title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
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Introduction | obesity, weight gain, IIH, Visual loss | OBESITY | Glucagon-like peptide-1 (GLP-1) is a gut neuropeptide secreted by the distal small intestine in response to a meal.Relevant to this trial is the role of GLP-1 receptor agonists in regulating fluid secretion. GLP-1 receptor agonists have been shown to reduce sodium reabsorption and promote diuresis through actions in th... | PMC10151178 |
Materials and methods | PMC10151178 | |||
Trial design and oversight | IIH | WEST | The trial was a prospective, randomized, parallel group, placebo-controlled trial in women with active IIH. Patients with a diagnosis of active IIH were identified and recruited from a single tertiary referral hospital (University Hospitals Birmingham NHS Foundation Trust). This study was approved by the West Midlands—... | PMC10151178 |
Participants | IIH | Women aged 18–60 years who met the diagnostic criteria for IIH were recruited. | PMC10151178 | |
Assessments | headache | Following enrolment, a 28-day headache diary was completed [capturing monthly headache days, headache severity (0–10 numerical rating scale), monthly analgesia days]. A telemetric ICP catheter (Raumedic) was implanted prior to the baseline visit through a 4 mm burr hole into the right frontal lobe.At baseline, medical ... | PMC10151178 | |
Body composition | Dual energy X-ray absorptiometry (DEXA) was performed using a total-body scanner (QDR 4500; Hologic), as previously described, | PMC10151178 | ||
Randomization and study treatment | Participants were randomized in a 1:1 ratio to either active treatment with exenatide (Byetta) or placebo using a computer-generated randomization list generated by the Birmingham Clinical Trials Unit. Treatment allocation was blinded to patient and investigators. A double check of allocation was performed by an unblin... | PMC10151178 | ||
Blood analysis | high-density lipoproteins, TG | The following fasted blood tests were processed at the hospital laboratory: creatinine (μmol/l), alanine aminotransferase (ALT; IU/l), high-density lipoproteins (HDL; mmol/l), total cholesterol (mmol/l), triglycerides (TG; mmol/l), haemoglobin A1c (HbA1C; mmol/mol). Samples not analysed immediately were centrifuged (10... | PMC10151178 | |
Fasting insulin and homeostasis model assessment of insulin resistance | INSULIN RESISTANCE | Fasting insulin (Mercodia) was measured using a commercially available assay, according to the manufacturer’s instructions. Homeostasis model assessment of insulin resistance (HOMA2-IR) was calculated using the program HOMA calculator v2.2.3. | PMC10151178 | |
Pharmacokinetics | Exenatide concentration was evaluated by ELISA. ELISA was performed on serum samples from seven patients receiving the active drug. Serum was collected at 10 time points: baseline, 2.5 h, 6 h, 11 h, 22 h and 24 h, Week 2 at baseline and 2.5 h post-dose, Week 12 at baseline and 2.5 h post-dose. An exenatide fluorescent ... | PMC10151178 | ||
Anti-exendin-4 antibody levels in serum | TYPE 2 DIABETES MELLITUS | In the light of reports of the development of anti-exenatide antibody in human studies administering exenatide in type 2 diabetes mellitus | PMC10151178 | |
Outcomes measure | Diabetic Retinopathy, headache | DIABETIC RETINOPATHY | The primary outcome was ICP at 2.5 h, 24 h and 12 weeks post-drug administration. ICP was recorded with p-Tel telemetric ICP catheter and MPR-1 reader (Raumedic). ICP was recorded continuously for 30-min periods at specified time points in a standardized supine position. For the first 2.5 h post-dosing, mean ICP was ca... | PMC10151178 |
Adverse event reporting | ADVERSE EVENT | Adverse events were recorded as was drug compliance (unused medication in the injector pens documented). | PMC10151178 | |
Sample size calculation | In a study of 25 patients, Sinclair | PMC10151178 | ||
Statistical analyses | SE, PMD | REGRESSION, SECONDARY, INTRAOCULAR PRESSURE | All primary analyses (primary and secondary outcomes including safety outcomes) were evaluated by intention-to-treat (ITT) analysis. Analysis was completed on received data, with every effort made to follow-up participants to minimize potential for bias. Final analyses were conducted after the final visit of the final ... | PMC10151178 |
Data availability | Anonymized individual participant data will be made available along with the trial protocol and statistical analysis plan. Proposals should be made to the corresponding author and will be reviewed by the Data Sharing Committee in discussion with the Chief Investigator. A formal Data Sharing Agreement may be required be... | PMC10151178 | ||
Results | PMC10151178 | |||
Patients | Between 1 November 2017 and 17 September 2018, 18 participants were screened, 16 enrolled and 15 randomly assigned to either the exenatide group (
| PMC10151178 | ||
Adherence to the protocol | DISEASE PROGRESSION | One participant was withdrawn before randomization due to disease progression requiring urgent CSF shunting ( | PMC10151178 | |
Demographics and baseline characteristics | IIH | Baseline characteristics confined a cohort of patients with active IIH ( | PMC10151178 | |
Primary outcome measure | The primary clinical outcome was the difference in ICP between exenatide and placebo, as measured by telemetric ICP monitoring at 2.5 h, 24 h and 12 weeks. The difference in ICP between arms at 2.5 h was −4.2 (2.1) [mean (SD) mmHg],
Primary outcome measures | PMC10151178 | ||
Secondary clinical outcomes | headache | SECONDARY | The key secondary outcome was monthly headache days, which reduced significantly in the exenatide arm, −7.7 (9.2) days [mean (SD)],
| PMC10151178 |
Vision | Visual acuity significantly improved in the exenatide arm compared to the placebo arm −0.1 (0.05) logMar units, | PMC10151178 | ||
Intraocular pressure | INTRAOCULAR PRESSURE | There was no significant change in intraocular pressure, difference between arms −0.1 (1.1), | PMC10151178 | |
Quality of life | Analysis of quality of life, using the SF-36, showed no significant changes in either the physical or mental component scores ( | PMC10151178 | ||
Body mass index | BMI in the placebo arm baseline was 38.6 (4.7) kg/m | PMC10151178 | ||
Safety blood test results | No significant changes were seen in the safety monitoring blood tests ( | PMC10151178 | ||
Adverse events | nausea | ADVERSE EVENTS, ADVERSE EVENT, THYROTOXICOSIS | Twelve adverse events were reported during the trial. Eight adverse events occurred in the exenatide arm, seven of which were nausea related to exenatide initiation. Four adverse events occurred in the placebo arm. One unrelated serious adverse event, thyrotoxicosis, was reported in the placebo arm. No patients withdre... | PMC10151178 |
Anti-exenatide antibodies | No anti-exenatide antibodies were detected in samples collected at baseline. In total, two of the seven patients on exenatide developed antibodies by Week 12. At Week 2 one patient had antibodies present (> 0.1 µg/ml) and these were also present at 12 weeks (> 0.1 µg/ml). A further patient was noted to have antibodies ... | PMC10151178 | ||
Drug concentrations measurements | The two patients with anti-exenatide antibodies at 12 weeks had higher (3- and 6-fold higher) than predicted exenatide concentrations at 12 weeks and were excluded from the 12 weeks data analysis. At baseline, Week 2 and Week 12, there was a sharp increase in exenatide concentrations in patient serum at 2.5 h following... | PMC10151178 | ||
Glucose and insulin | hypoglycaemia | HYPOGLYCAEMIA | No hypoglycaemia was encountered during the trial. There was no significant difference in fasted glucose and fasted insulin between the two trial arms at 12 weeks ( | PMC10151178 |
Vital signs | BLOOD | Blood pressure and heart rate were stable during the trial, mean arterial pressure was lower at 12 weeks in the exenatide group compared to placebo, −6.7 mmHg (3.6), | PMC10151178 | |
We looked in more detail at the changes in ICP in the first 2.5 h following drug administration. ICP was significantly lower in recordings taken over time points 90–120 min [mean (SD): −4.6 (2.1) mmHg,
ICP was then measured overnight between 24.00 and 07.00 h on the first day of dosing ( | PMC10151178 | |||
DEXA | IIH | We determined that IIH patients had a similar fat mass, lean mass and android–gynoid ratio in those treated with exenatide as compared to those on placebo with no significant differences detected at 12 weeks ( | PMC10151178 | |
Discussion | Headache, nausea, IIH, traumatic brain injury, meningitis, stroke, Weight loss, headache, headaches and visual loss | SIDE EFFECT, MENINGITIS, STROKE, HYDROCEPHALUS, OPTIC NERVE, SECONDARY, PATHOGENESIS, SYNDROME, TYPE 2 DIABETES, DISEASES | This is the first randomized controlled trial comparing the efficacy of the GLP-1 receptor agonist exenatide, with placebo to reduce ICP in patients with active IIH. We have found a significant and clinically meaningful reduction in ICP in the treatment arm as compared to the placebo arm both acutely and after 12 weeks... | PMC10151178 |
Supplementary Material | Click here for additional data file. | PMC10151178 | ||
Funding | THORN, BRAIN | This study was funded by University of Birmingham, UK, from 1 August 2016. Further funding was sought and from 1 August 2019 an investigator-led grant was obtained from Invex therapeutics. J.L.M. was funded by the Ministry of Defence for the duration of the study. A.Y. was funded by an Association of British Neurologis... | PMC10151178 | |
Competing interests | Chugai-Roche | J.L.M. was funded by the UK Ministry of Defence for the duration of the study. O.G. reports scientific consultancy fees from Invex therapeutics (2020). A.Y. reports receiving speaker fees from Teva, UK, outside the submitted work. K.B. works for UCB. Professor Mollan reports other Invex Therapeutics, other Heidelberg e... | PMC10151178 | |
Supplementary material | PMC10151178 | |||
References | PMC10151178 | |||
Background | hypotension | The optimal treatment of hypotension during spinal anaesthesia is uncertain. A novel double intravenous vasopressor automated (DIVA) system reduces hypotension compared to standard care, and was subsequently modified to an advanced-DIVA (ADIVA) system. The primary objective was to compare ADIVA versus DIVA on incidence... | PMC9878794 | |
Methods | We conducted a randomized-controlled trial in women undergoing elective cesarean delivery under spinal anesthesia. SBP and heart rate were measured continuously using a Nexfin monitor. ADIVA delivered 25 μg phenylephrine (heart rate > 60 beats.min | PMC9878794 | ||
Results | We analyzed 94 parturients (ADIVA: | PMC9878794 | ||
Conclusion | hypotensive | HYPOTENSIVE | ADIVA was associated with a greater proportion of hypotensive SBP readings, reduced phenylephrine consumption, and increased umbilical arterial pH than DIVA. Further research is needed to determine the optimal method of vasopressor delivery in parturients undergoing cesarean delivery. | PMC9878794 |
Trial registration | This study was registered on Clinicaltrials.gov registry (NCT03620942) on 08/08/2018. | PMC9878794 | ||
Keywords | PMC9878794 | |||
Introduction | Hypotension, hypotension | Hypotension occurs in up to 80% of women during cesarean delivery under spinal anesthesia [The optimum method of preventing or treating hypotension during cesarean delivery is uncertain, although vasopressors have demonstrated efficacy and are mainstays of contemporary clinical practice [We have previously described a ... | PMC9878794 | |
Methods | loss of sensation, premature rupture of amniotic membranes, cardiac disease, diabetes | HYPERTENSIVE DISORDER, COLD, CARDIAC DISEASE, DIABETES | This randomized controlled study was conducted from January 2020 to September 2021 at KK Women’s and Children’s Hospital, Singapore, after approval by the SingHealth Centralized Institutional Review Board (Ref: 2018/2213) on 06/04/2018 and registration on clinicaltrials.gov (NCT03620942) on 08/08/2018. Written informed... | PMC9878794 |
Percentage performance error (PE) | Percentage performance error was defined as the percentage difference between each SBP value from the baseline, and is calculated for the i | PMC9878794 | ||
Median absolute performance error (MDAPE) | MDAPE indicates the absolute magnitude of differences between measured and baseline SBP, and is a measure of inaccuracy. It is defined as the median of absolute PE (|PE|) values, calculated as follows where N | PMC9878794 | ||
Median performance error (MDPE) | MDPE is a measure of bias, and indicates whether SBP was systematically above or below the baseline, calculated as follows: | PMC9878794 | ||
Wobble | Wobble measures how much PE fluctuates around the MDPE with time for each parturient, calculated as follows: | PMC9878794 | ||
Divergence | REGRESSION | Divergence is the slope obtained from linear regression of each parturient’s |PE| with time, and assesses the trend of |PE| change over time, thereby indicating if the system accuracy is improving (negative divergence) or worsening (positive divergence) with time. Divergence (per minute) was calculated as follows where... | PMC9878794 | |
Statistical analyses | hypotension | Continuous and categorical variables were summarized as mean ± standard deviation (SD) or median (interquartile range (IQR) [range]) as appropriate, or number (proportion) respectively. Categorical and continuous variables were compared using the XA sample size of 92 parturients (46 in each group) is required to detect... | PMC9878794 | |
Discussion | bradycardia, hypertension, hypotensive, hypotension | ADVERSE EVENTS, HYPERTENSION, HYPOTENSIVE, COLD | In this randomized controlled study, we compared the performance of ADIVA versus DIVA in managing hypotension during spinal anesthesia for cesarean delivery. The use of ADIVA did not significantly change the incidence of hypotension, hypertension, bradycardia, ephedrine consumption, and other relevant clinical outcomes... | PMC9878794 |
Conclusion | hypotensive | HYPOTENSIVE | ADIVA did not significantly improve hemodynamic control and clinical outcomes during spinal anesthesia compared to DIVA. However, ADIVA was associated with a greater proportion of hypotensive SBP readings, reduced phenylephrine consumption, and increased umbilical arterial pH than DIVA. Further research is needed to de... | PMC9878794 |
Acknowledgements | The authors would like to thank the clinical research coordinators (Agnes Teo, Liu Juan, Dora Gan) and the staff of the major operating theaters at KK Women’s and Children’s Hospital, Singapore, for their support. | PMC9878794 | ||
Authors’ contributions | RS | HST, SN: Conceptualization, methodology, investigation, formal analysis, writing – original draft, review, and editing. JJIC: Methodology, investigation, writing – review and editing. CWT: Conceptualization, methodology, formal analysis, writing – review and editing. RS: Methodology, formal analysis, writing – review a... | PMC9878794 | |
Funding | We would like to acknowledge the SingHealth Foundation Grant SHF/CTG061/2017 Clinical Trials Grant for the funding support of this study. | PMC9878794 | ||
Availability of data and materials | The datasets generated and/or analyzed during this study are not publicly available due to institutional policy on data confidentiality but are available from the corresponding author on reasonable request. | PMC9878794 | ||
Declarations | PMC9878794 | |||
Ethics approval and consent to participate | This study received approval by SingHealth Centralized Institutional Review Board (Ref: 2018/2213) on 06/04/2018, with registration on Clinicaltrials.gov (NCT03620942) on 08/08/2018. Written informed consent was obtained from every participant by the investigators, and that this work was conducted in accordance with th... | PMC9878794 | ||
Consent for publication | Not applicable. | PMC9878794 | ||
Competing interests | Ban Leong Sng is an associate editor of BMC Anesthesiology. All other authors declare that they have no competing interests. | PMC9878794 | ||
References | PMC9878794 | |||
Background | ULCERATIVE COLITIS | There are no prospective trials comparing the two main reconstructive options after colectomy for Ulcerative colitis, ileal pouch anal anastomosis and ileorectal anastomosis. An attempt on a randomized controlled trial has been made but after receiving standardized information patients insisted on choosing operation th... | PMC10122388 | |
Methods | Ulcerative colitis | ULCERATIVE COLITIS, COMPLICATIONS | Adult Ulcerative colitis patients subjected to colectomy eligible for both ileal pouch anastomosis and ileorectal anastomosis are asked to participate and after receiving standardized information the get to choose reconstructive method. Patients declining reconstruction or not considered eligible for both methods will ... | PMC10122388 |
Discussion | Reconstruction after colectomy is a morbidity-associated as well as a resource-intensive activity with the sole purpose of enhancing function, QoL and patient satisfaction. The aim of this study is to provide the best possible information on the risks and benefits of each reconstructive treatment. | PMC10122388 | ||
Trial registration | ClinicalTrials.gov Identifier: NCT05628701 | PMC10122388 | ||
Keywords | Open access funding provided by Linköping University. | PMC10122388 | ||
Introduction | UC, IBD, Ulcerative Colitis | INFLAMMATORY BOWEL DISEASE, ULCERATIVE COLITIS | Ulcerative Colitis (UC) is a chronic inflammatory bowel disease (IBD) restricted to the mucosa of the rectum and colon [After subtotal colectomy there are four available options for patients. A reasonable option is to not proceed for further surgery and leave the rectum in place—the patient will live with a permanent i... | PMC10122388 |
Method/design | PMC10122388 | |||
Study objectives | stoma, UC-patients, UC | COMPLICATIONS | To compare, in a prospective setting, patient satisfaction, QoL, function, and complications between IRA and IPAA and permanent stoma among patients with UC subjected to subtotal colectomy.This study aims to answer what type of reconstruction, if any, UC-patients asks for following a colectomy, their satisfaction with ... | PMC10122388 |
Study design | stoma, UC | COMPLICATIONS | The CRUISE study is a prospective, non-randomized, non-blinded, multi-center, controlled trial on satisfaction, QoL, function, and complications between IRA and IPAA and permanent stoma among adult UC patients subjected to subtotal colectomy. All adult UC patients scheduled for a subtotal colectomy will be asked for in... | PMC10122388 |
Endpoints | COMPLICATIONS | The primary endpoint is satisfaction with the choice of reconstructive method or permanent stoma. Secondary endpoints are QoL, sexual function, bowel function and complications. | PMC10122388 | |
Study population | inflammation, UC | INFLAMMATION, RECTAL INFLAMMATION | The study population consists of all adult UC patients subjected to subtotal colectomy and eligible for both IRA and IPAA presenting at any of the participating centers.Inclusion criteria are patients with UC aged between 18 and 60, scheduled for or have previously undergone subtotal colectomy and ileostomy. Patients s... | PMC10122388 |
Sample size | The only available study on patient satisfaction, our primary outcome, between IRA and IPAA reports 98% and 88% satisfaction for the methods respectively [ | PMC10122388 | ||
Participating centers | Patients will be enrolled from three tertiary referral centers in Sweden (Linköping University hospital, Linköping, Sweden; Karolinska University hospital, Stockholm, Sweden; Sahlgrenska (Östra) University hospital, Gothenburg, Sweden) and one tertiary referral center in the UK (St Mark’s Hospital and Academic Institut... | PMC10122388 | ||
Ethics | The study was approved by the regional ethics review board in Stockholm, Sweden (Dnr: 2017/124–31/2, 2018/2224–32) and The London Brent Research Ethics Committee (REC), UK (reference number: 18/LO/1190). The study is conducted in accordance with the Helsinki declaration and good clinical practice. | PMC10122388 | ||
Trial registration | The protocol is registered and published at ClinicalTrials.gov Identifier: NCT05628701. | PMC10122388 | ||
Study outline | PMC10122388 | |||
Recruitment | Inflammation | INFLAMMATION, RECTAL INFLAMMATION | After colectomy, patients will receive standardized written as well as oral information from a consultant regarding the collection of QoL measurements, functional scores and the different treatment modalities before being asked for consent to participate in the study. The patient will be prescribed topical 5-ASA accord... | PMC10122388 |
IRA | The IRA can be performed both as an open or laparoscopic procedure, of which the latter is more common and preferred in modern practice. The ileostomy is closed, and the neoterminal ileum is in most cases anastomosed to the tip of the rectal remnant in the abdomen using a circular transanal stapling device or in some c... | PMC10122388 | ||
IPAA | The IPAA can be performed both as an open or, preferably as a laparoscopic or robotic procedure. A trans-anal minimal invasive method (TaTME) may be used to facilitate proctectomy [ | PMC10122388 | ||
Controls | proctitis, UC | PROCTITIS | In order to obtain a comprehensive overview of all UC patients that undergo colectomy, patients that decline reconstruction or those eligible only for one method of reconstruction (e.g. only IPAA due to refractory proctitis) will be asked to participate as controls. | PMC10122388 |
Failure | Patients converted from IRA to IPAA or from either reconstruction to a permanent ileostomy will be analyzed in an “intention-to-treat” manner. | PMC10122388 | ||
Data collection | PMC10122388 | |||
Instruments | bleeding, UC | BLEEDING, PERIOPERATIVE COMPLICATION | General QoL will be assessed with the SF-36 form [Data will also be obtained on smoking status, UC medication, age, indication for colectomy (chronic active disease/acute flare/dysplasia), BMI, endoscopic status in pouch/rectum, reoperations and for each operation: operation technique, operative time, bleeding, periope... | PMC10122388 |
Time frame | Baseline data will be collected after colectomy for all patients. The reconstructed patients will then be followed at 2 months, 6 months, 1 year, 2 years and 5 years. Those patients that receive a loop ileostomy at reconstruction will also be followed 2 months after reconstruction before closure of the loop. For those ... | PMC10122388 | ||
Statistical analysis | EVENTS, STILL | Analysis will be conducted according to the intention-to-treat principal. The primary outcome satisfaction, a proportion, will be compared with chi-square test. For the primary outcome two-tailed tests will be applied since the null hypothesis is that there is no difference between the two reconstructive methods. Secon... | PMC10122388 | |
Discussion | IPAA, bowel movements, proctitis, UC, UC [Failure, pouchitis, IBD | STILL, DISEASE, PROCTITIS, COMPLICATION, POUCHITIS, RECTAL CANCER, COMPLICATIONS | Reconstruction after colectomy is a morbidity-associated as well as a resource-intensive activity with the sole purpose of enhancing function, QoL and patient satisfaction. The actual disease has already been treated with the colectomy. Hence it is crucial to provide patients and care givers with the best possible info... | PMC10122388 |
Conclusion | Because we have failed to enroll patients in an RCT we believe this is the best available way to compare the outcomes between IRA and IPAA. This design will also provide a good overview of the entire UC population that required colectomy. | PMC10122388 | ||
Trial status | As of September 28, 2022, we have enrolled 37 IRA patients and 11 IPAA patients in the study arms and 23 IPAA and 18 ileostomy patients in the control arms. | PMC10122388 | ||
Acknowledgements | Mr Guy Worley made considerable contributions in the start-up of the study in the UK. | PMC10122388 | ||
Authors’ contributions | Guarantor: Mr Risto had full access to all of the data in the study and takes responsibility for the integrity study. Study concept and design: All co-authors. Interpretation of results: All co-authors. Drafting of the manuscript: Risto. Figures and tables: Risto and Nordenvall. Critical revision of the manuscript for ... | PMC10122388 | ||
Funding | Open access funding provided by Linköping University. The study was financed by grants from: The Swedish state under the agreement between the Swedish government and the county councils (the ALF-agreement), The Bengt Ihre research fund and the “Magtarmfonden” research fund. None of the funders have had any role in the ... | PMC10122388 | ||
Availability of data and materials | Not applicable, no data, only protocol. | PMC10122388 | ||
Declarations | PMC10122388 | |||
Ethics approval and consent to participate | The study was approved by the regional ethics review board in Stockholm, Sweden (Dnr: 2017/124–31/2, 2018/2224–32) and The London Brent Research Ethics Committee (REC), UK (18/LO/1190). Written consent is/will be signed by all participating patients. | PMC10122388 | ||
Consent for publication | Not applicable, no individual data. | PMC10122388 |
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