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References
PMC9982755
Abstract
migraine
MIGRAINE, DILATION, INTRACRANIAL VASCULAR
There are several endogenous molecules that can trigger migraine attacks when administered to humans. Notably, calcitonin gene-related peptide (CGRP) has been identified as a key player in a signalling cascade involved in migraine attacks, acting through the second messenger cyclic adenosine monophosphate (cAMP) in var...
PMC10690017
Introduction
migraine, Migraine
MIGRAINE, DISEASE, MIGRAINE
Migraine is a highly prevalent disease affecting more than 1 billion people worldwide.A key feature of migraine is that various environmental and endogenous trigger factors can initiate an attack.Thus, it is timely to ascertain whether migraine attack generation requires CGRP receptor activation. This can be establishe...
PMC10690017
Materials and methods
The protocol was approved by the Regional Health Research Ethics Committee of the Capital Region of Denmark (identifier: H-19073983), the Danish Data Protection Agency (P-2020-652) and the Danish Medicines Agency (identifier: 2020033418). We obtained a signed consent form at the time of screening before any protocol-re...
PMC10690017
Participants
migraine, ICHD-3
MIGRAINE, HEADACHE DISORDERS
Adults aged 18–65 years old with a diagnosis of migraine according to the International Classification of Headache Disorders, Third Edition (ICHD-3),
PMC10690017
Study design and procedures
migraine, headache
MIGRAINE
We enrolled participants in a randomized, double-blind, placebo-controlled, parallel trial at a single centre in Denmark ( Patients arrived between 08:00 a.m. and 12:00 p.m. on the experimental study days. Patients were in a supine-position during study-related procedures and assessments. Patients were not allowed to c...
PMC10690017
Headache characteristics and diary
migraine, headache
MIGRAINE, ADVERSE EVENTS
A headache specialist conducted a semi-structured interview at the screening visit. The interview included information on medical history, headache characteristics and frequency, family history of migraine and prior pharmacological treatment; these data were confirmed by review of medical records.On the experimental st...
PMC10690017
Haemodynamic variables
CORTEX
Patients rested in a quiet room for at least 30 min in a supine position before any measurements. During the in-hospital phase, we conducted electrocardiography and measured the blood pressure and heart rate. Furthermore, we used a high-resolution ultrasonography unit (Dermascan C; Cortex Technology: 20 MHz, bandwidth ...
PMC10690017
Statistical considerations and analysis
migraine
MIGRAINE
Sample size calculations were based on the difference between two unpaired groups reporting migraine attacks. After administration of CGRP, we assumed that 51% of participants would report migraine attack in the placebo-treatment arm and 20% in the active-treatment arm. After administration of cilostazol, we assumed th...
PMC10690017
Results
PMC10690017
Study population characteristics
A total of 80 patients provided informed consent from July 2020 to July 2021; 75 patients completed both experimental study days and were included in the final analysis ( Clinical characteristics of the study populationBMI = body mass index; SD = standard deviation.
PMC10690017
Intracellular mechanisms can induce migraine attacks independent of CGRP receptor activation
nausea, migraine-associated, phonophobia, migraine, Migraine, photophobia
MIGRAINE, MIGRAINE
We demonstrated that erenumab can alleviate migraine attack induction with CGRP with 10 of 37 [27% (95% CI, 13–41)] participants developing migraine attacks compared to 20 out of 38 [53% (95% CI, 37–69)] participants who received placebo ( Migraine attack induction rateCalcitonin gene-related peptide (CGRP): There was ...
PMC10690017
CGRP-mediated vasodilation is mitigated by a blockade of the CGRP receptor
DILATION
We found that erenumab significantly attenuated CGRP-induced dilation of the superficial temporal artery (AUC
PMC10690017
Adverse events
palpitations, migraine, flushing
ADVERSE EVENTS, MIGRAINE
The proportion of patients reporting warm sensations, palpitations and flushing in the erenumab group was lower than in the placebo group (Adverse eventsReports of adverse events following administration of calcitonin gene-related peptide (CGRP) and cilostazol in individuals with migraine randomized to erenumab or plac...
PMC10690017
Discussion
migraine
MIGRAINE, RECRUITMENT
A novel finding of our study is that migraine attacks induced by upregulation of intracellular cAMP levels are not affected by blocking the CGRP receptor. Our work provides clinical evidence that cAMP-evoked migraine attacks do not require CGRP receptor activation. We want to highlight three important observations in t...
PMC10690017
Conclusions
migraine
MIGRAINE
The present data provide further evidence for the crucial role of second messenger signalling in a migraine attack. We demonstrate that migraine attack generation does not require CGRP receptor activation. These findings highlight the relevance of targeting downstream signalling pathways or other molecules involved in ...
PMC10690017
Acknowledgements
Håkan
RITTER
M.A. was supported by the Lundbeck Foundation Professor Grant (R310-2018-3711). The authors thank Dr Haidar Al-Khazali, Dr Faisal Mohammad Amin, Dr Håkan Ashina, Dr Hande Coskun, Dr Afrim Iljazi, Dr Lanfranco Pellesi, Dr Henrik Winther Schytz, Dr Nita Katarina Frifelt Wienholtz, pharmacologist Fatima Azzahra Elbahi and...
PMC10690017
Data availability
Anonymized datasets generated and/or analysed during the current study are available upon reasonable request and following the acquisition of necessary permissions.
PMC10690017
Funding
This research was funded by and conducted in collaboration with Novartis Pharma AG, Basel, Switzerland.
PMC10690017
Competing interests
M.A. is a consultant, speaker or scientific advisor for AbbVie, Allergan, Amgen, Eli Lilly, Lundbeck, Novartis and Teva, and a primary investigator for ongoing AbbVie/Allergan, Amgen, Eli Lilly, Lundbeck, Novartis and Teva trials. M.A. has no ownership interest and does not own stocks of any pharmaceutical company. M.A...
PMC10690017
References
PMC10690017
Background
diabetic, Diabetic Retinopathy
EYE, DIABETIC RETINOPATHY, RETINA
Diabetic Retinopathy (DR) is an important public health issue in Nepal. Despite the availability of retinal services, people may not access them because of the lack of knowledge about DR and poor referral systems. DR screening uptake was low at Reiyukai Eiko Masunaga Eye Hospital(REMEH) since retina services were start...
PMC9905012
Methods
diabetic retinopathy, diabetic, diabetes
DIABETIC RETINOPATHY, DIABETES
The aim of our study was to investigate the effectiveness of providing health education to selected health personnel and establish a referral pathway on the attendance of diabetic patients for retinal screening at REMEH. This was a non-randomized, pre-post intervention study design. Total of three health education sess...
PMC9905012
Results
diabetes
DIABETES
The proportional increase in number of referrals of diabetes attendance post intervention increased from 50 to 95% and was statistically significant (
PMC9905012
Conclusion
This study shows that a well-planned health education intervention changes the knowledge in physicians about DR. There is an increase in the number of referrals and attendance of patients for DR screening with the change in knowledge and referral mechanism.
PMC9905012
Trial Registration
Clinical Trials.gov NCT04829084;
PMC9905012
Supplementary Information
The online version contains supplementary material available at 10.1186/s12913-023-09105-3.
PMC9905012
Keywords
PMC9905012
Background
Diabetic retinopathy, blindness, Diabetic Retinopathy, diabetic, vision loss, Non-proliferative Diabetic Retinopathy, diabetes
DIABETIC RETINOPATHY, DIABETIC RETINOPATHY, BLINDNESS, DIABETIC RETINOPATHY, COMPLICATION, RETINA, PROLIFERATIVE DIABETIC RETINOPATHY, MACULAR EDEMA, EYE, DIABETES
Diabetic retinopathy (DR) is a complication of diabetes damaging the retinal vessels that can lead to blindness if left untreated [The worldwide prevalence of Diabetic Retinopathy (DR) was found to be 34.6% [DR is an emerging cause of blindness in developing countries like Nepal. SK Mishra et al. showed that 10% of the...
PMC9905012
Method
PMC9905012
Research Objective
blindness
BLINDNESS
The aim of this study was to increase retinal screening uptake among patients with DM and to decrease DR-associated blindness by augmenting the referral pathway in a selected hospital in Nepal.
PMC9905012
Hypothesis
diabetes
DIABETES
Providing DR health education to selected health personnel and creating a referral pathway would increase the uptake of retinal services (screening and treatment) by diabetes patients referred to REMEH.
PMC9905012
Study design
This was a non-randomized pre- and post-intervention study without a control group.
PMC9905012
Study setting
diabetic
EYE
Reiyukai Eiko Masunaga Eye Hospital (REMEH) is an eye hospital. Scheer Memorial Hospital is the intervention hospital. It is a multispeciality hospital with no eye department and has been conducting regular diabetic clinics.There was no baseline data on referral of patients from Scheer to REMEH before the study.
PMC9905012
Study period
The total duration was 16 months from June 2020 to September 2021. The initial 8 months from June 2020 to January 2021 was for base line data collection (pre-intervention period). The remaining 8 months from February 2021 to September 2021 was the post intervention period.
PMC9905012
Study participants
diabetes mellitus, diabetic
DIABETES MELLITUS
Selected Health personnel of Scheer Memorial Hospital (The intervention hospital) who are directly involved in providing health services to diabetes mellitus patients in the diabetic clinic at Scheer. Physicians, paediatricians, medical officers and their assistants were included. Those health personnel who didn't atte...
PMC9905012
Sampling techniques
diabetes
DIABETES
Complete enumerations of all health personnel managing patients with diabetes in the intervention hospital.
PMC9905012
Inclusion criteria
diabetes
DIABETES
All health personnel involved in the management of patients with diabetes at the intervention hospital.
PMC9905012
Materials
The Information Education and Communication (IEC)material developed by the Indian Institute of Public Health-Hyderabad; India (IPHH) was used for intervention after converting into Nepalese language. The IEC materials were PPT, poster (Annex 
PMC9905012
Implementation of intervention
DM
RETINA
The retina specialist and the optometrist/outreach coordinator of REMEH conducted the intervention. The assistant manager of the hospital was responsible for the logistics. There was no control group in this study. A pilot was done before the main intervention started.A pilot was conducted In Feb 19,2021 to the health ...
PMC9905012
Data collection
Data collection included the pre-post intervention after health education at Scheer Memorial, as well as patient referral data at REMEH. Data was entered into the EXCEL sheet every week. The data tools are mentioned in the Annex (
PMC9905012
Data analysis
The baseline and post intervention patient referral data was compared and the proportional increase due to intervention was calculated. The change in knowledge of health personnel was assessed by pre and post assessment questionnaire. In patients’ data, Information on DR and duration of DM was collected, visual acuity ...
PMC9905012
Outcome
Primary outcome:1. Change in the proportion of referred patients from Scheer Memorial to REMEH when compared to baseline referrals before the intervention.Secondary outcome:2.Change in knowledge on DR in the Health Care Personnel (HCP) who participated in health education sessions in Scheer Memorial.
PMC9905012
Results
diabetes, Diabetes Mellitus, SD, ’
DIABETES MELLITUS, DIABETES
Of the 14 health care personnel enrolled in health education intervention 10(71.43%) were physicians with median experience of 4.5 years (IQR 3–6.75) and 4 (28.57%) were non physicians with median experience of 27.5 years. The male and female ratio in health care personnel was equal with an mean age of 35.8 years (SD ±...
PMC9905012
Discussion
diabetic retinopathy, DM, Diabetic retinopathy, ±, diabetes mellitus, SD, diabetic, diabetes
DIABETIC RETINOPATHY, DIABETIC RETINOPATHY, DIABETES MELLITUS, PCP, DIABETES
We conducted a non-randomized pre-post health education intervention study on health personnel with an objective to increase the referral of DM patients for DR screening. The health professionals were provided health education to create awareness and knowledge of DR using PPTs, posters, pamphlets, and referral slips. T...
PMC9905012
Conclusion
EYE
A well-planned health education intervention changes the knowledge in physicians about DR. With the change in knowledge and structured referral system, there is significant increase in the number of referrals and attendance of patients for DR screening. This study clearly shows the need to mobilize and link physicians ...
PMC9905012
Strength and limitations
DIABETIC RETINOPATHY
The strength of our study is that it is one of the first studies in Nepal that includes health care professionals involved in DM management and strengthens the referral for the screening of diabetic retinopathy. The pilot gave us information on re-comprehension of the content of the materials to be used for the main st...
PMC9905012
Acknowledgements
GILBERT
We gratefully acknowledge the SEVA Foundation and Indian Institute of Public Health – Hyderabad for their valuable guidance and support of this work and the staff at REMEH for their contribution to various aspects of the work of this initiative. The Study Group is funded by SEVA Foundation. We are also grateful to all ...
PMC9905012
Author’s contributions
TB, RS, PD
HBP
RS, PS, PD, ST, and TB conceptualized and designed the study. RS, PS, PD, PST, VA and HBP were responsible for the data handling. RS, ST, and TB drafted the manuscript. “All authors have read and approved the manuscript”.
PMC9905012
Funding
SEVA Foundation, Kathmandu, Nepal.
PMC9905012
Availability of data and materials
Datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
PMC9905012
Declarations
PMC9905012
Ethics approval and consent to participate
The research has been performed in accordance with the Declaration of Helsinki. The ethical approval for this study has been obtained from the Ethical Review Board of the Nepal Health Research Council (ERB Protocol Registration Number # 582/2020P). Written informed consent was taken from the participants.
PMC9905012
Consent for publication
Written informed consent has been taken from all subjects and/or their legal guardian(s) for publication of identifying information/images in an online open-access publication.
PMC9905012
Competing interests
The authors declare no competing interests.
PMC9905012
References
PMC9905012
Dr. Yan-xin Chen
liver and pancreatic cancer
was born and raised in the coastal city of Guangdong Province, China. He majored in anesthesiology and obtained a medical master’s degree from Southern Medical University. He completed his anesthesiology residency training at Southern Medical University, where he started his basic-medical research. His clinical interes...
PMC9803753
Background
POSTOPERATIVE COMPLICATIONS, INFLAMMATORY RESPONSE
Laparoscopic pancreaticoduodenectomy (LPD) may induce intense inflammatory response which might be related to the patient’s outcomes. Clinical dexmedetomidine (DEX) has been widely used for opioid-sparing anesthesia and satisfactory sedation. The objective of this study was to investigate the influence of DEX on inflam...
PMC9803753
Methods
POSTOPERATIVE COMPLICATIONS
Ninety-nine patients undergoing LPD were randomly assigned to two groups: normal saline (NS) and DEX. The primary outcome was the neutrophil-to-lymphocyte ratio (NLR) differences postoperatively within 48 h. Secondary outcomes were postoperative complications, the length of postoperative hospital stay and the incidence...
PMC9803753
Results
NLR at postoperative day 2 to baseline ratio decreased significantly in the DEX group (
PMC9803753
Conclusions
LPD
COMPLICATIONS, INFLAMMATORY RESPONSE
Intraoperative DEX reduced the early postoperative inflammatory response in LPD. It also reduced the use of narcotics that may related to reduced major complications, which need additional research further.
PMC9803753
Introduction
cancer death, Pancreatic cancer, death
PANCREATIC CANCER, POSTOPERATIVE COMPLICATIONS, INFLAMMATORY RESPONSE
Pancreatic cancer is currently the seventh leading cause of cancer death worldwide and the third leading cause of cancer-related death in the USA [Dexmedetomidine (DEX) is a highly selective As a result of the potential immunomodulation of DEX, we hypothesized that the use of DEX could attenuate the inflammatory respon...
PMC9803753
Methods
PMC9803753
Ethics
Ethical approval for this study (Z2017-129–01) was provided by the Ethics Committee of Guangdong Provincal Hospital of Chinese Medicine (Chairperson Professor Jun Liu), Guangzhou, China, on 8 September 2017. This randomized, double-blinded, controlled trial was registered on Chinese Clinical Trial Registry (ChiCTR 1,80...
PMC9803753
Study design
LPD
The inclusion criteria for patients were that they planned to receive LPD, aged 18 to 65 years, body mass index (BMI) <28.0 kg m
PMC9803753
Anesthesia management and groups
To ensure the randomization of groups, random number was generated by computer and stored in sequentially numbered envelopes. A nurse who did not participate in the trial prepared drug X [DEX or normal saline (NS)] according to the number in the envelope. Only this nurse was aware of patient allocation. General anaesth...
PMC9803753
Outcome measures
pancreatic fistula
INTRA-ABDOMINAL INFECTION, BILE LEAKAGE, POSTOPERATIVE COMPLICATIONS, POSTOPERATIVE COMPLICATION, POSTOPERATIVE HEMORRHAGE, COMPLICATIONS, SECONDARY, PANCREATIC FISTULA, LEAKAGE, DELAYED GASTRIC EMPTYING
The primary outcome was NLR differences perioperatively. The secondary outcomes were the postoperative complications, the incidence of postoperative ICU admission, and the length of postoperatively hospital stay. Postoperative complications include pancreatic fistula, bile leakage, chylous leakage, postoperative hemorr...
PMC9803753
Sample size and statistical analysis
According to previous studies [
PMC9803753
Discussion
inflammation, cancer
POSTOPERATIVE COMPLICATIONS, INFLAMMATION, CANCER, PANCREATIC CANCER, TUMOR ANGIOGENESIS
Surgical resection is the mainly possible cure for pancreatic cancer; however, surgery itself induces intense stress response to cause immunosuppression and excessive pro-inflammatory responses, which could promote tumor angiogenesis and increase postoperative complications [As an inflammatory indicator, NLR indicates ...
PMC9803753
Limitations
cancer type, cancer, tumor
CANCER, TUMOR, PERIAMPULLARY CARCINOMA
There are several limitations in this study. Firstly, the inflammatory indicators we examined were relatively single, and there may be differences in other immune cells and cytokines. Furthermore, long-term indicators are important for cancer prognosis, and we only collect short-term outcome indicators and pay more att...
PMC9803753
Funding
The Guangzhou Municipal Science and Technology Project, China (Grant No.202102010243).
PMC9803753
Declarations
PMC9803753
Conflict on interest
The authors declare that they have no conflicts of interest.
PMC9803753
Ethical approval
Ethical approval for this study (Z2017-129–01) was provided by the Ethics Committee of Guangdong Provincal Hospital of Chinese Medicine (Chairperson Professor Jun Liu), Guangzhou, China, on 8 September 2017.
PMC9803753
Informed consent
Informed consent was obtained from all individual participants included in the study.
PMC9803753
References
PMC9803753
Background
Chagas disease, EH
DISEASE, CHAGAS DISEASE
I have read the journal’s policy and the authors of this manuscript have the following competing interests: AMR and JA are members of the Research Career of CONICET, Argentina. JA has acted as a consultant to Bayer for the design, conduct and review of the CHICO and CHICO SECURE studies. UG is an employee of Bayer AG. ...
PMC10325040
Methods and principal findings
Chagas disease
CHAGAS DISEASE
In a phase 3, randomized, double-blind, parallel-group, historically controlled study (ClinicalTrials.gov NCT02625974), blood samples obtained from children diagnosed with Chagas disease and treated with nifurtimox for either 60 days or 30 days were analyzed using an ELISA with an F29 recombinant protein as the antigen...
PMC10325040
Conclusions
CHAGAS DISEASE
The results demonstrate a serological response to treatment with nifurtimox measured by the ELISA F29 test in children diagnosed with Chagas disease. The F29-based ELISA can be considered a potential early marker of response to antitrypanosomal therapy for Chagas disease.
PMC10325040
Trial registration
ClinicalTrials.gov
PMC10325040
Author summary
Chagas disease
AMERICAN TRYPANOSOMIASIS, PARASITIC DISEASE, CHAGAS DISEASE
Chagas disease (American trypanosomiasis) is a potentially life-threatening parasitic disease caused by
PMC10325040
Data Availability
The study protocol, statistical analysis plan and the results of the study are available at
PMC10325040
Introduction
Chagas disease
AMERICAN TRYPANOSOMIASIS, DISEASE, PARASITIC DISEASE, CHAGAS DISEASE
Chagas disease (American trypanosomiasis) is a potentially life-threatening parasitic disease that for many years has been endemic in 21 Latin American countries and areas of southern USA [The protozoan The diagnostics recommended by national organizations and the Pan American Health Organization (PAHO) includes the co...
PMC10325040
Methods
PMC10325040
Ethics statement
DEL
The study was approved by the respective independent ethics committees of participating investigational sites (Argentina: Comité de Ética, Hospital General de Agudos J. A. Fernández, Buenos Aires; Comité de Ética Independiente en Investigación Clínica "Dr. Carlos A. Barclay", Buenos Aires; Comité Institucional de Revis...
PMC10325040
Study design and procedures
Chagas disease
BLOOD, CHAGAS DISEASE
In a phase 3, randomized, double-blind, parallel-group, historically controlled study (ClinicalTrials.gov NCT02625974), blood samples obtained from children diagnosed with Chagas disease were analyzed using ELISA F29. Blood samples were obtained for ELISA F29 immediately before nifurtimox treatment (baseline), on Days ...
PMC10325040
ELISA F29 laboratory test
An ELISA containing a recombinant 29 kDa
PMC10325040
Outcomes
The serological response using ELISA F29 over time and the incidence rate of seronegative conversion measured by ELISA F29 were evaluated after treatment with nifurtimox. Furthermore, the time at which seronegative conversion was detected was compared for ELISA F29 and conventional serological methods: recombinant ELIS...
PMC10325040
Statistical analyses
Analysis of patient characteristics used the full analysis set (FAS), which included all patients who received at least one dose of study drug. For analysis of ELISA F29, a subpopulation was defined that included all patients in the FAS who had positive ELISA F29 results at baseline.The incidence rate of seronegative c...
PMC10325040
Results
PMC10325040
Patient characteristics
Among the 330 patients randomly assigned to nifurtimox treatment for 60 days or 30 days, 318 completed part 1 of the study (CHICO) [Among the 295 patients who were followed for 4 years post-treatment, 53.2% were females and 46.8% were males. The median age was 8.5 years (interquartile range: 2–13 years). About two-thir...
PMC10325040
Patient characteristics at randomization (FAS).
PMC10325040
ELISA F29
In both treatment groups, the number of patients with negative ELISA F29 results increased over the period of observation after the end of nifurtimox treatment. At the 4-year follow-up the proportion of patients with seronegative ELISA F29 values was 77.2% in the 60-day regimen and 66.3% in the 30-day regimen (
PMC10325040
Serological responses to 60-day and 30-day nifurtimox treatment using ELISA F29 over the study period (FAS).
A total of 99 of the 295 patients (33.6%) showed negative ELISA F29 values at baseline, and the proportion of such patients was similar in the two nifurtimox treatment groups (60-day regimen: 67 patients [34.0%]; 30-day regimen: 32 patients [32.7%]) (
PMC10325040
Serological responses to 60-day and 30-day nifurtimox treatment using ELISA F29 over the study period (subpopulation of FAS
*The subpopulation of FAS consists of all patients with positive ELISA F29 results at baseline.
PMC10325040
Kaplan-Meier survival curve of seronegative conversion in patients with positive ELISA F29 results at baseline.
PMC10325040
Comparison of serological response to nifurtimox treatment measured by ELISA F29 and by conventional serology
At the 4-year follow-up, the number of patients with seronegative ELISA F29 values was higher in both treatment groups compared with the number of patients with seronegative values measured by either recombinant ELISA, total purified antigen ELISA, or IHA (Number of patients with nonreactive values measured by ELISA F2...
PMC10325040
Discussion
Chagas disease
CHAGAS DISEASE, CHRONIC CHAGAS DISEASE
Until now, there has not been an adequate parameter that reflects the early response or failure of etiological treatment for Chagas disease. Currently, the evaluation of the negativization of serology demonstrated by more than one type of conventional assay is the accepted criterion to establish successful treatment fo...
PMC10325040
Supporting information
PMC10325040
Study site principal investigators of the CHICO and CHICO SECURE Study Groups. Investigators participated in both studies unless indicated otherwise.
(DOCX)Click here for additional data file.We thank the study participants and their families. The CHICO and CHICO SECURE Study Group members are listed in
PMC10325040