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Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Point-of-care ultrasound defines gastric content in elective surgical patients with type 2 diabetes mellitus: a prospective cohort study.Background:Delayed gastric emptying and the resultant "full stomach" is the most important risk factor for perioperative pulmonary aspiration. Using point-of-care gastric sonography, we aimed to investigate the prevalence of full stomach and its risk factors in elective surgical patients with type 2 diabetes.Methods:Type 2 diabetic and non-diabetic elective surgical patients were included from July 2017 to April 2018 in a 1:1 ratio. The study was retrospectively registered at July 2017, after enrollment of the first participant. Gastric ultrasound was performed 2 h after ingesting clear fluid or 6 h after a light meal. Full stomach was defined by the presence of gastric content in both semi-recumbent and right lateral decubitus positions. For patients with full or intermediate stomach, consecutive ultrasound scan was performed until empty stomach was detected. Logistic regression analyses were used to identify risk factors associated with full stomach.Results:Fifty-two type 2 diabetic and fifty non-diabetic patients were analyzed. The prevalence of full stomach was 48.1% (25/52) in diabetic patients, with 44.0% for 2-h fast after clear fluid and 51.9% for 6-h fast after a light meal, significantly higher than 8% (4/50) in non-diabetic patients (P = 0.000). The average time to empty stomach in diabetic patients was 146.50 ± 40.91 mins for clear liquid and 426.50 ± 45.25 mins for light meal, respectively. Further analysis indicated that presence of diabetes-related eye disease was an independent risk factor of full stomach in diabetic patients (OR = 4.83, P = 0.010).Conclusions:Almost half of type 2 diabetic patients have a full stomach following the current preoperative fasting guideline. Preoperative ultrasound assessment of gastric content in type 2 diabetic patients is suggested, especially for those with diabetes -related eye disease.Trial registration:The trial was registered at www.clinicaltrials.gov with registration number NCT03217630 . Retrospectively registered on 14th July 2017.

Primary Outcome Measures is Prevalence of full stomach; Extracted Interventionsis is Fasting 2 h after clear liquid or 6h after a light meal; 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.Assessing the effectiveness of mindfulness-based programs on mental health during pregnancy and early motherhood - a randomized control trial.Background:The process of entering motherhood is highly stressful for women, with 15-85% of new mothers experiencing postpartum blues or depression. This study was designed to evaluate the efficacy of a mindfulness-based childbirth and parenting program in improving psychological health during the postpartum period.Methods:This research was a randomized controlled trial with single blinding. Recruitment began after the participating hospital granted formal approval. A total of 74 women between 13 and 28-weeks gestation were allocated either to the intervention group or to the comparison group. The intervention program included a series of eight, 3-h classes held once weekly and 1 day of 7-h silent meditation. Psychological health was assessed at baseline and 3-months postpartum.Results:Significant differences in stress and depression were observed in both groups over time. Stress scores and depression scores were significantly better in the intervention group than in the comparison group at 3-months postpartum (F = 7.19, p = .009 and F = 7.36, p = .008, respectively). No significant difference between the groups was identified for mindfulness scores at 3-months postpartum.Conclusions:The intervention program effectively reduced postpartum self-perceived stress and depression, suggesting that this program provides acceptable and long-term benefits to women during pregnancy and the postpartum period. The teaching and practice of mindfulness meditation and parenting education during pregnancy may help reduce stress and depression in pregnant women as they transition into parenthood.Trial registration:The ClinicalTrials.gov identifier for this study is: NCT03185910 . The study was retrospectively registered on 14 June 2017.

Primary Outcome Measures is change of prenatal and postnatal stress; Extracted Interventionsis is MBCP education Hospital-based antenatal education; Conditions is Stress, Psychological|Pregnancy Related ;Sex is FEMALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso: A randomized controlled trial.Artemisinin resistance is threatening global efforts for malaria control and elimination. Primaquine (PQ) and methylene blue (MB) are gametocytocidal drugs that can be combined with artemisinin-based combination therapy (ACT) to reduce malaria transmission, including resistant strains. Children (6-59 months) with uncomplicated falciparum malaria in Burkina Faso were treated with artesunate-amodiaquine (AS-AQ) and randomized to MB (15 mg/kg/day for 3 days) or PQ (0.25 mg/kg at day 2) with the aim to show non-inferiority of the MB regimen with regard to haematological recovery at day 7 (primary endpoint). MB-AS-AQ could not be shown to be non-inferior to PQ-AS-AQ (mean Hb difference between treatment groups on day 7 was -0.352, 95% CI -0.832-0.128, p = 0.0767), however, haemoglobin recovery following treatment was alike in the two study arms (day 7: mean 0.2±1.4 g/dl vs. 0.5±0.9 g/dl, p = 0.446). Occurrence of adverse events was similar in both groups, except for vomiting, which was more frequent in the MB than in the PQ arm (20/50 vs 7/50, p = 0.003). Adequate clinical and parasitological response was above 95% in both groups, but significantly more asexual parasites were cleared in the MB arm compared to the PQ arm already on day 1 (48/50, 96%, vs 40/50, 80%, p = 0.014). Moreover, P. falciparum gametocyte prevalence and density were lower in the MB arm than in the PQ arm, which reached statistical significance on day 2 (prevalence: 2/50, 4%, vs 15/49, 31%, p<0.001; density: 9.6 vs 41.1/μl, p = 0.024). However, it should be considered that PQ was given only on day 2. MB-ACT appears to be an interesting alternative to PQ-ACT for the treatment of falciparum malaria. While there is a need to further improve MB formulations, MB-ACT may already be considered useful to reduce falciparum malaria transmission intensity, to increase treatment efficacy, and to reduce the risk for resistance development and spread. Trial registration: ClinicalTrials.gov NCT02851108.

Primary Outcome Measures is Change in Haemoglobin Compared to the Baseline; Extracted Interventionsis is Methylene Blue Primaquine; Conditions is Malaria, Falciparum ;Sex is ALL ;Age is CHILD

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Complete Revascularization with Multivessel PCI for Myocardial Infarction.Background:In patients with ST-segment elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) of the culprit lesion reduces the risk of cardiovascular death or myocardial infarction. Whether PCI of nonculprit lesions further reduces the risk of such events is unclear.Methods:We randomly assigned patients with STEMI and multivessel coronary artery disease who had undergone successful culprit-lesion PCI to a strategy of either complete revascularization with PCI of angiographically significant nonculprit lesions or no further revascularization. Randomization was stratified according to the intended timing of nonculprit-lesion PCI (either during or after the index hospitalization). The first coprimary outcome was the composite of cardiovascular death or myocardial infarction; the second coprimary outcome was the composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization.Results:At a median follow-up of 3 years, the first coprimary outcome had occurred in 158 of the 2016 patients (7.8%) in the complete-revascularization group as compared with 213 of the 2025 patients (10.5%) in the culprit-lesion-only PCI group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.91; P = 0.004). The second coprimary outcome had occurred in 179 patients (8.9%) in the complete-revascularization group as compared with 339 patients (16.7%) in the culprit-lesion-only PCI group (hazard ratio, 0.51; 95% CI, 0.43 to 0.61; P<0.001). For both coprimary outcomes, the benefit of complete revascularization was consistently observed regardless of the intended timing of nonculprit-lesion PCI (P = 0.62 and P = 0.27 for interaction for the first and second coprimary outcomes, respectively).Conclusions:Among patients with STEMI and multivessel coronary artery disease, complete revascularization was superior to culprit-lesion-only PCI in reducing the risk of cardiovascular death or myocardial infarction, as well as the risk of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. (Funded by the Canadian Institutes of Health Research and others; COMPLETE ClinicalTrials.gov number, NCT01740479.).

Primary Outcome Measures is Composite of Cardiovascular death or new myocardial Infarction; Extracted Interventionsis is Complete Revascularization Strategy; Conditions is Acute Myocardial Infarction|Coronary Artery 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.Safety and Efficacy of T-DM1 Plus Neratinib in Patients With Metastatic HER2-Positive Breast Cancer: NSABP Foundation Trial FB-10.Purpose:Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer eventually develop resistance to dual-antibody therapy with trastuzumab plus pertuzumab. Mechanisms of resistance have not been well elucidated. We evaluated the safety, tolerability, and efficacy of ado-trastuzumab emtansine (T-DM1) plus neratinib in patients who progressed on trastuzumab plus pertuzumab.Patients and methods:In this 3 + 3 dose-escalation study, patients with metastatic breast cancer who progressed on trastuzumab, pertuzumab, and a taxane were treated with T-DM1 at 3.6 mg/kg intravenously every 3 weeks and dose-escalating neratinib at 120, 160, 200, or 240 mg/d orally.Results:Twenty-seven patients were treated across four dose-levels of neratinib. Dose-limiting toxicity in cycle 1 was grade 3 diarrhea in six patients and grade 3 nausea in one; no patient experienced grade 4 diarrhea, and there were no grade 5 toxicities. Other grade 3 to 4 toxicities included nausea (11%), dehydration (11%), electrolyte abnormality (19%), thrombocytopenia (15%), elevated transaminase levels (7%), and fatigue (7%). Twelve (63%) of 19 evaluable patients had an objective response. Responses occurred at all neratinib doses. Plasma cell-free DNA at baseline showed ERBB2 (HER2) amplification in 10 of 27 patients. Deep and more durable responses occurred in patients with cell-free DNA ERBB2 amplification. Two complete responders had high expression of total HER2 and p95HER2 in baseline tissue.Conclusion:We report the recommended phase II dose of T-DM1 3.6 mg/kg and neratinib 160 mg/d for this combination. Possible resistance mechanisms to HER2 antibodies may be loss of the HER2 receptor and high expression of p95HER2. These data provide the basis for an ongoing phase II study to better define the activity of this regimen.

Primary Outcome Measures is Number of Evaluable Patients With Dose Limiting Toxicity Events in Phase 1; Extracted Interventionsis is Neratinib T-DM1; Conditions is Breast Cancer ;Sex is FEMALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.Purpose:To report the results of a phase II clinical trial of de-intensified chemoradiotherapy for patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma.Materials and methods:Major inclusion criteria were (1) having American Joint Committee on Cancer (AJCC) 7th edition T0-T3, N0-N2c, M0 (AJCC 8th edition T0-T3, N0-N2, M0), (2) being p16 positive, and (3) reporting minimal or remote smoking history. Treatment was limited to 60 Gy intensity-modulated radiotherapy with concurrent intravenous cisplatin 30 mg/m2 once per week. Patients with T0-T2 N0-1 (AJCC 7th edition) did not receive chemotherapy. All patients had a 10- to 12-week post-treatment positron emission tomography/computed tomography to assess for neck dissection. The primary end point was 2-year progression-free survival. Secondary end points included 2-year local-regional control, distant metastasis-free survival and overall survival, and patient-reported outcomes (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events).Results:One hundred fourteen patients were enrolled (median follow-up of 31.8 months), with 81% having a minimum follow-up of 2 years. Eighty percent of patients had 10 or fewer tobacco pack-years. Two-year local-regional control, distant metastasis-free survival, progression-free survival, and overall survival were as follows: 95%, 91%, 86%, and 95%, respectively. Mean pre- and 2-year post-treatment European Organisation for Research and Treatment of Cancer quality of life scores were as follows: global, 79/84 (lower worse); swallowing, 8/9 (higher worse); and dry mouth, 14/45 (higher worse). Mean pre- and 2-year post-treatment patient-reported outcomes version of the Common Terminology Criteria for Adverse Events scores (0 to 4 scale, higher worse) were as follows: swallowing, 0.5/0.7, and dry mouth, 0.4/1.3. Thirty-four percent of patients required a feeding tube (median, 10.5 weeks; none permanent). There were no grade 3 or higher late adverse events.Conclusion:Clinical outcomes with a de-intensified chemoradiotherapy regimen of 60 Gy intensity-modulated radiotherapy with concurrent low-dose cisplatin are favorable in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma. Neither neoadjuvant chemotherapy nor routine surgery is needed to obtain favorable results with de-escalation.

Primary Outcome Measures is 2 Year Progression Free Survival After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC); Extracted Interventionsis is Intensity Modulated Radiotherapy (IMRT) Cisplatin (or alternative) Assessment for surgical evaluation; Conditions is Carcinoma, Squamous Cell|Head and Neck Neoplasms|Oropharyngeal Neoplasms ;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 Trial of the Wee1 Inhibitor Adavosertib (AZD1775) in Combination With Gemcitabine and Radiation for Patients With Locally Advanced Pancreatic Cancer.Purpose:AZD1775 (adavosertib) is an inhibitor of the Wee1 kinase. In this study, we built on our preclinical studies to evaluate the safety and efficacy of AZD1775 in combination with gemcitabine and radiation in patients with newly diagnosed locally advanced pancreatic cancer.Patients and methods:Thirty-four patients with locally advanced pancreatic cancer were enrolled with the intention to receive four 21-day cycles of gemcitabine (1,000 mg/m2 days 1 and 8) with AZD1775 (once daily on days 1, 2, 8, and 9). Cycles 2 and 3 were administered concurrently with radiation, and cycles 5 to 8 were optional. AZD1775 was dose escalated using a time-to-event continual reassessment method on the basis of the rate of dose-limiting toxicities within the first 15 weeks of therapy. The primary objective was to determine the maximum tolerated dose of AZD1775 given in conjunction with gemcitabine and radiation. Secondary objectives were to estimate overall and progression-free survival and determine pharmacodynamic activity of AZD1775 in surrogate tissues.Results:The recommended phase II dose of AZD1775 was 150 mg/d. Eight patients (24%) experienced a dose-limiting toxicity, most commonly anorexia, nausea, or fatigue. The median overall survival for all patients was 21.7 months (90% CI, 16.7 to 24.8 months), and the median progression-free survival was 9.4 months (90% CI, 8.0 to 9.9 months). Hair follicle biopsy samples demonstrated evidence of Wee1 inhibition with decreased phosphorylation of cyclin-dependent kinase 1 staining by immunohistochemistry after AZD1775 administration at the recommended phase II dose.Conclusion:AZD1775 in combination with gemcitabine and radiation therapy was well tolerated at a dose that produced target engagement in a surrogate tissue. The overall survival is substantially higher than prior results combining gemcitabine with radiation therapy and warrants additional investigation.

Primary Outcome Measures is Maximum Tolerated Dose (MTD) of AZD1775 (MK-1775) When Used Concurrently With Gemcitabine and Radiation Therapy.; Extracted Interventionsis is MK-1775 Gemcitabine Radiation Therapy; Conditions is Adenocarcinoma of the Pancreas ;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 ralinepag, a novel oral IP agonist, in PAH patients on mono or dual background therapy: results from a phase 2 randomised, parallel group, placebo-controlled trial.Purpose:This phase 2 study was designed to assess the efficacy, safety and tolerability of immediate-release orally administered ralinepag, a selective, non-prostanoid prostacyclin receptor agonist with a 24-h terminal half-life, compared to placebo in adult patients with symptomatic pulmonary arterial hypertension (PAH).Methods:61 PAH patients who were receiving standard care, including mono or dual PAH-targeted background therapy were randomised 2:1 to ralinepag (n=40) or placebo (n=21). The starting dose of ralinepag was 10 μg twice daily. Dosage was then up-titrated as tolerated over the course of the 9-week dose-titration period, to a maximum total daily dose of 600 μg (300 μg twice daily). The primary efficacy end-point was the absolute change in pulmonary vascular resistance (PVR) from baseline to week 22. Additional end-points included percentage change in PVR from baseline, other haemodynamic parameters, 6-min walk distance (6MWD) and safety and tolerability.Results:Ralinepag significantly decreased PVR by 163.9 dyn·s·cm-5 compared to an increase of 0.7 dyn·s·cm-5 with placebo (p=0.02); the least-squares mean change from baseline PVR was -29.8% compared with placebo (p=0.03). 6MWD increased from baseline by 36.2 m with ralinepag and 29.4 m with placebo (p=0.90). Serious adverse events occurred in 10% of ralinepag patients and 29% of placebo patients. Study discontinuations occurred in 13% of ralinepag patients and 10% of placebo patients.Summary:Ralinepag reduced PVR compared with placebo in PAH patients on mono (41%) or dual combination (59%) background therapy.

Primary Outcome Measures is Change From Baseline in Pulmonary Vascular Resistance (PVR); Extracted Interventionsis is APD811 Placebo; Conditions is Pulmonary Arterial 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.Phase II California Cancer Consortium Trial of Gemcitabine-Eribulin Combination in Cisplatin-Ineligible Patients With Metastatic Urothelial Carcinoma: Final Report (NCI-9653).Purpose:Patients with metastatic urothelial carcinoma are often ineligible for cisplatin-based treatments. A National Cancer Institute Cancer Therapy Evaluation Program-sponsored trial assessed the tolerability and efficacy of a gemcitabine-eribulin combination in this population.Methods:Patients with treatment-naïve advanced or recurrent metastatic urothelial carcinoma of the bladder, ureter, or urethra not amenable to curative surgery and not candidates for cisplatin-based therapy were eligible. Cisplatin ineligibility was defined as creatinine clearance less than 60 mL/min (but ≥ 30 mL/min), grade 2 neuropathy, or grade 2 hearing loss. Treatment was gemcitabine 1,000 mg/m2 intravenously followed by eribulin 1.4 mg/m2, both on days 1 and 8, repeated in 21-day cycles until progression or unacceptable toxicity. A Simon two-stage phase II trial design was used to distinguish between Response Evaluation Criteria in Solid Tumors, version 1.1 objective response rates of 20% versus 50%.Results:Between June 2015 and March 2017, 24 eligible patients with a median age of 73 years (range, 62 to 88 years) underwent therapy. Performance status of 0, 1, or 2 was seen in 11, 11, and two patients, respectively. Sites of disease included: lymph nodes, 16; lungs, nine; liver, seven; bladder, five; bones, two. Median number of cycles received was four (range, one to 16). Of 24 patients, 12 were confirmed responders; the observed objective response rate was 50% (95% CI, 29% to 71%). Median overall survival was 11.9 months (95% CI, 5.6 to 20.4 months), and median progression-free survival was 5.3 months (95% CI, 4.5 to 6.7 months). The most common treatment-related any-grade toxicities were fatigue (83% of patients), neutropenia (79%), anemia (63%), alopecia (50%), elevated AST (50%), and constipation, nausea, and thrombocytopenia (42% each).Conclusion:Gemcitabine-eribulin treatment response and survival for cisplatin-ineligible patients compare favorably to other regimens. Additional research is needed.

Primary Outcome Measures is Observed Overall Response Rate; Extracted Interventionsis is Eribulin Mesylate Gemcitabine Hydrochloride; Conditions is Metastatic Ureter Carcinoma|Metastatic Urethral Carcinoma|Stage III Bladder Urothelial Carcinoma AJCC v6 and v7|Stage III Ureter Cancer AJCC v7|Stage III Urethral Cancer AJCC v7|Stage IV Bladder Urothelial Carcinoma AJCC v7|Stage IV Ureter Cancer AJCC v7|Stage IV Urethral Cancer AJCC v7|Ureter Urothelial Carcinoma|Urethral Urothelial Carcinoma ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma After Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy.Purpose:Locally advanced or metastatic urothelial carcinoma is an incurable disease with limited treatment options, especially for patients who were previously treated with platinum and anti-programmed death 1 or anti-programmed death ligand 1 (PD-1/L1) therapy. Enfortumab vedotin is an antibody-drug conjugate that targets Nectin-4, which is highly expressed in urothelial carcinoma.Methods:EV-201 is a global, phase II, single-arm study of enfortumab vedotin 1.25 mg/kg (intravenously on days 1, 8, and 15 of every 28-day cycle) in patients with locally advanced or metastatic urothelial carcinoma who were previously treated with platinum chemotherapy and anti-PD-1/L1 therapy. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent central review. Key secondary end points were duration of response, progression-free survival, overall survival, safety, and tolerability.Results:Enfortumab vedotin was administered to 125 patients with metastatic urothelial carcinoma. Median follow-up was 10.2 months (range, 0.5 to 16.5 months). Confirmed objective response rate was 44% (95% CI, 35.1% to 53.2%), including 12% complete responses. Similar responses were observed in prespecified subgroups, such as those patients with liver metastases and those with no response to prior anti-PD-1/L1 therapy. Median duration of response was 7.6 months (range, 0.95 to 11.30+ months). The most common treatment-related adverse events were fatigue (50%), any peripheral neuropathy (50%), alopecia (49%), any rash (48%), decreased appetite (44%), and dysgeusia (40%). No single treatment-related adverse events grade 3 or greater occurred in 10% or more of patients.Conclusion:Enfortumab vedotin demonstrated a clinically meaningful response rate with a manageable and tolerable safety profile in patients with locally advanced or metastatic urothelial carcinoma who were previously treated with platinum and anti-PD-1/L1 therapies.

Primary Outcome Measures is Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR); Extracted Interventionsis is Enfortumab vedotin; Conditions is Carcinoma, Transitional Cell|Urinary Bladder Neoplasms|Urologic Neoplasms|Renal Pelvis Neoplasms|Urothelial Cancer|Ureteral Neoplasms|Urethral Neoplasms ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Five-year follow-up of SWOG S0816: limitations and values of a PET-adapted approach with stage III/IV Hodgkin lymphoma.Patients with advanced-stage Hodgkin lymphoma (HL) demonstrated excellent 2-year progression-free survival (PFS) after receiving positron emission tomography (PET)-adapted therapy on SWOG S0816. Patients received 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Patients achieving complete response (CR) on PET scan following cycle 2 of ABVD (PET2) continued 4 additional cycles of ABVD. Patients not achieving CR on PET2 were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for 6 cycles. After a median follow-up of 5.9 years, a subset of 331 eligible patients with central review of PET2 was analyzed. PET2 was negative in 82% and positive in 18%. For all patients, the estimated 5-year PFS and OS was 74% (95% confidence interval [CI], 69%-79%) and 94% (95% CI, 91%-96%), respectively. For PET2- and PET2+ patients, the 5-year PFS was 76% (95% CI, 70%-81%) and 66% (95% CI, 52%-76%), respectively. Seven (14%) and 6 (2%) patients reported second cancers after treatment with eBEACOPP and ABVD, respectively (P = .001). Long-term OS of HL patients treated on S0816 remains high. Nearly 25% of PET2- patients experienced relapse events, demonstrating limitations ABVD therapy and of the negative predictive value of PET2. In PET2+ patients who received eBEACOPP, PFS was favorable, but was associated with a high rate of second malignancies compared with historical controls. Our results emphasize the importance of long-term follow-up, and the need for more efficacious and less toxic therapeutic approaches for advanced-stage HL patients. This trial was registered at www.clinicaltrials.gov as #NCT00822120.

Primary Outcome Measures is Percentage of HIV-negative Patients With 2-year Progression-free Survival (PFS) Treated With 2 Initial Cycles of Adriamycin; Extracted Interventionsis is bleomycin sulfate filgrastim ABVD regimen BEACOPP regimen cyclophosphamide dacarbazine doxorubicin hydrochloride etoposide prednisone procarbazine hydrochloride vinblastine sulfate vincristine sulfate; Conditions is Lymphoma|Nonneoplastic Condition ;Sex is ALL ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.The Effects Of Myofascial Release Technique Combined With Core Stabilization Exercise In Elderly With Non-Specific Low Back Pain: A Randomized Controlled, Single-Blind Study.Purpose:To evaluate the effects of Myofascial Release Technique (MRT) with a roller massager combined with core stabilization exercises (CSE) in elderly with non-specific low back pain (NSLBP).Patients and methods:A total of forty-five participants were randomly divided into two groups (CSE and CSE+MRT). A core stabilization exercise program was applied for the participants in the CSE group for 3 days per week for a total of 6 weeks. In addition to the core stabilization exercises, myofascial relaxation technique with a roller massager was performed for 3 days per week for 6 weeks for the participants in the CSE+MRT group. Participants were assessed in terms of pain, low back disability, lower body flexibility, kinesiophobia, core stability endurance, spinal mobility, gait characteristics and quality of life both pre- and post-treatment.Results:It was found that the improvement in core stability endurance (p=0.031) and spinal mobility (in the sagittal plane) (p=0.022) was greater in the CSE+MRT group compared to the CSE group. There was no significant difference between the two groups in terms of pain, low back disability, lower body flexibility, kinesiophobia, gait characteristics and quality of life (p>0.05).Conclusion:The current study suggests that myofascial release technique with a roller massager combined with core stabilization exercises can be a better choice in the treatment of NSLBP in elderly.Clinicaltrialsgov identifier:NCT03898089.

Primary Outcome Measures is Visual Analogue Scale; Extracted Interventionsis is Core Stability Exercise Core Stability Exercise plus Myofascial Release Technique Group; Conditions is Low Back Pain|Exercise|Elderly ;Sex is ALL ;Age is OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.A Smart Mobile Health Tool Versus a Paper Action Plan to Support Self-Management of Chronic Obstructive Pulmonary Disease Exacerbations: Randomized Controlled Trial.Background:Many patients with chronic obstructive pulmonary disease (COPD) suffer from exacerbations, a worsening of their respiratory symptoms that warrants medical treatment. Exacerbations are often poorly recognized or managed by patients, leading to increased disease burden and health care costs.Objective:This study aimed to examine the effects of a smart mobile health (mHealth) tool that supports COPD patients in the self-management of exacerbations by providing predictions of early exacerbation onset and timely treatment advice without the interference of health care professionals.Methods:In a multicenter, 2-arm randomized controlled trial with 12-months follow-up, patients with COPD used the smart mHealth tool (intervention group) or a paper action plan (control group) when they experienced worsening of respiratory symptoms. For our primary outcome exacerbation-free time, expressed as weeks without exacerbation, we used an automated telephone questionnaire system to measure weekly respiratory symptoms and treatment actions. Secondary outcomes were health status, self-efficacy, self-management behavior, health care utilization, and usability. For our analyses, we used negative binomial regression, multilevel logistic regression, and generalized estimating equation regression models.Results:Of the 87 patients with COPD recruited from primary and secondary care centers, 43 were randomized to the intervention group. We found no statistically significant differences between the intervention group and the control group in exacerbation-free weeks (mean 30.6, SD 13.3 vs mean 28.0, SD 14.8 weeks, respectively; rate ratio 1.21; 95% CI 0.77-1.91) or in health status, self-efficacy, self-management behavior, and health care utilization. Patients using the mHealth tool valued it as a more supportive tool than patients using the paper action plan. Patients considered the usability of the mHealth tool as good.Conclusions:This study did not show beneficial effects of a smart mHealth tool on exacerbation-free time, health status, self-efficacy, self-management behavior, and health care utilization in patients with COPD compared with the use of a paper action plan. Participants were positive about the supportive function and the usability of the mHealth tool. mHealth may be a valuable alternative for COPD patients who prefer a digital tool instead of a paper action plan.Trial registration:ClinicalTrials.gov NCT02553096; https://clinicaltrials.gov/ct2/show/NCT02553096.

Primary Outcome Measures is Number of exacerbation-free weeks; Extracted Interventionsis is ACCESS; 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."Unrigging the support wheels" - A qualitative study on patients' experiences with and perspectives on low-intensity CBT.Background:Low-intensity treatments imply reduced therapist contact due to an emphasis on self-help and the use of technologies to deliver treatment. The role of the remoteness, the reduced therapist contact, and the interplay of these components has not been differentiated from a patients' perspective so far. This study's purpose is to capture patients' experiences with telephone-based self-help cognitive behavioural therapy (tel-CBT).Methods:A subsample of mildly to moderately depressed patients (N = 13) who finished tel-CBT as part of a larger randomised controlled trial (RCT) in routine care were interviewed using a semi-structured questionnaire. Interviews were audiotaped, transcribed verbatim, and independently coded by two coders blind to treatment outcome. Using qualitative content analysis with deductive and inductive procedures, a two-level category system was established.Results:The category system contains four category clusters regarding expectations, self-help related aspects, telephone-related aspects, and implications for patients' treatment pathway, and subsumes a total of 15 categories. Self-help related aspects circulate around the interplay between written materials and professional input, trust and support in the therapeutic relationship and its relation to the initial personal contact, as well as CBT principles. Telephone-related aspects entail perceived advantages and disadvantages of the telephone on an organisational and content level as well as a discourse around distance and closeness in the interaction. Although patients raised doubts regarding the long-term effect of the intervention on symptomatology, patients expressed satisfaction with the treatment and reported an immediate as well as a longer lasting personal impact of the treatment. These results indicate user acceptance with tel-CBT.Conclusions:This qualitative analysis captures patients' experiences with tel-CBT and the perceived helpfulness of the diverse treatment components. This can facilitate refining aspects of low-intensity treatments and might improve dissemination.Trial registration:ClinicalTrials.gov NCT02667366. Registered on 3 December 2015.

Primary Outcome Measures is Change in depressive symptoms; Extracted Interventionsis is Tel-PT TAU and text messages; 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.Predictors of long-term adherence to continuous positive airway pressure in patients with obstructive sleep apnea and cardiovascular disease.Study objectives:Poor adherence to continuous positive airway pressure (CPAP) commonly affects therapeutic response in obstructive sleep apnea (OSA). We aimed to determine predictors of adherence to CPAP among participants of the Sleep Apnea and cardioVascular Endpoints (SAVE) trial.Methods:SAVE was an international, randomized, open trial of CPAP plus usual care versus usual care (UC) alone in participants (45-75 years) with co-occurring moderate-to-severe OSA (≥12 episodes/h of ≥4% oxygen desaturation) and established cardiovascular (CV) disease. Baseline sociodemographic, health and lifestyle factors, OSA symptoms, and 1-month change in daytime sleepiness, as well as CPAP side effects and adherence (during sham screening, titration week, and in the first month), were entered in univariate linear regression analyses to identify predictors of CPAP adherence at 24 months. Variables with p <0.2 were assessed for inclusion in a multivariate linear mixed model with country, age, and sex included a priori and site as a random effect.Results:Significant univariate predictors of adherence at 24 months in 1,121 participants included: early adherence measures, improvement in daytime sleepiness at 1 month, fixed CPAP pressure, some measures of OSA severity, cardiovascular disease history, breathing pauses, and very loud snoring. While observed adherence varied between countries, adherence during sham screening, initial titration, and the first month of treatment retained independent predictive value in the multivariate model along with fixed CPAP pressure and very loud snoring.Conclusions:Early CPAP adherence had the greatest predictive value for identifying those at highest risk of non-adherence to long-term CPAP therapy.Clinical trial registration:SAVE is registered with clinicaltrials.gov (NCT00738179).

Primary Outcome Measures is A composite of the CV endpoints of CV death; Extracted Interventionsis is Continuous Positive Airway Pressure (CPAP) Standard care; Conditions is Sleep Apnea|Cardiovascular 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.Depression prevention via digital cognitive behavioral therapy for insomnia: a randomized controlled trial.Study objectives:Insomnia is a common precursor to depression; yet, the potential for insomnia treatment to prevent depression has not been demonstrated. Cognitive behavioral therapy for insomnia (CBT-I) effectively reduces concurrent symptoms of insomnia and depression and can be delivered digitally (dCBT-I); however, it remains unclear whether treating insomnia leads to sustained reduction and prevention of depression. This randomized controlled trial examined the efficacy of dCBT-I in reducing and preventing depression over a 1-year follow-up period.Methods:Patients with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) insomnia disorder were randomly assigned to receive dCBT-I or an attentional control. The follow-up sample included 358 patients in the dCBT-I condition and 300 patients in the online sleep education condition. The primary outcome measure was relative rate ratios for depression at 1-year follow-up. Insomnia responses to treatment were also tested as predictors of incident depression at the 1-year follow-up.Results:At 1-year follow-up, depression severity continued to be significantly lower in the dCBT-I condition relative to control. In addition, the number of individuals who reported no depression at 1-year follow-up was 51% higher in the dCBT-I condition relative to control. In those with minimal to no depression at baseline, the incident rate of moderate-to-severe depression at 1-year follow-up was reduced by half in the dCBT-I condition relative to the control condition.Conclusion:dCBT-I showed robust effects as an intervention that prevents depression. Future research should examine dose-response requirements and further characterize mechanisms of action of dCBT-I for depression prevention.Clinical trial:Sleep to Prevent Evolving Affective Disorders; NCT02988375.

Primary Outcome Measures is Severity of Depression as Measured by the Quick Inventory of Depressive Symptomatology (QIDS) Pre-Treatment; Extracted Interventionsis is dCBTI Sleep Education; Conditions is Insomnia, Primary|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.Effect of continuous positive airway pressure on inflammatory, antioxidant, and depression biomarkers in women with obstructive sleep apnea: a randomized controlled trial.Study objectives:The effect of continuous positive airway pressure (CPAP) on mediators of cardiovascular disease and depression in women with obstructive sleep apnea (OSA) is unknown. We aimed to assess the effect of CPAP therapy on a variety of biomarkers of inflammation, antioxidant activity, and depression in women with OSA.Methods:We conducted a multicenter, randomized controlled trial in 247 women diagnosed with moderate-to-severe OSA (apnea-hypopnea index [AHI] ≥ 15). Women were randomized to CPAP (n = 120) or conservative treatment (n = 127) for 12 weeks. Changes in tumor necrosis factor α (TNFα), interleukin 6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), catalase (CAT), superoxide dismutase (SOD), and brain-derived neurotrophic factor (BDNF) were assessed. Additional analyses were conducted in subgroups of clinical interest.Results:Women had a median (25th-75th percentiles) age of 58 (51-65) years, body mass index 33.5 (29.0-38.3) kg/m2, and AHI 33.3 (22.8-49.3). No differences were found between groups in the baseline levels of the biomarkers. After 12 weeks of follow-up, there were no changes between groups in any of the biomarkers assessed. These results did not change when the analyses were restricted to sleepy women or to those with severe OSA. In women with CPAP use at least 5 hours per night, only TNFα levels decreased compared to the control group (-0.29 ± 1.1 vs -0.06 ± 0.53, intergroup difference -0.23 [95% CI = -0.03 to -0.50]; p = 0.043).Conclusions:Twelve weeks of CPAP therapy does not improve biomarkers of inflammation, antioxidant activity, or depression compared to conservative treatment in women with moderate-to-severe OSA.Trial registration:NCT02047071.

Primary Outcome Measures is Change from baseline in quality of life on the Quebec Sleep Questionnaire (QSQ) at week 12; Extracted Interventionsis is Continuous positive airways pressure; Conditions is Obstructive Sleep Apnea ;Sex is FEMALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Prevalence and correlates of partner violence among adolescent girls and young women: Evidence from baseline data of a cluster randomised trial in Tanzania.Background:Little has been documented about partner violence among adolescent girls and young women (AGYW) who are out of school, a factor associated with HIV acquisition. To understand areas for prioritising HIV prevention intervention efforts, we explored the prevalence and correlates of partner violence among out of school AGYW in Shinyanga, Tanzania.Methods:A cross-sectional analysis of data from AGYW aged 15-23 years recruited in a cluster randomised trial conducted between October and December 2017 was used to examine correlates of partner violence. Data were collected through an Audio Computer-Assisted Self-interview. Multivariate logistic regression analysis was used to evaluate the association.Results:2276 (75.5%) AGYW were sexually active. Of these, 816 (35.9%) reported having experienced violence from partners in the last six months. After adjusting for other covariates, being formerly married (AOR = 1.55, 95% CI:1.02, 2.37), having children (AOR = 1.79, 95% CI:1.47, 2.16), anxiety and depression symptoms (AOR = 3.27, 95%CI: 2.15, 4.96), having engaged in sex work in the past six months (AOR = 1.92, 95% CI: 1.45, 2.53) and economic deprivation (AOR = 1.61, 95% CI: 1.34,1.92) were significantly associated with partner violence.Conclusions:Almost one in three sexually active AGYW had experienced partner violence in the 6 months preceding the survey. The findings underscore the need for future research to focus on understanding the reasons and dynamics underlying high level of partner violence among AGYW. Furthermore, there is a need for implementing intervention programs that aim to reduce economic deprivation among AGYWs and address social norms and structures perpetuating violence against AGYW.Trial registration:ClinicalTrials.gov-ID NCT03597243.

Primary Outcome Measures is HSV-2 Incidence; Extracted Interventionsis is Cash Transfer; Conditions is HIV/AIDS|HSV-2 Infection ;Sex is FEMALE ;Age is CHILD, ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Longitudinal evaluation of asymptomatic Leishmania infection in HIV-infected individuals in North-West Ethiopia: A pilot study.Background:In endemic regions, asymptomatic Leishmania infection is common. In HIV patients, detection of asymptomatic Leishmania infection could potentially identify those at risk of visceral leishmaniasis (VL). However, data on the prevalence, incidence, and determinants of asymptomatic infection, and the risk of VL are lacking.Methods:We conducted a cross-sectional survey at a single ART centre, followed by a prospective cohort study amongst HIV-infected adults in HIV care in a district hospital in a VL-endemic area in North-West Ethiopia (9/2015-8/2016). Asymptomatic Leishmania infection was detected using the direct agglutination test (DAT), rK39-rapid diagnostic test (RDT)), PCR on peripheral blood and the KAtex urine antigen test, and defined as positivity on any Leishmania marker. All individuals were followed longitudinally (irrespective of the Leishmania test results). Risk factors for asymptomatic Leishmania infection were determined using logistic regression.Results:A total of 534 HIV-infected individuals enrolled in HIV care were included in the study. After excluding 13 patients with a history of VL and an 10 patients with incomplete baseline Leishmania tests, 511 were included in analysis. The median age was 38 years (interquartile range (IQR) 30-45), 62.6% were male. The median follow-up time was 12 months (IQR 9-12). No deaths were reported during the study period. Most (95.5%) were on antiretroviral treatment at enrolment, for a median of 52 months (IQR 27-79). The median CD4 count at enrolment was 377 cells/mm3 (IQR 250-518). The baseline prevalence of Leishmania infection was 12.8% in males and 4.2% in females. Overall, 7.4% tested positive for rK39, 4.3% for DAT, 0.2% for PCR and 0.2% for KAtex. Independent risk factors for a prevalent infection were male sex (odds ratio (OR) 3.2; 95% confidence intervals (CI) 14-7.0) and concurrent malaria infection (OR 6.1; 95% CI 1.9-18.9). Amongst the 49 prevalent (baseline) infections with further follow-up, the cumulative incidence of losing the Leishmania markers by one year was 40.1%. There were 36 incident infections during the course of the study, with a cumulative one-year risk of 9.5%. Only one case of VL was detected during follow-up.Conclusions:We found a high prevalence of asymptomatic Leishmania infection, persisting in most cases. The incidence was more modest and overt VL was rare. Larger and longer studies with more complete follow-up may help to decide whether a test and treat strategy would be justified in this context.Trial registration:ClinicalTrials.gov NCT02839603.

Primary Outcome Measures is The proportion of individuals with L.donovani asymptomatic infection at baseline in HIV coinfected adults enrolled in HIV care in a VL-HIV endemic region in North-West Ethiopia.; Extracted Interventionsis is nan; Conditions is Visceral Leishmaniasis ;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 Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis: The FORWARD Randomized Clinical Trial.Importance:Sprifermin is under investigation as a disease-modifying osteoarthritis drug.Objective:To evaluate the effects of sprifermin on changes in total femorotibial joint cartilage thickness in the more symptomatic knee of patients with osteoarthritis.Design, setting, and participants:FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) was a 5-year, dose-finding, multicenter randomized clinical trial conducted at 10 sites. Eligible participants were aged 40 to 85 years with symptomatic, radiographic knee osteoarthritis and Kellgren-Lawrence grade 2 or 3. Enrollment began in July 2013 and ended in May 2014; the last participant visit occurred on May 8, 2017. The primary outcome at 2 years and a follow-up analysis at 3 years are reported.Interventions:Participants were randomized to 1 of 5 groups: intra-articular injections of 100 μg of sprifermin administered every 6 months (n = 110) or every 12 months (n = 110), 30 μg of sprifermin every 6 months (n = 111) or every 12 months (n = 110), or placebo every 6 months (n = 108). Each treatment consisted of weekly injections over 3 weeks.Main outcomes and measures:The primary end point was change in total femorotibial joint cartilage thickness measured by quantitative magnetic resonance imaging at 2 years. The secondary end points (of 15 total) included 2-year change from baseline in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. The minimal clinically important difference (MCID) is unknown for the primary outcome; for total WOMAC score in patients with hip and knee osteoarthritis, the absolute MCID is 7 U (95% CI, 4 to 10 U) and the percentage MCID is 14% (95% CI, 9% to 18%).Results:Among 549 participants (median age, 65.0 years; 379 female [69.0%]), 474 (86.3%) completed 2-year follow-up. Compared with placebo, the changes from baseline to 2 years in total femorotibial joint cartilage thickness were 0.05 mm (95% CI, 0.03 to 0.07 mm) for 100 μg of sprifermin administered every 6 months; 0.04 mm (95% CI, 0.02 to 0.06 mm) for 100 μg of sprifermin every 12 months; 0.02 mm (95% CI, -0.01 to 0.04 mm) for 30 μg of sprifermin every 6 months; and 0.01 mm (95% CI, -0.01 to 0.03 mm) for 30 μg of sprifermin every 12 months. Compared with placebo, there were no statistically significant differences in mean absolute change from baseline in total WOMAC scores for 100 μg of sprifermin administered every 6 months or every 12 months, or for 30 μg of sprifermin every 6 months or every 12 months. The most frequently reported treatment-emergent adverse event was arthralgia (placebo: n = 46 [43.0%]; 100 μg of sprifermin administered every 6 months: n = 45 [41.3%]; 100 μg of sprifermin every 12 months: n = 50 [45.0%]; 30 μg of sprifermin every 6 months: n = 40 [36.0%]; and 30 μg of sprifermin every 12 months: n = 48 [44.0%]).Conclusions and relevance:Among participants with symptomatic radiographic knee osteoarthritis, the intra-articular administration of 100 μg of sprifermin every 6 or 12 months vs placebo resulted in an improvement in total femorotibial joint cartilage thickness after 2 years that was statistically significant, but of uncertain clinical importance; there was no significant difference for 30 μg of sprifermin every 6 or 12 months vs placebo. Durability of response also was uncertain.Trial registration:ClinicalTrials.gov Identifier: NCT01919164.

Primary Outcome Measures is Change From Baseline in Cartilage Thickness in the Total Femorotibial Joint as Evaluated by Quantitative Magnetic Resonance Imaging (qMRI) at Year 2; Extracted Interventionsis is Sprifermin Placebo; Conditions is Osteoarthritis, Knee ;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 Hospital-Initiated Program Combining Transitional Care and Long-term Self-management Support on Outcomes of Patients Hospitalized With Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial.Importance:Patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbations have high rehospitalization rates and reduced quality of life.Objective:To evaluate whether a hospital-initiated program that combined transition and long-term self-management support for patients hospitalized due to COPD and their family caregivers can improve outcomes.Design, setting, and participants:Single-site randomized clinical trial conducted in Baltimore, Maryland, with 240 participants. Participants were patients hospitalized due to COPD, randomized to intervention or usual care, and followed up for 6 months after hospital discharge. Enrollment occurred from March 2015 to May 2016; follow-up ended in December 2016.Interventions:The intervention (n = 120) involved a comprehensive 3-month program to help patients and their family caregivers with long-term self-management of COPD. It was delivered by nurses with special training on supporting patients with COPD using standardized tools. Usual care (n = 120) included transition support for 30 days after discharge to ensure adherence to discharge plan and connection to outpatient care.Main outcomes and measures:The primary outcome was number of COPD-related acute care events (hospitalizations and emergency department visits) per participant at 6 months. The co-primary outcome was change in participants' health-related quality of life measured by the St George's Respiratory Questionnaire (SGRQ) at 6 months after discharge (score, 0 [best] to 100 [worst]; 4-point difference is clinically meaningful).Results:Among 240 patients who were randomized (mean [SD] age, 64.9 [9.8] years; 61.7% women), 203 (85%) completed the study. The mean (SD) baseline SGRQ score was 62.3 (18.8) in the intervention group and 63.6 (17.4) in the usual care group. The mean number of COPD-related acute care events per participant at 6 months was 1.40 (95% CI, 1.01-1.79) in the intervention group vs 0.72 (95% CI, 0.45-0.97) in the usual care group (difference, 0.68 [95% CI, 0.22-1.15]; P = .004). The mean change in participants' SGRQ total score at 6 months was 2.81 in the intervention group and -2.69 in the usual care group (adjusted difference, 5.18 [95% CI, -2.15 to 12.51]; P = .11). During the study period, there were 15 deaths (intervention: 8; usual care: 7) and 339 hospitalizations (intervention: 202; usual care: 137).Conclusions and relevance:In a single-site randomized clinical trial of patients hospitalized due to COPD, a 3-month program that combined transition and long-term self-management support resulted in significantly greater COPD-related hospitalizations and emergency department visits, without improvement in quality of life. Further research is needed to determine reasons for this unanticipated finding.Trial registration:ClinicalTrials.gov Identifier: NCT02036294.

Primary Outcome Measures is Mean Number of Chronic Obstructive Pulmonary Disease (COPD)-Related Hospitalizations and Emergency Department (ED) Visits Per Patient Within Each Study Arm; Extracted Interventionsis is BREATHE program Usual Care; Conditions is Chronic Obstructive Pulmonary 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.Cardiac Magnetic Resonance Stress Perfusion Imaging for Evaluation of Patients With Chest Pain.Background:Stress cardiac magnetic resonance imaging (CMR) has demonstrated excellent diagnostic and prognostic value in single-center studies.Objectives:This study sought to investigate the prognostic value of stress CMR and downstream costs from subsequent cardiac testing in a retrospective multicenter study in the United States.Methods:In this retrospective study, consecutive patients from 13 centers across 11 states who presented with a chest pain syndrome and were referred for stress CMR were followed for a target period of 4 years. The authors associated CMR findings with a primary outcome of cardiovascular death or nonfatal myocardial infarction using competing risk-adjusted regression models and downstream costs of ischemia testing using published Medicare national payment rates.Results:In this study, 2,349 patients (63 ± 11 years of age, 47% female) were followed for a median of 5.4 years. Patients with no ischemia or late gadolinium enhancement (LGE) by CMR, observed in 1,583 patients (67%), experienced low annualized rates of primary outcome (<1%) and coronary revascularization (1% to 3%), across all years of study follow-up. In contrast, patients with ischemia+/LGE+ experienced a >4-fold higher annual primary outcome rate and a >10-fold higher rate of coronary revascularization during the first year after CMR. Patients with ischemia and LGE both negative had low average annual cost spent on ischemia testing across all years of follow-up, and this pattern was similar across the 4 practice environments of the participating centers.Conclusions:In a multicenter U.S. cohort with stable chest pain syndromes, stress CMR performed at experienced centers offers effective cardiac prognostication. Patients without CMR ischemia or LGE experienced a low incidence of cardiac events, little need for coronary revascularization, and low spending on subsequent ischemia testing. (Stress CMR Perfusion Imaging in the United States [SPINS]: A Society for Cardiovascular Resonance Registry Study; NCT03192891).

Primary Outcome Measures is Mortality; Extracted Interventionsis is Stress cardiac magnetic resonance (CMR) perfusion imaging; Conditions is Myocardial Ischemia ;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 of the adjuvanted recombinant zoster vaccine (RZV) by sex, geographic region, and geographic ancestry/ethnicity: A post-hoc analysis of the ZOE-50 and ZOE-70 randomized trials.Background:Herpes zoster (HZ) risk appears to vary by sex and geographic ancestry/ethnicity.Methods:In 2 randomized clinical trials, participants received 2 doses of adjuvanted recombinant zoster vaccine (RZV) or placebo intramuscularly, 2 months apart. In this post-hoc analysis, we investigate efficacy of RZV against HZ and postherpetic neuralgia (PHN) by sex, geographic region, and geographic ancestry/ethnicity in ≥50-year-olds (ZOE-50: NCT01165177) and ≥70-year-olds (pooled data from ZOE-50 and ZOE-70: NCT01165229).Results:Vaccine efficacy against HZ or PHN was similar in women and men. Across geographic regions, efficacy against HZ ranged between 95.7 and 97.2% in ≥50-year-olds, and between 87.3% and 95.1% in ≥70-year-olds; efficacy against PHN ranged between 86.8 and 100% in ≥70-year-olds. Across ancestral/ethnic groups, efficacy ranged between 88.1 and 100% against HZ and between 65.9 and 100% against PHN in ≥70-year-olds.Conclusions:While the ZOE-50/70 studies were not powered or pre-designed for these post-hoc analyses, RZV appears efficacious against HZ and PHN irrespective of sex, region, or geographic ancestry/ethnicity.

Primary Outcome Measures is Number of Subjects With Any Episodes of Herpes Zoster (HZ); Extracted Interventionsis is Herpes Zoster Vaccine GSK1437173A Placebo; Conditions is Herpes Zoster|Herpes Zoster Vaccine ;Sex is ALL ;Age is OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Young men who have sex with men's awareness, acceptability, and willingness to participate in HIV vaccine trials: Results from a nationwide online pilot study.Background:New cases of human immunodeficiency virus (HIV) among young men who have sex with men (YMSM) underscore the need to examine their willingness to use biomedical prevention methods, including an acceptable and efficacious HIV vaccine. We examined whether YMSM's vaccine altruism and vaccine-related socials concerns factors were associated with HIV vaccine acceptability across two vaccine efficacy scenarios, and their awareness and willingness to participate in HIV vaccine research.Methods:This secondary analysis uses data from a mHealth trial with YMSM at heightened HIV risk (N = 137; 50% racial/ethnic minority; M = 21.7 years). Most YMSM (91.2%) had tested for HIV, and 17.5% (N = 24) reported a prior STI.We used paired-samples t-test to compare differences in efficacy acceptability (50% vs 85%), followed by multivariable regressions examining whether vaccine attitudes (altruism and social concerns) were associated with vaccine acceptability and awareness and willingness to participate in HIV vaccine trials. We controlled for age, education, race/ethnicity, prior HIV testing, and STI diagnosis in our analyses.Results:Acceptability for the HIV vaccine with 85% efficacy (M = 8.86; SD = 1.76) was greater than acceptability in the 50% efficacy scenario (M = 7.60; SD = 2.58). Altruistic attitudes were associated with greater vaccine acceptability at 50% (β = 0.62) and 85% (β = 0.59) efficacy. Higher educational attainment was negatively associated with a vaccine with 50% efficacy (β = -0.20, but not for 85% efficacy. Greater vaccine-related social concerns were negatively associated with HIV vaccine research awareness (AOR = 0.38 (95% CI: 0.22, 0.67). Willingness to participate in a HIV vaccine trial was positively associated with age (β = 0.18) and altruism (β = 0.60), and negatively associated with education (β = -0.21).Conclusions:YMSM find HIV vaccines as an acceptable prevention modality and are willing to participate in HIV vaccine trials. Findings highlight the need to consider YMSM's altruistic and social concerns attitudes in HIV vaccine research and explore how to leverage these attitudes in research campaigns. ClinicalTrials.gov Identifier: NCT02842060.

Primary Outcome Measures is Number of Participants With Change in Number of Risky Sexual Partnerships; Extracted Interventionsis is myDEx NTHP; Conditions is HIV Infections ;Sex is MALE ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Low-dose ladostigil for mild cognitive impairment: A phase 2 placebo-controlled clinical trial.Objective:Ladostigil reduces oxidative stress and microglial activation in aging rats. We assessed its safety and potential efficacy in a 3-year, randomized, double-blind, placebo-controlled phase 2 clinical trial in patients with mild cognitive impairment (MCI) and medial temporal lobe atrophy.Methods:Patients 55 to 85 years of age with MCI, Clinical Dementia Rating (CDR) score of 0.5, Mini-Mental State Examination (MMSE) score >24, Wechsler Memory Scale-Revised Verbal Paired Associates I score ≤18, and Medial Temporal Lobe Atrophy Scale score >1 were stratified by APOE ε4 genotype and randomly assigned (1:1) to ladostigil 10 mg/d or placebo. Primary outcomes were safety and onset of Alzheimer disease dementia. Secondary endpoints were Neuropsychological Test Battery (NTB) composite, Disability Assessment in Dementia (DAD), and Geriatric Depression Scale (GDS) scores. Exploratory outcomes were NTB component, CDR, and MMSE scores. Biomarkers included MRI-derived whole-brain, hippocampus, and entorhinal cortex volumes.Results:Two hundred ten patients from 15 sites in Austria, Germany, and Israel were randomly allocated to placebo (107 patients) or ladostigil (103 patients). After 36 months, 21 of 103 patients on placebo and 14 of 99 patients receiving ladostigil progressed to Alzheimer disease (log-rank test p = 0.162). There were no significant effects on the NTB composite, DAD, or GDS score. Whole-brain and hippocampus volumes decreased more in the placebo than in the ladostigil group (whole brain, p = 0.025, Cohen d = 0.43; hippocampus, p = 0.043, d = 0.43). Serious adverse events were reported by 28 of 107 patients treated with placebo and 26 of 103 with ladostigil.Conclusion:Ladostigil was safe and well tolerated but did not delay progression to dementia. Its association with reduced brain and hippocampus volume loss suggests a potential effect on atrophy.Clinicaltrialsgov identifier:NCT01429623.Classification of evidence:This study provides Class II evidence that for patients with MCI and medial temporal lobe atrophy, ladostigil did not significantly decrease the risk of the development of Alzheimer disease.

Primary Outcome Measures is Conversion From Mild Cognitive Impairment to Alzheimer's Disease Compared to Placebo; Extracted Interventionsis is ladostigil hemitartrate Placebo; Conditions is Mild Cognitive Impairment|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.Immunogenicity and Safety of a Sabin Strain-Based Inactivated Polio Vaccine: A Phase 3 Clinical Trial.Background:The Sabin strain-based inactivated polio vaccine (sIPV) plays a vital role in eradicating poliomyelitis in developing countries.Methods:The study was designed as a randomized, controlled, double-blinded, noninferiority trial. A total of 1200 healthy infants aged 60-90 days were enrolled and randomly assigned to receive 3 doses of either sIPV (the experimental arm) or IPV (the control arm) at days 0, 30, and 60. Immunogenicity and safety outcomes were assessed using the per-protocol and safety populations, respectively.Results:A total of 553 and 562 participants in the sIPV and IPV groups, respectively, were included in the per-protocol population. Seroconversion rates in the sIPV and IPV groups were 98.0% and 94.1%, respectively, for type 1 poliovirus (P < .01); 94.8% and 84.0%, respectively, for type 2 (P < .01); and 98.9% and 97.7%, respectively, for type 3 (P = .11). A total of 599 and 600 participants in the sIPV and IPV groups, respectively, were included in the safety population. Fever was the most common adverse event, occurring in 61.6% and 49.8% of participants in the experimental and control arms, respectively (P < .01).Conclusions:The sIPV demonstrated an immunogenicity profile noninferior to that of the conventional IPV and had a good safety profile.Clinical trials registration:NCT03526978.

Primary Outcome Measures is The seroconversion rates (SCRs) of each group after primary immunization.; Extracted Interventionsis is Investigational sIPV Control IPV; Conditions is Poliomyelitis ;Sex is ALL ;Age is CHILD

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Patient perspectives on hypertension management in health system of Sri Lanka: a qualitative study.Introduction:Uncontrolled hypertension is the leading risk factor for mortality globally, including low-income and middle-income countries (LMICs). However, pathways for seeking hypertension care and patients' experience with the utilisation of health services for hypertension in LMICs are not well understood.Objectives:This study aimed to explore patients' perspectives on different dimensions of accessibility and availability of healthcare for the management of uncontrolled hypertension in Sri Lanka.Setting:Primary care in rural areas in Sri Lanka.Participants:20 patients with hypertension were purposively sampled from an ongoing study of Control of Blood Pressure and Risk Attenuation in rural Bangladesh, Pakistan, Sri Lanka.Method:We conducted in-depth interviews with patients. Interviews were audio-recorded and transcribed into local language (Sinhala) and translated to English. Thematic analysis was used and patient pathways on their experiences accessing care from government and private clinics are mapped out.Results:Overall, most patients alluded to the fact that their hypertension was diagnosed accidentally in an unrelated visit to a healthcare provider and revealed lack of adherence and consuming alternatives as barriers to control hypertension. Referring to the theme 'Accessibility and availability of hypertension care', patients complained of distance to the hospitals, long waiting time and shortage of medicine supplies at government clinics as the main barriers to accessing health services. They often resorted to private physicians and paid out of pocket when they experienced acute symptoms attributable to hypertension. Considering the theme 'Approachability and ability to perceive', the majority of patients mentioned increasing public awareness, training healthcare professionals for effective communication as areas of improvement. Under the theme 'Appropriateness and ability to engage', few patients were aware of the names or purpose of their medications and reportedly missed doses frequently. Reminders from family members were considered a major facilitator to adherence to antihypertensive medications. Patients welcomed the idea of outreach services for hypertension and health education closer to home in the theme 'Things the patients reported to improve the system'.Conclusion:Patients identified several barriers to accessing hypertension care in Sri Lanka. Measures recommended improving hypertension management in Sri Lanka including public education on hypertension, better communication between healthcare professionals and patients, and efforts to improve access and understanding of antihypertensive medications.Trial registration number:NCT02657746.

Primary Outcome Measures is Blood pressure reading:change in systolic blood pressure (SBP) from baseline to follow-up at 24 months post randomization.; Extracted Interventionsis is multi-component interventions; 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.Results of MyPlan 2.0 on Physical Activity in Older Belgian Adults: Randomized Controlled Trial.Background:The beneficial effects of physical activity (PA) for older adults are well known. However, few older adults reach the health guideline of 150 min per week of moderate-to-vigorous PA (MVPA). Electronic health (eHealth) interventions are effective in increasing PA levels in older adults in the short term but, rarely, intermediate-term effects after a period without the support of a website or an app have been examined. Furthermore, current theory-based interventions focus mainly on preintentional determinants, although postintentional determinants should also be included to increase the likelihood of successful behavior change.Objective:This study aimed to investigate the effect of the theory-based eHealth intervention, MyPlan 2.0, focusing on pre- and postintentional determinants on both accelerometer-based and self-reported PA levels in older Belgian adults in the short and intermediate term.Methods:This study was a randomized controlled trial with three data collection points: baseline (N=72), post (five weeks after baseline; N=65), and follow-up (three months after baseline; N=65). The study took place in Ghent, and older adults (aged ≥65 years) were recruited through a combination of random and convenience sampling. At all the time points, participants were visited by the research team. Self-reported domain-specific PA was assessed using the International Physical Activity Questionnaire, and accelerometers were used to objectively assess PA. Participants in the intervention group got access to the eHealth intervention, MyPlan 2.0, and used it independently for five consecutive weeks after baseline. MyPlan 2.0 was based on the self-regulatory theory and focused on both pre- and postintentional processes to increase PA. Multilevel mixed-models repeated measures analyses were performed in R (R Foundation for Statistical Computing).Results:Significant (borderline) positive intervention effects were found for accelerometer-based MVPA (baseline-follow-up: intervention group +5 min per day and control group -5 min per day; P=.07) and for accelerometer-based total PA (baseline-post: intervention group +20 min per day and control group -24 min per day; P=.05). MyPlan 2.0 was also effective in increasing self-reported PA, mainly in the intermediate term. A positive intermediate-term intervention effect was found for leisure-time vigorous PA (P=.02), moderate household-related PA (P=.01), and moderate PA in the garden (P=.04). Negative intermediate-term intervention effects were found for leisure-time moderate PA (P=.01) and cycling for transport (P=.07).Conclusions:The findings suggest that theory-based eHealth interventions focusing on pre- and postintentional determinants have the potential for behavior change in older adults. If future studies including larger samples and long-term follow-up can confirm and clarify these findings, researchers and practitioners should be encouraged to use a self-regulation perspective for eHealth intervention development.Trial registration:Clinicaltrials.gov NCT03194334; https://clinicaltrials.gov/ct2/show/NCT03783611.

Primary Outcome Measures is change in accelerometer-based physical activity; Extracted Interventionsis is MyPlan 2.0.; Conditions is Physical Activity|Older Adults ;Sex is ALL ;Age is OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.PREPARE: protocol for a stepped wedge trial to evaluate whether a risk stratification model can reduce preterm deliveries among women with suspected or confirmed preterm pre-eclampsia.Background:Preeclampsia (PE) is a major cause of short and long-term morbidity for affected infants, including consequences of fetal growth restriction and iatrogenic prematurity. In Brazil, this is a special problem as PE accounts for 18% of preterm births (PTB). In the PREPARE (Prematurity REduction by Pre-eclampsia cARE) study, we will test a novel system of integrated care based on risk stratification and knowledge transfer, to safely reduce PTB.Methods:This is a stepped wedge cluster randomised trial that will include women with suspected or confirmed PE between 20 + 0 and 36 + 6 gestational weeks. All pregnant women presenting with these findings at seven tertiary centres in geographically dispersed sites, throughout Brazil, will be considered eligible and evaluated in terms of risk stratification at admission. At randomly allocated time points, sites will transition to risk stratification performed according to sFlt-1/PlGF (Roche Diagnostics) measurement and fullPIERS score with both results will be revealed to care providers. The healthcare providers of women stratified as low risk for adverse outcomes (sFlt-1/PlGF ≤38 AND fullPIERS< 10% risk) will receive the recommendation to defer delivery. sFlt-1/PlGF will be repeated once and fullPIERS score twice a week. Rates of prematurity due to preeclampsia before and after the intervention will be compared. Additionally, providers will receive an active program of knowledge transfer about WHO recommendations for preeclampsia, including recommendations regarding antenatal corticosteroids for foetal benefits, antihypertensive therapy and magnesium sulphate for seizure prophylaxis. This study will have 90% power to detect a reduction in PTB associated with PE from a population estimate of 1.5 to 1.0%, representing a 33% risk reduction, and 80% power to detect a reduction from 2.0 to 1.5% (25% risk reduction). The necessary number of patients recruited to achieve these results is 750. Adverse events, serious adverse events, both anticipated and unanticipated will be recorded.Discussion:The PREPARE intervention expects to reduce PTB and improve care of women with PE without significant adverse side effects. If successful, this novel pathway of care is designed for rapid translation to healthcare throughout Brazil and may be transferrable to other low and middle income countries.Trial registration:ClinicalTrials.gov : NCT03073317.

Primary Outcome Measures is patients with preterm preeclampsia; Extracted Interventionsis is FullPIERS and sFlit/PLGF (Soluble fms-Like Tyrosine Kinase-1-to-Placental Growth Factor Ratio); Conditions is Pre-Eclampsia|Premature Birth ;Sex is FEMALE ;Age is CHILD, ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Feasibility and effectiveness of electronic vs. paper partograph on improving birth outcomes: A prospective crossover study design.Background:The partograph has been endorsed by World Health Organization (WHO) since 1994 which presents an algorithm for assessing maternal and foetal conditions and labor progression. Monitoring labour with a partograph can reduce adverse pregnancy outcomes such as prolonged labor, emergency C-sections, birth asphyxia and stillbirths. However, partograph use is still very low, particularly in low and middle income countries (LMICs). In Bangladesh the reported partograph user rate varies from 1.4% to 33.0%. Recently, an electronic version of the partograph, with the provision of online data entry and user aid for emergency clinical support, has been tested successfully in different settings. With this proven evidence, we conducted and operations research to test the feasibility and effectiveness of implementing an e-partograph, for the first time, in 2 public hospitals in Bangladesh.Methods:We followed a prospective crossover design. Two secondary level referral hospitals, Jessore and Kushtia District Hospital (DH) were the study sites. All pregnant women who delivered in the study hospitals were the study participants. All nurse-midwives working in the labor ward of study hospitals were trained on appropriate use of both types of partograph along with standard labour management guidelines. Collected quantitative data was analyzed using SPSS 23 statistical software. Discrete variables were expressed as percentages and presented as frequency distribution and cross tabulations. Chi square tests were employed to test the association between exposure and outcome variables. Potential confounding factors were adjusted using multivariate binary logistic regression methods. Ethical approval was obtained from the institutional review board of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b).Findings:In total 2918 deliveries were conducted at Jessore DH and 2312 at Kushtia DH during one-year study period. Of them, 1012 (506 in each facility) deliveries were monitored using partograph (paper or electronic). The trends of facility based C-section rates was downwards in both the hospitals; 43% to 37% in Jessore and from 36% to 25% in Kushtia Hospital. There was a significant reduction of prolonged labour with e-partograph use. In Kushtia DH, the prolonged labour rate was 42% during phase 1 with the paper version which came down to 29% during phase-2 with the e-partograph use. The similar result was observed in Jessore DH where the prolonged labour rate reduced to 7% with paper partograph from the reported 30% prolonged labour with e-partograph. The e-partograph user rate was higher than the paper partograph during both phases (phase 1: 3.31, CI: 2.04-5.38, p < .001 and in phase 2: 15.20 CI: 6.36-36.33, p < .001) after adjusting for maternal age, parity, gestational age, religion, mother's education, husband's education, and fetal sex.Conclusion:The partograph user rate has significantly improved with the e- partograph and was associated with an overall reduction in cesarean births. Use of the e-partograph was also associated with reduced rates of prolonged labour. This study has added to the growing body of evidence on the positive impact of e-partograph use. We recommend implementing e-partograph intervention at scale in both public and private hospitals in Bangladesh.Trial registration:ClinicalTrials.gov NCT03509103.

Primary Outcome Measures is User rate of Electronic Partograph; Extracted Interventionsis is Electronic Partograph; Conditions is Prolonged Labor ;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.Pre-operative trichiatic eyelash pattern predicts post-operative trachomatous trichiasis.Importance:Trichiasis surgery programs globally have faced high rates of poor surgical outcomes. Identifying correctable risk factors for improving long-term outcomes is essential for countries targeting elimination of trachoma as a public health problem.Objective:To determine whether the location of trichiatic eyelashes prior to surgery influences development of post-operative trichiasis (PTT) within two years after surgery.Design:Secondary data analysis of four randomized clinical trials evaluating methods to improve trichiasis surgery outcomes. These include the Surgery for Trichiasis, Antibiotics for Recurrence (STAR) trial, Partnership for Rapid Elimination of Trachoma (PRET-Surgery), absorbable versus silk sutures trial, and epilation versus surgery for minor trichiasis trial.Setting:Primary trials were conducted in rural areas of Ethiopia and Tanzania.Interventions or exposures:Trichiasis surgery performed with either the bilamellar tarsal rotation procedure or posterior lamellar rotation procedure.Main outcomes:Prevalence of PTT within two years after surgery, location of trichiatic eyelashes pre-operatively and post-operatively.Results:6,747 eyelids that underwent first-time trichiasis surgery were included. PTT rates varied by study, ranging from 10-40%. PTT was less severe (based on number of trichiatic eyelashes) than initial trichiasis for 72% of those developing PTT, and only 2% of eyelids were worse at follow up than pre-operatively. Eyelids with central only-trichiasis pre-operatively had lower rates of PTT than eyelids with peripheral only trichiasis in each of the three trials that included severe TT cases. 10% of eyelids with peripheral trichiasis pre-operatively that develop PTT have central TT post-operatively.Conclusions and relevance:Pre-operative central trichiasis is less likely than peripheral trichiasis to be associated with subsequent PTT. Regardless of type of surgery, surgeon skill levels, or pre-operative trichiasis severity, the presence of peripheral trichiasis pre-operatively is associated with higher rates of PTT. Making an incision that extends the length of the eyelid and adequately rotating the nasal and temporal aspects of the eyelid when suturing may help to minimize the chance of developing peripheral PTT.Trial registration:ClinicalTrials.gov PRET: NCT00886015; Suture: NCT005228560; Epilation: NCT00522912.

Primary Outcome Measures is Trichiasis; Extracted Interventionsis is Trichiasis surgery Epilation; Conditions is Trachomatous Trichiasis ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Forced diuresis with matched hydration during transcatheter aortic valve implantation for Reducing Acute Kidney Injury: a randomized, sham-controlled study (REDUCE-AKI).Aims:Acute kidney injury (AKI) is a common complication following transcatheter aortic valve implantation (TAVI) and is associated with increased risk for short- and long-term mortality. In patients undergoing percutaneous coronary intervention (PCI), forced diuresis with matched hydration has been shown to reduce the incidence of AKI by ∼50%. The aim of the present study was to evaluate whether forced diuresis with matched intravenous hydration reduces AKI in patients undergoing TAVI.Methods and results:Reducing Acute Kidney Injury (REDUCE-AKI) was a single-centre, prospective, randomized, double-blind sham-controlled clinical trial, designed to examine the effect of an automated matched saline infusion with urine output for the prevention of AKI in patients undergoing TAVI. A total of 136 TAVI patients were randomized, 68 in each group. Mean age was 83.9 ± 5 years and 41.2% were males. There were no differences in baseline characteristics between the two groups. The rate of AKI was not statistically different between the groups (25% in the active group vs. 19.1% in the sham group, P = 0.408). There was a significant increase in long-term mortality in the active group (27.9% vs. 13. 2% HR 3.744, 95% CI 1.51-9.28; P = 0.004). The study was terminated prematurely by the Data Safety Monitoring Board for futility and a possible signal of harm.Conclusions:Unlike in PCI, forced diuresis with matched hydration does not prevent AKI in patients undergoing TAVI, and might be associated with increased long-term mortality. Future studies should focus on understanding the mechanisms behind these findings.Clinicaltrials.gov registration:NCT01866800, 30 April 2013.

Primary Outcome Measures is Reduction of acute kidney injury (stage 1 or above) at 48-72 hours.; Extracted Interventionsis is Renal Guard Conventional Treatment; Conditions is Radiographic Contrast Agent Nephropathy|Aortic Valve Stenosis With Insufficiency ;Sex is ALL ;Age is OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Improvement of Working Memory is a Mechanism for Reductions in Delay Discounting Among Mid-Age Individuals in an Urban Medically Underserved Area.Background:Delay discounting, or the tendency to devalue rewards as a function of their delayed receipt, is associated with myriad negative health behaviors. Individuals from medically underserved areas are disproportionately at risk for chronic health problems. The higher rates of delay discounting and consequent adverse outcomes evidenced among low-resource and unstable environments suggest this may be an important pathway to explain health disparities among this population.Purpose:The current study examined the effectiveness of a computerized working memory training program to decrease rates of delay discounting among residents of a traditionally underserved region.Methods:Participants (N = 123) were recruited from a community center serving low income and homeless individuals. Subjects completed measures of delay discounting and working memory and then took part in either an active or control working memory training.Results:Analyses indicated that participants in the active condition demonstrated significant improvement in working memory and that this improvement mediated the relation between treatment condition and reductions in delay discounting.Conclusions:Results suggest that a computerized intervention targeting working memory may be effective in decreasing rates of delay discounting in adults from medically underserved areas (ClinicalTrials.gov number NCT03501706).

Primary Outcome Measures is Change in Delay Discounting (DD); Extracted Interventionsis is Sequenced Recall of Digits--Auditory Sequenced Reverse Recall of Digits--Auditory Sequenced Recall of Words--Visual Verbal Memory--Visual; Conditions is Delay Discounting ;Sex is ALL ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Optimal strategy of switching from clopidogrel to ticagrelor in Chinese acute coronary syndrome patients with complicated coronary artery disease: the switching from clopidogrel to ticagrelor (SHIFT-CACS) study.Background:The dose and time point for switching from clopidogrel to ticagrelor remain controversial, especially for Chinese acute coronary syndrome (ACS) patients with complicated coronary artery disease (CAD). Hence, the purpose of this study was to further explore the optimal dose and time point for the switching strategy to balance the increase in platelet inhibition and the decrease in adverse events in Chinese ACS patients with complicated CAD managed by percutaneous coronary intervention (PCI).Methods:From July 2017 to December 2017, the prospective, randomized, open-label study (the SwitcHIng from clopidogrel to ticagrelor study) assigned the eligible Chinese ACS patients with complicated CAD managed by PCI (n = 102) for 90 mg of ticagrelor at 12 h (T-90 mg-12 h), 90 mg of ticagrelor at 24 h (T-90 mg-24h) or 180 mg ticagrelor at 24 h (T-180 mg-24 h) after the last dose of clopidogrel. The primary endpoint was the comparison of maximal platelet aggregation (MPA) values at 2 h after switching strategies among the three groups. In addition, the MPA values at baseline, 8 h and before discharge and the rates of high on-treatment platelet reactivity were evaluated, the incidences of bleeding episodes and dyspnea during hospitalization and at 30-day follow-up in our study were also recorded. The MPA was measured by light transmittance aggregometry in our study. A repeated-measures analysis of variance (ANOVA) model and one-way ANOVA were used to compare data for the primary endpoint.Results:The MPA values were significantly decreased in the T-180 mg-24 h group compared with the T-90 mg-12 h group (P = 0.017) and decreased numerically compared with the T-90 mg-24 h group (P = 0.072) at 2 h. In particular, the MPA values were markedly reduced in the T-90 mg-24 h group compared with the T-90 mg-12 h group at 8 h after switching treatment (P = 0.002). There was no significant difference among the three groups in all bleedings and dyspnea events.Conclusions:The optimal treatment strategy recommended in this study for Chinese ACS patients with complicated CAD managed by PCI is 180 or 90 mg of ticagrelor at 24 h after the last dose of clopidogrel. In addition, a negative interaction was detected in this study between the overlap for clopidogrel and ticagrelor at 12 h after the last dose of clopidogrel.Trial registration:ClinicalTrials.gov, NCT03577652; http://clinicaltrials.gov/ct2/show/NCT03577652.

Primary Outcome Measures is Platelet function assessments; Extracted Interventionsis is Ticagrelor; Conditions is Coronary Artery Disease|Ticagrelor ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (BIOSTEMI): a single-blind, prospective, randomised superiority trial.Background:Newer-generation drug-eluting stents that combine ultrathin strut metallic platforms with biodegradable polymers might facilitate vascular healing and improve clinical outcomes in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI) compared with contemporary thin strut second-generation drug-eluting stents. We did a randomised clinical trial to investigate the safety and efficacy of ultrathin strut biodegradable polymer sirolimus-eluting stents versus thin strut durable polymer everolimus-eluting stents in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI.Methods:The BIOSTEMI trial was an investigator-initiated, multicentre, prospective, single-blind, randomised superiority trial at ten hospitals in Switzerland. Patients aged 18 years or older with acute STEMI who were referred for primary PCI were eligible to participate. Patients were randomly allocated (1:1) to either biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Central randomisation was done based on a computer-generated allocation sequence with variable block sizes of 2, 4, and 6, which was stratified by centre, diabetes status, and presence or absence of multivessel coronary artery disease, and concealed using a secure web-based system. Patients and treating physicians were aware of group allocations, whereas outcome assessors were masked to the allocated stent. The experimental stent (Orsiro; Biotronik; Bülach, Switzerland) consisted of an ultrathin strut cobalt-chromium metallic stent platform releasing sirolimus from a biodegradable polymer. The control stent (Xience Xpedition/Alpine; Abbott Vascular, Abbott Park, IL, USA) consisted of a thin strut cobalt-chromium stent platform that releases everolimus from a durable polymer. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial reinfarction (Q-wave and non-Q-wave), and clinically-indicated target lesion revascularisation, within 12 months of the index procedure. All analyses were done with the individual participant as the unit of analysis and according to the intention-to-treat principle. The trial was registered with ClinicalTrials.gov, number NCT02579031.Findings:Between April 26, 2016, and March 9, 2018, we randomly assigned 1300 patients (1623 lesions) with acute myocardial infarction to treatment with biodegradable polymer sirolimus-eluting stents (649 patients and 816 lesions) or durable polymer everolimus-eluting stents (651 patients and 806 lesions). At 12 months, follow-up data were available for 614 (95%) patients treated with biodegradable polymer sirolimus-eluting stents and 626 (96%) patients treated with durable polymer everolimus-eluting stents. The primary composite endpoint of target lesion failure occurred in 25 (4%) of 649 patients treated with biodegradable polymer sirolimus-eluting stents and 36 (6%) of 651 patients treated with durable polymer everolimus-eluting stents (difference -1·6 percentage points; rate ratio 0·59, 95% Bayesian credibility interval 0·37-0·94; posterior probability of superiority 0·986). Cardiac death, target vessel myocardial reinfarction, clinically-indicated target lesion revascularisation, and definite stent thrombosis were similar between the two treatment groups in the 12 months of follow-up.Interpretation:In patients with acute STEMI undergoing primary PCI, biodegradable polymer sirolimus-eluting stents were superior to durable polymer everolimus-eluting stents with respect to target lesion failure at 1 year. This difference was driven by reduced ischaemia-driven target lesion revascularisation in patients treated with biodegradable polymer sirolimus-eluting stents compared with durable polymer everolimus-eluting stents.Funding:Biotronik.

Primary Outcome Measures is Number of patients with target lesion failure (TLF); Extracted Interventionsis is Orsiro Xience; Conditions is Coronary Artery Disease|Acute Coronary 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.A community-based comprehensive intervention to reduce cardiovascular risk in hypertension (HOPE 4): a cluster-randomised controlled trial.Background:Hypertension is the leading cause of cardiovascular disease globally. Despite proven benefits, hypertension control is poor. We hypothesised that a comprehensive approach to lowering blood pressure and other risk factors, informed by detailed analysis of local barriers, would be superior to usual care in individuals with poorly controlled or newly diagnosed hypertension. We tested whether a model of care involving non-physician health workers (NPHWs), primary care physicians, family, and the provision of effective medications, could substantially reduce cardiovascular disease risk.Methods:HOPE 4 was an open, community-based, cluster-randomised controlled trial involving 1371 individuals with new or poorly controlled hypertension from 30 communities (defined as townships) in Colombia and Malaysia. 16 communities were randomly assigned to control (usual care, n=727), and 14 (n=644) to the intervention. After community screening, the intervention included treatment of cardiovascular disease risk factors by NPHWs using tablet computer-based simplified management algorithms and counselling programmes; free antihypertensive and statin medications recommended by NPHWs but supervised by physicians; and support from a family member or friend (treatment supporter) to improve adherence to medications and healthy behaviours. The primary outcome was the change in Framingham Risk Score 10-year cardiovascular disease risk estimate at 12 months between intervention and control participants. The HOPE 4 trial is registered at ClinicalTrials.gov, NCT01826019.Findings:All communities completed 12-month follow-up (data on 97% of living participants, n=1299). The reduction in Framingham Risk Score for 10-year cardiovascular disease risk was -6·40% (95% CI 8·00 to -4·80) in the control group and -11·17% (-12·88 to -9·47) in the intervention group, with a difference of change of -4·78% (95% CI -7·11 to -2·44, p<0·0001). There was an absolute 11·45 mm Hg (95% CI -14·94 to -7·97) greater reduction in systolic blood pressure, and a 0·41 mmol/L (95% CI -0·60 to -0·23) reduction in LDL with the intervention group (both p<0·0001). Change in blood pressure control status (<140 mm Hg) was 69% in the intervention group versus 30% in the control group (p<0·0001). There were no safety concerns with the intervention.Interpretation:A comprehensive model of care led by NPHWs, involving primary care physicians and family that was informed by local context, substantially improved blood pressure control and cardiovascular disease risk. This strategy is effective, pragmatic, and has the potential to substantially reduce cardiovascular disease compared with current strategies that are typically physician based.Funding:Canadian Institutes of Health Research; Grand Challenges Canada; Ontario SPOR Support Unit and the Ontario Ministry of Health and Long-Term Care; Boehringer Ingelheim; Department of Management of Non-Communicable Diseases, WHO; and Population Health Research Institute. VIDEO ABSTRACT.

Primary Outcome Measures is The mean difference in change in Framingham Risk Score (FRS) between the intervention and control communities from baseline to 1 year.; Extracted Interventionsis is Intervention Usual Care; Conditions is Hypertension|Cardiovascular 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.Penicillin V four times daily for five days versus three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci: randomised controlled, open label, non-inferiority study.Objective:To determine whether total exposure to penicillin V can be reduced while maintaining adequate clinical efficacy when treating pharyngotonsillitis caused by group A streptococci.Design:Open label, randomised controlled non-inferiority study.Setting:17 primary healthcare centres in Sweden between September 2015 and February 2018.Participants:Patients aged 6 years and over with pharyngotonsillitis caused by group A streptococci and three or four Centor criteria (fever ≥38.5°C, tender lymph nodes, coatings of the tonsils, and absence of cough).Interventions:Penicillin V 800 mg four times daily for five days (total 16 g) compared with the current recommended dose of 1000 mg three times daily for 10 days (total 30 g).Main outcome measures:Primary outcome was clinical cure five to seven days after the end of antibiotic treatment. The non-inferiority margin was prespecified to 10 percentage points. Secondary outcomes were bacteriological eradication, time to relief of symptoms, frequency of relapses, complications and new tonsillitis, and patterns of adverse events.Results:Patients (n=433) were randomly allocated to the five day (n=215) or 10 day (n=218) regimen. Clinical cure in the per protocol population was 89.6% (n=181/202) in the five day group and 93.3% (n=182/195) in the 10 day group (95% confidence interval -9.7 to 2.2). Bacteriological eradication was 80.4% (n=156/194) in the five day group and 90.7% (n=165/182) in the 10 day group. Eight and seven patients had relapses, no patients and four patients had complications, and six and 13 patients had new tonsillitis in the five day and 10 day groups, respectively. Time to relief of symptoms was shorter in the five day group. Adverse events were mainly diarrhoea, nausea, and vulvovaginal disorders; the 10 day group had higher incidence and longer duration of adverse events.Conclusions:Penicillin V four times daily for five days was non-inferior in clinical outcome to penicillin V three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci. The number of relapses and complications did not differ between the two intervention groups. Five day treatment with penicillin V four times daily might be an alternative to the currently recommended 10 day regimen.Trial registration:EudraCT 2015-001752-30; ClinicalTrials.gov NCT02712307.

Primary Outcome Measures is Clinical cure; Extracted Interventionsis is Phenoxymethylpenicillin; Conditions is Tonsillitis ;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.Wirelessly observed therapy compared to directly observed therapy to confirm and support tuberculosis treatment adherence: A randomized controlled trial.Background:Excellent adherence to tuberculosis (TB) treatment is critical to cure TB and avoid the emergence of resistance. Wirelessly observed therapy (WOT) is a novel patient self-management system consisting of an edible ingestion sensor (IS), external wearable patch, and paired mobile device that can detect and digitally record medication ingestions. Our study determined the accuracy of ingestion detection in clinical and home settings using WOT and subsequently compared, in a randomized control trial (RCT), confirmed daily adherence to medication in persons using WOT or directly observed therapy (DOT) during TB treatment.Methods and findings:We evaluated WOT in persons with active Mycobacterium tuberculosis complex disease using IS-enabled combination isoniazid 150 mg/rifampin 300 mg (IS-Rifamate). Seventy-seven participants with drug-susceptible TB in the continuation phase of treatment, prescribed daily isoniazid 300 mg and rifampin 600 mg, used IS-Rifamate. The primary endpoints of the trial were determination of the positive detection accuracy (PDA) of WOT, defined as the percentage of ingestions detected by WOT administered under direct observation, and subsequently the proportion of prescribed doses confirmed by WOT compared to DOT. Initially participants received DOT and WOT simultaneously for 2-3 weeks to allow calculation of WOT PDA, and the 95% confidence interval (CI) was estimated using the bootstrap method with 10,000 samples. Sixty-one participants subsequently participated in an RCT to compare the proportion of prescribed doses confirmed by WOT and DOT. Participants were randomized 2:1 to receive WOT or maximal in-person DOT. In the WOT arm, if ingestions were not remotely confirmed, the participant was contacted within 24 hours by text or cell phone to provide support. The number of doses confirmed was collected, and nonparametric methods were used for group and individual comparisons to estimate the proportions of confirmed doses in each randomized arm with 95% CIs. Sensitivity analyses, not prespecified in the trial registration, were also performed, removing all nonworking (weekend and public holiday) and held-dose days. Participants, recruited from San Diego (SD) and Orange County (OC) Divisions of TB Control and Refugee Health, were 43.1 (range 18-80) years old, 57% male, 42% Asian, and 39% white with 49% Hispanic ethnicity. The PDA of WOT was 99.3% (CI 98.1; 100). Intent-to-treat (ITT) analysis within the RCT showed WOT confirmed 93% versus 63% DOT (p < 0.001) of daily doses prescribed. Secondary analysis removing all nonworking days (weekends and public holidays) and held doses from each arm showed WOT confirmed 95.6% versus 92.7% (p = 0.31); WOT was non-inferior to DOT (difference 2.8% CI [-1.8%, 9.1%]). One hundred percent of participants preferred using WOT. WOT associated adverse events were <10%, consisting of minor skin rash and pruritus associated with the patch. WOT provided longitudinal digital reporting in near real time, supporting patient self-management and allowing rapid remote identification of those who needed more support to maintain adherence. This study was conducted during the continuation phase of TB treatment, limiting its generalizability to the entire TB treatment course.Conclusions:In terms of accuracy, WOT was equivalent to DOT. WOT was superior to DOT in supporting confirmed daily adherence to TB medications during the continuation phase of TB treatment and was overwhelmingly preferred by participants. WOT should be tested in high-burden TB settings, where it may substantially support low- and middle-income country (LMIC) TB programs.Trial registration:ClinicalTrials.gov NCT01960257.

Primary Outcome Measures is Step 1: Positive Detection Accuracy (PDA); Extracted Interventionsis is Digital Health Feedback System SOC DOT; Conditions is Tuberculosis ;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 Case for Promoting Movement Medicine: Preventing Disability in the LIFE Randomized Controlled Trial.Background:The movement profile of older adults with compromised function is unknown, as is the relationship between these profiles and the development of major mobility disability (MMD)-a critical clinical outcome. We first describe the dimensions of movement in older adults with compromised function and then examine whether these dimensions predict the onset of MMD.Methods:Older adults at risk for MMD (N = 1,022, mean age = 78.7 years) were randomized to receive a structured physical activity intervention or health education control. We assessed MMD in 6-month intervals (average follow-up of 2.2 years until incident MMD), with activity assessed at baseline, 6-, 12- and 24-month follow-up via accelerometry.Results:A principal components analysis of 11 accelerometer-derived metrics yielded three components representing lifestyle movement (LM), extended bouts of moderate-to-vigorous physical activity (MVPA), and stationary body posture. LM accounted for the greatest proportion of variance in movement (53%). Within health education, both baseline LM (HR = 0.74; 95% CI 0.62 to 0.88) and moderate-to-vigorous physical activity (HR = 0.69; 95% CI 0.54 to 0.87) were associated with MMD, whereas only LM was associated with MMD within physical activity (HR = 0.74; 95% CI 0.61 to 0.89). There were similar nonlinear relationships present for LM in both physical activity and health education (p < .04), whereby risk for MMD was lower among individuals with higher levels of LM.Conclusions:Both LM and moderate-to-vigorous physical activity should be central in treatment regimens for older adults at risk for MMD.Trial registration:clinicaltrials.gov Identifier NCT01072500.

Primary Outcome Measures is Major Mobility Disability; Extracted Interventionsis is Physical Activity Successful Aging; Conditions is Sedentary Lifestyle|Risk of Disability|Aging ;Sex is ALL ;Age is OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.An Open Trial of Behavioral Activation in Veterans With Major Depressive Disorder or Posttraumatic Stress Disorder in Primary Care.Objective:Integrated behavioral health programs provide brief evaluations and interventions to patients with psychiatric symptoms in primary care. These programs seek to decrease stigma and improve access to mental health services. Several psychotherapeutic interventions are available to providers, each with its own strengths and weaknesses. One treatment with particular promise is behavioral activation treatment for depression (BATD) due to its potential clinical efficacy, transdiagnostic potential, and ease of dissemination and implementation in primary care settings. The objective of this study was to investigate the efficacy of BATD across 2 DSM-5 diagnoses: major depressive disorder (MDD) and posttraumatic stress disorder (PTSD).Methods:Participants were recruited from October 2014 to December 2017. Thirty-one participants were referred from primary care and consented to receive a 12-session trial of BATD. Participants endorsed criteria consistent with a principal diagnosis of either MDD (n = 20) or PTSD (n = 11). Self-report measures were completed at baseline and immediately posttreatment to monitor treatment progress in symptoms of PTSD and MDD.Results:Twelve of the 31 participants completed all 12 sessions of BATD, although over 70% completed at least 4 sessions. Participants demonstrated significant symptom improvement across symptoms of MDD and PTSD (all P < .004). No disorder group differences were evidenced for symptom reduction, treatment completion, or treatment satisfaction.Conclusions:The present study provides support for the efficacy of BATD for patients with MDD and PTSD. These findings may have implications for the dissemination and implementation efforts for psychotherapies in integrated primary care settings.Trial registration:ClinicalTrials.gov identifier: NCT01947647.

Primary Outcome Measures is DASS-Depression; Extracted Interventionsis is Transdiagnostic Behavior Therapy Behavioral Activation Therapy; Conditions is Major Depressive Disorder|Persistent Depressive Disorder|Posttraumatic Stress Disorder|Panic Disorder|Social Phobia|Specific Phobia|Generalized Anxiety Disorder|Obsessive Compulsive Disorder ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Person-centred, integrated and pro-active care for multi-morbid elderly with advanced care needs: a propensity score-matched controlled trial.Background:Person-centred care (PCC) focusing on personalised goals and care plans derived from "What matters to you?" has an impact on single disease outcomes, but studies on multi-morbid elderly are lacking. Furthermore, the combination of PCC, Integrated Care (IC) and Pro-active care are widely recognised as desirable for multi-morbid elderly, yet previous studies focus on single components only, leaving synergies unexplored. The effect of a synergistic intervention, which implements 1) Person-centred goal-oriented care driven by "What matters to you?" with 2) IC and 3) pro-active care is unknown.Methods:Inspired by theoretical foundations, complexity science, previous health service research and a patient-driven evaluation of care quality, we designed the Patient-Centred Team (PACT) intervention across primary and secondary care. The PACT team collaborate with the patient to make and deliver a person-centred, integrated and proactive multi-morbidity care-plan. The control group receives conventional care. The study design is a pragmatic six months prospective, controlled clinical trial based on hospital electronic health record data of 439 multi-morbid frail elderly at risk for emergency (re) admissions referred to PACT and 779 propensity score matched controls in Norway, 2014-2016. Outcomes are emergency admissions, the sum of emergency inpatient bed days, 30-day readmissions, planned and emergency outpatient visits and mortality at three and six months follow-up.Results:The Rate Ratios (RR) for emergency admissions was 0,9 (95%CI: 0,82-0,99), for sum of emergency bed days 0,68 (95%CI:0,52-0,79) and for 30-days emergency readmissions 0,72 (95%CI: 0,41-1,24). RRs were 2,3 (95%CI: 2,02-2,55) and 0,9 (95%CI: 0,68-1,20) for planned and emergency outpatient visits respectively. The RR for death at 3 months was 0,39 (95% CI: 0,22-0,70) and 0,57 (95% CI: 0,34-0,94) at 6 months.Conclusion:Compared with propensity score matched controls, the care process of frail multi-morbid elderly who received the PACT intervention had a reduced risk of high-level emergency care, increased use of low-level planned care, and substantially reduced mortality risk. Further study of process differences between groups is warranted to understand the genesis of these results better.Trial registration:ClinicalTrials.gov (identifier: NCT02541474 ), registered Sept 2015.

Primary Outcome Measures is SF-12; Extracted Interventionsis is Integrated care; Conditions is Frail Elderly w/ Multimorbidity & Functional Limitations ;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 1/2a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa.BACKGROUNDRecessive dystrophic epidermolysis bullosa (RDEB) patients have mutations in the COL7A1 gene and thus lack functional type VII collagen (C7) protein; they have marked skin fragility and blistering. This single-center phase 1/2a open-label study evaluated the long-term efficacy, safety, and patient-reported outcomes in RDEB patients treated with gene-corrected autologous cell therapy.METHODSAutologous keratinocytes were isolated from participant skin biopsies. Epidermal sheets were prepared from cells transduced with a retrovirus carrying the full-length human COL7A1 gene. These gene-corrected autologous epidermal sheets measured 5 × 7 cm (35 cm2) and were transplanted onto 6 wound sites in each of 7 adult participants (n = 42 sites total) from 2013 to 2017. Participants were followed for 2 to 5 years.RESULTSNo participants experienced any serious related adverse events. Wound healing of 50% or greater by Investigator Global Assessment was present in 95% (36 of 38) of treated wounds versus 0% (0 of 6) of untreated control wounds at 6 months (P < 0.0001). At year 1, 68% (26 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.025). At year 2, 71% (27 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.019).CONCLUSIONC7 expression persisted up to 2 years after treatment in 2 participants. Treated wounds with 50% or greater healing demonstrated improvement in patient-reported pain, itch, and wound durability. This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with ex vivo, C7 gene-corrected autologous cell therapy. This approach was safe and promoted wound healing that was associated with improved patient-reported outcomes.TRIAL REGISTRATIONClinicaltrials.gov identifier: NCT01263379.FUNDINGEpidermolysis Bullosa Research Partnership, Epidermolysis Bullosa Medical Research Foundation, NIH R01 AR055914, Office of Research and Development at the Palo Alto Veteran's Affairs Medical Center, and the Dermatology Foundation.

Primary Outcome Measures is Number of Wounds by Healing Category Per Investigator Visual Assessment; Extracted Interventionsis is LZRSE-Col7A1 Engineered Autologous Epidermal Sheets; Conditions is Epidermolysis Bullosa Dystrophica|Epidermolysis Bullosa ;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.Isoniazid Preventive Therapy in HIV-Infected Pregnant and Postpartum Women.Background:The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown.Methods:In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years.Results:A total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], -4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, -0.39; 95% CI, -1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, -0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9).Conclusions:The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. (Funded by the National Institutes of Health; IMPAACT P1078 TB APPRISE ClinicalTrials.gov number, NCT01494038.).

Primary Outcome Measures is Incidence Rate of Combined Endpoint: Grade 3 or Higher Adverse Events (AEs) Related to Treatment; Extracted Interventionsis is Isoniazid (INH) Placebo for isoniazid (INH); Conditions is HIV Infections|Tuberculosis ;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.Ligelizumab for Chronic Spontaneous Urticaria.Background:In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose-response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H1-antihistamines at approved or increased doses, alone or in combination with H2-antihistamines or leukotriene-receptor antagonists.Methods:In a phase 2b dose-finding trial, we randomly assigned patients to receive ligelizumab at a dose of 24 mg, 72 mg, or 240 mg, omalizumab at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, or a single 120-mg dose of ligelizumab. Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose-response relationship for the complete control of hives (indicated by a weekly hives-severity score of 0, on a scale from 0 to 21, with higher scores indicating greater severity); the primary end point of this response was assessed at week 12. Complete symptom control was indicated by a weekly urticaria activity score of 0 (on a scale from 0 to 42, with higher scores indicating greater severity). Safety was analyzed throughout the trial.Results:A total of 382 patients underwent randomization. At week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of hives, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. A dose-response relationship was established. At week 12, a total of 30%, 44%, and 40% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of symptoms, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. In this small and short trial, no safety concerns regarding ligelizumab or omalizumab emerged.Conclusions:A higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT02477332.).

Primary Outcome Measures is Percentage of Participants With Complete Hives Response (HSS7=0); Extracted Interventionsis is QGE031 Omalizumab Placebo; Conditions is Chronic Spontaneous Urticaria ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Linked dual-class HIV resistance mutations are associated with treatment failure.We hypothesized that HIV-1 with dual-class but not single-class drug resistance mutations linked on the same viral genome, present in the virus population before initiation of antiretroviral therapy (ART), would be associated with failure of ART to suppress viremia. To test this hypothesis, we utilized an ultrasensitive single-genome sequencing assay that detects rare HIV-1 variants with linked drug resistance mutations (DRMs). A case (ART failure) control (nonfailure) study was designed to assess whether linkage of DRMs in pre-ART plasma samples was associated with treatment outcome in the nevirapine/tenofovir/emtricitabine arm of the AIDS Clinical Trials Group A5208/Optimal Combined Therapy After Nevirapine Exposure (OCTANE) Trial 1 among women who had received prior single-dose nevirapine. Ultrasensitive single-genome sequencing revealed a significant association between pre-ART HIV variants with DRMs to 2 drug classes linked on the same genome (dual class) and failure of combination ART with 3 drugs to suppress viremia. In contrast, linked, single-class DRMs were not associated with ART failure. We conclude that linked dual-class DRMs present before the initiation of ART are associated with ART failure, whereas linked single-class DRMs are not.

Primary Outcome Measures is Time From Randomization to Virologic Failure or Death for Participants Who Had SD NVP Exposure Prior to Study Entry; Extracted Interventionsis is Emtricitabine Emtricitabine/Tenofovir disoproxil fumarate Lopinavir/Ritonavir Nevirapine Tenofovir disoproxil fumarate; Conditions is HIV Infections ;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.Ticagrelor in Patients with Stable Coronary Disease and Diabetes.Background:Patients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear.Methods:In this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria.Results:A total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P = 0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P = 0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P = 0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02).Conclusions:In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.).

Primary Outcome Measures is Composite of Cardiovascular (CV) Death; Extracted Interventionsis is Ticagrelor 60 mg Ticagrelor placebo; Conditions is Diabetes Mellitus, Type 2 ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087.Programmed death-1 inhibitors are approved for patients with relapsed or refractory classic Hodgkin lymphoma (RRcHL). We present the 2-year follow-up of the phase 2 KEYNOTE-087 study of pembrolizumab in 210 patients, based on HL progression after autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV; cohort 1); salvage chemotherapy and BV, with ineligibility for SCT owing to chemorefractory disease (cohort 2); and progression after SCT without BV (cohort 3). With a median follow-up of 27.6 months, the objective response rate (ORR) by blinded independent central review was 71.9% (95% CI, 65.3-77.9), the complete response rate (CRR) was 27.6%, and the partial response (PR) rate was 44.3%. Median duration of response was 16.5 months (range, 0.0+ to 27.0+ [+, no progressive disease at last assessment]) in all patients, 22.1 months in cohort 1, 11.1 months in cohort 2, and 24.4 months in cohort 3. Median progression-free survival was not reached in all patients with CR: 13.8 months (95% CI, 12.0-22.1) for patients with PR and 10.9 months (95% CI, 5.6-11.1) for patients with stable disease. Median overall survival was not reached in all patients or in any cohort. Treatment-related adverse events (TRAEs) of any grade occurred in 153 (72.9%) patients; grades 3 and 4 occurred in 25 (12.0%) patients; none resulted in death. Results confirmed effective antitumor activity, durability of response, and manageable safety of pembrolizumab monotherapy in RRcHL, regardless of prior treatment and including chemoresistant cHL. This trial was registered at www.clinicaltrials.gov as #NCT02453594.

Primary Outcome Measures is Overall Response Rate (ORR); Extracted Interventionsis is pembrolizumab; Conditions is Hodgkin Lymphoma ;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 Combination l-Citrulline and Metformin Treatment on Motor Function in Patients With Duchenne Muscular Dystrophy: A Randomized Clinical Trial.Importance:Nitric oxide precursors, such as the amino acid l-arginine and the biguanide antidiabetic drug metformin, have been associated with metabolism and muscle function in patients with Duchenne muscular dystrophy (DMD). The treatment of DMD remains an unmet medical need.Objective:To evaluate the benefits and harms of a combination of l-citrulline and metformin treatment among patients with DMD.Design, setting, and participants:A single-center randomized double-blind placebo-controlled parallel-group clinical trial was conducted between December 12, 2013, and March 30, 2016, at the University Children's Hospital Basel in Switzerland. A total of 47 ambulant male patients aged 6.5 to 10 years with genetically confirmed DMD were recruited locally and from the patient registries of Switzerland, Germany, Austria, and France. Data were analyzed from April 6, 2016, to September 5, 2019.Interventions:Patients in the treatment group received 2500 mg of l-citrulline and 250 mg of metformin (combination therapy) 3 times a day for 26 weeks compared with patients in the control group, who received placebo.Main outcomes and measures:The primary end point was the change in transfer and standing posture, as assessed by the first dimension of the Motor Function Measure, version 32, from baseline to week 26. Secondary end points included assessments of timed function, quantitative muscle force, biomarkers for muscle necrosis, and adverse events. The 2 prespecified subgroups comprised patients who were able to walk 350 m or more in 6 minutes (stable subgroup) and patients who were not able to walk 350 m in 6 minutes (unstable subgroup) at baseline.Results:Among 49 ambulant male children with DMD who were screened for eligibility, 47 patients with a mean (SD) age of 8.2 (1.1) years were randomized to a treatment group receiving combination therapy (n = 23) or a control group receiving placebo (n = 24), and 45 patients completed the study. No significant differences between groups were found in the results of timed function and muscle force tests for overall, proximal and axial, and distal motor function. Among patients receiving combination therapy, the Motor Function Measure first dimension subscore decrease was 5.5% greater than that of patients receiving placebo (95% CI, -1.0% to 12.1%; P = .09). The administration of combination therapy had significantly favorable effects on the first dimension subscore decrease among the 29 patients in the stable subgroup (6.7%; 95% CI, 0.9%-12.6%; P = .03) but not among the 15 patients in the unstable subgroup (3.9%; 95% CI, -13.2% to 20.9%; P = .63). Overall, the treatment was well tolerated with only mild adverse effects.Conclusions and relevance:Treatment with combination therapy was not associated with an overall reduction in motor function decline among ambulant patients with DMD; however, a reduction in motor function decline was observed among the stable subgroup of patients treated with combination therapy. The statistically nonsignificant difference of distal motor function in favor of combination therapy and the reduced degeneration of muscle tissue appear to support the treatment concept, but the study may have lacked sufficient statistical power. Further research exploring this treatment option with a greater number of patients is warranted.Trial registration:ClinicalTrials.gov identifier: NCT01995032.

Primary Outcome Measures is Mean change of motor function measure (MFM) D1 subscore (assessing standing and transfers); Extracted Interventionsis is 750 mg metformin and 7.5 g L-citrulline daily p.o. Placebo; Conditions is Duchenne's Muscular Dystrophy (DMD) ;Sex is ALL ;Age is CHILD

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of Frequency of Changing Point-of-Use Reminder Signs on Health Care Worker Hand Hygiene Adherence: A Cluster Randomized Clinical Trial.Importance:Although hand hygiene (HH) is considered the most effective strategy for preventing hospital-acquired infections, HH adherence rates remain poor.Objective:To examine whether the frequency of changing reminder signs affects HH adherence among health care workers.Design, setting, and participants:This cluster randomized clinical trial in 9 US Department of Veterans Affairs acute care hospitals randomly assigned 58 inpatient units to 1 of 3 schedules for changing signs designed to promote HH adherence among health care workers: (1) no change; (2) weekly; and (3) monthly. Hand hygiene rates among health care workers were documented at entry and exit to patient rooms during the baseline period from October 1, 2014, to March 31, 2015, of normal signage and throughout the intervention period of June 8, 2015, to December 28, 2015. Data analyses were conducted in April 2018.Interventions:Hospital units were randomly assigned into 3 groups: (1) no sign changes throughout the intervention period, (2) signs changed weekly, and (3) signs changed monthly.Main outcomes and measures:Hand hygiene adherence as measured by covert observation. Interrupted time series analysis was used to examine changes in HH adherence from baseline through the intervention period by group.Results:Among 58 inpatient units, 19 units were assigned to the no change group, 19 units were assigned to the weekly change group, and 20 units were assigned to the monthly change group. During the baseline period, 9755 HH opportunities were observed at room entry and 10 095 HH opportunities were observed at room exit. During the intervention period, a total of 15 855 HH opportunities were observed at room entry, and 16 360 HH opportunities were observed at room exit. Overall HH adherence did not change from baseline compared with the intervention period at either room entry (4770 HH events [48.9%] vs 3057 HH events [50.1%]; P = .14) or exit (6439 HH events [63.8%] vs 4087 HH events [65.2%]; P = .06). In units that changed signs weekly, HH adherence declined from baseline at room entry (-1.9% [95% CI, -2.7% to -0.8%] per week; P < .001) and exit (-0.8% [95% CI, -1.5% to 0.1%] per week; P = .02). No significant changes in HH adherence were observed in other groups.Conclusions and relevance:The frequency of changing reminder signs had no effect on HH rates overall. Units assigned to change signs most frequently demonstrated worsening adherence. Considering the abundance of signs in the acute care environment, the frequency of changing signs did not appear to provide a strong enough cue by itself to promote behavioral change.Trial registration:ClinicalTrials.gov Identifier: NCT02223455.

Primary Outcome Measures is Hand Hygiene Compliance; Extracted Interventionsis is Hand Hygiene Signs; Conditions is Hand Hygiene|Health Care Associated Infection|Compliance ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Stepped Care Internet-Delivered vs Face-to-Face Cognitive-Behavior Therapy for Pediatric Obsessive-Compulsive Disorder: A Trial Protocol for a Randomized Noninferiority Trial.Importance:Internet-delivered cognitive behavior therapy is an effective treatment for children and adolescents with obsessive-compulsive disorder and has the potential to markedly increase access to treatment for patients while being cost-effective for health care organizations.Objective:To investigate whether internet-delivered cognitive behavior therapy implemented within a stepped care model is noninferior to, and cost-effective compared with, the gold standard of face-to-face cognitive behavior therapy for pediatric obsessive-compulsive disorder.Design, setting, and participants:Multicenter, single-blind, randomized clinical noninferiority trial implemented at 2 specialist pediatric obsessive-compulsive disorder clinics in Stockholm and Gothenburg, Sweden. Participants are 152 children and adolescents aged 7 to 17 years with obsessive compulsive disorder, recruited through the 2 clinics and online self-referral. Patients will be randomized 1:1 to the stepped care intervention or face-to-face therapy. Blind evaluations will be conducted after treatment and at 3-month and 6-month follow-ups. At the 6-month follow-up (primary end point), noninferiority will be tested and resource use will be compared between the 2 treatment groups. Data will be analyzed according to intention-to-treat principles.Intervention:Patients randomized to stepped care will first receive internet-delivered cognitive behavior therapy for 16 weeks; patients who are classified as nonresponders 3 months after treatment completion will receive additional face-to-face therapy. The control group will receive 16 weeks of face-to-face cognitive behavior therapy immediately following randomization and nonresponders at the 3-month follow-up will, as in the stepped care group, receive additional face-to-face therapy.Main outcomes and measures:Noninferiority is defined as a 4-point difference on the primary outcome measure (Children's Yale-Brown Obsessive Compulsive Scale).Discussion:Recruitment started October 6, 2017, and was completed May 24, 2019. Results from the primary end point will be available by May 2020. The naturalistic follow-ups (1, 2, and 5 years after the end of treatment) will continue to 2025. There are no interim analyses planned or stopping rules for the trial.Trial registration:ClinicalTrials.gov identifier: NCT03263546.

Primary Outcome Measures is Children's Yale Brown Obsessive-Compulsive Scale (CY-BOCS); Extracted Interventionsis is Internet-delivered cognitive behavioral therapy (ICBT) Cognitive behavioral therapy (CBT); Conditions is Obsessive-Compulsive Disorder ;Sex is ALL ;Age is CHILD

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Biopsying, fragmentation and autotransplantation of fresh ovarian cortical tissue in infertile women with diminished ovarian reserve.Study question:Can ovarian biopsying per se and/or autotransplantation of fragmented ovarian cortical tissue activate dormant follicles and increase the number of recruitable follicles for IVF/ICSI in women with diminished ovarian reserve (DOR)?Summary answer:Ovarian biopsying followed by immediate autotransplantation of fragmented cortical tissue failed to increase the number of recruitable follicles for IVF/ICSI 10 weeks after the procedure either at the graft site or in the biopsied ovary, but 12 of the 20 women subsequently had a clinical pregnancy during the 1-year follow-up.What is known already:Infertile women with DOR constitute a group of patients with poor reproductive outcome mainly due to the low number of mature oocytes available for IVF/ICSI. Recent studies have shown that in vitro activation of residual dormant follicles by both chemical treatment and tissue fragmentation has resulted in return of menstrual cycles and pregnancies in a fraction of amenorrhoeic women with premature ovarian insufficiency.Study design, size, duration:This is a prospective clinical cohort study including 20 women with DOR treated at the fertility clinic, Rigshospitalet, Denmark, during April 2016-December 2017. Non-pregnant patients were on average followed for 280 days (range 118-408), while women who conceived were followed until delivery. Study follow-up of non-pregnant patients ended in September 2018.Participants, materials, setting, methods:The study included infertile women aged 30-39 years with preserved menstrual cycles, indication for IVF/ICSI and repeated serum measurements of anti-Müllerian hormone (AMH) ≤ 5 pmol/L. Patients were randomized to have four biopsies taken from either the left or the right ovary by laparoscopy followed by fragmentation of the cortical tissue to an approximate size of 1 mm3 and autotransplanted to a peritoneal pocket. The other ovary served as a control. Patients were followed weekly for 10 weeks with recording of hormone profile, antral follicle count (AFC), ovarian volume and assessment for ectopic follicle growth. After 10 weeks, an IVF/ICSI-cycle with maximal ovarian stimulation was initiated.Main results and the role of chance:No difference in the number of mature follicles after ovarian stimulation 10 weeks after the procedure in the biopsied versus the control ovaries was observed (1.0 vs. 0.7 follicles, P = 0.35). In only three patients, growth of four follicles was detected at the graft site 24-268 days after the procedure. From one of these follicles, a metaphase II (MII) oocyte was retrieved and fertilized, but embryonic development failed. Overall AMH levels did not change significantly after the procedure (P = 0.2). The AFC increased by 0.14 (95% CI: 0.06;0.21) per week (P < 0.005), and the biopsied ovary had on average 0.6 (95% CI: 0.3;-0.88) follicles fewer than the control ovary (P = 0.01). Serum levels of androstenedione and testosterone increased significantly by 0.63 nmol/L (95% CI: 0.21;1.04) and 0.11 nmol/L (95% CI: 0.01;0.21) 1 week after the procedure, respectively, and testosterone increased consecutively over the 10 weeks by 0.0095 nmol/L (95% CI: 0.0002;0.0188) per week (P = 0.045). In 7 of the 20 patients, there was a serum AMH elevation 5 to 8 weeks after the procedure. In this group, mean AMH increased from 2.08 pmol/L (range 1.74-2.34) to 3.94 pmol/L (range 3.66-4.29) from Weeks 1-4 to Weeks 5-8. A clinical pregnancy was obtained in 12 of the 20 (60%) patients with and without medically assisted reproduction (MAR) treatments. We report a cumulated live birth rate per started IVF/ICSI cycle of 18.4%.Limitations, reason for caution:Limitations of the study were the number of patients included and the lack of a non-operated control group. Moreover, 9 of the 20 women had no male partner at inclusion and were treated with donor sperm, but each of these women had an average of 6.8 (range 4-9) unsuccessful MAR treatments with donor sperm prior to inclusion.Wider implications of the findings:Although 12 out of 20 patients became pregnant during the follow-up period, the current study does not indicate that biopsying, fragmenting and autotransplanting of ovarian cortical tissue increase the number of recruitable follicles for IVF/ICSI after 10 weeks. However, a proportion of the patients may have a follicular response in Weeks 5-8 after the procedure. It could therefore be relevant to perform a future study on the possible effects of biopsying per se that includes stimulation for IVF/ICSI earlier than week 10.Study funding/competing interest(s):This study is part of the ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS. The funders had no role in the study design, data collection and interpretation, or decision to submit the work for publication. None of the authors have a conflict of interest.Trial registration number:NCT02792569.

Primary Outcome Measures is Number of follicles > 12 mm; Extracted Interventionsis is Biopsy of ovarian cortical tissue; Conditions is Infertility ;Sex is FEMALE ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of Comprehensive Care Coordination on Medicaid Expenditures Compared With Usual Care Among Children and Youth With Chronic Disease: A Randomized Clinical Trial.Importance:Medicaid spending on children and young adults with chronic disease could be decreased through care coordination programs by reducing unnecessary hospital and emergency care.Objective:To assess whether a comprehensive care coordination program reduces Medicaid expenditures by decreasing hospital and emergency department (ED) utilization.Design, setting, and participants:This randomized clinical trial included 6259 children and young adults with chronic disease who received public insurance through Illinois Medicaid. In April 2016, eligible youth were randomized to receive comprehensive care coordination through the Coordinated Healthcare for Complex Kids (CHECK) program (n = 3126) or usual care (n = 3119) to measure the effect of the CHECK program on Medicaid expenditures and health care utilization using a difference-in-differences (DID) approach. Data were collected from May 1, 2014, to April 30, 2017, and analyzed in May 2018.Interventions:Care coordination, mental health care, education, and social support were provided to CHECK participants and their family members. Services were tailored based on family and participant need.Main outcomes and measures:Mean annual Medicaid expenditures, mean annual health care utilization by category (ED and inpatient), and chronic disease type and risk level.Results:A total of 6259 participants (mean [SD] age, 11.3 [6.4] years; 2918 [46.6%] female; 2594 [41.4%] with medium and high risk) were randomized. Following the exclusion of 14 outliers, 6245 participants were analyzed. The mean (SD) annual Medicaid expenditure before the intervention was $1633 ($4006) for the intervention group and $1703 ($4466) for the usual care group, which decreased to a mean (SD) of $1341 ($3004) and $1413 ($3785), respectively, after the intervention (DID, -$1; 95% CI, -$199 to $196; P = .99). The mean (SD) inpatient utilization before the intervention was 63.0 (344.4) per 1000 person-years (PYs) for the intervention group and 69.3 (370.9) per 1000 PYs for the usual care group, which decreased to 43.5 (297.2) per 1000 PYs and 47.8 (304.9) per 1000 PYs, respectively, after the intervention (DID, 2.0; 95% CI, -17.9 to 21.8; P = .85). Among participants with asthma, those in the intervention group had a greater mean (SD) decrease in ED utilization compared with usual care, but the difference was not significant (-225.9 [65.3] vs -104.5 [80.0] visits per 1000 PY; DID, -121.5; 95% CI, -268.9 to 26.0; P = .11). Similarly, enrolled participants with sickle cell disease had a smaller but not significant mean (SD) increase in ED utilization compared with usual care (583.3 [839.0] vs 3761.9 [4611.2] visits per 1000 PYs; DID, -3178.6; 95% CI, -10 724.3 to 4367.2; P = .41).Conclusions and relevance:Overall Medicaid expenditures and health care utilization (hospital and ED) decreased similarly for both CHECK participants and the usual care group.Trial registration:ClinicalTrials.gov identifier: NCT04057521.

Primary Outcome Measures is Annual inpatient healthcare utilization per 1000 patient years; Extracted Interventionsis is Care Coordination; Conditions is Asthma|Diabetes Mellitus|Sickle Cell Disease|Premature Birth ;Sex is ALL ;Age is CHILD, ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Diminishing Effects After Recurrent Use of Self-Guided Internet-Based Interventions in Depression: Randomized Controlled Trial.Background:Self-guided internet-based interventions have several advantages over guided interventions and are generally effective in treating psychiatric symptoms.Objective:We aimed to investigate whether the use of a new self-guided internet-based intervention (MOOD) would lead to a significant reduction in depressive symptoms compared with a care-as-usual (CAU) control group in a sample of individuals with depressive symptoms, most of whom had already used a different self-guided internet-based intervention in a previous trial.Methods:A total of 125 individuals were randomized to the intervention condition (MOOD) and received access to the intervention for a period of six weeks or a CAU group. After six weeks, all participants were invited to take part in the post assessment. The Beck Depression Inventory-II served as the primary outcome.Results:Both intention-to-treat as well as per-protocol analyses indicated that the depressive symptomatology decreased in both conditions but showed no advantage for those who had used MOOD. Subsequent moderation analyses suggested that those individuals who had less experience with psychotherapy benefitted to a greater extent compared with those with more experience.Conclusions:Self-guided internet-based interventions are deemed a suitable first-step approach to the treatment of depression. However, our results indicate that they are more efficacious in those with less psychotherapy experience.Trial registration:ClinicalTrials.gov NCT03795480; http://clinicaltrials.gov/ct2/show/NCT03795480.

Primary Outcome Measures is Beck Depression Inventory (BDI); Extracted Interventionsis is MOOD; Conditions is Depressive Symptoms ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Tracheostomy and long-term mortality in ICU patients undergoing prolonged mechanical ventilation.Introduction:In critically ill patients undergoing prolonged mechanical ventilation (MV), the difference in long-term outcomes between patients with or without tracheostomy remains unexplored.Methods:Ancillary study of a prospective international multicentre observational cohort in 21 centres in France and Belgium, including 2087 patients, with a one-year follow-up after admission. We included patients with a MV duration ≥10 days, with or without tracheostomy. We explored the one-year mortality with a classical Cox regression model (adjustment on age, SAPS II, baseline diagnosis and withdrawal of life-sustaining therapies) and a Cox regression model using tracheostomy as a time-dependant variable.Results:29.5% patients underwent prolonged MV, out of which 25.6% received tracheostomy and 74.4% did not. At one-year, 45.2% patients had died in the tracheostomy group and 51.5% patients had died in the group without tracheostomy (p = 0.001). In the Cox-adjusted regression model, tracheostomy was not associated with improved one-year outcome (HR CI95 0.7 [0.5-1.001], p = 0.051), as well as in the model using tracheostomy as a time-dependent variable (OR CI 95 1 [0.7-1.4], p = 0.9).Conclusions:In our study, there was no statistically significant difference in the one-year mortality of patients undergoing prolonged MV when receiving tracheostomy or not.Trial registration:NCT01367093.

Primary Outcome Measures is All cause mortality at one year after ICU discharge; Extracted Interventionsis is nan; Conditions is Intensive Care Unit Syndrome|Tracheal Intubation Morbidity ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Text messaging for maternal and infant retention in prevention of mother-to-child HIV transmission services: A pragmatic stepped-wedge cluster-randomized trial in Kenya.Background:Timely diagnosis of infant HIV infection is essential for antiretroviral therapy (ART) initiation. In a randomized controlled trial, we found the Texting Improves Testing (TextIT) intervention (a theory-based text messaging system) to be efficacious for improving infant HIV testing rates and maternal retention in prevention of mother-to-child HIV transmission (PMTCT) programs. Using an implementation science approach, we aimed to evaluate real-world effectiveness of the intervention.Methods and findings:In a pragmatic, cluster-randomized, stepped-wedge trial with 2 time periods of observation, we randomly allocated 10 clinics to begin implementing the intervention immediately and 10 clinics to begin implementing 6 months later. To approximate real-world conditions, inclusion criteria were broad. Women at clinics implementing the intervention received up to 14 text messages during pregnancy and after delivery and had the option to respond to text messages, call, or send inquiry text messages to a designated clinic phone. The primary outcomes were infant HIV testing and maternal retention in care during the first 8 weeks after delivery. We used modified Poisson regression with robust variance estimation to estimate the relative risk and 95% confidence intervals (CIs). Generalized estimating equations were applied on individual-level data to account for clustering by site. Between February 2015 and December 2016, 4,681 women were assessed for study participation, and 2,515 were included. Participant characteristics at enrollment did not differ by study arm. Overall median age was 27 years (interquartile range [IQR] 23-30), median gestational age was 30 weeks (IQR 28-34), 99% were receiving ART, and 87% who enrolled during intervention phases owned a phone. Of 2,326 infants analyzed, 1,466 of 1,613 (90.9%) in the intervention group and 609 of 713 (85.4%) in the control group met the primary outcome of HIV virologic testing performed before 8 weeks after birth (adjusted relative risk [aRR] 1.03; 95% CI 0.97-1.10; P = 0.3). Of 2,472 women analyzed, 1,548 of 1,725 (90%) in the intervention group and 571 of 747 (76%) in the control group met the primary outcome of retention in care during the first 8 weeks after delivery (aRR 1.12; 95% CI 0.97-1.30; P = 0.1). This study had two main limitations. Staff at all facilities were aware of ongoing observation, which may have contributed to increased rates of infant HIV testing and maternal retention in care at both intervention and control facilities, and programmatic initiatives to improve maternal and infant retention in care were ongoing at all facilities at the time of this study, which likely limited the ability to demonstrate effectiveness of the trial intervention.Conclusions:In this study, a larger proportion of infants in the intervention group received HIV testing compared with the control group, but the difference was small and not statistically significant. There was also a nonsignificant increase in maternal postpartum retention in the intervention periods. Despite the lack of a significant effect of the intervention, key lessons emerged, both for strengthening PMTCT and for implementation research in general. Perhaps most important, improving the implementation of usual care may have been sufficient to substantially improve infant HIV testing rates.Trial registration:ClinicalTrials.gov Trial Number NCT02350140.

Primary Outcome Measures is Postpartum retention in prevention of mother-to-child HIV transmission programs; Extracted Interventionsis is Text messaging from beginning Text messaging after 6 months of control; Conditions is HIV ;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.Effect of a Novel Transition Program on Disability After Stroke: A Trial Protocol.Importance:A gap in care for stroke survivors exists at the point of transition from inpatient rehabilitation to home, when survivors encounter new environmental barriers because of the cognitive and sensorimotor sequelae of stroke. Resolving these barriers and improving independence in the community have the potential to significantly improve stroke survivors' long-term morbidity.Objective:To investigate the efficacy and safety of a novel enhanced rehabilitation transition program to reduce environmental barriers and improve daily activity performance and community participation among stroke survivors.Design, setting, and participants:This is a phase 2b, single-blind, parallel-group, randomized clinical trial. Participants will be randomized using a 1:1 allocation ratio, stratified by Functional Independence Measure and age, to either attentional control or the intervention. Community Participation Transition After Stroke (COMPASS) is a complex intervention that uses 2 complementary evidence-based interventions: home modifications and strategy training delivered in the home. Community participation after stroke, measured by the Reintegration to Normal Living Index, is the primary outcome. Secondary outcomes include quality of life after stroke, measured by the Stroke Impact Scale, and daily activity performance and magnitude of environmental barriers in the home, both measured by the In-Home Occupational Performance Evaluation. An intention-to-treat analysis will be used. A total of 180 participants, who are 50 years or older, were independent in activities of daily living prior to stroke, and are undergoing inpatient rehabilitation following stroke with a plan to be discharged home, will be included in the study.Discussion:Stroke is a leading cause of serious long-term disability in the United States. The COMPASS study is ongoing. To date, 99 participants have been recruited and 77 randomized, with 37 in the treatment group and 40 in the control group. Resumption of previous activities immediately after discharge can improve immediate and long-term community participation. Results from this study will fill a critical gap in stroke rehabilitation evidence by providing important information about the long-term community participation and daily activity performance among stroke survivors as well as environmental barriers in their homes.Trial registration:ClinicalTrials.gov identifier: NCT03485820.

Primary Outcome Measures is Reintegration to Normal Living Index (RNLI); Extracted Interventionsis is COMPASS Stroke education; Conditions is Ischemic Stroke|Hemorrhagic 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.A dose titration study of fentanyl buccal soluble film for breakthrough cancer pain in Taiwan.Background:Fentanyl buccal soluble film (FBSF), a new formulation of fentanyl, is developed for the treatment of breakthrough pain (BTP) in opioid-tolerant patients with cancer.Aims:This study aimed to assess the feasible dose range of FBSF required for Taiwanese population.Methods and results:This was an open-label, multicenter, noncomparative study. Cancer patients who were aged 20 years or older and had a stable regimen equivalent to 60 to 1000 mg/day of oral morphine, 20 to 120 mg/day of intravenous morphine, or 25 to 300 μg/h of transdermal fentanyl for at least 1 week were enrolled. The primary endpoint was the feasible dose range of FBSF. Secondary endpoints included difference in pain intensity at 30 minutes (PID30), percentage of episodes requiring rescue medication, and overall satisfaction. Adverse events (AEs) and serious AEs (SAEs) were recorded for safety measurements. The final effective dose in the per-protocol (PP) population (n = 30) ranged from 200 to 800 μg, of which 26 subjects (86.7%) achieved an effective dose range of 200 to 400 μg. Among the 283 BTP episodes recorded in the maintenance period, the mean PID30 was 4.0, and only 13 events (4.6%) required rescue medication. For 63.6% of the BTP episodes, patients rated their satisfaction as good to excellent. Only 5% of AEs were considered drug-related.Conclusions:Individualized dose titration is recommended for BTP management for patients' benefit. Overall, FBSF was effective and well tolerated and was positively correlated with patients' background opioid dose for persistent pain management.

Primary Outcome Measures is Optimal dose calculation of Painkyl®; Extracted Interventionsis is Fentanyl buccal soluble film (FBSF); Conditions is Breakthrough Cancer Pain ;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 Advanced Platelet-rich Fibrin on Wound Healing after Third Molar Extraction: A Split-mouth Randomized Double-blind Study.Aim:To evaluate the potential of advanced platelet-rich fibrin (A-PRF) as a regenerative biomaterial for bone regeneration and postoperative sequelae after impacted third molar extractions.Materials and methods:This was a split-mouth, randomized, double-blind clinical trial. A total of 10 female patients in King Abdulaziz University Dental Hospital with bilateral impacted third molars were recruited into the study. Surgical extractions were performed on both sides of the mandible. Randomization was done by a coin toss; A-PRF was placed on the one side while the other side did not receive any intervention. Each patient acted as their own control. Both the patients and the investigators were blinded about the A-PRF side. The outcome on periodontal regeneration was made measuring pocket depth (PD), gum recession (GR), and clinical attachment level (CAL) before and at 1- and 3-months postoperatively. Pain, swelling, and healing were assessed on the 7th postoperative day. p value less than 0.05 was considered statistically significant.Results:An estimated 10 patients completed the study. There were no significant differences in PD, CAL, and GR between the two groups at any time point, although the data obtained were slightly favoring the A-PRF. However, a statistically significant reduction in pain and swelling was observed in the A-PRF group compared to the controls (p < 0.05).Conclusion:The findings of this study demonstrate A-PRF as a potential biomaterial for lessening the severity of pain and swelling after third molar surgery. Long-term trials with a larger sample size and more methodically sound assessment tools are needed to obtain more meaningful results on periodontal regeneration.Clinical significance:Placement of A-PRF clot in the extraction socket could lessen postoperative pain and increase patient comfort after third molar extraction.Trial registration:NCT03703479. Registered 8 October 2018 How to cite this article: Zahid TM, Nadershah M. Effect of Advanced Platelet-rich Fibrin on Wound Healing after Third Molar Extraction: A Split-mouth Randomized Double-blind Study. J Contemp Dent Pract 2019;20(10):1164-1170.

Primary Outcome Measures is Clinical Attachment Loss (CAL) (also called Periodontal Attachment Loss); Extracted Interventionsis is autologous blood clot made from the patient own clot without any additive; Conditions is Wound Heal ;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 Prospective Randomized Multicenter Controlled Trial on Salvianolate for Treatment of Unstable Angina Pectoris in A Chinese Elderly Population.Objective:To evaluate the efficacy and safety of salvianolate in elderly patients with unstable angina pectoris (UAP).Methods:A prospective double-blind randomized placebo-controlled multicenter trial in elderly patients with UAP from 13 third-grade class-A hospitals in China was performed. A total of 318 patients were randomly allocated in a 1:1 ratio to an experimental group (160 patients) and a control group (158 patients). The experimental group was treated with salvianolate for 14 days on the basis of conventional medicine, and the control group was given a placebo for 14 days with the same criteria. Follow-up was lasted 28 days in both groups. The primary endpoint was biweekly frequency of angina pectoris attacks. The secondary endpoints included biweekly dosage of nitroglycerin, the Seattle Angina Questionnaire, angina pectoris severity and duration, myocardial injury markers, high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), as well as major adverse cardiovascular events (MACEs). Safety was assessed according to adverse events and serious adverse events.Results:Baseline characteristics were similar between treatment groups. Compared with those in the control group, the frequency of biweekly angina attacks (2.92 vs . 4.08, P=0.025), the biweekly dosage of nitroglycerin, as well as the severity and duration of angina attacks (P<0.01) were reduced by salvianolate. The Seattle Angina Questionnaire score was also significantly improved in the experimental group than in the control group (P<0.05). No significant differences were observed between the two groups with respect to the incidence of MACEs. Salvianolate was well tolerated.Conclusions:Salvianolate appear to have efficacy and well tolerated for elderly patients with UAP. [ClinicalTrials.gov identifier: NCT03037047].

Primary Outcome Measures is symptom of angina pectoris; Extracted Interventionsis is 0.9% Sodium Chloride Injection salvianolate injection; Conditions is Unstable Angina ;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 controlled pilot study of the effects of 6-week high intensity hatha yoga protocol on health-related outcomes among students.Objective:Modern hatha yoga exercises (YE) provide an alternative form of physical activity which may reduce stress, facilitate recovery and improve health. This study investigated the short-term effects of high intensity hatha yoga exercises (HIY) on health-related outcomes.Methods:A 6-week randomized controlled study was performed to compare HIY with a control group not changing their exercise behavior. Healthy students (N = 44; median age: 25 years, range 20-39 years; HIY: n = 21, including 3 men; control group: n = 23, including 3 men) novice to yoga participated in the intervention which included one weekly class and recommended home training. Participants provided self-reports in questionnaires before and after the intervention. Self-reports included anxiety and depression (Hospital Anxiety and Depression Scale), stress (Perceived Stress Scale), sleep quality (Pittsburgh Sleep Quality Index), insomnia (Insomnia Severity Index), subjective health complaints (Common Symptoms in General Practice Index) and self-rated health (single-item).Results:After the 6-week intervention, there were no between-group differences in anxiety, depression, stress, sleep or self-rated health. However, when investigating associations within the HIY-group, a higher HIY-dose was related to less depression (r = 0.47; p = 0.03), improved sleep quality (r = 0.55; p = 0.01), and less insomnia (r = 0.49; p = 0.02).Conclusions:There were no short-term between-group effects of HIY on mental distress, sleep or self-rated health. However, within the HIY-group, a higher dose was associated with improved mental health in terms of depression and with improved sleep. Although future studies with larger samples are needed, these preliminary findings suggest short-term positive effects of HIY on health-related outcomes among students.Trial registration number:NCT01305096.

Primary Outcome Measures is Change in heart rate variability; Extracted Interventionsis is Yoga intervention; Conditions is Stress, Psychological, Physiological ;Sex is ALL ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effects of mirthful laughter on pain tolerance: A randomized controlled investigation.Introduction:Chronic pain is a debilitating condition that affects many people. Currently, there is no single treatment known to cure or assure relief from chronic pain. Accordingly, the management of patients' discomfort is an integral part of treating chronic pain. Such treatment, however, is not effective for many patients. We investigated whether mirthful laughter provided by comic relief can influence pain tolerance and muscle soreness in young healthy participants.Methods:Forty participants underwent a randomized controlled cross-over designed experiment. Each participant was exposed to a comedy video eliciting mirthful laughter and an uninteresting documentary. Delayed onset muscle soreness was induced in one leg at a time by eccentric exercise. Pain tolerance was tested using blunt force application and assessed subjectively using a visual analog scale.Results:Watching the comedy video elicited a significantly greater irregular breathing pattern compared with watching the documentary video (p < 0.001). After watching the comedy, the participants' positive affect was increased (Δ2 ± 1) while it was largely decreased (Δ-11 ± 2) after watching the documentary video (p < 0.001). Pain tolerance was decreased by 17 ± 5 N after viewing the documentary video (p < 0.001), but did not change significantly after watching the comedy.Conclusions:Thirty minutes of watching a comedy eliciting laughter favorably influenced pain tolerance in healthy humans. CLINICAL TRIAL NO.: #NCT02896075.

Primary Outcome Measures is Peak Force of Pain Tolerance Measurement; Extracted Interventionsis is 30 Minute Comedy Video 30 Minute Documentary Video; Conditions is Pain ;Sex is ALL ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.The Safety, Pharmacokinetics, and Pharmacodynamics of SHR2285, an Oral Small Molecule Factor XIa Inhibitor, in Healthy Chinese Volunteers.Background and objective:There is an unmet need for a safer anticoagulant since bleeding remains a concern with currently approved anticoagulants. Coagulation factor XI (FXI) is an attractive anticoagulant drug target with limited a role in physiological hemostasis. The objective of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of SHR2285, a novel small molecule FXIa inhibitor, in healthy Chinese volunteers.Methods:The study consisted of single ascending doses part (part 1: 25-600 mg) and multiple ascending doses part (part 2: 100, 200, 300, and 400 mg). In both parts, subjects were randomized in a 3:1 ratio to receive SHR2285 or placebo orally. Blood, urine and feces samples were collected to describe its pharmacokinetic and pharmacodynamic profile.Results:In total, 103 healthy volunteers completed the study. SHR2285 was well tolerated. SHR2285 was absorbed rapidly with median time to maximum plasma concentration (Tmax) of 1.50 to 3.00 h. The geometric median half-life (t1/2) of SHR2285 varied from 8.74 to 12.1 h across 25-600 mg single dose. Total systemic exposure of metabolite SHR164471 was approximately 1.77- to 3.61-fold that of the parent drug. The plasma concentration of SHR2285 and SHR164471 reached steady state by the morning of Day 7, with low accumulation ratio (0.956-1.20 and 1.18-1.56, respectively). The increase in pharmacokinetic exposure of SHR2285 and SHR164471 was less than dose proportional. Food has minimal effect on the pharmacokinetics of SHR2285 and SHR164471. SHR2285 produced an exposure-dependent prolongation of activated partial thromboplastin time (APTT) and a decrease in FXI activity. The maximum FXI activity inhibition rate (geometric mean) at steady state was 73.27%, 85.58%, 87.77% and 86.27% for 100-400 mg, respectively.Conclusions:SHR2285 was generally safe and well tolerated in healthy subjects across a wide range of doses. SHR2285 exhibited a predictable pharmacokinetic profile and an exposure-related pharmacodynamic profile.Clinicaltrials:gov Identifier NCT04472819; registered on July 15, 2020.

Primary Outcome Measures is Number of subjects with adverse events and severity of adverse events.; Extracted Interventionsis is SHR2285 tablet Placebo; Conditions is Thrombosis ;Sex is ALL ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Interim survival analysis of the randomized phase III GEMSTONE-302 trial: sugemalimab or placebo plus chemotherapy as first-line treatment for metastatic NSCLC.The randomized, double-blinded, multi-center, phase III GEMSTONE-302 ( NCT03789604 ) study evaluated the efficacy and safety of sugemalimab versus placebo in combination with chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (NSCLC). In this study, 479 treatment-naive patients with stage IV squamous or non-squamous NSCLC without known EGFR sensitizing mutations, ALK, ROS1 or RET fusions were randomized (2:1) to receive 1,200 mg of sugemalimab (n = 320) or placebo (n = 159) every 3 weeks in combination with platinum-based chemotherapy for up to four cycles, followed by maintenance therapy with sugemalimab or placebo for squamous NSCLC and sugemalimab or placebo plus pemetrexed for non-squamous NSCLC. Placebo-treated patients could cross over to receive sugemalimab monotherapy on disease progression. The primary endpoint was investigator-assessed progression-free survival (PFS) and the secondary endpoints included overall survival (OS) and objective response rate. Sugemalimab plus chemotherapy has demonstrated significant PFS prolongation in the primary analysis as reported previously. As of 22 November 2021, the prespecified interim OS analysis showed significant improvement with the addition of sugemalimab to chemotherapy (median OS = 25.4 versus 16.9 months; hazard ratio = 0.65; 95% confidence interval = 0.50-0.84; P = 0.0008). Sugemalimab plus chemotherapy provided superior PFS and OS compared to placebo plus chemotherapy, supporting the use of sugemalimab as a first-line treatment option for metastatic NSCLC.

Primary Outcome Measures is Progression-free survival (PFS) in all subjects evaluated by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; Extracted Interventionsis is CS1001 monoclonal antibody CS1001 placebo; 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.A Cognitive Biotype of Depression and Symptoms, Behavior Measures, Neural Circuits, and Differential Treatment Outcomes: A Prespecified Secondary Analysis of a Randomized Clinical Trial.Importance:Cognitive deficits in depression have been associated with poor functional capacity, frontal neural circuit dysfunction, and worse response to conventional antidepressants. However, it is not known whether these impairments combine together to identify a specific cognitive subgroup (or "biotype") of individuals with major depressive disorder (MDD), and the extent to which these impairments mediate antidepressant outcomes.Objective:To undertake a systematic test of the validity of a proposed cognitive biotype of MDD across neural circuit, symptom, social occupational function, and treatment outcome modalities.Design, setting, and participants:This secondary analysis of a randomized clinical trial implemented data-driven clustering in findings from the International Study to Predict Optimized Treatment in Depression, a pragmatic biomarker trial in which patients with MDD were randomized in a 1:1:1 ratio to antidepressant treatment with escitalopram, sertraline, or venlafaxine extended-release and assessed at baseline and 8 weeks on multimodal outcomes between December 1, 2008, and September 30, 2013. Eligible patients were medication-free outpatients with nonpsychotic MDD in at least the moderate range, and were recruited from 17 clinical and academic practices; a subset of these patients underwent functional magnetic resonance imaging. This prespecified secondary analysis was performed between June 10, 2022, and April 21, 2023.Main outcomes and measures:Pretreatment and posttreatment behavioral measures of cognitive performance across 9 domains, depression symptoms assessed using 2 standard depression scales, and psychosocial function assessed using the Social and Occupational Functioning Assessment Scale and World Health Organization Quality of Life scale were analyzed. Neural circuit function engaged during a cognitive control task was measured using functional magnetic resonance imaging.Results:A total of 1008 patients (571 [56.6%] female; mean [SD] age, 37.8 [12.6] years) participated in the overall trial and 96 patients participated in the imaging substudy (45 [46.7%] female; mean [SD] age, 34.5 [13.5] years). Cluster analysis identified what may be referred to as a cognitive biotype of 27% of depressed patients with prominent behavioral impairment in executive function and response inhibition domains of cognitive control. This biotype was characterized by a specific profile of pretreatment depressive symptoms, worse psychosocial functioning (d = -0.25; 95% CI, -0.39 to -0.11; P < .001), and reduced activation of the cognitive control circuit (right dorsolateral prefrontal cortex: d = -0.78; 95% CI, -1.28 to -0.27; P = .003). Remission was comparatively lower in the cognitive biotype positive subgroup (73 of 188 [38.8%] vs 250 of 524 [47.7%]; P = .04) and cognitive impairments persisted regardless of symptom change (executive function: ηp2 = 0.241; P < .001; response inhibition: ηp2 = 0.750; P < .001). The extent of symptom and functional change was specifically mediated by change in cognition but not the reverse.Conclusions and relevance:Our findings suggest the presence of a cognitive biotype of depression with distinct neural correlates, and a functional clinical profile that responds poorly to standard antidepressants and instead may benefit from therapies specifically targeting cognitive dysfunction.Trial registration:ClinicalTrials.gov Identifier: NCT00693849.

Primary Outcome Measures is To determine whether the genetic-brain-cognition function markers (or combination of markers) 'normalise' with acute drug treatment in MDD; Extracted Interventionsis is Escitalopram Sertraline Venlafaxine-XR; Conditions is Major Depressive Disorder ;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 6-Month HIV Preexposure Prophylaxis Dispensing With Interim Self-testing on Preexposure Prophylaxis Continuation at 12 Months: A Randomized Noninferiority Trial.Importance:Daily oral HIV preexposure prophylaxis (PrEP) delivery requires quarterly clinic visits for HIV testing and drug refilling that are costly to health systems and clients.Objective:To evaluate whether 6-month PrEP dispensing supported with interim HIV self-testing (HIVST) results in noninferior PrEP continuation outcomes at 12 months compared with standard quarterly clinic visits.Design, setting, and participants:This randomized noninferiority trial was conducted from May 2018 to May 2021 with 12 months of follow-up among PrEP clients aged 18 years or older who were returning for their first refill at a research clinic in Kiambu County, Kenya.Intervention:Participants were randomized 2:1 to (1) 6-month PrEP dispensing with semiannual clinic visits and interim HIVST at 3 months or (2) standard-of-care (SOC) PrEP delivery with 3-month dispensing, quarterly clinic visits, and clinic-based HIV testing.Main outcomes and measures:Prespecified 12-month outcomes included recent HIV testing (any in past 6 months), PrEP refilling, and PrEP adherence (detectable tenofovir-diphosphate concentrations in dried blood spots). Binomial regression models were used to estimate risk differences (RDs), and a 1-sided 95% CI lower bound (LB) of -10% or greater was interpreted as noninferior.Results:A total of 495 participants were enrolled, with 329 enrolled in the intervention group and 166 enrolled in the SOC group; 330 (66.7%) were women, 295 (59.6%) were in serodifferent relationships, and the median (IQR) age was 33 (27-40) years. At 12 months, 241 individuals in the intervention group (73.3%) and 120 in the SOC group (72.3%) returned to clinic. In the intervention group, recent HIV testing was noninferior (230 individuals [69.9%]) compared with the SOC group (116 [69.9%]; RD, -0.33%, 95% CI LB, -7.44%). PrEP refilling in the intervention group (196 [59.6%]) was inconclusive compared with the SOC group (104 [62.7%]; RD, -3.25%; 95% CI LB, -10.84%), and PrEP adherence was noninferior in the intervention group (151 [45.9%]) compared with the SOC group (70 [42.2%]; RD, 4.96%; 95% CI LB, -2.46%). No HIV seroconversions were observed over the follow-up period.Conclusions and relevance:In this analysis of secondary trial end points at 1 year, semiannual PrEP dispensing with interim HIVST resulted in noninferior recent HIV testing and PrEP adherence compared with SOC quarterly PrEP dispensing. This novel model has the potential to optimize PrEP delivery.Trial registration:ClinicalTrials.gov Identifier: NCT03593629.

Primary Outcome Measures is Number of Participants With Adherence to PrEP at 6 Months; Extracted Interventionsis is 6-month PrEP + blood-based HIV self-test 6-month PrEP + oral fluid HIV self-test; Conditions is HIV-1-infection ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Pertuzumab Plus Trastuzumab in Patients With Lung Cancer With ERBB2 Mutation or Amplification: Results From the Targeted Agent and Profiling Utilization Registry Study.Purpose:The Targeted Agent and Profiling Utilization Registry Study is a pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from a cohort of patients with lung cancer and ERBB2 mutation or amplification treated with pertuzumab plus trastuzumab (P + T) are reported.Methods:Eligible patients had advanced lung cancer of any histology, no standard treatment options, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and tumors with ERBB2 mutation or amplification. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) per RECIST v. 1.1 or stable disease (SD) of at least 16 weeks duration (SD16+). Secondary end points included safety, duration of response, duration of SD, progression-free survival, and overall survival.Results:Twenty-eight patients with lung cancer (27 non-small-cell, 1 small-cell) and ERBB2 mutation (n = 15), ERBB2 amplification (n = 12), or both (n = 1) were enrolled from November 2016 to July 2020. All patients were evaluable for efficacy and toxicity. Three patients with partial response (two ERBB2 mutation; one both mutation and amplification) and seven patients with SD16+ (five ERBB2 mutation; two amplification) were observed for a DC rate of 37% (95% CI, 21 to 50; P = .005) and OR rate of 11% (95% CI, 2 to 28). Five patients had one or more grade 3 or 4 adverse or serious adverse events at least possibly related to P + T.Conclusion:Combination P + T showed evidence of antitumor activity in heavily pretreated patients with non-small-cell lung cancer and ERBB2 mutation or amplification, particularly those with ERBB2 exon 20 insertion mutations.

Primary Outcome Measures is Objective Response Rate defined as % of participants in a cohort with complete or partial response or with stable disease according to standard response criteria; Extracted Interventionsis is Palbociclib Sunitinib Temsirolimus Trastuzumab and Pertuzumab Vemurafenib and Cobimetinib Regorafenib Olaparib Pembrolizumab Nivolumab and Ipilimumab Abemaciclib Talazoparib Atezolizumab and PHESGO Atezolizumab and Talazoparib Entrectinib Larotrectinib Tucatinib plus Trastuzumab Subcutaneous (SC) Futibatinib; Conditions is Lymphoma, Non-Hodgkin|Multiple Myeloma|Advanced Solid 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.Intracranial Activity of Selpercatinib in Chinese Patients With Advanced RET Fusion-Positive Non-Small-Cell Lung Cancer in the Phase II LIBRETTO-321 Trial.Purpose:Selpercatinib, a highly selective, potent RET inhibitor with CNS activity, demonstrated sustained antitumor responses and intracranial activity in patients with RET-altered advanced non-small-cell lung cancer (NSCLC) in the global LIBRETTO-001 and Chinese LIBRETTO-321 trials. We report a prospective case series based on updated data from patients with brain metastases at baseline in LIBRETTO-321.Materials and methods:We included patients with advanced NSCLC and brain metastasis with a centrally confirmed KIF5B/CCDC6/NCOA4-RET fusion. Patients with previously treated or untreated CNS metastases were included if asymptomatic or neurologically stable. Patients received oral selpercatinib 160 mg, twice daily, until progression. Objective systemic and intracranial response was independently assessed per RECIST v1.1. The data cutoff (DCO) was March 31, 2022.Results:In total, 8/26 (31%) patients were included: 1/8 (13%) had previous brain surgery but no previous systemic therapy and 3/8 (38%) had received brain radiotherapy. Best overall systemic response was partial response (PR) in 6/8 patients (75%) and stable disease (SD) in 2/8 (25%). Among patients with measurable baseline CNS lesions, 4/5 (80%) achieved a confirmed intracranial response (3/5 PRs and 1/5 complete response [CR]). The best overall intracranial response was CR in 3/8 (38%), PR in 3/8 (38%), and SD in 1/8 (13%) and nonprogressive disease/non-CR in 1/8 (13%); 2/8 patients (25%) had CNS-only disease progression. The duration of treatment was 2.8-24.0 months, and 5/8 patients (63%) had treatment ongoing at DCO. Of 8 patients, 5 (63%) had grade ≥3 treatment-related adverse events (TRAEs) requiring dose modification. There were no treatment discontinuations because of TRAEs.Conclusion:Selpercatinib demonstrated clinically meaningful and durable intracranial activity in Chinese patients with brain metastases from RET-altered NSCLC, consistent with the global LIBRETTO-001 trial.

Primary Outcome Measures is Primary Analysis Set: Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) as Assessed by Independent Review Committee (IRC); Extracted Interventionsis is Selpercatinib; Conditions is Solid Tumor|Medullary Thyroid 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.Effect of Mifepristone vs Placebo for Treatment of Adenomyosis With Pain Symptoms: A Randomized Clinical Trial.Importance:Adenomyosis is a common chronic gynecological disorder, and its treatment is an unmet need. New therapies need to be developed. Mifepristone is being tested for adenomyosis treatment.Objective:To determine whether mifepristone is effective and safe for adenomyosis treatment.Design, setting, and participants:This multicenter, placebo-controlled, double-blind randomized clinical trial was conducted in 10 hospitals in China. In total, 134 patients with adenomyosis pain symptoms were enrolled. Trial enrollment began in May 2018 and was completed in April 2019, and analyses were conducted from October 2019 to February 2020.Interventions:Participants were randomized 1:1 to receive mifepristone 10 mg or placebo orally once a day for 12 weeks.Main outcomes and measures:The primary end point was the change in adenomyosis-associated dysmenorrhea intensity, evaluated by the visual analog scale (VAS) after 12 weeks of treatment. Secondary end points included the change in menstrual blood loss, increased level of hemoglobin in patients with anemia, CA125 level, platelet count, and uterine volume after 12 weeks of treatment. Safety was assessed according to adverse events, vital signs, gynecological examinations, and laboratory evaluations.Results:In total, 134 patients with adenomyosis and dysmenorrhea were randomly assigned, and 126 patients were included in the efficacy analysis, including 61 patients (mean [SD] age, 40.2 [4.6] years) randomized to receive mifepristone and 65 patients (mean [SD] age, 41.7 [5.0] years) randomized to received the placebo. The characteristics of the included patients at baseline were similar between groups. The mean (SD) change in VAS score was -6.63 (1.92) in the mifepristone group and -0.95 (1.75) in the placebo group (P < .001). The total remission rates for dysmenorrhea in the mifepristone group were significantly better than those in the placebo group (effective remission: 56 patients [91.8%] vs 15 patients [23.1%]; complete remission: 54 patients [88.5%] vs 4 patients [6.2%]). All the secondary end points showed significant improvements after mifepristone treatment for menstrual blood loss, hemoglobin (mean [SD] change from baseline: 2.13 [1.38] g/dL vs 0.48 [0.97] g/dL; P < .001), CA125 (mean [SD] change from baseline: -62.23 [76.99] U/mL vs 26.89 [118.70] U/mL; P < .001), platelet count (mean [SD] change from baseline: -28.87 [54.30]×103/µL vs 2.06 [41.78]×103/µL; P < .001), and uterine volume (mean [SD] change from baseline: -29.32 [39.34] cm3 vs 18.39 [66.46] cm3; P < .001). Safety analysis revealed no significant difference between groups, and no serious adverse events were reported.Conclusions and relevance:This randomized clinical trial showed that mifepristone could be a new option for treating patients with adenomyosis, based on its efficacy and acceptable tolerability.Trial registration:ClinicalTrials.gov Identifier: NCT03520439.

Primary Outcome Measures is changes in chronic pelvic pain associated with adenomyosis; Extracted Interventionsis is Mifepristone Placebo; Conditions is Adenomyosis ;Sex is FEMALE ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect and Safety of Pioglitazone-Metformin Tablets in the Treatment of Newly Diagnosed Type 2 Diabetes Patients with Nonalcoholic Fatty Liver Disease in Shaanxi Province: A Randomized, Double-Blinded, Double-Simulated Multicenter Study.Objective:The aim of study was to evaluate the effect and safety of pioglitazone-metformin combined treatment in the newly diagnosed type 2 diabetes patients with nonalcoholic fatty liver disease.Methods:A total of 120 newly diagnosed type 2 diabetes patients with nonalcoholic fatty liver disease from 8 centers were randomly divided into the control group (metformin hydrochloride) and the test group (pioglitazone hydrochloride and metformin hydrochloride).Results:Compared to the control group, after treatment, the proportion of people with mild and moderate fatty liver increased, and the proportion of people with severe fatty liver decreased, and this change was more obvious in the population with moderate and severe fatty liver. The level of γ-GT decreased in both groups before and after treatment, which was statistically significant, and there was also a statistically significant difference in the level of γ-GT between the two groups after 24 weeks. There were no significant statistically differences in blood lipid, body weight, and waist circumference between the test group and the control group. Logistic regression analysis found that BMI is one of the risk factors for fatty liver. There was also no significant difference in the incidence of serious adverse events between the two groups (control group: 10.00% and test group: 6.67%, P = 0.74).Conclusion:Combined treatment with pioglitazone-metformin can effectively reduce liver fat content and gamma-GT level in newly diagnosed diabetic patients with nonalcoholic fatty liver disease, and adverse events do not increase compared with the control group, showing good safety and tolerance. This trial is registered with ClinicalTrials.gov NCT03796975.

Primary Outcome Measures is Decreased of liver fat content of fatty liver after 24 weeks treatment as assessed by B-ultrasound; Extracted Interventionsis is Combination of Pioglitazone and Metformin Tablets Metformin Hydrochloride Tablets; Conditions is Type 2 Diabetes Mellitus|Non-alcoholic Fatty Liver Disease|Efficacy ;Sex is ALL ;Age is ADULT, OLDER_ADULT