native type A to type V and increased retrograded starch. However, extrusion temperature did not significantly affect iron solubility or iron bioavailability. The geometric mean fractional iron absorption of iron from fortified rice extruded with CA/TSC (8.2%; 95% CI: 7.9%, 11.0%) was more than twice that from extruded rice without CA/TSC (3.0%; 95% CI: 2.7%, 3.4%; P < 0.001).Conclusions:Higher extrusion temperatures did not affect iron bioavailability from extruded rice in young women, but co-extrusion of CA/TSC with FePP sharply increased iron absorption independently from extrusion temperature. This trial is registered at www.clinicaltrials.gov as NCT03703726.

Primary Outcome Measures is Change from baseline in the isotopic ratio of iron in blood at week 2; Extracted Interventionsis is Reference meal Test meal A Test meal B Test meal C Test meal D Test meal E Test meal F; Conditions is Iron-deficiency ;Sex is FEMALE ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Safety and efficacy of ciprofol vs. propofol for sedation in intensive care unit patients with mechanical ventilation: a multi-center, open label, randomized, phase 2 trial.Background:Ciprofol (HSK3486; Haisco Pharmaceutical Group Co., Ltd., Chengdu, China), developed as a novel 2,6-disubstituted phenol derivative showed similar tolerability and efficacy characteristics as propofol when applicated as continuous intravenous infusion for 12 h maintenance sedation in a previous phase 1 trial. The phase 2 trial was designed to investigate the safety, efficacy, and pharmacokinetic characteristics of ciprofol for sedation of patients undergoing mechanical ventilation.Methods:In this multicenter, open label, randomized, propofol positive-controlled, phase 2 trial, 39 Chinese intensive care unit patients receiving mechanical ventilation were enrolled and randomly assigned to a ciprofol or propofol group in a 2:1 ratio. The ciprofol infusion was started with a loading infusion of 0.1-0.2 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 0.30 mg·kg -1 ·h -1 , which could be adjusted to an infusion rate of 0.06 to 0.80 mg·kg -1 ·h -1 , whereas for propofol the loading infusion dose was 0.5-1.0 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 1.50 mg·kg -1 ·h -1 , which could be adjusted to 0.30-4.00 mg·kg -1 ·h -1 to achieve -2 to +1 Richmond Agitation-Sedation Scale sedation within 6-24 h of drug administration.Results:Of the 39 enrolled patients, 36 completed the trial. The median (min, max) of the average time to sedation compliance values for ciprofol and propofol were 60.0 (52.6, 60.0) min and 60.0 (55.2, 60.0) min, with median difference of 0.00 (95% confidence interval: 0.00, 0.00). In total, 29 (74.4%) patients comprising 18 (69.2%) in the ciprofol and 11 (84.6%) in the propofol group experienced 86 treatment emergent adverse events (TEAEs), the majority being of severity grade 1 or 2. Drug- and sedation-related TEAEs were hypotension (7.7% vs. 23.1%, P = 0.310) and sinus bradycardia (3.8% vs. 7.7%, P = 1.000) in the ciprofol and propofol groups, respectively. The plasma concentration-time curves for ciprofol and propofol were similar.Conclusions:ciprofol is comparable to propofol with good tolerance and efficacy for sedation of Chinese intensive care unit patients undergoing mechanical ventilation in the present study setting.Trial registration:ClinicalTrials.gov, NCT04147416.

Primary Outcome Measures is Mean time to sedation; Extracted Interventionsis is HSK3486 0.1-0.2 /0.3 mg / kg group Propofol 0.5-1.0/1.5 mg/kg group; Conditions is Sedation ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.nan

Primary Outcome Measures is Number of Participants With First Occurrence of a Myocardial Infarction (MI); Extracted Interventionsis is Intensive control of SBP Standard control of SBP; Conditions is Hypertension ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Long-term efficacy and safety of canakinumab in patients with mevalonate kinase deficiency: results from the randomised Phase 3 CLUSTER trial.Objectives:To evaluate the long-term efficacy and safety of canakinumab in patients with mevalonate kinase deficiency during the open label extension (weeks 41-113) of the randomized controlled CLUSTER trial.Methods:During a 72-week period, patients received open-label canakinumab 150 or 300 mg, every 4 or 8 weeks. The disease activity was evaluated every 8 weeks using physician global assessment and counting the number of flares. Concentrations of CRP and serum amyloid A protein were measured. The safety was studied by determination and classification of observed adverse events. The safety and efficacy were analysed separately in three subgroups of patients receiving a cumulative dose of less than <35 mg/kg, ≥35 to <70 mg/kg or ≥70 mg/kg.Results:Of the 74 patients who started the CLUSTER study, 66 entered Epoch 4 and 65 completed it. During the 72-week period, 42 (64%) patients experienced no flares, while 13 (20%) had one flare, as compared with a median of 12 flares per year reported at baseline. Low physician global assessment scores were seen at the end of the study for all groups with >90% reporting minimal disease activity or none at all. Median CRP concentrations were consistently equal or lower than 10 mg/l, while median serum amyloid A concentrations remained only slightly above the normal range of 10 mg/l. The study showed no new or unexpected adverse events.Conclusion:Canakinumab proved effective to control disease activity and prevent flares in mevalonate kinase deficiency during the 72-week study period. No new safety concerns were reported.Trial registration:NCT02059291. https://clinicaltrials.gov.

Primary Outcome Measures is Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks); Extracted Interventionsis is Canakinumab Placebo; Conditions is Hereditary Periodic Fevers ;Sex is ALL ;Age is CHILD, ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Relationship of anifrolumab pharmacokinetics with efficacy and safety in patients with systemic lupus erythematosus.Objectives:To characterize the relationship of anifrolumab pharmacokinetics with efficacy and safety in patients with moderate to severe SLE despite standard therapy, using pooled data from two phase 3 trials.Methods:TULIP-1 and TULIP-2 were randomized, placebo-controlled, 52-week trials of intravenous anifrolumab (every 4 weeks for 48 weeks). For the exposure-response analysis, BILAG-based Composite Lupus Assessment (BICLA) or SLE Responder Index [SRI(4)] response rates at week 52 in each quartile/tertile of average anifrolumab serum concentration (Cave) were compared for anifrolumab and placebo in all-comers, patients who completed treatment, and IFN gene signature (IFNGS)-high patients who completed treatment, using average marginal effect logistic regression. Relationships between exposure and key safety events were assessed graphically.Results:Of patients in TULIP-1/TULIP-2 who received anifrolumab (150 mg, n = 91; 300 mg, n = 356) or placebo (n = 366), 574 completed treatment, of whom 470 were IFNGS high. In the exposure-efficacy analyses, BICLA and SRI(4) treatment differences favouring anifrolumab 300 mg vs placebo were observed across Cave subgroups and all analysis populations. Logistic regression identified Cave as a significant covariate for predicted BICLA response, as higher anifrolumab Cave predicted greater efficacy. There was no evidence of exposure-driven incidence of key safety events through week 52 in patients receiving anifrolumab 150 or 300 mg.Conclusion:While higher Cave predicted greater efficacy, consistent positive benefit favouring anifrolumab 300 mg vs placebo was observed in BICLA and SRI(4) responses across Cave subgroups in the TULIP trials. There was no evidence of exposure-driven safety events.Clinicaltrial.gov numbers:NCT02446912, NCT02446899.

Primary Outcome Measures is Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52; Extracted Interventionsis is Anifrolumab Placebo; Conditions is Active Systemic Lupus Erythematosus ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Response to secukinumab on synovitis using Power Doppler ultrasound in psoriatic arthritis: 12-week results from a phase III study, ULTIMATE.Objectives:To investigate the dynamics of response of synovitis to IL-17A inhibition with secukinumab in patients with active PsA using Power Doppler ultrasound.Methods:The randomized, placebo-controlled, Phase III ULTIMATE study enrolled PsA patients with active ultrasound synovitis and clinical synovitis and enthesitis having an inadequate response to conventional DMARDs and naïve to biologic DMARDs. Patients were randomly assigned to receive either weekly subcutaneous secukinumab (300 or 150 mg according to the severity of psoriasis) or placebo followed by 4-weekly dosing thereafter. The primary outcome was the mean change in the ultrasound Global EULAR and OMERACT Synovitis Score (GLOESS) from baseline to week 12. Key secondary endpoints included ACR 20 and 50 responses.Results:Of the 166 patients enrolled, 97% completed 12 weeks of treatment (secukinumab, 99%; placebo, 95%). The primary end point was met, and the adjusted mean change in GLOESS was higher with secukinumab than placebo [-9 (0.9) vs -6 (0.9), difference (95% CI): -3 (-6, -1); one-sided P=0.004] at week 12. The difference in GLOESS between secukinumab and placebo was significant as early as one week after initiation of treatment. All key secondary endpoints were met. No new or unexpected safety findings were reported.Conclusion:This unique ultrasound study shows that apart from improving the signs and symptoms of PsA, IL-17A inhibition with secukinumab leads to a rapid and significant reduction of synovitis in PsA patients.Trial registration:ClinicalTrials.gov; NCT02662985.

Primary Outcome Measures is Difference Between Secukinumab and Placebo in Terms of Joint Synovitis as Measured by the Power Doppler Ultrasonography (PDUS) Global OMERACT-EULAR Synovitis Score (GLOESS); Extracted Interventionsis is AIN457 (secukinumab) Placebo; Conditions is Psoriatic Arthritis ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.SM03, an anti-human CD22 monoclonal antibody, for active rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled study.Objective:SM03, a novel chimaeric mAb specific to B cell-restricted antigen CD22, has been developed to treat RA and other B-cell-related diseases. This 24-week phase II randomized, double-blind, multi-dose, placebo-controlled study aimed to evaluate the efficacy and safety of SM03 in moderately-to-severely active RA patients in China.Methods:One hundred and fifty-six patients on background MTX were randomized in a 1:1:1 ratio to receive a cumulative dose of 3600 mg (high dose, 600 mg × 6 infusions at weeks 0, 2, 4, 12, 14 and 16) or 2400 mg SM03 (low dose, 600 mg × 4 infusions at weeks 0, 2, 12 and 14) or the placebo. The primary outcome was the 24-week ACR 20% improvement criteria (ACR20) response rate. Safety was also assessed.Results:The 24-week ACR20 response rate was significantly higher with high- (65.3%, P = 0.002) and low-dose SM03 (56.9%, P = 0.024) than with placebo (34.0%), but comparable between the high- and low-dose group. The rate of adverse events was not statistically different among the high-dose group (35.3%), the low-dose group (51.9%) and the placebo group (34.6%). Thirteen (12.6%) patients receiving SM03 reported treatment-emergent infections, including 3.9% patients in the high-dose group. No patients reported severe treatment-emergent infections or malignancies.Conclusions:In active RA Chinese patients receiving background MTX, SM03 at a cumulative dose of both 2400 mg and 3600 mg is efficacious and well-tolerated throughout the 24 weeks of treatment. Moreover, SM03 has demonstrated a good safety profile.Trial registration:ClinicalTrials.gov, https://clinicaltrials.gov, NCT04192617.

Primary Outcome Measures is Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24; Extracted Interventionsis is SM03 Placebo Methotrexate; Conditions is Rheumatoid Arthritis ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Impact of filgotinib on sacroiliac joint magnetic resonance imaging structural lesions at 12 weeks in patients with active ankylosing spondylitis (TORTUGA trial).Objective:To assess the effect of filgotinib, which preferentially inhibits Janus kinase 1 (JAK1), on MRI measures of structural change in the SI joint in patients with active AS in the TORTUGA trial.Methods:Adults with active AS and inadequate response/intolerance to two or more NSAIDs were randomized 1:1 to filgotinib 200 mg (n = 58) or placebo (n = 58) once daily for 12 weeks. In this post hoc analysis, T1-weighted MRI scans of the SI joint were evaluated by two independent readers using Spondyloarthritis Research Consortium of Canada (SPARCC) Sacroiliac Joint Structural Score (SSS) definitions for erosion, backfill, fat metaplasia and ankylosis. Correlations between SPARCC SSS and improvement in clinical outcomes were also assessed.Results:MRI scans from 87 patients (48 filgotinib, 39 placebo) were evaluated. At baseline there were no notable differences between filgotinib and placebo for any MRI structural lesion types. From baseline to week 12, filgotinib was associated with a significant reduction in SI joint erosion score (P = 0.02) and an increase in backfill score (P = 0.005) vs placebo, with no significant between-group differences for ankylosis (P = 0.46) or fat metaplasia (P = 0.17). At week 12, the change in SPARCC MRI SI joint inflammation scores correlated positively with erosion scores but negatively with backfill scores.Conclusion:The significant changes in MRI structural lesions induced by filgotinib in the SI joint by week 12 demonstrate that tissue repair can be observed very soon after starting treatment with a JAK1 preferential inhibitor. This could have prognostic implications for development of ankylosis.Trial registration:ClinicalTrials.gov, http://clinicaltrials.gov, NCT03117270.

Primary Outcome Measures is Ankylosing Spondylitis disease activity score (ASDAS) in filgotinib treated subjects as compared to placebo; Extracted Interventionsis is filgotinib Placebo Oral Tablet; Conditions is Ankylosing Spondylitis ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Adipose tissue-derived stromal vascular fraction for treating hands of patients with systemic sclerosis: a multicentre randomized trial Autologous AD-SVF versus placebo in systemic sclerosis.Objective:To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients.Methods:We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution 800/CRS system. The placebo was lactated Ringer's solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hand function, vasculopathy, hand pain, skin fibrosis, sensitivity of the finger pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction, and safety.Results:Forty patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 months' follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of -9.2 [12.2] in the AD-SVF group vs -7.6 [13.2] in the placebo group). At 6 months, hand function improved in both groups.Conclusion:This study showed an improvement of hand function in both groups over time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap should be encouraged to accurately assess the benefit of AD-SVF therapy.Trial registration:ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015.

Primary Outcome Measures is Cochin hand functional scale; Extracted Interventionsis is Stromal Vascular fraction Ringer lactate; Conditions is Scleroderma, Systemic ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Safety and immunogenicity of three doses of non-typeable Haemophilus influenzae-Moraxella catarrhalis (NTHi-Mcat) vaccine when administered according to two different schedules: a phase 2, randomised, observer-blind study.Background:Non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) infections are frequently associated with exacerbations of chronic obstructive pulmonary disease (COPD). Results were reported with a two-dose (0-2 months) schedule of an investigational AS01E-adjuvanted NTHi-Mcat vaccine containing three surface proteins from NTHi and one from Mcat. We evaluated the safety and immunogenicity of three NTHi-Mcat vaccine doses administered in two different schedules to adults with a smoking history (≥ 10 pack-years), immunologically representing the COPD population.Methods:In this 18-month, randomised (1:1), observer-blind study with 6-month open follow-up, 200 healthy adults aged 40-80 years received NTHi-Mcat vaccine at 0-2-6 months and placebo at 12 months (0-2-6 group), or vaccine at 0-2-12 months and placebo at 6 months (0-2-12 group). Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days, respectively, post-vaccination, and potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) throughout the study. Immune responses were assessed.Results:No safety concerns were identified with the third vaccine dose or overall. Most solicited AEs were mild/moderate. Unsolicited AEs were reported in 16%, 16.1% and 14.4% of participants in the 0-2-6 group post-dose 1, 2 and 3, respectively, and 20%, 20.4% and 9.7%, respectively, in the 0-2-12 group. In 24 months, SAEs were reported in 12 participants in the 0-2-6 group and 9 in the 0-2-12 group (18 events in each group). There were three deaths (unknown cause, 0-2-6 group; myocardial infarction, lung cancer in 0-2-12 group). pIMDs were reported in three participants in the 0-2-6 group (non-serious inflammatory bowel disease, gout, psoriasis) and three in the 0-2-12 group (serious ulcerative colitis, two with non-serious gout). The SAEs, deaths and pIMDs were considered not causally related to vaccination. Antigen-specific antibody concentrations were higher at 12 months post-dose 1 with the 0-2-6 schedule than with the 0-2-12 schedule and at 12 months post-dose 3 were similar between schedules, remaining higher than baseline.Conclusions:No safety concerns were identified when the investigational NTHi-Mcat vaccine was administered via a 0-2-6 months or 0-2-12 months schedule to older adults with a smoking history. Persistent immune responses were observed after the third vaccine dose. Trial registration https://clinicaltrials.gov/ ; NCT03443427, registered February 23, 2018.

Primary Outcome Measures is Number of Subjects Reported With Each Solicited Local Adverse Event (AE) (Any and Grade 3) Within Each Vaccination Schedule; Extracted Interventionsis is NTHi Mcat investigational vaccine (GSK3277511A) Placebo; Conditions is Respiratory Disorders ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Indirect comparison of 48-week efficacy and safety of long-acting cabotegravir and rilpivirine maintenance every 8 weeks with daily oral standard of care antiretroviral therapy in participants with virologically suppressed HIV-1-infection.Background:Efficacy and safety of long-acting cabotegravir (CAB) + rilpivirine (RPV) every 8 weeks (Q8W) versus daily oral standard of care (SoC) maintenance in treatment-experienced individuals with virologically suppressed human immunodeficiency virus type 1 (HIV-1) has not been directly compared in randomized clinical trials. This analysis aimed to indirectly compare these regimens.Methods:An adjusted indirect treatment comparison of CAB + RPV Q8W with daily oral SoC was performed, using Phase 3 data from studies of CAB + RPV every 4 weeks (Q4W) vs SoC (ATLAS/FLAIR, n = 591 per group) and a Phase 3b trial of CAB + RPV Q8W vs Q4W (ATLAS-2M [excluding participants with prior CAB + RPV exposure]; n = 327 per group). Eligible participants were virologically suppressed (viral load < 50 HIV-1 ribonucleic acid (RNA) copies/mL), treatment-experienced individuals with HIV-1-infection. Treatment efficacy and safety assessments at Week 48 included virologic suppression and lack of virologic suppression (proportion of participants with plasma HIV-1 RNA < 50 copies/mL or ≥ 50 copies/mL, respectively; both as per FDA snapshot algorithm), CD4-cell count change from baseline, no virologic data, discontinuations due to adverse events (AEs), and overall AEs, serious AEs and Grade 3-5 AEs excluding injection-site reactions. A subgroup analysis stratified by baseline third active drug class was performed.Results:Baseline characteristics between the Q4W arms of ATLAS/FLAIR and ATLAS-2M showed no significant differences or differences were not judged to be clinically relevant, apart from participants switching from a baseline third active drug class; more participants switched from integrase strand inhibitors in ATLAS/FLAIR, and from non-nucleoside reverse transcriptase inhibitors in ATLAS-2M. Injections of CAB + RPV Q8W showed no significant differences across efficacy and safety outcomes versus daily oral SoC. Univariate subgroup analysis found there were no significant differences on virologic suppression or lack of virologic suppression for any baseline third active drug class subgroup. These results suggest that CAB + RPV Q8W is non-inferior to daily oral SoC.Conclusions:This analysis supports the therapeutic potential of CAB + RPV Q8W for virologically suppressed people living with HIV-1 infection seeking an alternative maintenance treatment option to daily oral SoC.Trial registration:NCT02938520, NCT02951052, NCT03299049.

Primary Outcome Measures is Number of Participants With Virologic Failure (HIV-1 Ribonucleic Acid [RNA] >=50 Copies Per Millilter [mL]) Using Snapshot Algorithm at Week 48; Extracted Interventionsis is Cabotegravir (CAB) tablet Rilpivirine (RPV) tablet Cabotegravir - Injectable Suspension (CAB LA) Rilpivirine - Injectable Suspension (RPV LA) 2 NRTIs plus an INI, NNRTI, or PI; Conditions is Infection, Human Immunodeficiency Virus|HIV Infections ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Responding to Elder Abuse in GERiAtric care (REAGERA) educational intervention for healthcare providers: a non-randomised stepped wedge trial.Introduction:Elder abuse is prevalent and associated with different forms of ill health. Despite this, healthcare providers are often unaware of abusive experiences among older patients and many lack training about elder abuse. The overall aim of this study is to determine the effectiveness of an educational intervention on healthcare providers' propensity to ask older patients questions about abusive experiences.Methods and analysis:Healthcare providers at hospital clinics and primary healthcare centres in Sweden will undergo full-day education about elder abuse between the fall of 2021 and spring of 2023. The education consists of (1) theory and group discussions; (2) forum theatre, a form of interactive theatre in which participants are given the opportunity to practise how to manage difficult patient encounters; and (3) post-training reflection on changing practices.The design is a non-randomised cluster, stepped wedge trial in which all participants (n=750) gradually transit from control group to intervention group with 6-month interval, starting fall 2021. Data are collected using the Responding to Elder Abuse in GERiAtric care-Provider questionnaire which was distributed to all clusters at baseline. All participants will also be asked to answer the questionnaire in conjunction with participating in the education as well as at 6-month and 12-month follow-up. Main outcome is changes in self-reported propensity to ask older patients questions about abuse post-intervention compared with pre-intervention. Linear mixed models including cluster as a random effect will be used to statistically evaluate the outcome.Ethics and dissemination:The study has been approved by the Swedish Ethical Review Authority. The results will be published in peer-reviewed journals and conference proceedings. If the intervention is successful, a manual of the course content will be published so that the education can be disseminated to other clinics.Trial registration number:NCT05065281.

Primary Outcome Measures is Change between baseline and follow up concerning asking questions about abuse; Extracted Interventionsis is Education; Conditions is Healthy ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of individually tailored nutritional counselling on protein and energy intake among older people receiving home care at risk of or having malnutrition: a non-randomised intervention study.Background:With ageing, food intake may decrease and lead to an insufficient nutrient intake causing protein-energy malnutrition (PEM) which is associated with adverse health effects and increased mortality. The aim of this study was to investigate the effects of individually tailored dietary counseling focused on protein intake among home care clients with PEM or at risk of developing PEM. The secondary aim was to study the intake of energy and other nutrients.Methods:This intervention study is part of the non-randomised population-based multidisciplinary Nutrition, Oral Health and Medication study (NutOrMed study). The intervention group comprised 112 and the control group 87 home care clients (≥75 years) with PEM or risk of PEM. PEM was defined by Mini Nutritional Assessment score < 24 and/or plasma albumin < 35 g/L. The nutrients intake was assessed from 24-hour dietary recall at the baseline and after the six-month intervention. The intervention consisted of an individually tailored dietary counseling; the persons were instructed to increase their food intake with protein and energy dense food items, the number of meals and consumption of protein-, energy- and nutrient-rich snacks for six months.Results:After the six-month nutritional intervention, the mean change in protein intake increased 0.04 g/kgBW (95% CI 0.05 to 0.2), fibre 0.8 g (95% CI 0.2 to 4.3), vitamin D 8.5 μg (95% CI 0.7 to 4.4), E 0.6 mg (95% CI 0.4 to 2.2), B12 0.7 μg (95% CI 0.02 to 2.6), folate 8.7 μg (95% CI 1.5 to 46.5), iron 0.4 mg 95% CI 0.6 to 2.4), and zinc 0.5 mg (95% CI 0.6 to 2.2) in the intervention group compared with the control group. The proportion of those receiving less than 1.0 g/kg/BW protein decreased from 67 to 51% in the intervention group and from 84 to 76% in the control group. Among home care clients with a cognitive decline (MMSE< 18), protein intake increased in the intervention group by 0.2 g/kg/BW (p = 0.048) but there was no change in the control group.Conclusion:An individual tailored nutritional intervention improves the intake of protein and other nutrients among vulnerable home care clients with PEM or its risk and in persons with cognitive decline.Trial registration:ClinicalTrials.gov : NCT02214758. Date of trial registration: 12/08/2014.

Primary Outcome Measures is Change from baseline in nutritional status on the Mini Nutritional Assessment (MNA) test and s-albumin level at months 6; Extracted Interventionsis is Nutrition and oral health interventions; Conditions is Nutrition, Oral Health ;Sex is ALL ;Age is OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Mycobacterium tuberculosis-Specific T-Cell Responses Are Impaired During Late Pregnancy With Elevated Biomarkers of Tuberculosis Risk Postpartum.Background:Pregnancy is a risk factor for progression from latent tuberculosis infection to symptomatic tuberculosis. However, how pregnancy influences T-cell responses to Mycobacterium tuberculosis is unknown.Methods:We measured M. tuberculosis-specific cytokines, T-cell memory markers, and overall CD4+ and CD8+ T-cell activation by flow cytometry from 49 women (18 with and 31 without HIV) who became pregnant while enrolled in a randomized controlled trial of preexposure prophylaxis for HIV. We analyzed data using COMPASS, an established statistical method for evaluating overall antigen-specific T-cell responses.Results:Pregnant women with latent tuberculosis infection demonstrated significantly diminished M. tuberculosis-specific CD4+ cytokine responses in the third trimester (COMPASS polyfunctional score [PFS], 0.07) compared before (PFS, 0.15), during (PFS, 0.13 and 0.16), and after pregnancy (PFS, 0.14; P = .0084, Kruskal-Wallis test). Paradoxically, M. tuberculosis-specific CD8+ cytokines and nonspecifically activated T-cells increased during late pregnancy. Nonspecific T-cell activation, a validated biomarker for progression from latent tuberculosis infection to tuberculosis disease, increased in latent tuberculosis infection-positive women postpartum, compared with latent tuberculosis infection-negative women.Conclusions:Pregnancy-related functional T-cell changes were most pronounced during late pregnancy. Both M. tuberculosis-specific T-cell changes during pregnancy and increases in immune activation postpartum may contribute to increased risk for tuberculosis progression.Clinical trials registration:NCT0557245.

Primary Outcome Measures is Incidence of HIV-1 Seroconversion Among HIV-1 Uninfected Participants; Extracted Interventionsis is Tenofovir Disoproxil Fumarate (TDF) Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) Placebo; Conditions is HIV-1 Infections|HIV Infections ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Volumetric measurements are preferred in the evaluation of mutant IDH inhibition in non-enhancing diffuse gliomas: Evidence from a phase I trial of ivosidenib.Background:Since IDH-mutant (mIDH) low-grade gliomas (LGGs) progress slowly and have a relatively long survival, there is a significant need for earlier measurements of clinical benefit. Guidance using the LGG RANO criteria recommends serial bidirectional (2D) measurements on a single slice; however, questions remain as to whether volumetric (3D) measurements are better, since they would allow for more accurate measurements in irregular shaped lesions and allow readers to better assess areas of subtle change.Methods:Twenty-one (out of 24) non-enhancing, recurrent mIDH1 LGGs were enrolled in a phase I, multicenter, open-label study of oral ivosidenib (NCT02073994), and with imaging pre- and post-treatment as part of this exploratory ad hoc analysis. 2D and 3D measurements on T2-weighted FLAIR images were centrally evaluated at an imaging contract research organization using a paired read and forced adjudication paradigm. The effects of 2D vs 3D measurements on progression-free survival (PFS), growth rate measurement variability, and reader concordance and adjudication rates were quantified.Results:3D volumetric measurements showed significantly longer estimated PFS (P = .0181), more stable (P = .0063) and considerably slower measures of tumor growth rate (P = .0037), the highest inter-reader agreement (weighted kappa = 0.7057), and significantly lower reader discordance rates (P = .0002) with 2D LGG RANO.Conclusion:3D volumetric measurements are better for determining response assessment in LGGs due to more stable measures of tumor growth rates (ie, less "yo-yo-ing" of measurements over time), highest inter-reader agreement, and lowest reader discordance rates. Continued evaluation in future studies is warranted to determine whether these measurements reflect clinical benefit.

Primary Outcome Measures is Safety/tolerability: incidence of adverse events; Extracted Interventionsis is AG-120; Conditions is Cholangiocarcinoma|Chondrosarcoma|Glioma|Other Advanced Solid Tumors ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Can Patient Expectations Modulate the Short-Term Effects of Dry Needling on Sensitivity Outcomes in Patients with Mechanical Neck Pain? A Randomized Clinical Trial.Objective:Dry needling is commonly used for the management of patients with musculoskeletal pain. However, the effects of patient expectations are uncertain. Our aim was to determine the effect of patient expectations on short-term clinical outcomes after the application of a single session of dry needling in individuals with neck pain.Methods:We conducted a randomized, placebo-controlled clinical trial including 50 patients with mechanical neck pain. Participants received a single session of dry needling or sham needling in a blinded design. Predicted patient expectation was categorized as positive, neutral, or negative. Outcomes including neck pain intensity (visual analog scale, 0-100), pressure pain thresholds, and self-perceived improvement (Global Rating of Change, -7 to +7) were assessed at baseline, 1 day after the intervention (immediately after), and 7 days after the intervention (1 week after) by a blinded assessor. Repeated-measures analyses of covariance were conducted to assess the effects of real/sham needling adjusted by patient expectations.Results:Individuals receiving dry needling exhibited better outcomes immediately and 1 week after the intervention than did those receiving sham needling (all P < 0.01). No general effects of patient expectations, either related to pain recovery or functional improvement, were observed on the clinical outcomes, except for a small association of questionable clinical relevance between positive expectations and localized pressure pain thresholds in the dry needling group.Conclusion:This study did not find a significant effect of predicted patient expectations on the short-term effects of dry needling on pain intensity and pressure pain thresholds in people with mechanical neck pain.

Primary Outcome Measures is Changes in Neck Pain Intensity between baseline and follow-up periods; Extracted Interventionsis is Dry Needling Sham Needling; Conditions is Neck Pain ;Sex is ALL ;Age is CHILD

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Long-term Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Children and Adults: A Randomized, Placebo-Controlled, Phase 2 Study.Background:We report long-term safety and immunogenicity of Takeda's tetravalent dengue vaccine candidate (TAK-003) in healthy children and adults living in dengue-endemic areas in Puerto Rico, Columbia, Singapore, and Thailand.Methods:In part 1 of this phase 2, randomized, placebo-controlled trial we sequentially enrolled 1.5-45 year olds (n = 148) into 4 age-descending groups, randomized 2:1 to receive 2 doses of TAK-003 or placebo 90 days apart. In part 2, 1-11 year olds (n = 212) were enrolled and randomized 3:1 to TAK-003 or placebo groups. We assessed neutralizing antibody titers for the 4 dengue serotypes (DENV) up to month 36 in part 1, and symptomatic dengue and serious adverse events (SAEs) up to month 36 in both parts.Results:At month 36, seropositivity rates were 97.3%, 98.7%, 88.0% and 56.0% for DENV-1, -2, -3 and -4, respectively. Seropositivity rates varied significantly for DENV-4 according to serostatus at baseline (89.5% in seropositives versus 21.6% in seronegatives). No vaccine-related SAEs were reported.Conclusions:The trial demonstrated persistence of neutralizing antibody titers against TAK-003 over 3 years in children and adults living in dengue-endemic countries, with limited contribution from natural infection. TAK-003 was well tolerated.Clinical trials registration:NCT01511250.

Primary Outcome Measures is Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity; Extracted Interventionsis is TDV Placebo; Conditions is Healthy ;Sex is ALL ;Age is CHILD, ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Sequential use of midazolam and dexmedetomidine for long-term sedation may reduce weaning time in selected critically ill, mechanically ventilated patients: a randomized controlled study.Background:Current sedatives have different side effects in long-term sedation. The sequential use of midazolam and dexmedetomidine for prolonged sedation may have distinct advantages. We aimed to evaluate the efficacy and safety of the sequential use of midazolam and either dexmedetomidine or propofol, and the use of midazolam alone in selected critically ill, mechanically ventilated patients.Methods:This single-center, randomized controlled study was conducted in medical and surgical ICUs in a tertiary, academic medical center. Patients enrolled in this study were critically ill, mechanically ventilated adult patients receiving midazolam, with anticipated mechanical ventilation for ≥ 72 h. They passed the spontaneous breathing trial (SBT) safety screen, underwent a 30-min-SBT without indication for extubation and continued to require sedation. Patients were randomized into group M-D (midazolam was switched to dexmedetomidine), group M-P (midazolam was switched to propofol), and group M (sedation with midazolam alone), and sedatives were titrated to achieve the targeted sedation range (RASS - 2 to 0).Results:Total 252 patients were enrolled. Patients in group M-D had an earlier recovery, faster extubation, and more percentage of time at the target sedation level than those in group M-P and group M (all P < 0.001). They also experienced less weaning time (25.0 h vs. 49.0 h; HR1.47, 95% CI 1.05 to 2.06; P = 0.025), and a lower incidence of delirium (19.5% vs. 43.8%, P = 0.002) than patients in group M. Recovery (P < 0.001), extubation (P < 0.001), and weaning time (P = 0.048) in group M-P were shorter than in group M, while the acquisition cost of sedative drug was more expensive than other groups (both P < 0.001). There was no significant difference in adverse events among these groups (all P > 0.05).Conclusions:The sequential use of midazolam and dexmedetomidine was an effective and safe sedation strategy for long-term sedation and could provide clinically relevant benefits for selected critically ill, mechanically ventilated patients.Trial registration:NCT02528513 . Registered August 19, 2015.

Primary Outcome Measures is Weaning time; Extracted Interventionsis is midazolam Fentanyl propofol Dexmedetomidine Procedure Procedure midazolam(used for passing the SBT safety screen); Conditions is Mechanical Ventilation|Complication|Delirium ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Efficacy and safety of umbilical cord-derived mesenchymal stem cells in Chinese adults with type 2 diabetes: a single-center, double-blinded, randomized, placebo-controlled phase II trial.Background:To determine the efficacy and safety of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in Chinese adults with type 2 diabetes mellitus (T2DM).Methods:In this single-center, double-blinded, randomized, placebo-controlled phase II trial, 91 patients were randomly assigned to receive intravenous infusion of UC-MSCs (n = 45) or placebo (n = 46) three times with 4-week intervals and followed up for 48 weeks from October 2015 to December 2018. The primary endpoint was the percentage of patients with glycated hemoglobin (HbA1c) levels of < 7.0% and daily insulin reduction of ≥ 50% at 48 weeks. Additional endpoints were changes of metabolic control, islet β-cell function, insulin resistance, and safety.Results:At 48 weeks, 20% of the patients in the UC-MSCs group and 4.55% in the placebo group reached the primary endpoint (p < 0.05, 95% confidence interval (CI) 2.25-28.66%). The percentage of insulin reduction of the UC-MSCs group was significantly higher than that of the placebo group (27.78% versus 15.62%, p < 0.05). The levels of HbA1c decreased 1.31% (9.02 ± 1.27% to 7.52 ± 1.07%, p < 0.01) in the UC-MSCs group, and only 0.63% in the placebo group (8.89 ± 1.11% to 8.19 ± 1.02%, p˃0.05; p = 0.0081 between both groups). The glucose infusion rate (GIR) increased significantly in the UC-MSCs group (from 3.12 to 4.76 mg/min/kg, p < 0.01), whereas no significant change was observed in the placebo group (from 3.26 to 3.60 mg/min/kg, p ˃ 0.05; p < 0.01 between both groups). There was no improvement in islet β-cell function in both groups. No major UC-MSCs transplantation-related adverse events occurred.Conclusions:UC-MSCs transplantation could be a potential therapeutic approach for Chinese adults with T2DM. Trial registration This study was registered on ClinicalTrials.gov (identifier: NCT02302599).

Primary Outcome Measures is The efficacy of umbilical cord mesenchymal stem cells in Chinese adults with T2D; Extracted Interventionsis is Umbilical cord mesenchymal stem cells Controlled suspension liquid; Conditions is Type 2 Diabetes|Mesenchymal Stem Cells ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.A randomized, double-blind, placebo-controlled trial of vitamin D supplementation with or without calcium in community-dwelling vitamin D deficient subjects.Background:Although vitamin D deficiency is highly prevalent in the Middle East, very few studies have attempted to measure its health impact.Aims:We aimed to assess whether vitamin D3 and calcium, either alone or in combination, have health benefit.Methods:In a 2 × 2 factorial design double-blind, placebo-controlled trial, Community free living adults living in the city of Al Ain, UAE were randomly assigned to receive daily 2000 IU oral vitamin D3 alone, 600 mg calcium alone, oral vitamin D3 (2000 IU per day) combined with 600 mg calcium, or a placebo for 6 months. Primary outcomes were self-rated health and bone turnover markers.Results:Of the 545 randomized, 277 subjects completed 6 months follow up. 25(OH)D levels marginally increased in the two groups received vitamin D3 alone or combined with calcium compared to the decline seen in those who received calcium supplement alone or a placebo. Sub-group analysis revealed that parathyroid hormone (PTH) concentration decreased and Calcium/creatinine ratio increased significantly in the combined vitamin D and Calcium group compared to the vitamin D alone or Calcium alone in contrast to the increase seen in the placebo group [p < 0.05 for between group difference at 6 months]. There were no statistically significant differences between the supplement and placebo groups at the 6 months follow-up in body weight, body mass index (BMI), blood pressure, body pains and general health.Conclusion:PTH concentration decreased and calcium/creatinine ratio increased in subjects who received vitamin D and Calcium together compared to those who received vitamin D alone.Trial registration:NCT02662491 , First registered on 25 January 2016 ( https://register.Clinicaltrials:gov/prs/app/action/SelectProtocol?sid=S00060CE&selectaction=Edit&uid=U0001M6P&ts=3&cx=scu4cb , Last update: 05 August 2019.

Primary Outcome Measures is Muscle pains; Extracted Interventionsis is Vitamin D and calcium Vitamin D Calcium Placebo; Conditions is Vitamin D Deficiency ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Findings from a pilot open-label trial of N-acetylcysteine for the treatment of pediatric mania and hypomania.Background:Pediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the risk of serious side effects. Therefore, this study assessed the efficacy and tolerability of N-acetylcysteine (NAC), in children and adolescents with bipolar spectrum disorder.Methods:We conducted a 12-week open-label trial of NAC for treatment of mania and hypomania in children and adolescents ages 5-17 with bipolar spectrum disorder including participants with full and subthreshold manic symptoms, accepting those with and without mixed states with co-occurring depression, and Young Mania Rating Scale scores ≥ 20 and < 40. Symptoms of mania and depression were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Children's Depression Rating Scale (CDRS), and Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) scales for mania and depression.Results:This study had a high drop-out rate with only 53% completing all 12 weeks. There was a significant reduction in YMRS, HDRS, and CDRS mean scores from baseline to endpoint. Of the 24 exposed participants, 54% had an anti-manic response measured by a reduction in YMRS ≥ 30% and 46% had a CGI-I mania score ≤ 2 at endpoint. Additionally, 62% of participants had an anti-depressive response measured by a reduction in HDRS ≥ 30%, 31% had an anti-depressive response measured by a reduction in CDRS ≥ 30%, and 38% had a CGI-I depression score ≤ 2 at endpoint.Conclusions:These pilot open-label findings in a small sample provide preliminary data supporting the tolerability and safety of NAC in a pediatric population. The findings of this pilot scale study indicating improvement in mania and depression are promising, but require replication with a monotherapy randomized placebo controlled clinical trial and larger sample.Trial registration:ClinicalTrials.gov Identifier: NCT02357290 . First Registration 06/02/2015.

Primary Outcome Measures is Mean Change in the Young Mania Rating Scale (YMRS) Score; Extracted Interventionsis is Open-label Treatment with N-Acetylcysteine; Conditions is Bipolar Disorder ;Sex is ALL ;Age is CHILD

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Accuracy of a score predicting the presence of an atypical pathogen in hospitalized patients with moderately severe community-acquired pneumonia.Background:Atypical pathogens (AP), present in some patients with community-acquired pneumonia (CAP), are intrinsically resistant to betalactam drugs, the mainstay of empirical antibiotic treatment. Adding antibiotic coverage for AP increases the risk of adverse effects and antimicrobial selection pressure, while withholding such coverage may worsen the prognosis if an AP is causative. A clinical model predicting the presence of AP would allow targeting atypical coverage for patients most likely to benefit.Methods:This is a secondary analysis of a multicentric randomized controlled trial that included 580 adults patients hospitalized for CAP. A predictive score was built using independent predictive factors for AP identified through multivariate analysis. Accuracy of the score was assessed using area under the receiver operating curve (AUROC), sensitivity, and specificity.Results:Prevalence of AP was 5.3%. Age < 75 years (OR 2.7, 95% CI 1.2-6.2), heart failure (OR 2.6, 95% CI 1.1-6.1), absence of chest pain (OR 3.0, 95% CI 1.1-8.2), natremia < 135 mmol/L (OR 3.0, 95% CI 1.4-6.6) and contracting the disease in autumn (OR 2.7, 95% CI 1.3-5.9) were independently associated with AP. A predictive score using these factors had an AUROC of 0.78 (95% CI 0.71-0.85). A score of 0 or 1 (present in 33% of patients) had 100% sensitivity and 35% specificity.Conclusion:Use of a score built on easily obtained clinical and laboratory data would allow safe withholding of atypical antibiotic coverage in a significant number of patients, with an expected positive impact on bacterial resistance and drug adverse effects.Trial registration:NCT00818610.

Primary Outcome Measures is Time to Clinical Stability (hours); Extracted Interventionsis is Beta lactam (amoxicillin / clav. acid OR cefuroxime) Beta-lactam (amoxicillin / clav. acid OR cefuroxime) AND macrolide (clarithromycin); Conditions is Community-acquired Pneumonia ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Altered epithelial barrier functions in the colon of patients with spina bifida.Our objectives were to better characterize the colorectal function of patients with Spina Bifida (SB). Patients with SB and healthy volunteers (HVs) completed prospectively a standardized questionnaire, clinical evaluation, rectal barostat, colonoscopy with biopsies and faecal collection. The data from 36 adults with SB (age: 38.8 [34.1-47.2]) were compared with those of 16 HVs (age: 39.0 [31.0-46.5]). Compared to HVs, rectal compliance was lower in patients with SB (p = 0.01), whereas rectal tone was higher (p = 0.0015). Ex vivo paracellular permeability was increased in patients with SB (p = 0.0008) and inversely correlated with rectal compliance (r = - 0.563, p = 0.002). The expression of key tight junction proteins and inflammatory markers was comparable between SB and HVs, except for an increase in Claudin-1 immunoreactivity (p = 0.04) in SB compared to HVs. TGFβ1 and GDNF mRNAs were expressed at higher levels in patients with SB (p = 0.02 and p = 0.008). The levels of acetate, propionate and butyrate in faecal samples were reduced (p = 0.04, p = 0.01, and p = 0.02, respectively). Our findings provide evidence that anorectal and epithelial functions are altered in patients with SB. The alterations in these key functions might represent new therapeutic targets, in particular using microbiota-derived approaches.Clinical Trials: NCT02440984 and NCT03054415.

Primary Outcome Measures is Number of enteric neurons per ganglion; Extracted Interventionsis is endoscopy; Conditions is Healthy ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Feasibility of decentralised, task-shifted hepatitis C testing and treatment services in urban Myanmar: implications for scale-up.Objectives:To assess the feasibility considerations for a decentralised, one-stop-shop model of care implemented in Yangon, Myanmar.Setting:Two primary care level clinics in urban Yangon, Myanmar.Design:This is a feasibility study of a highly effective care model. Using Intervention Complexity Framework by Gericke et al, we collated and analysed programmatic data and evaluation data to outline key project implementation requirements and experiences.Participants:Programmatic data were collected from clinical records, GeneXpert device test and maintenance reports, national guidelines, product and device instructions and site monitoring visit reports. Healthcare providers involved in delivering care model contributed interview data.Results:The main feasibility considerations are appropriate storage for test kits and treatments (in response to temperature and humidity requirements), installation of a continuous stable electricity supply for the GeneXpert device, air-conditioning for the laboratory room hosting GeneXpert, access to a laboratory for pretreatment assessments and clear referral pathways for specialist consultation when required. Lessons from our project implementation experiences included the extensive time requirements for patient education, the importance of regular error monitoring and stock storage reviews and that flexible appointment scheduling and robust reminder system likely contributed to high retention in care.Conclusions:Detailed documentation and dissemination of feasibility requirements and implementation considerations is vital to assist others to successfully implement a similar model of care elsewhere. We provide 10 recommendations for successful implementation.Trial registration number:The trial was registered at ClinicalTrials.gov NCT03939013 on May 6, 2019. This manuscript presents post-results data on feasibility.

Primary Outcome Measures is Proportion of Ab positive patients who receive GeneXpert HCV VL test; Extracted Interventionsis is Xpert HCV VL; Conditions is Hepatitis C ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of Self-monitoring of Blood Pressure on Diagnosis of Hypertension During Higher-Risk Pregnancy: The BUMP 1 Randomized Clinical Trial.Importance:Inadequate management of elevated blood pressure (BP) is a significant contributing factor to maternal deaths. Self-monitoring of BP in the general population has been shown to improve the diagnosis and management of hypertension; however, little is known about its use in pregnancy.Objective:To determine whether self-monitoring of BP in higher-risk pregnancies leads to earlier detection of pregnancy hypertension.Design, setting, and participants:Unblinded, randomized clinical trial that included 2441 pregnant individuals at higher risk of preeclampsia and recruited at a mean of 20 weeks' gestation from 15 hospital maternity units in England between November 2018 and October 2019. Final follow-up was completed in April 2020.Interventions:Participating individuals were randomized to either BP self-monitoring with telemonitoring (n = 1223) plus usual care or usual antenatal care alone (n = 1218) without access to telemonitored BP.Main outcomes and measures:The primary outcome was time to first recorded hypertension measured by a health care professional.Results:Among 2441 participants who were randomized (mean [SD] age, 33 [5.6] years; mean gestation, 20 [1.6] weeks), 2346 (96%) completed the trial. The time from randomization to clinic recording of hypertension was not significantly different between individuals in the self-monitoring group (mean [SD], 104.3 [32.6] days) vs in the usual care group (mean [SD], 106.2 [32.0] days) (mean difference, -1.6 days [95% CI, -8.1 to 4.9]; P = .64). Eighteen serious adverse events were reported during the trial with none judged as related to the intervention (12 [1%] in the self-monitoring group vs 6 [0.5%] in the usual care group).Conclusions and relevance:Among pregnant individuals at higher risk of preeclampsia, blood pressure self-monitoring with telemonitoring, compared with usual care, did not lead to significantly earlier clinic-based detection of hypertension.Trial registration:ClinicalTrials.gov Identifier: NCT03334149.

Primary Outcome Measures is Time from recruitment to diagnosis of raised blood pressure; Extracted Interventionsis is Self-Monitoring of Blood Pressure; Conditions is Pregnancy, High Risk|Pre-Eclampsia|Hypertension|Hypertension, Pregnancy-Induced ;Sex is FEMALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of Self-monitoring of Blood Pressure on Blood Pressure Control in Pregnant Individuals With Chronic or Gestational Hypertension: The BUMP 2 Randomized Clinical Trial.Importance:Inadequate management of elevated blood pressure is a significant contributing factor to maternal deaths. The role of blood pressure self-monitoring in pregnancy in improving clinical outcomes for the pregnant individual and infant is unclear.Objective:To evaluate the effect of blood pressure self-monitoring, compared with usual care alone, on blood pressure control and other related maternal and infant outcomes, in individuals with pregnancy hypertension.Design, setting, and participants:Unblinded, randomized clinical trial that recruited between November 2018 and September 2019 in 15 hospital maternity units in England. Individuals with chronic hypertension (enrolled up to 37 weeks' gestation) or with gestational hypertension (enrolled between 20 and 37 weeks' gestation). Final follow-up was in May 2020.Interventions:Participants were randomized to either blood pressure self-monitoring using a validated monitor and a secure telemonitoring system in addition to usual care (n = 430) or to usual care alone (n = 420). Usual care comprised blood pressure measured by health care professionals at regular antenatal clinics.Main outcomes and measures:The primary maternal outcome was the difference in mean systolic blood pressure recorded by health care professionals between randomization and birth.Results:Among 454 participants with chronic hypertension (mean age, 36 years; mean gestation at entry, 20 weeks) and 396 with gestational hypertension (mean age, 34 years; mean gestation at entry, 33 weeks) who were randomized, primary outcome data were available from 444 (97.8%) and 377 (95.2%), respectively. In the chronic hypertension cohort, there was no statistically significant difference in mean systolic blood pressure for the self-monitoring groups vs the usual care group (133.8 mm Hg vs 133.6 mm Hg, respectively; adjusted mean difference, 0.03 mm Hg [95% CI, -1.73 to 1.79]). In the gestational hypertension cohort, there was also no significant difference in mean systolic blood pressure (137.6 mm Hg compared with 137.2 mm Hg; adjusted mean difference, -0.03 mm Hg [95% CI, -2.29 to 2.24]). There were 8 serious adverse events in the self-monitoring group (4 in each cohort) and 3 in the usual care group (2 in the chronic hypertension cohort and 1 in the gestational hypertension cohort).Conclusions and relevance:Among pregnant individuals with chronic or gestational hypertension, blood pressure self-monitoring with telemonitoring, compared with usual care, did not lead to significantly improved clinic-based blood pressure control.Trial registration:ClinicalTrials.gov Identifier: NCT03334149.

Primary Outcome Measures is Time from recruitment to diagnosis of raised blood pressure; Extracted Interventionsis is Self-Monitoring of Blood Pressure; Conditions is Pregnancy, High Risk|Pre-Eclampsia|Hypertension|Hypertension, Pregnancy-Induced ;Sex is FEMALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Prevention of Cardiovascular Events and Mortality With Icosapent Ethyl in Patients With Prior Myocardial Infarction.Background:REDUCE-IT was a double-blind trial that randomized 8,179 statin-treated patients with controlled low-density lipoprotein cholesterol and moderately elevated triglycerides to icosapent ethyl (IPE) or placebo. There was a significant reduction in the primary endpoint, including death from cardiovascular (CV) causes. The specific impact of IPE among patients with prior myocardial infarction (MI) was unknown.Objectives:Our goal was to examine the benefit of IPE on ischemic events among patients with prior MI in REDUCE-IT.Methods:We performed post hoc analyses of patients with prior MI. The primary endpoint was CV death, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary endpoint was CV death, MI, or stroke.Results:A total of 3,693 patients had a history of prior MI. The primary endpoint was reduced from 26.1% to 20.2% with IPE vs placebo; HR: 0.74 (95% CI: 0.65-0.85; P = 0.00001). The key secondary endpoint was reduced from 18.0% to 13.3%; HR: 0.71 (95% CI: 0.61-0.84; P = 0.00006). There was also a significant 35% relative risk reduction in total ischemic events (P = 0.0000001), a 34% reduction in MI (P = 0.00009), a 30% reduction in CV death (P = 0.01), and a 20% lower rate of all-cause mortality (P = 0.054), although there was a slight increase in atrial fibrillation. Sudden cardiac death and cardiac arrest were also significantly reduced by 40% and 56%, respectively.Conclusions:Patients with a history of prior MI in REDUCE-IT treated with IPE demonstrated large and significant relative and absolute risk reductions in ischemic events, including CV death. (A Study of AMR101 to Evaluate Its Ability to Reduce Cardiovascular Events in High Risk Patients With Hypertriglyceridemia and on Statin. The Primary Objective is to Evaluate the Effect of 4 g/Day AMR101 for Preventing the Occurrence of a First Major Cardiovascular Event. [REDUCE-IT]; NCT01492361).

Primary Outcome Measures is Composite of CV Death; Extracted Interventionsis is AMR101 Placebo Statin therapy; Conditions is Cardiovascular Diseases ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial.Background:Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis.Methods:In a randomized, double-blind, multicenter trial, men from the community with an AVC score >300 arbitrary units (AU) on cardiac noncontrast computer tomography were randomized to daily treatment with tablet 720 µg MK-7 plus 25 µg vitamin D or matching placebo for 24 months. The primary outcome was the change in AVC score. Selected secondary outcomes included change in aortic valve area and peak aortic jet velocity on echocardiography, heart valve surgery, change in aortic and coronary artery calcification, and change in dp-ucMGP (dephosphorylated-undercarboxylated matrix Gla-protein). Safety outcomes included all-cause death and cardiovascular events.Results:From February 1, 2018, to March 21, 2019, 365 men were randomized. Mean age was 71.0 (±4.4) years. The mean (95% CI) increase in AVC score was 275 AU (95% CI, 225-326 AU) and 292 AU (95% CI, 246-338 AU) in the intervention and placebo groups, respectively. The mean difference on AVC progression was 17 AU (95% CI, -86 to 53 AU; P=0.64). The mean change in aortic valve area was 0.02 cm2 (95% CI, -0.09 to 0.12 cm2; P=0.78) and in peak aortic jet velocity was 0.04 m/s (95% CI, -0.11 to 0.02 m/s; P=0.21). The progression in aortic and coronary artery calcification score was not significantly different between patients treated with MK-7 plus vitamin D and patients receiving placebo. There was no difference in the rate of heart valve surgery (1 versus 2 patients; P=0.99), all-cause death (1 versus 4 patients; P=0.37), or cardiovascular events (10 versus 10 patients; P=0.99). Compared with patients in the placebo arm, a significant reduction in dp-ucMGP was observed with MK-7 plus vitamin D (-212 pmol/L versus 45 pmol/L; P<0.001).Conclusions:In elderly men with an AVC score >300 AU, 2 years MK-7 plus vitamin D supplementation did not influence AVC progression.Registration:URL: https://www.Clinicaltrials:gov; Unique identifier: NCT03243890.

Primary Outcome Measures is Aortic valve calcification; Extracted Interventionsis is Menaquinone-7 720 µg/day including the recommended daily dose of vitamin D (25 µg/day). Placebo; Conditions is Aortic Valve Stenosis|Multidetector Computed Tomography|Vitamin K 2|Randomised Clinical Trial ;Sex is MALE ;Age is OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Single Ascending Dose Study of a Short Interfering RNA Targeting Lipoprotein(a) Production in Individuals With Elevated Plasma Lipoprotein(a) Levels.Importance:Lipoprotein(a) (Lp[a]) is an important risk factor for atherothrombotic cardiovascular disease and aortic stenosis, for which there are no treatments approved by regulatory authorities.Objectives:To assess adverse events and tolerability of a short interfering RNA (siRNA) designed to reduce hepatic production of apolipoprotein(a) and to assess associated changes in plasma concentrations of Lp(a) at different doses.Design, setting, and participants:A single ascending dose study of SLN360, an siRNA targeting apolipoprotein(a) synthesis conducted at 5 clinical research unit sites located in the US, United Kingdom, and Australia. The study enrolled adults with Lp(a) plasma concentrations of 150 nmol/L or greater at screening and no known clinically overt cardiovascular disease. Participants were enrolled between November 18, 2020, and July 21, 2021, with last follow-up on December 29, 2021.Interventions:Participants were randomized to receive placebo (n = 8) or single doses of SLN360 at 30 mg (n = 6), 100 mg (n = 6), 300 mg (n = 6), or 600 mg (n = 6), administered subcutaneously.Main outcomes and measures:The primary outcome was evaluation of safety and tolerability. Secondary outcomes included change in plasma concentrations of Lp(a) to a maximum follow-up of 150 days.Results:Among 32 participants who were randomized and received the study intervention (mean age, 50 [SD, 13.5] years; 17 women [53%]), 32 (100%) completed the trial. One participant experienced 2 serious adverse event episodes: admission to the hospital for headache following SARS-CoV-2 vaccination and later for complications of cholecystitis, both of which were judged to be unrelated to study drug. Median baseline Lp(a) concentrations were as follows: placebo, 238 (IQR, 203-308) nmol/L; 30-mg SLN360, 171 (IQR, 142-219) nmol/L; 100-mg SLN360, 217 (IQR, 202-274) nmol/L; 300-mg SLN360, 285 (IQR, 195-338) nmol/L; and 600-mg SLN360, 231 (IQR, 179-276) nmol/L. Maximal median changes in Lp(a) were -20 (IQR, -61 to 3) nmol/L, -89 (IQR, -119 to -61) nmol/L, -185 (IQR, -226 to -163) nmol/L, -268 (IQR, -292 to -189) nmol/L, and -227 (IQR, -270 to -174) nmol/L, with maximal median percentage changes of -10% (IQR, -16% to 1%), -46% (IQR, -64% to -40%), -86% (IQR, -92% to -82%), -96% (IQR, -98% to -89%), and -98% (IQR, -98% to -97%), for the placebo group and the 30-mg, 100-mg, 300-mg, and 600-mg SLN360 groups, respectively. The duration of Lp(a) lowering was dose dependent, persisting for at least 150 days after administration.Conclusions and relevance:In this phase 1 study of 32 participants with elevated Lp(a) levels and no known cardiovascular disease, the siRNA SLN360 was well tolerated, and a dose-dependent lowering of plasma Lp(a) concentrations was observed. The findings support further study to determine the safety and efficacy of this siRNA.Trial registration:ClinicalTrials.gov Identifier: NCT04606602; EudraCT Identifier: 2020-002471-35.

Primary Outcome Measures is Incidence of treatment-emergent adverse events; Extracted Interventionsis is SLN360 Placebo; Conditions is Hyperlipidemias|Dyslipidemias|Elevated Lp(a) ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Predicting the likelihood of successful medical treatment of early pregnancy loss: development and internal validation of a clinical prediction model.Study question:What are clinical predictors for successful medical treatment in case of early pregnancy loss (EPL)?Summary answer:Use of mifepristone, BMI, number of previous uterine aspirations and the presence of minor clinical symptoms (slight vaginal bleeding or some abdominal cramps) at treatment start are predictors for successful medical treatment in case of EPL.What is known already:Success rates of medical treatment for EPL vary strongly, between but also within different treatment regimens. Up until now, although some predictors have been identified, no clinical prediction model has been developed yet.Study design, size, duration:Secondary analysis of a multicentre randomized controlled trial in 17 Dutch hospitals, executed between 28 June 2018 and 8 January 2020.Participants/materials, setting, methods:Women with a non-viable pregnancy between 6 and 14 weeks of gestational age, who opted for medical treatment after a minimum of 1 week of unsuccessful expectant management. Potential predictors for successful medical treatment of EPL were chosen based on literature and expert opinions. We internally validated the prediction model using bootstrapping techniques.Main results and the role of chance:237 out of 344 women had a successful medical EPL treatment (68.9%). The model includes the following variables: use of mifepristone, BMI, number of previous uterine aspirations and the presence of minor clinical symptoms (slight vaginal bleeding or some abdominal cramps) at treatment start. The model shows a moderate capacity to discriminate between success and failure of treatment, with an AUC of 67.6% (95% CI = 64.9-70.3%). The model had a good fit comparing predicted to observed probabilities of success but might underestimate treatment success in women with a predicted probability of success of ∼70%.Limitations, reasons for caution:The vast majority (90.4%) of women were Caucasian, potentially leading to less optimal model performance in a non-Caucasian population. Limitations of our model are that we have not yet been able to externally validate its performance and clinical impact, and the moderate accuracy of the prediction model of 0.67.Wider implications of the findings:We developed a prediction model, aimed to improve and personalize counselling for medical treatment of EPL by providing a woman with her individual chance of complete evacuation.Study funding/competing interest(s):The Triple M Trial, upon which this secondary analysis was performed, was funded by the Healthcare Insurers Innovation Foundation (project number 3080 B15-191).Trial registration number:Clinicaltrials.gov: NCT03212352.

Primary Outcome Measures is Complete evacuation; Extracted Interventionsis is Mifepristone Misoprostol; Conditions is Early Pregnancy Failure ;Sex is FEMALE ;Age is CHILD, ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Sentinel lymph node mapping versus sentinel lymph node mapping with systematic lymphadenectomy in endometrial cancer: an open-label, non-inferiority, randomized trial (ALICE trial).Background:Growing evidence suggest that sentinel lymph node (SLN) biopsy in endometrial cancer accurately detects lymph node metastasis. However, prospective randomized trials addressing the oncological outcomes of SLN biopsy in endometrial cancer without lymphadenectomy are lacking.Primary objectives:The present study aims to confirm that SLN biopsy without systematic node dissection does not negatively impact oncological outcomes.Study hypothesis:We hypothesized that there is no survival benefit in adding systematic lymphadenectomy to sentinel node mapping for endometrial cancer staging. Additionally, we aim to evaluate morbidity and impact in quality of life (QoL) after forgoing systematic lymphadenectomy.Trial design:This is a collaborative, multicenter, open-label, non-inferiority, randomized trial. After total hysterectomy, bilateral salpingo-oophorectomy and SLN biopsy, patients will be randomized (1:1) into: (a) no further lymph node dissection or (b) systematic pelvic and para-aortic lymphadenectomy.Major inclusion and exclusion criteria:Inclusion criteria are patients with high-grade histologies (endometrioid G3, serous, clear cell, and carcinosarcoma), endometrioid G1 or G2 with imaging concerning for myometrial invasion of ≥50% or cervical invasion, clinically suitable to undergo systematic lymphadenectomy.Primary endpoints:The primary objective is to compare 3-year disease-free survival and the secondary objectives are 5-year overall survival, morbidity, incidence of lower limb lymphedema, and QoL after SLN mapping ± systematic lymphadenectomy in high-intermediate and high-risk endometrial cancer.Sample size:178 participants will be randomized in this study with an estimated date for completing accrual of December 2024 and presenting results in 2027.Trial registration number:NCT03366051.

Primary Outcome Measures is Recurrence; Extracted Interventionsis is Sentinel Node Mapping Lymphadenectomy; Conditions is Endometrial Cancer|Lymph Node Metastases ;Sex is FEMALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Standard care vs. TRIVEntricular pacing in Heart Failure (STRIVE HF): a prospective multicentre randomized controlled trial of triventricular pacing vs. conventional biventricular pacing in patients with heart failure and intermediate QRS left bundle branch block.Aims:To determine whether triventricular (TriV) pacing is feasible and improves CRT response compared to conventional biventricular (BiV) pacing in patients with left bundle branch block (LBBB) and intermediate QRS prolongation (120-150 ms).Methods and results:Between October 2015 and November 2019, 99 patients were recruited from 11 UK centres. Ninety-five patients were randomized 1:1 to receive TriV or BiV pacing systems. The primary endpoint was feasibility of TriV pacing. Secondary endpoints assessed symptomatic and remodelling response to CRT. Baseline characteristics were balanced between groups. In the TriV group, 43/46 (93.5%) patients underwent successful implantation vs. 47/49 (95.9%) in the BiV group. Feasibility of maintaining CRT at 6 months was similar in the TriV vs. BiV group (90.0% vs. 97.7%, P = 0.191). All-cause mortality was similar between TriV vs. BiV groups (4.3% vs. 8.2%, P = 0.678). There were no significant differences in echocardiographic LV volumes or clinical composite scores from baseline to 6-month follow-up between groups.Conclusion:Implantation of two LV leads to deliver and maintain TriV pacing at 6 months is feasible without significant complications in the majority of patients. There was no evidence that TriV pacing improves CRT response or provides additional clinical benefit to patients with LBBB and intermediate QRS prolongation and cannot be recommended in this patient group.Clinical trial registration number:Clinicaltrials.gov: NCT02529410.

Primary Outcome Measures is Feasibility of achieving and maintaining triventricular pacing at 6 months; Extracted Interventionsis is Cardiac Resynchronisation Therapy; Conditions is Heart Failure ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Q waves are the strongest electrocardiographic variable associated with primary prophylactic implantable cardioverter-defibrillator benefit: a prospective multicentre study.Aim:The association of standard 12-lead electrocardiogram (ECG) markers with benefits of the primary prophylactic implantable cardioverter-defibrillator (ICD) has not been determined in the contemporary era. We analysed traditional and novel ECG variables in a large prospective, controlled primary prophylactic ICD population to assess the predictive value of ECG in terms of ICD benefit.Methods and results:Electrocardiograms from 1477 ICD patients and 700 control patients (EU-CERT-ICD; non-randomized, controlled, prospective multicentre study; ClinicalTrials.gov Identifier: NCT02064192), who met ICD implantation criteria but did not receive the device, were analysed. The primary outcome was all-cause mortality. In ICD patients, the co-primary outcome of first appropriate shock was used. Mean follow-up time was 2.4 ± 1.1 years to death and 2.3 ± 1.2 years to the first appropriate shock. Pathological Q waves were associated with decreased mortality in ICD patients [hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.35-0.84; P < 0.01] and patients with pathological Q waves had significantly more benefit from ICD (HR 0.44, 95% CI 0.21-0.93; P = 0.03). QTc interval increase taken as a continuous variable was associated with both mortality and appropriate shock incidence, but commonly used cut-off values, were not statistically significantly associated with either of the outcomes.Conclusion:Pathological Q waves were a strong ECG predictor of ICD benefit in primary prophylactic ICD patients. Excess mortality among Q wave patients seems to be due to arrhythmic death which can be prevented by ICD.

Primary Outcome Measures is All-Cause Mortality; Extracted Interventionsis is nan; Conditions is Coronary Artery Disease|Myocardial Infarction|Dilated Cardiomyopathy|Implantable Defibrillator User ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Pharmacokinetics and Safety of 3 Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women.Background:Pregnancy increases the risk of tuberculosis and its complications. A 3-month regimen of weekly isoniazid and rifapentine (3HP) is safe and effective for tuberculosis prevention in adults and children, including those with HIV, but 3HP has not been evaluated in pregnancy.Methods:IMPAACT 2001 was a phase I/II trial evaluating the pharmacokinetics and safety of 3HP among pregnant women with indications for tuberculosis preventative therapy in Haiti, Kenya, Malawi, Thailand, and Zimbabwe (NCT02651259). Isoniazid and rifapentine were provided at standard doses (900 mg/week). Pharmacokinetic sampling was performed with the first (second/third trimester) and twelfth (third trimester/postpartum) doses. Nonlinear mixed-effects models were used to estimate drug population pharmacokinetics.Results:Of 50 participants, 20 had HIV and were taking efavirenz-based antiretroviral therapy. Among women without HIV, clearance of rifapentine was 28% lower during pregnancy than postpartum (1.20 vs 1.53 L/hour, P < .001), with area under the concentration-time curve (AUCSS) of 786 and 673 mg × hour/L, respectively. In pregnant women with HIV, clearance was 30% higher than women without HIV (P < .001), resulting in lower AUCss (522 mg × hour/L); clearance did not change significantly between pregnancy and postpartum. Pregnancy did not impact isoniazid pharmacokinetics. There were no drug-related serious adverse events, treatment discontinuations, or tuberculosis cases in women or infants.Conclusions:3HP does not require dose adjustment in pregnancy. Rifapentine clearance is higher among women with HIV, but all women achieved exposures of rifapentine and isoniazid associated with successful tuberculosis prevention. The data support proceeding with larger safety-focused studies of 3HP in pregnancy.Clinical trials registration:ClinicalTrials.gov, NCT02651259.

Primary Outcome Measures is Clearance Relative to Bioavailability (CL/F) for Rifapentine (RPT) for Intensive and Sparse PK; Extracted Interventionsis is Rifapentine (RPT) Isoniazid (INH) Pyridoxine (vitamin B6); Conditions is Tuberculosis ;Sex is FEMALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of Mailing Educational Material to Patients With Atrial Fibrillation and Their Clinicians on Use of Oral Anticoagulants: A Randomized Clinical Trial.Importance:Only about half of patients with atrial fibrillation (AF) who are at increased risk for stroke are treated with an oral anticoagulant (OAC), despite guideline recommendations for their use. Educating patients with AF about prevention of stroke with OACs may enable them as agents of change to initiate OAC treatment.Objective:To determine whether an educational intervention directed to patients and their clinicians stimulates the use of OACs in patients with AF who are not receiving OACs.Design, setting, and participants:The Implementation of a Randomized Controlled Trial to Improve Treatment With Oral Anticoagulants in Patients With Atrial Fibrillation (IMPACT-AFib) trial was a prospective, multicenter, open-label, pragmatic randomized clinical trial conducted from September 25, 2017, to May 1, 2019, embedded in health plans that participate in the US Food and Drug Administration's Sentinel System. It used the distributed database comprising health plan members to identify eligible patients, their clinicians, and outcomes. IMPACT-AFib enrolled patients with AF, a CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age 65-74 [1 point] or ≥75 years [2 points], diabetes, and stroke, transient ischemic attack or thromboembolism [2 points]-vascular disease, and sex category [female]) score of 2 or more, no evidence of OAC prescription dispensing in the preceding 12 months, and no hospitalization-related bleeding event within the prior 6 months.Interventions:Randomization to a single mailing of patient and/or clinician educational materials vs control.Main outcomes and measures:Analysis was performed on a modified intention-to-treat basis. The primary end point was the proportion of patients with at least 1 OAC prescription dispensed or at least 4 international normalized ratio test results within 1 year of the intervention.Results:Among 47 333 patients, there were 24 909 men (52.6%), the mean (SD) age was 77.9 (9.7) years, mean (SD) CHA2DS2-VASc score was 4.5 (1.7), 22 404 patients (47.3%) had an ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score of 5 or more, and 8890 patients (18.8%) had a history of hospitalization for bleeding. There were 2328 of 23 546 patients (9.9%) in the intervention group with initiation of OAC at 1 year compared with 2330 of 23 787 patients (9.8%) in the control group (adjusted OR, 1.01 [95% CI, 0.95-1.07]; P = .79).Conclusions and relevance:Among a large population with AF with a guideline indication for OACs for stroke prevention who were randomized to a mailed educational intervention or to usual care, there was no clinically meaningful, numerical, or statistically significant difference in rates of OAC initiation. More-intensive interventions are needed to try and address the public health issue of underuse of anticoagulation for stroke prevention among patients with AF.Trial registration:ClinicalTrials.gov Identifier: NCT03259373.

Primary Outcome Measures is Proportion of patients with evidence of at least one OAC dispensing (prescription fill) (defined as one OAC dispensing or 4 INR (International Normalized Ratio) tests); Extracted Interventionsis is Early Patient-Level and Provider-Level Educational Intervention Delayed Provider-Level Educational Intervention; Conditions is Atrial Fibrillation|Stroke ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of Brief Produce Exposure and Unconstrained Grocery Gift Cards on Caregiver Influence on Diet of Elementary Age Children: A Randomized Clinical Trial.Importance:Children's diets affect health trajectories but are difficult to influence, especially for resource-constrained families.Objective:To assess the effectiveness of providing 4 weeks of grocery gift cards and small produce boxes to caregivers on their ability to support healthy shifts in children's diets.Design, setting, and participants:This 2-group randomized clinical trial was conducted from May to July 2021, with 4 weeks of intervention and follow-up at 8 weeks. Resources were provided curbside at 3 schools, 3 housing sites, and 1 after-school site for use at home. Participants consisted of 1 index child ages 5 to 11 years with 1 index caregiver from 68 low-income families. Data were analyzed from July 2021 through March 2022.Interventions:During each week for 4 weeks, caregivers were offered 10-lb (4.5 kg) boxes of fruits and vegetables, $10.00 grocery gift cards, an additional $10.00 gift card over the last 3 weeks triggered by a task completion, and a 1-time choice of a $25.00 food preparation tool.Main outcomes and measures:Index child and caregiver diets were measured together over the phone at baseline, 4 weeks, and 8 weeks using the 2019 to 2020 Texas School Physical Activity and Nutrition (SPAN) tool, which measures the number of times food items were eaten over the prior day to report a SPAN Healthy Eating Index (SHEI) score and subscores for specific categories of foods (range, 0-57, with higher scores indicating a more healthful diet).Results:Among 68 children (mean [SD] age, 8.2 [1.7] years; 35 [51.5%] girls) and caregivers (mean [SD] age, 37.9 [7.9] years; 63 mothers [92.6%]) from primarily low-income families, 26 caregivers were Hispanic or Latino (38.2%), while 18 caregivers were Black (26.4%), 25 caregivers were White (36.7%), and 24 caregivers had more than 1 race (35.3%). Most families were below the federal poverty level (41 of 60 families that reported income [68.3%]). Per participating caregiver, a mean (SD) 2.7 [1.4] fruit and vegetable boxes and $42.35 ($25.46) worth of gift cards were picked up over 4 weeks. Mean (SE) child SPAN SHEI increased from 32.03 (0.62) times/d to 33.75 (0.69) times/d at 4 weeks (ie, postintervention) and 34.03 (0.69) times/d 4 weeks later (ie, at 8 weeks of follow-up). Mean (SE) child fruit and vegetable intake increased from 5.31 (0.47) times/d to 5.78 (0.51) times/d postintervention and 6.03 (0.51) times/d at follow-up. Children in the control group did not have improved diet (overall mean [SE] SHEI: 31.48 [0.58] times/d at baseline, 31.68 [0.54] times/d postintervention, and 31.81 [0.52] times/d at follow-up; mean [SE] fruit and vegetable intake: 5.21 [0.45] times/d at baseline, 4.77 [0.45] times/d postintervention, and 4.68 [0.41] times/d at follow-up). Compared with children in the control group, mean SHEI was increased for children in the intervention group by 2.07 times/d postintervention and 2.23 times/d at follow-up. Improvements as a function of program dose were statistically significant for child SHEI (P = .01) and fruit and vegetable intake (P = .03). No significant changes in caregiver diets were found.Conclusions and relevance:This study found that easily accessed fruits and vegetables and unconstrained grocery store cards provided directly to caregivers over 4 weeks resulted in improvements in child diet, which were sustained over 4 additional weeks. Future work may investigate whether diet improvement from a brief intervention optimized for caregiver flexibility reflects a natural maximum or potential for greater improvements on extension.Trial registration:ClinicalTrials.gov Identifier: NCT04827654.

Primary Outcome Measures is School Physical Activity and Nutrition (SPAN) questionnaire elementary version; Extracted Interventionsis is Weekly produce box and gift card; Conditions is Diet, Healthy ;Sex is ALL ;Age is CHILD

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial.Importance:Developing interventions against age-related memory decline and for older adults experiencing neurodegenerative disease is one of the greatest challenges of our generation. Spermidine supplementation has shown beneficial effects on brain and cognitive health in animal models, and there has been preliminary evidence of memory improvement in individuals with subjective cognitive decline.Objective:To determine the effect of longer-term spermidine supplementation on memory performance and biomarkers in this at-risk group.Design, setting, and participants:This 12-month randomized, double-masked, placebo-controlled phase 2b trial (the SmartAge trial) was conducted between January 2017 and May 2020. The study was a monocenter trial carried out at an academic clinical research center in Germany. Eligible individuals were aged 60 to 90 years with subjective cognitive decline who were recruited from health care facilities as well as through advertisements in the general population. Data analysis was conducted between January and March 2021.Interventions:One hundred participants were randomly assigned (1:1 ratio) to 12 months of dietary supplementation with either a spermidine-rich dietary supplement extracted from wheat germ (0.9 mg spermidine/d) or placebo (microcrystalline cellulose). Eighty-nine participants (89%) successfully completed the trial intervention.Main outcomes and measures:Primary outcome was change in memory performance from baseline to 12-month postintervention assessment (intention-to-treat analysis), operationalized by mnemonic discrimination performance assessed by the Mnemonic Similarity Task. Secondary outcomes included additional neuropsychological, behavioral, and physiological parameters. Safety was assessed in all participants and exploratory per-protocol, as well as subgroup, analyses were performed.Results:A total of 100 participants (51 in the spermidine group and 49 in the placebo group) were included in the analysis (mean [SD] age, 69 [5] years; 49 female participants [49%]). Over 12 months, no significant changes were observed in mnemonic discrimination performance (between-group difference, -0.03; 95% CI, -0.11 to 0.05; P = .47) and secondary outcomes. Exploratory analyses indicated possible beneficial effects of the intervention on inflammation and verbal memory. Adverse events were balanced between groups.Conclusions and relevance:In this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo. Exploratory analyses indicated possible beneficial effects on verbal memory and inflammation that need to be validated in future studies at higher dosage.Trial registration:ClinicalTrials.gov Identifier: NCT03094546.

Primary Outcome Measures is Change in Memory performance from neuropsychological test; Extracted Interventionsis is Polyamine Placebo; Conditions is Subjective Cognitive Decline (SCD) ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of Timing and Coordination Training on Mobility and Physical Activity Among Community-Dwelling Older Adults: A Randomized Clinical Trial.Importance:Standard exercise interventions targeting underlying physiologic system impairments have limited success in improving walking. Augmenting standard interventions with timing and coordination training, which incorporates the principles of motor learning and integrates multiple systems, may be more successful.Objective:To determine whether a standard strength and endurance program incorporating timing and coordination training (standard-plus) improves gait speed more than strength and endurance training alone.Design, setting, and participants:The Program to Improve Mobility in Aging (PRIMA) study was an assessor-blinded, randomized, 2-group intervention trial that included a 12-week intervention and 24-week follow-up period. The trial was conducted at a university research clinic from 2016 to 2020. Participants included 249 community-dwelling older adults (aged ≥65 years) with gait speed between 0.60 and 1.20 m/s. Statistical analysis was performed from December 2020 to March 2021.Interventions:Participants were randomized to standard strength and endurance (n = 125) or standard-plus, including timing and coordination training (n = 124), 50 to 60 minutes, twice a week for 12 weeks.Main outcomes and measures:Primary outcome of gait speed and secondary outcomes representing components of the intervention (leg strength and power, 6-minute walk test, chair sit-and-reach test, and figure of 8 walk test) and activity and participation (Late Life Function and Disability Instrument and daily physical activity measured by accelerometry) were measured at 12, 24, and 36 weeks.Results:Among 249 randomized participants, 163 (65.5%) were female, 22 (8.8%) were Black, 219 (88.0%) were White; mean (SD) age was 77.4 (6.6) years; mean (SD) gait speed was 1.07 (0.16) m/s; and 244 (98.0%) completed the intervention. The 2 groups did not have significantly different improvements in gait speed or secondary outcomes representing the components of the intervention at any time point. For gait speed, individuals in the standard-plus group had a mean (SD) improvement of 0.079 (0.135) m/s over 12 weeks, 0.065 m/s (0.141) over 24 weeks, and 0.059 (0.150) m/s over 36 weeks; individuals in the standard group improved gait speed by 0.081 (0.124) m/s over 12 weeks, 0.051 (0.129) m/s over 24 weeks, and 0.065 (0.148) m/s over 36 weeks.Conclusions and relevance:This randomized clinical trial found no difference in gait speed change between the standard and standard-plus intervention groups, and both groups showed sustained improvements in mobility 24 weeks after the intervention.Trial registration:ClinicalTrials.gov Identifier: NCT02663778.

Primary Outcome Measures is Gait speed; Extracted Interventionsis is Strength training Endurance training Flexibility training Task Specific timing and coordination training Physical activity behavioral intervention; Conditions is Gait, Unsteady ;Sex is ALL ;Age is OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Long-term Effect of Face-to-Face vs Virtual Reality Cardiopulmonary Resuscitation (CPR) Training on Willingness to Perform CPR, Retention of Knowledge, and Dissemination of CPR Awareness: A Secondary Analysis of a Randomized Clinical Trial.Importance:Increased bystander cardiopulmonary resuscitation (CPR) is essential to improve survival after cardiac arrest. Although most studies focus on technical CPR skills, the randomized Lowlands Saves Lives trial prespecified a follow-up survey on other important aspects that affect the widespread performance of CPR.Objective:To investigate bystander willingness to perform CPR on a stranger, theoretical knowledge retention, and dissemination of CPR awareness 6 months after undergoing short face-to-face and virtual reality (VR) CPR trainings.Design, setting, and participants:A prespecified 6-month posttraining survey was conducted among 320 participants in the Lowlands Saves Lives trial, a randomized comparison between 20-minute face-to-face, instructor-led CPR training and VR training. Participants were recruited at the Lowlands music festival, with a designated area to conduct scientific projects (August 16-18, 2019; the Netherlands). Statistical analysis was performed from March 1, 2020, to July 31, 2021.Interventions:Two standardized 20-minute protocols on CPR and automated external defibrillator use: instructor-led face-to-face training using CPR manikins or VR training using the Resuscitation Council (UK)-endorsed Lifesaver VR smartphone application and a pillow to practice compressions.Main outcomes and measures:Primary outcomes were willingness to perform CPR on a stranger, theoretical knowledge retention, and dissemination of CPR awareness as reported by the entire cohort. As secondary analyses, the results of the 2 training modalities were compared.Results:Of 381 participants, 320 consented to this follow-up survey; 188 participants (115 women [61%]; median age, 26 years [IQR, 22-32 years]) completed the entire survey and were accordingly included in the secondary analysis. The overall proportion of participants willing to perform CPR on a stranger was 77% (144 of 188): 81% (79 of 97) among face-to-face participants and 71% (65 of 91) among VR participants (P = .02); 103 participants (55%) reported feeling scared to perform CPR (P = .91). Regarding theoretical knowledge retention, a median of 7 (IQR, 6-8) of 9 questions were answered correctly in both groups (P = .81). Regarding dissemination of CPR awareness, 65% of participants (123 of 188) told at least 1 to 10 family members or friends about the importance of CPR, and 15% (29 of 188) had participated in certified, instructor-led training at the time of the survey, without differences between groups.Conclusions and relevance:In this 6-month posttraining survey, young adult participants of short CPR training modules reported high willingness (77%) to perform CPR on a stranger, with slightly higher rates for face-to-face than for VR participants. Theoretical knowledge retention was good, and the high dissemination of awareness suggests that these novel CPR training modules staged at a public event are promising sensitizers for involvement in CPR, although further challenges include mitigating the fear of performing CPR.Trial registration:ClinicalTrials.gov Identifier: NCT04013633.

Primary Outcome Measures is Chest compression quality; Extracted Interventionsis is Lifesaver virtual reality training Face-to-face training; Conditions is Cardiac Arrest|Cardiopulmonary Arrest|Out-Of-Hospital Cardiac Arrest ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of a Novel Intervention Targeting Appetitive Traits on Body Mass Index Among Adults With Overweight or Obesity: A Randomized Clinical Trial.Importance:Behavioral weight loss (BWL) programs result in weight loss for some, but most individuals regain the weight. The behavioral susceptibility theory proposes that genetically determined appetitive traits, such as food responsiveness (FR) and satiety responsiveness (SR), interact with the environment and lead to overeating and weight gain; the regulation of cues (ROC) intervention was developed specifically to target FR and SR.Objective:To evaluate the efficacy of ROC, ROC combined with BWL (ROC+), BWL, and an active comparator (AC) over 12 months of treatment and 12 months of follow-up.Design, setting, and participants:This randomized clinical trial was conducted from December 2015 to December 2019 in a university clinic. A total of 1488 volunteers from the community inquired about the study; 1217 were excluded or declined to participate. Eligibility criteria included body mass index (BMI) of 25 to 45, age 18 to 65 years, and lack of comorbidities or other exclusionary criteria that would interfere with participation. Data were analyzed from September 2021 to January 2022.Interventions:ROC uniquely targeted FR and SR. BWL included energy restriction, increasing physical activity, and behavior therapy techniques. ROC+ combined ROC with BWL. AC included mindfulness, social support, and nutrition education.Main outcomes and measures:Change in body weight as measured by BMI.Results:A total of 271 adults (mean [SD] age, 46.97 [11.80] years; 81.6% female [221 participants]; mean [SD] BMI, 34.59 [5.28]; 61.9% White [167 participants]) were assessed at baseline, midtreatment, posttreatment, and 6-month and 12-month follow-up. Sixty-six participants were randomized to AC, 69 to ROC, 67 to ROC+, and 69 to BWL. Results showed that ROC, ROC+, and BWL interventions resulted in significantly lower BMI at the end of treatment (BMI ROC, -1.18; 95% CI, -2.10 to -0.35; BMI ROC+, -1.56; 95% CI, -2.43 to -0.67; BMI BWL, -1.58; 95% CI, -2.45 to -0.71). Compared with BWL, BMI at the end of treatment was not significantly different from ROC or ROC+ (BMI ROC, 0.40; 95% CI, -0.55 to 1.36; BMI ROC+, 0.03; 95% CI, -0.88 to 0.93); however, the BMI of the AC group was substantially higher (BMI AC, 1.58; 95% CI, 0.72 to 2.45). BMI reductions at 24 months after randomization were similar for ROC, ROC+, and BWL. Importantly, FR was a moderator of treatment effects with more weight loss for participants who scored higher in FR in the ROC and ROC+ groups.Conclusions and relevance:These findings suggest that ROC and ROC+ provide alternative weight loss approaches for adults. These models could be particularly effective for individuals who struggle with FR and could be used as a precision approach for weight loss.Trial registration:ClinicalTrials.gov Identifier: NCT02516839.

Primary Outcome Measures is body mass index as measured by height and weight; Extracted Interventionsis is Regulation of Cues (ROC) Behavioral Weight Loss (BWL) BWL + ROC Nutrition Education, Stress Management and Social Support; Conditions is Overweight|Obesity ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of Lifestyle Coaching or Enhanced Pharmacotherapy on Blood Pressure Control Among Black Adults With Persistent Uncontrolled Hypertension: A Cluster Randomized Clinical Trial.Importance:Greater difficulty in controlling blood pressure (BP) and adverse lifestyle practices such as higher salt intake or less physical activity may account for some of the differences between BP control rates in Black vs White adults, thereby exposing Black adults to a higher risk of vascular events.Objective:To determine whether a lifestyle coaching intervention or an enhanced pharmacotherapy protocol is more effective than usual care in improving BP control rates in Black adults treated within an integrated health care delivery system.Design, setting, and participants:Shake, Rattle & Roll, a cluster randomized clinical trial, was conducted from June 5, 2013, to June 11, 2018, in a large integrated health care delivery system. Enrollment was completed during a 12-month period and interventions were implemented for 12 months. Follow-up lasted 48 months after enrollment. Panels of Black adult members of the health care delivery system with BP of at least 140/90 mm Hg from 98 adult primary care physicians were randomly assigned at the primary care physician level to usual care (UC group [n = 1129]), enhanced pharmacotherapy monitoring (EP group [n = 346]) of current BP management protocol, or diet and lifestyle coaching consisting of photographs, stories, and recipes, for example, that are appropriate for Black adults (LC group [n = 286]) focused on the Dietary Approaches to Stop Hypertension (DASH) diet. Data were analyzed from June 1, 2016, to March 25, 2022.Interventions:The UC group received care per customary protocol. The EP group was contacted by a research nurse and/or a clinical pharmacist to discuss barriers to hypertension control, and drug therapy emphasized the use of thiazide diuretic intensification and addition of spironolactone as needed. The LC group received as many as 16 telephone sessions with a lifestyle coach and an emphasis on implementing reduction of sodium intake and the DASH diet.Main outcomes and measures:Intention-to-treat analysis of BP control rates at end of the 12-month intervention.Results:Among the 1761 participants, the mean (SD) age was 61 (13) years, and 1214 (68.9%) were women. At the end of the 12-month intervention period, there was no significant difference in BP control rate among study groups (UC, 61.8% [95% CI, 58.8%-64.9%]; EP, 64.5% [95% CI, 59.0%-69.4%]; LC, 67.8% [95% CI, 62.1%-73.2%]; LC vs EP, P = .07). However, greater BP control was present in the LC group vs UC at 24 months (UC, 61.2% [95% CI, 57.3%-64.7%]; EP, 67.6% [95% CI, 61.9%-72.8%]; LC, 72.4% [95% CI, 66.9%-78.1%]; LC vs UC, P = .001), and 48 months (UC, 64.5% [95% CI, 61.6%-67.2%]; EP, 66.5% [95% CI, 61.3%-71.3%]; LC, 73.1% [95% CI, 67.6%-77.9%]; LC vs UC, P = .006) after enrollment. The contribution of BP medication adherence to explain group differences was inconclusive.Conclusions and relevance:In this cluster randomized clinical trial including Black adults with persistent uncontrolled hypertension, a 12-month LC intervention was more effective at controlling BP than UC at 24 and 48 months after enrollment. Further research is needed to explore the potential implementation of this intervention into clinical practice.Trial registration:ClinicalTrials.gov Identifier: NCT01892592.

Primary Outcome Measures is Percentage of Blacks / African Americans with HTY with controlled blood pressure (BP) after 1 year.; Extracted Interventionsis is Diet and Lifestyle; Conditions is Hypertension ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Association of a Community Population and Clinic Education Intervention Program With Guideline-Based Aspirin Use for Primary Prevention of Cardiovascular Disease: A Nonrandomized Controlled Trial.Importance:Low-dose aspirin is used for primary prevention of cardiovascular disease in approximately one-third of the US adult population. Overuse and underuse are common and not concordant with guidelines.Objective:To test a community and clinic education intervention to improve guideline-based aspirin use for the primary prevention of cardiovascular disease.Design, setting, and participants:The Ask About Aspirin project was a nonrandomized controlled trial conducted from, July 1, 2015, to March 31, 2020, using professional education, traditional media, and digital media to improve guideline-based aspirin use. The adult population (aged 45-79 years for men and 55-79 years for women) and primary care clinics in Minnesota were the education targets. The 4 adjacent states were controls.Interventions:The statewide campaign distributed billboards, newspaper articles and other print material, and radio announcements. An Ask About Aspirin website was heavily promoted. Primary care clinics identified appropriate aspirin candidates, and clinicians received continuing education about aspirin.Main outcomes and measures:Guideline-based aspirin use by the target population.Results:Cross-sectional random telephone surveys of 8342 men aged 45 to 79 years and women aged 55 to 79 years were conducted at baseline, 2 years, and 4 years after the intervention. Participation was similar between men and women (baseline: 973 [49%] vs 1001 [51%]; year 4: 912 [50%] vs 930 [50%]). Age during the study also was similar (baseline: 64.7 [IQR, 64.4-65.1] years; year 4: 66.2 [IQR, 65.8-66.5] years). A validated questionnaire evaluated aspirin use. The Ask About Aspirin website had more than 1 million visits; 124 primary care clinics with more than 1000 participating clinicians were part of the education program. Small, nonsignificant increases in discussions with clinicians regarding aspirin resulted (baseline: 341 of 1001 [34%]; year 4: 339 of 930 [36%]; P = .27). Overall aspirin use decreased after the release of new US Preventive Services Task Force guidelines in 2016 and 3 aspirin randomized clinical trials in 2018 suggested reduced aspirin use (baseline: 816 of 1974 [41%]; year 4: 629 of 1842 [34%]; P < .001). Decreases were also noted from year 2 to year 4 in appropriate use (year 2: 597 of 1208 [49%]; year 4: 478 of 1191 [40%]; P < .001) and overuse (year 2: 170 of 602 [28%]; year 4: 151 of 651 [23%]; P = .04). There were no significant differences between Minnesota and the control states.Conclusions and relevance:In this nonrandomized controlled trial, a multiyear statewide campaign was not associated with increased appropriate aspirin use for cardiovascular disease prevention. Contextual factors during the project, including guideline changes and media controversy following the new trials, undermined study goals. These findings suggest that although education programs using social media for cardiovascular disease prevention can result in millions of hits, the use of this strategy to encourage behavior change is problematic, even with supportive clinical sites.Trial registration:ClinicalTrials.gov Identifier: NCT02607917.

Primary Outcome Measures is Appropriate aspirin use.; Extracted Interventionsis is Mass Media plus clinic intervention. Media; Conditions is Myocardial Infarction|Stroke ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of a Novel Online Group-Coaching Program to Reduce Burnout in Female Resident Physicians: A Randomized Clinical Trial.Importance:Female resident physicians are disproportionately affected by burnout, which can have serious consequences for their well-being and career trajectory. Growing evidence supports the use of professional coaching to reduce burnout in resident physicians, yet individual coaching is resource intensive and infeasible for many training programs.Objective:To assess whether a structured professional group-coaching program for female resident physicians would lead to decreased burnout.Design, setting, and participants:This pilot randomized clinical trial was conducted from January 1 to June 30, 2021, among 101 female resident physicians in graduate medical education at the University of Colorado who voluntarily enrolled in the trial after a recruitment period. Surveys were administered to participants before and after the intervention.Intervention:With the use of a computer-generated 1:1 algorithm, 50 participants were randomly assigned to the intervention group and 51 participants were randomly assigned to the control group. The intervention group was offered a 6-month, web-based group-coaching program, Better Together Physician Coaching, developed and facilitated by trained life coaches and physicians. The control group received residency training as usual, with no coaching during the study. The control group was offered the 6-month coaching program after study completion.Main outcomes and measures:The primary outcome of burnout was measured using the Maslach Burnout Inventory, defined by 3 Likert-type 7-point subscales: emotional exhaustion, depersonalization, and professional accomplishment. Higher scores on the emotional exhaustion and depersonalization subscales and lower scores on the professional accomplishment subscale indicate higher burnout. Secondary outcomes of impostor syndrome, self-compassion, and moral injury were assessed using the Young Impostor Syndrome Scale, Neff's Self-Compassion Scale-Short Form, and the Moral Injury Symptom Scale-Healthcare Professionals, respectively. An intention-to-treat analysis was performed.Results:Among the 101 female residents in the study, the mean (SD) age was 29.4 (2.3) years, 96 (95.0%) identified as heterosexual, and 81 (80.2%) identified as White. There were 19 residents (18.8%) from surgical subspecialties, with a range of training levels represented. After 6 months of professional coaching, emotional exhaustion decreased in the intervention group by a mean (SE) of 3.26 (1.25) points compared with a mean (SE) increase of 1.07 (1.12) points in the control group by the end of the study (P = .01). The intervention group experienced a significant reduction in presence of impostor syndrome compared with controls (mean [SE], -1.16 [0.31] vs 0.11 [0.27] points; P = .003). Self-compassion scores increased in the intervention group by a mean (SE) of 5.55 (0.89) points compared with a mean (SE) reduction of 1.32 (0.80) points in the control group (P < .001). No statistically significant differences in depersonalization, professional accomplishment, or moral injury scores were observed. Owing to the differential follow-up response rates in the treatment groups (88.2% in the control group [45 of 51]; 68.0% in the intervention group [34 of 50]), a sensitivity analysis was performed to account for the missing outcomes, with similar findings.Conclusions and relevance:In this randomized clinical trial, professional coaching reduced emotional exhaustion and impostor syndrome scores and increased self-compassion scores among female resident physicians.Trial registration:ClinicalTrials.gov Identifier: NCT05280964.

Primary Outcome Measures is Change from baseline Burnout at 6 months; Extracted Interventionsis is Better Together Physician Coaching; Conditions is Burnout|Self-compassion|Moral Injury|Impostor Phenomenon ;Sex is FEMALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Efficacy and Safety of Difelikefalin in Japanese Patients With Moderate to Severe Pruritus Receiving Hemodialysis: A Randomized Clinical Trial.Importance:Patients with pruritus receiving hemodialysis frequently experience oppressive physical and psychiatric symptoms that directly affect their quality of life and increase mortality. However, treatment options are limited.Objective:To determine the clinically recommended dose of difelikefalin, a κ-opioid receptor agonist, based on the efficacy, dose response, safety, and pharmacokinetics.Design, setting, and participants:This randomized, double-blind, placebo-controlled, 4-arm phase 2 trial was conducted from February 1, 2019, to October 22, 2019, at 94 sites in Japan. Patients with moderate to severe pruritus receiving hemodialysis were enrolled.Interventions:Difelikefalin (0.25, 0.5, and 1.0 μg/kg) and placebo were intravenously administered 3 times a week at the end of each hemodialysis session for 8 weeks.Main outcome and measures:The primary end point was the change from baseline in the weekly mean Worst Itching Intensity Numerical Rating Scale (NRS) score at week 8. Secondary outcomes measured changes in itch-related quality-of-life score using the Skindex-16 and 5-D itch scale. Safety was assessed according to adverse events, laboratory tests, vital signs, body weight, and 12-lead electrocardiogram.Results:A total of 247 Japanese patients (186 male [75%]; mean [SD] age, 64.5 [11.7] years) were randomized to placebo (n = 63), 0.25 μg/kg of difelikefalin (n = 61), 0.5 μg/kg of difelikefalin (n = 61), or 1.0 μg/kg of difelikefalin (n = 62). The changes from baseline in the adjusted mean (SE) of the 24-hour Worst Itching Intensity NRS score at week 8 were -2.86 (0.29) in the placebo group, -2.97 (0.29) in the 0.25 μg/kg of difelikefalin group, -3.65 (0.30) in the 0.5 μg/kg of difelikefalin group, and -3.64 (0.30) in the 1.0 μg/kg of difelikefalin group. Significant differences were found in the 0.5 μg/kg of difelikefalin group (adjusted mean difference, -0.80; 95% CI, -1.55 to -0.04; P = .04) and the 1.0 μg/kg of difelikefalin group (adjusted mean difference, -0.78; 95% CI, -1.54 to -0.03; P = .04) compared with placebo. The Skindex-16 overall score and 5-D itch scale total score indicated an improvement with treatment with 0.5 and 1.0 μg/kg of difelikefalin (adjusted weekly mean [SE] Skindex-16 overall score at week 8, -27.79 [2.05]; 95% CI, -31.83 to -23.74 for 0.5 μg/kg of difelikefalin and -22.69 [2.04]; 95% CI, -26.71 to -18.68 for 1.0 μg/kg of difelikefalin; adjusted weekly mean [SE] 5-D itch scale total score at week 8, -6.5 [0.4]; 95% CI, -7.2 to -5.8 for 0.5 μg/kg of difelikefalin and -6.8 [0.3]; 95% CI, -7.5 to -6.2 for 1.0 μg/kg of difelikefalin). The incidence of adverse events was 67% (42 of 63 patients) in the placebo group, 72% (44 of 61 patients) in the 0.25 μg/kg of difelikefalin group, 77% (47 of 61 patients) in the 0.5 μg/kg of difelikefalin group, and 85% (53 of 62 patients) in the 1.0 μg/kg of difelikefalin group. No dependency was reported.Conclusions and relevance:The findings of this phase 2 randomized clinical trial of difelikefalin suggest that 0.5 μg/kg of difelikefalin should be the clinically recommended dose as a new option for treating moderate to severe pruritus in patients undergoing hemodialysis because of its efficacy, acceptable tolerability, and manageable safety profile.Trial registration:ClinicalTrials.gov Identifier: NCT03802617.

Primary Outcome Measures is Change in Numerical Rating Scale (NRS) score of itch; Extracted Interventionsis is MR13A9 Placebo; Conditions is Uremic Pruritus ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Total versus partial posterior fundoplication in the surgical repair of para-oesophageal hernias: randomized clinical trial.Background:Fundoplication is an essential step in para-oesophageal hernia (POH) repair, but which type minimizes postoperative mechanical complications is controversial.Methods:This was a randomized, double-blind clinical trial conducted between May 2009 and October 2018. Patients with symptomatic POH were allocated to either a total (Nissen) or a posterior partial (Toupet) fundoplication after hernia reduction and crural repair. The primary outcome was dysphagia (Ogilvie dysphagia scores) at 6 months postoperatively. Secondary outcomes were peri- and postoperative complications, swallowing difficulties assessed by the Dakkak dysphagia score, gastro-oesophageal reflux, quality of life (QoL), and radiologically confirmed hernia recurrence.Results:A total of 70 patients were randomized to a Nissen (n = 32) or a Toupet (n = 38) fundoplication. Compared with baseline, Ogilvie dysphagia scores were stable at the 3- and 6-month follow-up in the Nissen group (P = 0.075 and 0.084 respectively) but significantly improved in the Toupet group (from baseline mean (s.d.): 1.4 (1.1) to 0.5 ( 0.8) at 3 months, and 0.5 (0.6) at 6 months; P = 0.003 and P = 0.001 respectively). At 6 months, Dakkak dysphagia scores were significantly higher in the Nissen group than in the Toupet group (mean (s.d.): 10.4 (7.9) versus 5.1 (7.2); P = 0.003). QoL scores improved throughout the follow-up. However, at 3 and 6 months postoperatively, the absolute median improvement (⍙) from preoperative values in the mental component scores of the Short Form-36 QoL questionnaire was significantly higher in the Toupet group (median (i.q.r.): 7.1 (-0.6 to 15.2) versus 1.0 (-5.4 to 3.3) at 3 months, and 11.2 (1.4 to 18.3) versus 0.4 (-9.4 to 7.5) at 6 months; (P = 0.010 and 0.003 respectively)). At 6 months, radiologically confirmed POH recurrence occurred in 11 of 24 patients (46 per cent) of the Nissen group and in 15 of 32 patients (47 per cent) of the Toupet group (P = 1.001).Conclusions:A partial posterior wrap (Toupet fundoplication) showed reduced obstructive complications and improved QoL compared with a total (Nissen) fundoplication following POH repair.Registration number: NCT04436159 (http://www.clinicaltrials.gov).

Primary Outcome Measures is Ogilvie dysphagia score; Extracted Interventionsis is Addition of 360 fundoplication after crural closure Addition of 180 posterior fundoplication after crural closure; Conditions is Paraesophageal Hernia|Gastro Esophageal Reflux ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Comparison of Collaborative Goal Setting With Enhanced Education for Managing Diabetes-Associated Distress and Hemoglobin A1c Levels: A Randomized Clinical Trial.Importance:Type 2 diabetes is a prevalent and morbid condition. Poor engagement with self-management can contribute to diabetes-associated distress and hinder diabetes control.Objective:To evaluate the implementation and effectiveness of Empowering Patients in Chronic Care (EPICC), an evidence-based intervention to improve diabetes-associated distress and hemoglobin A1c (HbA1c) levels after the intervention and after 6-month maintenance.Design, setting, and participants:This hybrid (implementation-effectiveness) randomized clinical trial was performed in Veterans Affairs clinics across Illinois, Indiana, and Texas from July 1, 2015, to June 30, 2017. Participants included adults with uncontrolled type 2 diabetes (HbA1c level >8.0%) who received primary care during the prior year in participating clinics. Data collection was completed on November 30, 2018, and data analysis was completed on June 30, 2020. All analyses were based on intention to treat.Interventions:Participants in EPICC attended 6 group sessions based on a collaborative goal-setting theory led by health care professionals. Clinicians conducted individual motivational interviewing sessions after each group. Usual care was enhanced (EUC) with diabetes education.Main outcomes and measures:The primary outcome consisted of changes in HbA1c levels after the intervention and during maintenance. Secondary outcomes included the Diabetes Distress Scale (DDS), Morisky Medication Adherence Scale, and Lorig Self-efficacy Scale. Secondary implementation outcomes included reach, adoption, and implementation (number of sessions attended per patient).Results:A total of 280 participants with type 2 diabetes (mean [SD] age, 67.2 [8.4] years; 264 men [94.3]; 134 non-Hispanic White individuals [47.9%]) were equally randomized to EPICC or EUC. Participants receiving EPICC had significant postintervention improvements in HbA1c levels (F1, 252 = 9.12, Cohen d = 0.36 [95% CI, 0.12-0.59]; P = .003) and DDS (F1, 245 = 9.06, Cohen d = 0.37 [95% CI, 0.13-0.60]; P = .003) compared with EUC. During maintenance, differences between the EUC and EPICC groups remained significant for DDS score (F1, 245 = 8.94, Cohen d = 0.36 [95% CI, 0.12-0.59]; P = .003) but not for HbA1c levels (F1, 252 = 0.29, Cohen d = 0.06 [95% CI, -0.17 to 0.30]; P = .60). Improvements in DDS scores were modest. There were no differences between EPICC and EUC in improvements after intervention or maintenance for either adherence or self-efficacy. Among all 4002 eligible patients, 280 (7.0%) enrolled in the study (reach). Each clinic conducted all planned EPICC sessions and cohorts (100% adoption). The EPICC group participants attended a mean (SD) of 4.34 (1.98) sessions, with 54 (38.6%) receiving all 6 sessions.Conclusions and relevance:A patient-empowerment approach using longitudinal collaborative goal setting and motivational interviewing is feasible in primary care. Improvements in HbA1c levels after the intervention were not sustained after maintenance. Modest improvements in diabetes-associated distress after the intervention were sustained after maintenance. Innovations to expand reach (eg, telemedicine-enabled shared appointments) and sustainability are needed.Trial registration:ClinicalTrials.gov Identifier: NCT01876485.

Primary Outcome Measures is Changes in Percent Glycosylated Hemoglobin (HbA1c) Levels During Intervention; Extracted Interventionsis is Empowering Patients in Chronic Care (EPIC) Enhanced Usual Care (EUC); Conditions is Diabetes Mellitus ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Evaluation of multiple micronutrient supplementation and medium-quantity lipid-based nutrient supplementation in pregnancy on child development in rural Niger: A secondary analysis of a cluster randomized controlled trial.Background:It is estimated that over 250 million children under 5 years of age in low- and middle-income countries (LMICs) do not reach their full developmental potential. Poor maternal diet, anemia, and micronutrient deficiencies during pregnancy are associated with suboptimal neurodevelopmental outcomes in children. However, the effect of prenatal macronutrient and micronutrient supplementation on child development in LMIC settings remains unclear due to limited evidence from randomized trials.Methods and findings:We conducted a 3-arm cluster-randomized trial (n = 53 clusters) that evaluated the efficacy of (1) prenatal multiple micronutrient supplementation (MMS; n = 18 clusters) and (2) lipid-based nutrient supplementation (LNS; n = 18 clusters) as compared to (3) routine iron-folic acid (IFA) supplementation (n = 17 clusters) among pregnant women in the rural district of Madarounfa, Niger, from March 2015 to August 2019 (ClinicalTrials.gov identifier NCT02145000). Children were followed until 2 years of age, and the Bayley Scales of Infant and Toddler Development III (BSID-III) were administered to children every 3 months from 6 to 24 months of age. Maternal report of WHO gross motor milestone achievement was assessed monthly from 3 to 24 months of age. An intention-to-treat analysis was followed. Child BSID-III data were available for 559, 492, and 581 singleton children in the MMS, LNS, and IFA groups, respectively. Child WHO motor milestone data were available for 691, 781, and 753 singleton children in the MMS, LNS, and IFA groups, respectively. Prenatal MMS had no effect on child BSID-III cognitive (standardized mean difference [SMD]: 0.21; 95% CI: -0.20, 0.62; p = 0.32), language (SMD: 0.16; 95% CI: -0.30, 0.61; p = 0.50) or motor scores (SMD: 0.18; 95% CI: -0.39, 0.74; p = 0.54) or on time to achievement of the WHO gross motor milestones as compared to IFA. Prenatal LNS had no effect on child BSID-III cognitive (SMD: 0.17; 95% CI: -0.15, 0.49; p = 0.29), language (SMD: 0.11; 95% CI: -0.22, 0.44; p = 0.53) or motor scores (SMD: -0.04; 95% CI: -0.46, 0.37; p = 0.85) at the 24-month endline visit as compared to IFA. However, the trajectory of BSID-III cognitive scores during the first 2 years of life differed between the groups with children in the LNS group having higher cognitive scores at 18 and 21 months (approximately 0.35 SD) as compared to the IFA group (p-value for difference in trajectory <0.001). Children whose mothers received LNS also had earlier achievement of sitting alone (hazard ratio [HR]: 1.57; 95% CI: 1.10 to 2.24; p = 0.01) and walking alone (1.52; 95% CI: 1.14 to 2.03; p = 0.004) as compared to IFA, but there was no effect on time to achievement of other motor milestones. A limitation of our study is that we assessed child development up to 2 years of age, and, therefore, we may have not captured effects that are easier to detect or emerge at older ages.Conclusions:There was no benefit of prenatal MMS on child development outcomes up to 2 years of age as compared to IFA. There was evidence of an apparent positive effect of prenatal LNS on cognitive development trajectory and time to achievement of selected gross motor milestones.Trial registration:ClinicalTrials.gov NCT02145000.

Primary Outcome Measures is Laboratory-confirmed episode of severe rotavirus gastroenteritis; Extracted Interventionsis is Rotavirus vaccine (BRV-PV) Placebo; Conditions is Severe Rotavirus Gastroenteritis ;Sex is ALL ;Age is CHILD

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Demographic and Clinical Characteristics Associated With the Failure of Nonoperative Management of Uncomplicated Appendicitis in Children: Secondary Analysis of a Nonrandomized Clinical Trial.Importance:The factors associated with the failure of nonoperative management of appendicitis and the differences in patient-reported outcomes between successful and unsuccessful nonoperative management remain unknown.Objectives:To investigate factors associated with the failure of nonoperative management of appendicitis and compare patient-reported outcomes between patients whose treatment succeeded and those whose treatment failed.Design, setting, and participants:This study was a planned subgroup secondary analysis conducted in 10 children's hospitals that included 370 children aged 7 to 17 years with uncomplicated appendicitis enrolled in a prospective, nonrandomized clinical trial between May 1, 2015, and October 31, 2018, with 1-year follow-up comparing nonoperative management with antibiotics vs surgery for uncomplicated appendicitis. Statistical analysis was performed from November 1, 2019, to February 12, 2022.Interventions:Nonoperative management with antibiotics vs surgery.Main outcomes and measures:Failure of nonoperative management and patient-reported outcomes. The relative risk (RR) of failure based on sociodemographic and clinical characteristics was calculated. Patient-reported outcomes were compared based on the success or failure of nonoperative management.Results:Of 370 patients (34.6% of 1068 total patients; 229 boys [61.9%]; median age, 12.3 years [IQR, 10.0-14.6 years]) enrolled in the nonoperative group, treatment failure occurred for 125 patients (33.8%) at 1 year, with 53 patients (14.3%) undergoing appendectomy during initial hospitalization and 72 patients (19.5%) experiencing delayed treatment failure after hospital discharge. Higher patient-reported pain at presentation was associated with increased risk of in-hospital treatment failure (RR, 2.1 [95% CI, 1.0-4.4]) but not delayed treatment failure (RR, 1.3 [95% CI, 0.7-2.3]) or overall treatment failure at 1 year (RR, 1.5 [95% CI, 1.0-2.2]). Pain duration greater than 24 hours was associated with decreased risk of delayed treatment failure (RR, 0.3 [95% CI, 0.1-1.0]) but not in-hospital treatment failure (RR, 1.2 [95% CI, 0.5-2.7]) or treatment failure at 1 year (RR, 0.7 [95% CI, 0.4-1.2]). There was no increased risk of treatment failure associated with age, white blood cell count, sex, race, ethnicity, primary language, insurance status, transfer status, symptoms at presentation, or imaging results. Health care satisfaction at 30 days and patient-reported, health-related quality of life at 30 days and 1 year were not different. Satisfaction with the decision was higher with successful nonoperative management at 30 days (28.0 vs 27.0; difference, 1.0 [95% CI, 0.01-2.0]) and 1 year (28.1 vs 27.0; difference, 1.1 [95% CI, 0.2-2.0]).Conclusions and relevance:This analysis suggests that a higher pain level at presentation was associated with a higher risk of initial failure of nonoperative management and that a longer duration of pain was associated with lower risk of delayed treatment failure. Although satisfaction was high in both groups, satisfaction with the treatment decision was higher among patients with successful nonoperative management at 1 year.Trial registration:ClinicalTrials.gov Identifier: NCT02271932.

Primary Outcome Measures is Success rate; Extracted Interventionsis is Non-operative; Conditions is Appendicitis ;Sex is MALE ;Age is CHILD

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Oral hymecromone decreases hyaluronan in human study participants.BACKGROUNDHyaluronan (HA), an extracellular matrix glycosaminoglycan, has been implicated in the pathophysiology of COVID-19 infection, pulmonary hypertension, pulmonary fibrosis, and other diseases, but is not targeted by any approved drugs. We asked whether hymecromone (4-methylumbelliferone [4-MU]), an oral drug approved in Europe for biliary spasm treatment that also inhibits HA in vitro and in animal models, could be repurposed as an inhibitor of HA synthesis in humans.METHODSWe conducted an open-label, single-center, dose-response study of hymecromone in healthy adults. Subjects received hymecromone at 1200 (n = 8), 2400 (n = 9), or 3600 (n = 9) mg/d divided into 3 doses daily, administered orally for 4 days. We assessed safety and tolerability of hymecromone and analyzed HA, 4-MU, and 4-methylumbelliferyl glucuronide (4-MUG; the main metabolite of 4-MU) concentrations in sputum and serum.RESULTSHymecromone was well tolerated up to doses of 3600 mg/d. Both sputum and serum drug concentrations increased in a dose-dependent manner, indicating that higher doses lead to greater exposures. Across all dose arms combined, we observed a significant decrease in sputum HA from baseline after 4 days of treatment. We also observed a decrease in serum HA. Additionally, higher baseline sputum HA levels were associated with a greater decrease in sputum HA.CONCLUSIONAfter 4 days of exposure to oral hymecromone, healthy human subjects experienced a significant reduction in sputum HA levels, indicating this oral therapy may have potential in pulmonary diseases where HA is implicated in pathogenesis.TRIAL REGISTRATIONClinicalTrials.gov NCT02780752.FUNDINGStanford Medicine Catalyst, Stanford SPARK, Stanford Innovative Medicines Accelerator program, NIH training grants 5T32AI052073-14 and T32HL129970.

Primary Outcome Measures is Change in sputum hyaluronan concentration over the study period; Extracted Interventionsis is hymecromone; Conditions is Healthy|Respiratory Disease ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non-small Cell Lung Cancer in the Global Phase III ALEX Trial.Purpose:We retrospectively assessed prognostic value of circulating cell-free DNA (cfDNA) using data from the phase III ALEX study in treatment-naïve, advanced ALK+ non-small cell lung cancer (NSCLC).Patients and methods:Patients were randomized to receive twice-daily alectinib 600 mg (n = 152) or crizotinib 250 mg (n = 151). cfDNA was quantified from baseline plasma samples, with patients stratified into ≤median and >median cfDNA biomarker-evaluable populations (BEP). Effect of cfDNA concentration on outcomes was analyzed using a Cox regression model with treatment group as covariate, and in multivariate analyses.Results:Median cfDNA concentration in the BEP was 11.53 ng/mL (n = 276). A positive correlation was found between cfDNA concentration and number of lesions, organ lesion sites, and tumor size (sum of longest diameter; all P < 0.0001). In both treatment arms, patients in the >median BEP were more likely to experience disease progression than the ≤median BEP [alectinib adjusted HR = 2.04; 95% confidence interval (CI), 1.07-3.89; P = 0.0305 and crizotinib adjusted HR = 1.83; 95% CI, 1.11-3.00, P = 0.0169]. Median progression-free survival was longer with alectinib than crizotinib in both ≤median and >median BEPs (P < 0.0001). Overall survival data remain immature; survival probability was lower in the >median versus ≤median BEP in both treatment arms (alectinib HR = 2.52; 95% CI, 1.08-5.88; P = 0.0333 and crizotinib HR = 2.63; 95% CI, 1.27-5.47; P = 0.0096).Conclusions:These data suggest that plasma cfDNA concentration may have prognostic value in advanced ALK+ NSCLC. Prospectively designed studies are warranted to investigate this finding.

Primary Outcome Measures is Progression-Free Survival (PFS) by Investigator Assessment; Extracted Interventionsis is Alectinib Crizotinib; Conditions is Non-Small Cell Lung Cancer ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Dose Escalation Data from the Phase 1 Study of the Liposomal Formulation of Eribulin (E7389-LF) in Japanese Patients with Advanced Solid Tumors.Purpose:We report the dose-escalation part of a phase I study of liposomal eribulin (E7389-LF) in Japanese patients with advanced solid tumors and no alternative standard therapy.Patients and methods:Patients ≥20 years old were enrolled. E7389-LF doses of 1.0 to 1.5 mg/m2 once every two weeks (Q2W) or 1.0 to 2.5 mg/m2 once every three weeks (Q3W) were planned. The primary objective was to determine the MTD by evaluating dose-limiting toxicities (DLT). Secondary objectives included safety/tolerability assessments, objective response rate (ORR), and progression-free survival; serum biomarker assessment was an exploratory objective.Results:Twenty-one patients were enrolled and treated; 12 in the Q3W group (1.0 mg/m2, n = 3; 1.5 mg/m2, n = 3; 2.0 mg/m2, n = 6) and 9 in the Q2W group (1.0 mg/m2, n=3; 1.5 mg/m2, n = 6). The Q3W and Q2W MTDs were 2.0 mg/m2 and 1.5 mg/m2, respectively. One patient receiving 2.0 mg/m2 Q3W had a DLT of grade 3 febrile neutropenia. The most common grade 3 treatment-emergent adverse events were neutropenia (66.7% in Q3W and Q2W) and leukopenia (Q3W, 58.3%; Q2W, 33.3%). One patient in the Q3W group (2.0 mg/m2) and 3 in the Q2W group (1.0 mg/m2, n = 1; 1.5 mg/m2, n = 2) achieved a partial response [overall ORR, 19.0%; 95% confidence interval (CI), 5.4-41.9]. Endothelial [TEK receptor tyrosine kinase (TEK), intercellular adhesion molecule 1 (ICAM1), vascular endothelial growth factor receptor 3 (VEGFR3), platelet/endothelial cell adhesion molecule 1 (PECAM1)], vasculature (collagen IV), and immune-related [interferon gamma (IFNγ), C-X-C motif chemokine ligand 11 (CXCL11), C-X-C motif chemokine ligand 10 (CXCL10)] biomarker levels were increased.Conclusions:E7389-LF was well tolerated at 2.0 mg/m2 Q3W and 1.5 mg/m2 Q2W. Considering the toxicity profile of both regimens, the recommended dose was 2.0 mg/m2 Q3W. Expansion cohorts are ongoing.

Primary Outcome Measures is Maximum tolerated dose (MTD) of E7389 liposomal formulation (E7389-LF); Extracted Interventionsis is E7389-LF; Conditions is Solid Tumor ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Preclinical Characterization and Phase I Trial Results of a Bispecific Antibody Targeting PD-L1 and 4-1BB (GEN1046) in Patients with Advanced Refractory Solid Tumors.Checkpoint inhibitors (CPI) have revolutionized the treatment paradigm for advanced solid tumors; however, there remains an opportunity to improve response rates and outcomes. In preclinical models, 4-1BB costimulation synergizes with CPIs targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis by activating cytotoxic T-cell-mediated antitumor immunity. DuoBody-PD-L1×4-1BB (GEN1046) is an investigational, first-in-class bispecific immunotherapy agent designed to act on both pathways by combining simultaneous and complementary PD-L1 blockade and conditional 4-1BB stimulation in one molecule. GEN1046 induced T-cell proliferation, cytokine production, and antigen-specific T-cell-mediated cytotoxicity superior to clinically approved PD-(L)1 antibodies in human T-cell cultures and exerted potent antitumor activity in transplantable mouse tumor models. In dose escalation of the ongoing first-in-human study in heavily pretreated patients with advanced refractory solid tumors (NCT03917381), GEN1046 demonstrated pharmacodynamic immune effects in peripheral blood consistent with its mechanism of action, manageable safety, and early clinical activity [disease control rate: 65.6% (40/61)], including patients resistant to prior PD-(L)1 immunotherapy.Significance:DuoBody-PD-L1×4-1BB (GEN1046) is a first-in-class bispecific immunotherapy with a manageable safety profile and encouraging preclinical and early clinical activity. With its ability to confer clinical benefit in tumors typically less sensitive to CPIs, GEN1046 may fill a clinical gap in CPI-relapsed or refractory disease or as a combination therapy with CPIs. See related commentary by Li et al., p. 1184. This article is highlighted in the In This Issue feature, p. 1171.

Primary Outcome Measures is Dose limiting toxicity (DLT); Extracted Interventionsis is Acasunlimab Acasunlimab in combination with docetaxel (in a single expansion cohort) Acasunlimab in combination with pembrolizumab (in a separate expansion cohort) Acasunlimab in combination with pembrolizumab and standard chemotherapy (in separate expansion cohorts); Conditions is Solid Tumors|Non-small Cell Lung Cancer|Urothelial Carcinoma|Endometrial Carcinoma|Triple Negative Breast Cancer|Squamous Cell Carcinoma of the Head and Neck|Cervical Cancer ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Phase II Study of ONC201 in Neuroendocrine Tumors including Pheochromocytoma-Paraganglioma and Desmoplastic Small Round Cell Tumor.Purpose:Tumor dopamine-like DRD2 receptor expression is higher in pheochromocytoma-paraganglioma (PC-PG) compared with other cancers. ONC201 is a bitopic DRD2 antagonist with preclinical ONC201 activity in desmoplastic small round cell tumor (DSRCT).Patients and methods:Patients (N = 30) with neuroendocrine tumors were treated on this investigator-initiated trial (NCT03034200). ONC201 dose and schedule were 625 mg orally weekly in cohorts A (PC-PG) + B (other neuroendocrine tumors) and 625 mg orally on 2 consecutive days each week in cohort C, which included 5 responding patients. The primary endpoint was radiographic response measured using RECIST. Secondary endpoints included progression-free survival, overall survival, and safety.Results:In arm A (n = 10; all PC-PG), 50% (5/10) exhibited a partial response (PR) and 2 additional patients had stable disease (SD) >3 months. Median duration of therapy for arm A patients was 9 months (range: 1.5-33 months) with 5 patients treated >1 year. In arm B (n = 12), there were 1 PR (DSRCT) and 2 SD (DSRCT; neuroblastoma) >3 months. Median duration of therapy in arm A was 18 months (range: 1-33 months) and arm B was 3 months (range: 1.5-33 months). Arm C PC-PG (N = 8) showed 1 PR and 7 SD at 3 months, with median duration of therapy >10 months. There was no decline in Karnofsky performance status at week 12 for 28 of 30 patients and no dose modification due to treatment-related adverse events.Conclusions:Oral ONC201 was well tolerated in patients with metastatic neuroendocrine tumors and associated with clinical benefit, including tumor responses, particularly in some patients with DSRCT and the majority of patients with PC-PG. See related commentary by Owen and Trikalinos, p. 1748.

Primary Outcome Measures is Tumor response according to RECIST Criteria; Extracted Interventionsis is ONC201; Conditions is Recurrent Neuroendocrine Tumor|Metastatic Neuroendocrine Tumor ;Sex is ALL ;Age is CHILD, ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Evaluating the Effect of a COVID-19 Predictive Model to Facilitate Discharge: A Randomized Controlled Trial.Background:We previously developed and validated a predictive model to help clinicians identify hospitalized adults with coronavirus disease 2019 (COVID-19) who may be ready for discharge given their low risk of adverse events. Whether this algorithm can prompt more timely discharge for stable patients in practice is unknown.Objectives:The aim of the study is to estimate the effect of displaying risk scores on length of stay (LOS).Methods:We integrated model output into the electronic health record (EHR) at four hospitals in one health system by displaying a green/orange/red score indicating low/moderate/high-risk in a patient list column and a larger COVID-19 summary report visible for each patient. Display of the score was pseudo-randomized 1:1 into intervention and control arms using a patient identifier passed to the model execution code. Intervention effect was assessed by comparing LOS between intervention and control groups. Adverse safety outcomes of death, hospice, and re-presentation were tested separately and as a composite indicator. We tracked adoption and sustained use through daily counts of score displays.Results:Enrolling 1,010 patients from May 15, 2020 to December 7, 2020, the trial found no detectable difference in LOS. The intervention had no impact on safety indicators of death, hospice or re-presentation after discharge. The scores were displayed consistently throughout the study period but the study lacks a causally linked process measure of provider actions based on the score. Secondary analysis revealed complex dynamics in LOS temporally, by primary symptom, and hospital location.Conclusion:An AI-based COVID-19 risk score displayed passively to clinicians during routine care of hospitalized adults with COVID-19 was safe but had no detectable impact on LOS. Health technology challenges such as insufficient adoption, nonuniform use, and provider trust compounded with temporal factors of the COVID-19 pandemic may have contributed to the null result.Trial registration:ClinicalTrials.gov identifier: NCT04570488.

Primary Outcome Measures is Reduction in days from first low-risk score to discharge; Extracted Interventionsis is EPIC risk score display; Conditions is COVID|Corona Virus Infection|Adverse Event ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Cobimetinib in Pediatric and Young Adult Patients with Relapsed or Refractory Solid Tumors (iMATRIX-cobi): A Multicenter, Phase I/II Study.Background:The MAPK pathway is an emerging target across a number of adult and pediatric tumors. Targeting the downstream effector of MAPK, MEK1, is a proposed strategy to control the growth of MAPK-dependent tumors.Objective:iMATRIX-cobi assessed the safety, pharmacokinetics, and anti-tumor activity of cobimetinib, a highly selective MEK inhibitor, in children and young adults with relapsed/refractory solid tumors.Patients and methods:This multicenter Phase I/II study enrolled patients aged 6 months to < 30 years with solid tumors with known/expected MAPK pathway involvement. Patients received cobimetinib tablet or suspension formulation on Days 1-21 of a 28-day cycle. Dose escalation followed a rolling 6 design. The primary endpoint was safety; secondary endpoints were pharmacokinetics and anti-tumor activity.Results:Of 56 enrolled patients (median age 9 years [range 3-29]), 18 received cobimetinib tablets and 38 cobimetinib suspension. Most common diagnoses were low-grade glioma (LGG; n = 32, including n = 12 in the expansion cohort) and plexiform neurofibroma within neurofibromatosis type 1 (n = 12). Six patients (11 %) experienced dose-limiting toxicities (including five ocular toxicity events), which established a pediatric recommended Phase II dose (RP2D) of 0.8 mg/kg tablet and 1.0 mg/kg suspension. Most frequently reported treatment-related adverse events were gastrointestinal and skin disorders. Steady state mean exposure (Cmax, AUC0-24) of cobimetinib at the RP2D (1.0 mg/kg suspension) was ~ 50 % lower than in adults receiving the approved 60 mg/day dose. Overall response rate was 5.4 % (3/56; all partial responses in patients with LGG).Conclusions:The safety profile of cobimetinib in pediatrics was similar to that reported in adults. Clinical activity was observed in LGG patients with known/suspected MAPK pathway activation. Cobimetinib combination regimens may be required to improve response rates in this pediatric population.Clinical trial registration:ClinicalTrials.gov NCT02639546, registered December 24, 2015.

Primary Outcome Measures is Percentage of Participants With Dose-Limiting Toxicities (DLTs); Extracted Interventionsis is Cobimetinib; Conditions is Solid Tumors ;Sex is ALL ;Age is CHILD, ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.The efficacy and safety of tacrolimus and entecavir combination therapy in the treatment of hepatitis B virus-associated glomerulonephritis: a multi-center, placebo controlled, and single-blind randomized trial.Background:The proteinuria remission in hepatitis B virus-associated glomerulonephritis (HBV-GN) patients with massive proteinuria treated with antiviral therapy was low. Tacrolimus (TAC) is effective in primary nephropathy and can inhibit HBV infection by inhibiting HBV binding to sodium taurocholate cotransporting polypeptide on liver cells. This study evaluated the efficacy and safety of TAC combined with ETV compared with entecavir (ETV) monotherapy in HBV-GN.Methods:Patients diagnosed with HBV-GN were recruited for this prospective, randomized, controlled, multicenter, single-blinded study in China. Patients were given TAC and ETV therapy (the TAC+ETV group) or placebo and ETV therapy (the ETV group) for 26 weeks. The efficacy endpoints included proteinuria remission, including complete and partial remission (CR and PR), the change of 24-hour proteinuria (24 h UP) and HBV DNA titer. The safety endpoints were the incidence of HBV virologic breakthrough and adverse events.Results:There were 14 patients in the TAC+ETV group and 17 patients in the ETV group. In the intention-to-treat analyses, 64.3% (9/14) of patients in the TAC+ETV group and 58.8% (10/17) in the ETV group achieved PR or CR at 26 weeks (P=0.38). At week 14, 42.9% (6/14) and 41.2% (7/17) of patients in the TAC+ETV group and the ETV group, respectively, achieved PR or CR (P=0.23). At week 26, the 24 h UP had decreased by 2.63±6.33 g from baseline in the TAC+ETV group and 1.42±4.34 g in the ETV group (P=0.55). The serum albumin increased by 11.1±7.30 g/L from baseline in the TAC+ETV group and 3.81±5.09 g/L in the ETV group (P<0.001). Log10 HBV DNA decreased by 1.49±2.04 from baseline in the TAC+ETV group and 2.47±2.08 in the ETV group (P=0.37); 28.6% (4/14) patients had HBV DNA virologic breakthrough in the ETV group, while none in the TAC+ETV group (P=0.29).Conclusions:In adult HBV-GN patients, TAC and ETV combination therapy may significantly improve serum albumin levels without increasing the risk of HBV reactivation compared with entecavir monotherapy.Trial registration:ClinicalTrials.gov Identifier NCT03062813.

Primary Outcome Measures is Remission rate of proteinuria; Extracted Interventionsis is Tacrolimus &entecavir placebo & entecavir; Conditions is Hepatitis B Virus Associated Nephrotic Syndrome ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of Face-Down Positioning vs Support-the-Break Positioning After Macula-Involving Retinal Detachment Repair: The PostRD Randomized Clinical Trial.Importance:A lack of consensus exists with regard to the optimal positioning regimen for patients after macula-involving retinal detachment (RD) repair.Objective:To evaluate the effect of face-down positioning vs support-the-break positioning on retinal displacement and distortion after macula-involving RD repair.Design, setting, and participants:A prospective 6-month single-masked randomized clinical trial was conducted at a multicenter tertiary referral setting from May 16, 2016, to May 1, 2018. Inclusion criteria were fovea-involving rhegmatogenous RD; central visual loss within 14 days; patients undergoing primary vitrectomy and gas surgery, under local anesthetic; patients able to give written informed consent; and 18 years old and older. Analysis was conducted following a modified intention-to-treat principle, with patients experiencing a redetachment or failure to attach the macula being excluded from analysis.Interventions:Participants were randomized 1:1 to receive face-down positioning or support-the-break positioning for a 24-hour period postoperatively. Positioning compliance was not monitored.Main outcomes and measures:The proportion of patients with retinal displacement on autofluorescence imaging at 6 months postoperatively. Secondary outcomes included proportion of patients with displacement at 2 months; amplitude of displacement at 2 and 6 months; corrected Early Treatment Diabetic Retinopathy Study visual acuity; objective Distortion Scores; and quality of life questionnaire scores at 6 months.Results:Of the 262 randomized patients, 239 were analyzed (171 male [71.5%]; mean [SD] age, 60.8 [9.8] years). At 6 months, retinal displacement was detected in 42 of 100 (42%) in the face-down positioning group vs 58 of 103 (56%) in the support-the-break positioning group (odds ratio, 1.77; 95%CI, 1.01-3.11; P = .04). The degree of displacement was lower in the face-down group. Groups were similar in corrected visual acuity (face-down, 74 letters vs support-the-break, 75 letters), objective D Chart Distortion Scores (range: 0, no distortion to 41.6, severe distortion; with face-down at 4.5 vs support-the-break at 4.2), and quality of life scores (face-down 89.3 vs support-the-break 89.0) at 2 and 6 months. Retinal redetachment rate was similar in both groups (face-down group, 12.2% and support-the-break group, 13.7%). Retinal folds were less common in the face-down positioning group vs the support-the-break positioning group (5.3% vs 13.5%, respectively; odds ratio, 2.8; 95% CI, 1.2-7.4; P = .03). Binocular diplopia was more common in the support-the-break group compared with the face-down positioning group (7.6% vs 1.5%, respectively; odds ratio, 5.3; 95% CI, 1.3-24.6; P = .03). Amplitude of displacement was associated with worse visual acuity (r = -0.5; P < .001) and distortion (r = 0.28; P = .008).Conclusions and relevance:In this study, findings suggest that face-down positioning was associated with a reduction in the rate and amplitude of postoperative retinal displacement after macula-involving RD repair and with a reduction in binocular diplopia. No association was found with visual acuity or postoperative distortion.Trial registration:ClinicalTrials.gov Identifier: NCT02748538.

Primary Outcome Measures is To assess the proportion of patients in each treatment group with retinal displacement at 26 weeks after surgery; Extracted Interventionsis is nan; Conditions is Retinal Detachment ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Negative Pressure Wound Therapy vs Conventional Wound Treatment in Subcutaneous Abdominal Wound Healing Impairment: The SAWHI Randomized Clinical Trial.Importance:Negative pressure wound therapy (NPWT) is an established treatment option, but there is no evidence of benefit for subcutaneous abdominal wound healing impairment (SAWHI).Objective:To evaluate the effectiveness and safety of NPWT for SAWHI after surgery in clinical practice.Design, setting, and participants:The multicenter, multinational, observer-blinded, randomized clinical SAWHI study enrolled patients between August 2, 2011, and January 31, 2018. The last follow-up date was June 11, 2018. The trial included 34 abdominal surgical departments of hospitals in Germany, Belgium, and the Netherlands, and 539 consecutive, compliant adult patients with SAWHI after surgery without fascia dehiscence were randomly assigned to the treatment arms in a 1:1 ratio stratified by study site and wound size using a centralized web-based tool. A total of 507 study participants (NPWT, 256; CWT, 251) were assessed for the primary end point in the modified intention-to-treat (ITT) population.Interventions:Negative pressure wound therapy and conventional wound treatment (CWT).Main outcomes and measures:The primary outcome was time until wound closure (delayed primary closure or by secondary intention) within 42 days. Safety analysis comprised the adverse events (AEs). Secondary outcomes included wound closure rate, quality of life (SF-36), pain, and patient satisfaction.Results:Of the 507 study participants included in the modified ITT population, 287 were men (56.6%) (NPWT, 155 [60.5%] and CWT, 132 [52.6%]) and 220 were women (43.4%) (NPWT, 101 [39.5%] and CWT 119 [47.4%]). The median (IQR) age of the participants was 66 (18) years in the NPWT arm and 66 (20) years in the CWT arm. Mean time to wound closure was significantly shorter in the NPWT arm (36.1 days) than in the CWT arm (39.1 days) (difference, 3.0 days; 95% CI 1.6-4.4; P < .001). Wound closure rate within 42 days was significantly higher with NPWT (35.9%) than with CWT (21.5%) (difference, 14.4%; 95% CI, 6.6%-22.2%; P < .001). In the therapy-compliant population, excluding study participants with unauthorized treatment changes (NPWT, 22; CWT, 50), the risk for wound-related AEs was higher in the NPWT arm (risk ratio, 1.51; 95% CI, 0.99-2.35).Conclusions and relevance:Negative pressure wound therapy is an effective treatment option for SAWHI after surgery; however, it causes more wound-related AEs.Trial registration:ClinicalTrials.gov Identifier: NCT01528033.

Primary Outcome Measures is Time to Complete Wound Closure; Extracted Interventionsis is Vacuum Assisted Closure® Standard conventional wound therapy; Conditions is Wound Healing Disorder|Impaired Wound Healing|Abdominal Wound Healing Disorder|Abdominal Wound Healing Impairment|Acute Postsurgical Subcutaneous Wound ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Evaluation of Ixekizumab Treatment for Patients With Pityriasis Rubra Pilaris: A Single-Arm Trial.Importance:Pityriasis rubra pilaris is a rare and disabling cutaneous disease that is frequently recalcitrant to conventional therapies and appears to involve interleukin (IL)-17 overexpression.Objective:To investigate the clinical response and safety of ixekizumab in treating pityriasis rubra pilaris.Design, setting, and participants:Single-arm, investigator-initiated trial conducted in adult patients with moderate to severe pityriasis rubra pilaris at a single-center academic university from June 2018 to January 2020. A total of 41 patients were screened, 12 were enrolled, and 11 completed the full duration of therapy. A referred, consecutive sample was used during participant selection. The treatment period and primary outcome occurred over 24 weeks with additional patient follow-up through 36 weeks.Intervention:Subcutaneous administration of ixekizumab, a humanized IgG4 antibody that binds IL-17A, at the US Food and Drug Administration-approved dosing schedule for treatment of psoriasis for 24 weeks.Main outcomes and measures:The primary outcome was the mean change in Psoriasis Area and Severity Index at 24 weeks. Secondary outcomes included change in affected body surface area, quality of life, induction of sustained remission, and association of improvement with CARD14 genetic variations and cutaneous cytokine expression.Results:A total of 12 white patients (mean [SD] age, 49.8 [15.1] years; 8 male [67%]) were enrolled between June 2018 and April 2019, with 11 completing the full course of intervention. The mean (SEM) improvements in Psoriasis Area and Severity Index, affected body surface area, and Dermatology Life Quality Index were 15.2 (2.1) (P < .0001), 29.8% (9.3%) (P = .009), and 9.5 (2.5) (P = .004), respectively. The 4 participants with the most improvement in Psoriasis Area and Severity Index at week 24 stayed in remission at week 36 (defined as lack of increase in Psoriasis Area and Severity Index from week 24 through week 36), off therapy. Relative dermal IL-17A expression decreased by a 1.9 log-fold change. No participants had known pathogenic CARD14 variations. There were no serious adverse events.Conclusions and relevance:In this single-armed trial, ixekizumab was associated with reduced clinical signs and symptoms of pityriasis rubra pilaris in a subset of patients, including those in whom other systemic therapies have failed.Trial registration:ClinicalTrials.gov Identifier: NCT03485976.

Primary Outcome Measures is Clinical Improvement in PRP Severity and Body Surface Area; Extracted Interventionsis is Ixekizumab; Conditions is Pityriasis Rubra Pilaris ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Efficacy and Safety of Pembrolizumab Plus Docetaxel vs Docetaxel Alone in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer: The PROLUNG Phase 2 Randomized Clinical Trial.Importance:Because of socioeconomic factors, many patients with advanced non-small cell lung cancer (NSCLC) do not receive immunotherapy in the first-line setting. It is unknown if the combination of immunotherapy with chemotherapy can provide clinical benefits in immunotherapy-naive patients with disease progression after treatment with platinum-based chemotherapy.Objective:To evaluate the safety and efficacy of the combination of pembrolizumab plus docetaxel in patients with previously treated advanced NSCLC following platinum-based chemotherapy regardless of EGFR variants or programmed cell death ligand 1 status.Design, setting, and participants:The Pembrolizumab Plus Docetaxel for Advanced Non-Small Cell Lung Cancer (PROLUNG) trial randomized 78 patients with histologically confirmed advanced NSCLC in a 1:1 ratio to receive either pembrolizumab plus docetaxel or docetaxel alone from December 2016 through May 2019.Interventions:The experimental arm received docetaxel on day 1 (75 mg/m2) plus pembrolizumab on day 8 (200 mg) every 3 weeks for up to 6 cycles followed by pembrolizumab maintenance until progression or unacceptable toxic effects. The control arm received docetaxel monotherapy.Main outcomes and measures:The primary end point was overall response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival, and safety.Results:Among 78 recruited patients, 32 (41%) were men, 34 (44%) were never smokers, and 25 (32%) had an EGFR/ALK alteration. Forty patients were allocated to receive pembrolizumab plus docetaxel, and 38 were allocated to receive docetaxel. A statistically significant difference in ORR, assessed by an independent reviewer, was found in patients receiving pembrolizumab plus docetaxel vs patients receiving docetaxel (42.5% vs 15.8%; odds ratio, 3.94; 95% CI, 1.34-11.54; P = .01). Patients without EGFR variations had a considerable difference in ORR of 35.7% vs 12.0% (P = .06), whereas patients with EGFR variations had an ORR of 58.3% vs 23.1% (P = .14). Overall, PFS was longer in patients who received pembrolizumab plus docetaxel (9.5 months; 95% CI, 4.2-not reached) than in patients who received docetaxel (3.9 months; 95% CI, 3.2-5.7) (hazard ratio, 0.24; 95% CI, 0.13-0.46; P < .001). For patients without variations, PFS was 9.5 months (95% CI, 3.9-not reached) vs 4.1 months (95% CI, 3.5-5.3) (P < .001), whereas in patients with EGFR variations, PFS was 6.8 months (95% CI, 6.2-not reached) vs 3.5 months (95% CI, 2.3-6.2) (P = .04). In terms of safety, 23% (9 of 40) vs 5% (2 of 38) of patients experienced grade 1 to 2 pneumonitis in the pembrolizumab plus docetaxel and docetaxel arms, respectively (P = .03), while 28% (11 of 40) vs 3% (1 of 38) experienced any-grade hypothyroidism (P = .002). No new safety signals were identified.Conclusions and relevance:In this phase 2 study, the combination of pembrolizumab plus docetaxel was well tolerated and substantially improved ORR and PFS in patients with advanced NSCLC who had previous progression after platinum-based chemotherapy, including NSCLC with EGFR variations.Trial registration:ClinicalTrials.gov Identifier: NCT02574598.

Primary Outcome Measures is Overall Response Rate; Extracted Interventionsis is MK-3475 Docetaxel; Conditions is Carcinoma, Non-Small-Cell Lung ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Comparative pharmacokinetics of a montelukast/levocetirizine fixed-dose combination chewable tablet versus individual administration of montelukast and levocetirizine after a single oral administration in healthy Korean male subjects.Objective:Asthma patients often have co-existing symptoms of allergic rhinitis and are often prescribed with both asthma and rhinitis treatments such as montelukast and levocetirizine. The objective of this study was to compare the pharmacokinetic profiles of a montelukast/levocetirizine fixed-dose combination chewable tablet with individual administration of montelukast and levocetirizine in healthy subjects.Materials and methods:A randomized, open-label, single-dose crossover study was conducted in healthy male subjects. One of the following treatments was administered in each period: co-administration of 1 chewable tablet of montelukast 5 mg and 1 tablet of levocetirizine 5 mg or administration of 1 chewable tablet of montelukast/levocetirizine 5/5 mg fixed-dose combination. Serial blood samples were collected up to 48 hours post dose. Plasma drug concentrations were measured by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters, including maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from dosing to the last measurable concentration (AUClast), were determined by non-compartmental analysis. The geometric least-square mean (GLSM) ratios and associated 90% confidence intervals (CIs) of Cmax and AUClast were calculated to evaluate pharmacokinetic equivalence.Results:A total of 22 subjects were included in pharmacokinetic analysis. The GLSM ratios and 90% CIs of Cmax and AUClast were 1.0054 (0.9535 - 1.0601) and 1.0628 (1.0013 - 1.1281) for montelukast and 1.0105 (0.9488 - 1.0764) and 1.0396 (0.9935 - 1.0879) for levocetirizine, respectively.Conclusion:The pharmacokinetic parameters of montelukast and levocetirizine when administered as separate tablets or as a fixed-dose combination were compared, and the parameters met the pharmacokinetic equivalence criteria. (ClinicalTrials.gov Identifier: NCT03371849).

Primary Outcome Measures is AUClast of Montelukast; Extracted Interventionsis is montelukast and levocetirizine FDC Singulair + xyzal; Conditions is Healthy ;Sex is MALE ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Efficacy and Safety of Continuous Risankizumab Therapy vs Treatment Withdrawal in Patients With Moderate to Severe Plaque Psoriasis: A Phase 3 Randomized Clinical Trial.Importance:Risankizumab selectively inhibits interleukin 23, a cytokine that contributes to psoriatic inflammation.Objective:To evaluate the efficacy and safety of risankizumab vs placebo and continuous treatment vs withdrawal in adults with moderate to severe plaque psoriasis.Design, setting, and participants:Multinational, phase 3, randomized, double-blind, placebo-controlled trial conducted from March 6, 2016, to July 26, 2018. A total of 507 eligible patients had stable moderate to severe chronic plaque psoriasis for 6 months or longer, body surface area involvement greater than or equal to 10%, Psoriasis Area and Severity Index (PASI) greater than or equal to 12, and a static Physician's Global Assessment (sPGA) score greater than or equal to 3. Intention-to-treat analysis was conducted.Interventions:Patients were randomized (4:1, interactive response technology) to risankizumab, 150 mg, subcutaneously, or placebo at weeks 0 and 4 (part A1). All patients received risankizumab at week 16. At week 28, patients randomized to risankizumab who achieved an sPGA score of 0/1 were rerandomized 1:2 to risankizumab or placebo every 12 weeks (part B).Main outcomes and measures:Co-primary end points for the part A1 phase included proportions of patients achieving greater than or equal to 90% improvement in PASI (PASI 90) and sPGA score of 0/1 at week 16. The PASI measures severity of erythema, infiltration, and desquamation weighted by area of skin involvement over the head, trunk, upper extremities, and lower extremities; scores range from 0 (no disease) to 72 (maximal disease activity). The sPGA assesses average thickness, erythema, and scaling of all psoriatic lesions; scores range from 0 (clear) to 4 (severe), with 0/1 indicating clear or almost clear. Primary and secondary end points in part B included proportion of rerandomized patients achieving an sPGA score of 0/1 at week 52 (primary) and week 104 (secondary).Results:Of 563 patients screened, 507 were randomized to risankizumab (n = 407) or placebo (n = 100). Most patients were men (356 [70.2%]); median age was 51 years (interquartile range, 38-60 years). At week 16, 298 patients (73.2%) in the treatment group vs 2 patients (2.0%) receiving placebo achieved a PASI 90 response, and 340 patients (83.5%) receiving risankizumab vs 7 patients (7.0%) receiving placebo achieved sPGA 0/1 scores (placebo-adjusted differences: PASI 90: 70.8%; 95% CI, 65.7%-76.0%; sPGA 0/1: 76.5%; 95% CI, 70.4%-82.5%; P < .001 for both). At week 28, 336 responders were rerandomized to risankizumab (n = 111) or treatment withdrawal (n = 225). At week 52, the sPGA 0/1 score was achieved by 97 patients (87.4%) receiving risankizumab vs 138 patients (61.3%) receiving placebo. At week 104, the sPGA 0/1 score was achieved by 90 patients (81.1%) receiving risankizumab vs 16 patients (7.1%) receiving placebo (placebo-adjusted differences: week 52: 25.9%; 95% CI, 17.3%-34.6%; week 104: 73.9%; 95% CI, 66.0%-81.9%; P < .001 for both). Rates of treatment-emergent adverse events were similar between risankizumab (186 [45.7%]) and placebo (49 [49.0%]) in part A1 and remained stable over time.Conclusions and relevance:Risankizumab showed superior efficacy compared with placebo through 16 weeks and treatment withdrawal through 2 years. Risankizumab was well tolerated, with no unexpected safety findings during the 2-year trial.Trial registration:ClinicalTrials.gov Identifier: NCT02672852.

Primary Outcome Measures is Percentage of Participants Achieving 90% Improvement Psoriasis Area and Severity Index (PASI) Score (PASI90) From Baseline to Week 16; Extracted Interventionsis is Risankizumab Placebo; Conditions is Psoriasis ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Community activism as a strategy to reduce intimate partner violence (IPV) in rural Rwanda: Results of a community randomised trial.Background:There is considerable interest in community organising and activism as a strategy to shift patriarchal gender norms, attitudes and beliefs and thus reduce intimate partner violence (IPV). Yet there is limited insight into how activism actually translates into reduced violence, including how aspects of programme implementation or cultural context may affect impact. This study evaluates the community activism/mobilisation portion of Indashyikirwa, a multi-component, IPV prevention programme implemented in rural Rwanda. The activism part of Indashyikirwa was based on SASA!, a promising program model from Uganda with demonstrated effectiveness.Methods:We implemented two separate cross-sectional surveys as part of a larger community randomised controlled trial to assess the impact of the community portion of Indashyikirwa on preventing physical and/or sexual IPV and other secondary outcomes at a community level. The survey consisted of a random household-based sample of 1400 women and 1400 men at both waves. Surveys were conducted before community-level activities commenced and were repeated 24 months later with a new cross-sectional sample. Longitudinal, qualitative data were collected as part of an embedded process evaluation.Results:There was no evidence of an intervention effect at a community level on any of the trial's primary or secondary outcomes, most notably women's experience of physical and/or sexual IPV from a current male partner in the past 12 months (adjusted odds ratio (aOR) = 1.25; 95% confidence interval (CI) = 0.92-1.70, P = 0.16), or men's perpetration of male-to-female physical and/or sexual IPV (aOR = 1.02; 95% CI = 0.72-1.45, P = 0.89). Process evaluation data suggest that delays due to challenges in adapting and implementing SASA!-style activites in rural Rwanda may account for the trial's failure to measure an effect. Additionally, the intervention strategy of informal activism was not well suited to the Rwandan context and required considerable modification.Conclusions:Failure to reduce violence when implementing an adaptation of SASA! in rural Rwanda highlights the importance of allowing sufficient time for adapting evidence-based programming (EBP) to ensure cultural appropriateness and fidelity. This evaluation held little chance of demonstrating impact since the project timeline forced endline evaluation only months after certain elements of the programme became operational. Donors must anticipate longer time horizons (5 to 7 years) when contemplating evaluations of novel or newly-adapted programmess for reducing IPV at a population level. These findings also reinforce the value of including embedded process evaluations when investing in rigorous trials of complex phenomena such as community activism.Trial registration:ClinicalTrials.gov, NCT03477877.

Primary Outcome Measures is Intimate partner violence with main partner (Couples Cohort); Extracted Interventionsis is Indashyikirwa Couples Training Indashyikirwa Activist Training Indashyikirwa Opinion Leader Training Indashyikirwa Women's Spaces Village Savings and Loan Association (VSLA); Conditions is Intimate Partner Violence ;Sex is ALL ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Association Between Bedroom Particulate Matter Filtration and Changes in Airway Pathophysiology in Children With Asthma.Importance:Fine particles (particulate matter 2.5 μm [PM2.5]), a ubiquitous air pollutant, can deposit in the small airways that play a vital role in asthma. It appears to be unknown whether the use of a PM2.5 filtration device can improve small airway physiology and respiratory inflammation in children with asthma.Objective:To discover what pathophysiological changes in the small airways are associated with using a PM2.5-removing device in the bedrooms of children with asthma.Design, setting, and participants:Children with mild or moderate asthma were enrolled in this double-blind, crossover study. The participants used a true filtration device and a sham filtration device in their bedrooms in a random order for 2 weeks each with a 2-week washout interval. The study was conducted in a suburb of Shanghai, China, during a low-ozone season.Exposures:Ozone and PM2.5 were measured inside bedrooms and outside a window.Main outcomes and measures:Impulse oscillometry, spirometry, and fractional exhaled nitric oxide were measured at the beginning and the end of each intervention. Peak expiratory flow was measured twice daily at home.Results:Forty-three children (5-13 years old; 26 boys [60%]) participated. Outdoor 24-hour mean PM2.5 concentrations were moderately high, ranging from 28.6 to 69.8 μg/m3 (median, 53 μg/m3). During true filtration, bedroom PM2.5 concentrations were a mean (SD) of 63.4% (35.9%) lower than during sham filtration. Compared with sham filtration, true filtration was significantly associated with improved airway mechanics, reflected in a 24.4% (95% CI, 11.8%-37.1%) reduction in total airway resistance, a 43.5% (95% CI, 13.7%-73.3%) reduction in small airway resistance, a 22.2% (95% CI, 2.2%-42.2%) reduction in resonant frequency, and a 73.1% (95% CI, 0.3%-145.8%) increase in airway reactance. True filtration was also associated with significant improvements in fractional exhaled nitric oxide (a 27.6% [95% CI, 8.9%-42.4%] reduction) and peak expiratory flow (a 1.6% [95% CI, 0.8%-2.5%] increase). These improvements were significantly associated with bedroom PM2.5 reduction. Improvements in small airway function were nonsignificant (8.4% [95% CI, -1.4% to 18.3%]) in all participants but significant (13.2% [95% CI, 1.2%-25.1%]) in participants without eosinophilic airway inflammation at baseline. No improvements were observed for forced vital capacity, forced expiratory volume during the first second, and the ratio of these in all participants or subgroups.Conclusions and relevance:Per these results, indoor PM2.5 filtration can be a practical method to improve air flow in an asthmatic lung through improved airway mechanics and function as well as reduced inflammation. This warrants a clinical trial to confirm.Trial registration:ClinicalTrials.gov Identifier: NCT03282864.

Primary Outcome Measures is Fractional exhaled nitric oxide (FeNO); Extracted Interventionsis is Bedroom air filtered by an air filtration device to remove airborne pollutants; Conditions is Asthma in Children ;Sex is ALL ;Age is CHILD