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3.2. Sarcopenia Evaluation Related Indicators | sarcopenia | SARCOPENIA | There was no significant difference in the indicators of sarcopenia between the two groups before the intervention ( | PMC9937758 |
3.3. Functional Independence | There was no significant difference in the functional independence between the two groups before the intervention ( | PMC9937758 | ||
3.4. Postoperative Recovery | fracture | The time of fracture healing and hospital stay in patients of research group were all significantly lower than those in patients of control group ( | PMC9937758 | |
3.5. Nursing Satisfaction | The number of patients in the control group was 16, 22, and 12 who were very satisfied, satisfied, and dissatisfied with their care, compared with 24, 23, and 3 in the research group, respectively. The patients in the study group had a satisfaction rate of 94.00%, which was significantly higher than that of the patients in the control group (76.00%) ( | PMC9937758 | ||
4. Discussion | age-dependent loss of muscle mass, muscle atrophy, fracture, sarcopenia, pain, muscle exercise, fractures, Sarcopenia, Undernutrition, femoral fractures, mobility impairments, sarcopenic femoral fractures | DISORDER, MUSCLE ATROPHY, SARCOPENIA, METABOLIC DISEASE, UNDERNUTRITION, SARCOPENIA | Sarcopenia, an age-dependent loss of muscle mass and function, is a common disorder in older adults and is associated with adverse health outcomes. Sarcopenia patients suffer from loss of muscle strength and mobility impairments, which reduce their quality of life, with higher risk for falls, fractures, metabolic disease, and mortality [In this study, we found that compared with patients in the control group, patients in the research group receiving nutritional intervention combined with muscle exercise had higher BMI, grip strength, calf circumference, faster walking speed, and body muscle rate after the intervention, which suggests that nutritional intervention combined with muscle exercise can effectively improve symptoms in patients with sarcopenia. Undernutrition is an important cause of sarcopenia in middle-aged and elderly people, and it is also the main direction for the prevention and treatment of sarcopenia [Furthermore, muscle exercise is also very important for improving symptoms in patients with sarcopenia. On the one hand, regular aerobic training can improve the activity of muscle mitochondrial enzymes, increase capillary density, promote nerve repair and motor unit mobility, thereby increasing skeletal muscle strength and exercise capacity [In this study, we also found that the postoperative recovery of the patients in the research group was better than that of the patients in the control group, including higher functional independence scores, shorter fracture healing times and hospital stay time, and lower postoperative VAS pain scores, which indicates that our intervention not only improves sarcopenia symptoms but also accelerates recovery in patients with femoral fractures. Adequate nutrition and protein supplementation can not only slow down muscle atrophy but also help increase muscle strength and help patients with femoral fractures get out of bed early to exercise [All in all, our results in this study indicated that nutritional intervention combined with muscle exercise could help improve sarcopenia symptoms and promote fracture recovery in patients with sarcopenic femoral fractures. However, as a single center study, there are problems such as a single research population and a small sample size. In the future, we need to expand the sample size to verify the accuracy of the results. | PMC9937758 |
Acknowledgments | This study was funded by Basic Research Incubation Project of the Third Affiliated Hospital of Chongqing Medical University, Chongqing, China (No. KY08046). | PMC9937758 | ||
Data Availability | All data of this study are available from the corresponding author upon request. | PMC9937758 | ||
Conflicts of Interest | All authors declare that they have no known competing financial interests or personal relationships. | PMC9937758 | ||
Authors' Contributions | femoral fracture | NN and JY contributed to the conception and design of the study. ZY, JZ, XL, YC, XX, and PL contributed to data collection. NN and JY drafted the manuscript. All authors gave the final approval.Baseline data in two groups.Comparison of sarcopenia-related indicators in two groups of sarcopenic femoral fracture patients before and after treatment (mean ± SD).Comparison of functional independence between the two groups of patients (mean ± SD).Comparison of postoperative recovery between the two groups of patients (mean ± SD).Comparison of nursing satisfaction of two groups of patients ( | PMC9937758 | |
Introduction | T2DM, diabetes | TYPE 2 DIABETES MELLITUS, DIABETES | India currently has more than 74.2 million people with Type 2 Diabetes Mellitus (T2DM). This is predicted to increase to 124.9 million by 2045. In combination with controlling blood glucose levels among those with T2DM, preventing the onset of diabetes among those at high risk of developing it is essential. Although many diabetes prevention interventions have been implemented in resource-limited settings in recent years, there is limited evidence about their long-term effectiveness, cost-effectiveness, and sustainability. Moreover, evidence on the impact of a diabetes prevention program on cardiovascular risk over time is limited. | PMC10030347 |
Objectives | diabetes, ECG abnormalities, microalbuminuria, Diabetes | DIABETES, RECRUITMENT, DIABETES | The overall aim of this study is to evaluate the long-term cardiometabolic effects of the Kerala Diabetes Prevention Program (K-DPP). Specific aims are 1) to measure the long-term effectiveness of K-DPP on diabetes incidence and cardiometabolic risk after nine years from participant recruitment; 2) to assess retinal microvasculature, microalbuminuria, and ECG abnormalities and their association with cardiometabolic risk factors over nine years of the intervention; 3) to evaluate the long-term cost-effectiveness and return on investment of the K-DPP; and 4) to assess the sustainability of community engagement, peer-support, and other related community activities after nine years. | PMC10030347 |
Methods | T2DM | The nine-year follow-up study aims to reach all 1007 study participants (500 intervention and 507 control) from 60 randomized polling areas recruited to the original trial. Data are being collected in two phases. In phase 1 (Survey), we are admintsering a structured questionnaire, undertake physical measurements, and collect blood and urine samples for biochemical analysis. In phase II, we are inviting participants to undergo retinal imaging, body composition measurements, and ECG. All data collection is being conducted by trained Nurses. The primary outcome is the incidence of T2DM. Secondary outcomes include behavioral, psychosocial, clinical, biochemical, and retinal vasculature measures. Data analysis strategies include a comparison of outcome indicators with baseline, and follow-up measurements conducted at 12 and 24 months. Analysis of the long-term cost-effectiveness of the intervention is planned. | PMC10030347 | |
Discussion | diabetes | DIABETES | Findings from this follow-up study will contribute to improved policy and practice regarding the long-term effects of lifestyle interventions for diabetes prevention in India and other resource-limited settings. | PMC10030347 |
Trial registration | Australia and New Zealand Clinical Trials Registry–(updated from the original trial)ACTRN12611000262909; India: CTRI/2021/10/037191.
| PMC10030347 | ||
Keywords | PMC10030347 | |||
Introduction | Diabetes, diabetes | DIABETES, TYPE 2 DIABETES, DIABETES | Based on recent estimates, there are 537 million people with diabetes globally with 433 million (80.6%) living in low and middle-income countries such as India [India has the second highest number of people with diabetes (74.2 million), accounting for 1 in 7 of all adults living with diabetes worldwide, and this is expected to increase to 124.9 million by 2045. About 57% of the estimated number of people with diabetes in India are undiagnosed [The efficacy, effectiveness, and implementation of lifestyle interventions aimed at preventing the onset of type 2 diabetes have been well-established at least in high-income countries. A review of 38 implementation trials has demonstrated a reduction in type 2 diabetes incidence of between 40–60% [In this study protocol paper, we briefly discuss the findings of a community-based diabetes prevention program conducted in the Indian state of Kerala, the Kerala Diabetes Prevention Program (K-DPP), from 2013–2016. We also present the rationale to conduct a nine-year follow-up of the original K-DPP participants; the aims, measures to be undertaken, and the analysis plan. | PMC10030347 |
Summary of Kerala Diabetes Prevention Program (K-DPP) findings at 12 and 24 months | Diabetes | TYPE 2 DIABETES, DIABETES | The Kerala Diabetes Prevention Program (K-DPP) is a cluster randomized trial of a group-based and peer-led lifestyle intervention among adults at high-risk for type 2 diabetes in Kerala, India [ | PMC10030347 |
Rationale for long-term follow-up of K-DPP participants | PMC10030347 | |||
Diabetes incidence and cardiometablic risk | Diabetes, diabetes | EVENTS, DIABETES, DIABETES | There is limited long-term data on the effect of lifestyle interventions on diabetes incidence and cardiomentabolic risk, especially in low- and middle-income countries. Extended follow-up studies of previous lifestyle intervention studies, such as the Da Qing Diabetes Prevention Study and the U.S. Diabetes Prevention Program, showed benefits in reducing cardiovascular events after many years of follow-up [ | PMC10030347 |
Multimorbidity | Diabetes mellitus, multimorbidity | DIABETES MELLITUS, COMPLICATIONS | Diabetes mellitus is one of the main drivers of multimorbidity as it is associated with a large number of risk factors and complications [ | PMC10030347 |
Retinal vasculature | retinopathy, obesity, retinal arteriolar, impaired fasting glucose, diabetes | RETINOPATHY, OBESITY, CARDIOVASCULAR DISEASE, HYPERTENSION, DIABETES | Changes in the retinal microvasculature, such as retinal arteriolar narrowing, venular dilatation, and retinopathy, have been associated with various systemic conditions, including impaired fasting glucose, obesity, blood pressure, incident hypertension, incident diabetes, and cardiovascular disease [ | PMC10030347 |
Methods | PMC10030347 | |||
Study aims | microalbuminuria, diabetes | RECRUITMENT, DIABETES | The overall aim of this study is to evaluate the long-term effects of the K-DPP on diabetes incidence and cardiometabolic risk at nine years following participant recruitment.The specific objectives are:To estimate the effects of K-DPP on diabetes incidence and cardiometabolic risk at nine yearsTo assess retinal microvasculature, microalbuminuria, and electrocardiogram (ECG) abnormalities and their association with incident diabetes and cardiometabolic risk factorsTo evaluate the cost-effectiveness and return on investment of the K-DPP at nine yearsTo assess the sustainability of community engagement, peer support, and other related community activities after nine years | PMC10030347 |
Study design and setting/context | The current study is the nineth-year follow-up assessment of the K-DPP. The protocol paper for the original trial has been published elsewhere [ | PMC10030347 | ||
Study population | Diabetes, diabetes | DIABETES, DIABETES | The study population for K-DPP is adults 30–60 years of age who were at high risk for diabetes based on the Indian Diabetes Risk Score (IDRS ≥ 60) [ | PMC10030347 |
Sample size | PMC10030347 | |||
Primary outcomes | diabetes | CVD, DIABETES | Based on the available data at 12 and 24 months, we anticipate more than 90% of K-DPP participants at baseline can provide complete and valid data for all key measures underlying diabetes incidence and 10-year CVD risk predicted using the Framingham Risk Score [ | PMC10030347 |
Secondary outcomes | Loss to follow-up has been very low so far, i.e., < 5% at 24 months and a 7-year cohort study conducted in the same region had a follow-up rate of 92% [ | PMC10030347 | ||
Intervention | Detailed description of the cultural adaptation and development of the K-DPP intervention has been published previously [ | PMC10030347 | ||
Data collection procedures | PMC10030347 | |||
Strategy to reach out to participants after nine years | During the preparation phase of the K-DPP follow-up study, participants were contacted via phone to check their availability and willingness to participate in the follow-up study. Unique K-DPP identification numbers and contact details of the study participants and local resource persons (LRP) from the previous assessments were used to reach to participants. For the survey data collection, the study team visited the homes of participants. Repeat visits are being organized if participants are not available on the first visit. The participants who denied consent are not part of the current evaluation. Concerted efforts to reach out to the missing participants (The participants who are not available at the time of data collection and whose contact details could not be traced) are being made. For community-based clinics, participants are invited to undertake the measurements. | PMC10030347 | ||
Long-term effectiveness outcomes | muscle mass, renal disease, multimorbidity, diabetes | CVD, RENAL DISEASE, SECONDARY, BLOOD, DIABETES | The key study outcomes are the incidence of diabetes and CVD risk at nine years after the intervention. Other primary outcomes include Blood pressure, weight, HbA1c, triglycerides, SF-36, and tobacco. Additionally, body mass index, fat percent, muscle mass, waist circumference, diastolic blood pressure, Fasting Plasma Glucose, lipid profile (total cholesterol, LDL cholesterol, and HDL cholesterol), current alcohol use, diet, and physical activity will be assessed. New measures of pre-clinical retinal microvasculature, heart function and renal disease are also being assessed. We are also considering multimorbidity as a secondary outcome in this follow-up study. | PMC10030347 |
Anthropometry and behavioral measures | muscle mass | BLOOD | Anthropometry (weight, total body fat percent, muscle mass, waist circumference) and Blood Pressure are measured using standard protocols. Self-reported physical activity and sedentary behavior are estimated using the Global physical activity questionnaire (GPAQ). Fruit and vegetable consumption, alcohol use, and tobacco use are assessed using the WHO STEPs Questionnaire.Two TANITA machines (model SC330) used in the previous rounds of assessment were sent to the designated national TANITA service center for recalibration. Weight and body composition parameters will be measured using these TANITA body composition analyzers while the participant is standing still without footwear, with one foot on each side of the scale, facing forward, and arms at their side. | PMC10030347 |
Retinal vasculature measurement | tortuosity | A CANON CR-2/Plus/AF RX non-mydriatic retinal camera is being used to obtain retinal images. Two images of each eye are being taken (macular centred and disc centred), following a standard protocol. Image quality will be continuously monitored throughout the study. Images will be graded using fully automated software providing measures of arteriolar and venular diameter and tortuosity. The refractive status of the eyes are being assessed using aCanon RK-F2 Autorefractometer. | PMC10030347 | |
ECG | We are using ECG equipment (KardioScreen-1612) to acquire the report that is being asssed to determine whether the ECG waves and intervals are normal or pathological. A standard operating procedure adapted from the American College of Cardiology guidelines [ | PMC10030347 | ||
Biochemistry | All biochemical measurements are following standard procedures. Samples are being centrifuged within 30 min of collection, and transported with dry ice to a nationally accredited laboratory. Plasma glucose are being measured with the Hexokinase method on a COBAS 6000 analyzer, with kits supplied by Roche Diagnostics. The quality of plasma glucose measurements from the proposed laboratory is good for the K-DPP trial; the intra-class correlation coefficient approached 1.0. HbA1c is being measured by High-Performance Liquid Chromatography on a D-10 BIORAD analyzer and lipids by enzymatic methods on COBAS 6000, kits supplied by Roche. | PMC10030347 | ||
Microalbuminuria | PUC | The random urine samples are being processed using Roche/Hitachi Cobas 501 analyzer system by Immunoturbidimetric assay with Roche reagent cassettes. Before running the samples, quality control procedures are being followed using Roche precinorm PUC and Precipath PUC. Besides, a monthly Biorad EQAS urine chemistry programme including microalbumin and creatinine is also being followed. Cobas 501 system automatically calculates microalbumin 24-h, random and microalbumin and creatinine ratio. | PMC10030347 | |
Economic evaluation | illness | The economic evaluation involves cost-effectiveness analysis of the intervention from both the health system and societal perspectives. The key outcome measure will be Quality Adjusted Life Years (QALY), which will be estimated using the utility values (SF-6D) derived from the SF-36 survey form. Costs being assessed include both direct medical and non-medical costs and indirect (lost days of productivity) costs associated with the intervention. These are be based on information on staff inputs by duration and type and resource use collected during the study. Any additional “knock-on” effect on hospital admissions or outpatient service use is being quantified and costed for each study participant. We are calculating direct costs to the health service and patients from health facility records, project financial accounts, and participant responses to a survey including questions on health service use and spending. These analyses will be based on updated estimates for health facility costs and personal costs Personal costs to individuals will be collected as part of the questionnaire administered to study participants at nine years. These include transportation costs and out-of-pocket spending for health services use, especially for medications and will capture how the individual financed these costs (e.g., borrowing, asset sales, dis-savings). Any indirect costs to patients arising from being absent from work due to the intervention or illness are also being estimated. Savings from lowered health service use associated with the intervention are subtracted from intervention costs to derive incremental costs at the 9-year mark. | PMC10030347 | |
Program sustainability | We are assessing three key features of K-DPP program sustainability at nine years from intervention using a structured interview with K-DPP participants. This assessment focuses on the past 12 months preceding the assessment. The five main areas of assessment for program sustainability are:Participation in group/educational sessions and/or peer group activitiesContact with peer leaders and/or group membersCurrent and future interest to participate in group sessions/activitiesRecent efforts made in relation to improving lifestyle factorsFactors that would encourage or hinder participation in peer group activities | PMC10030347 | ||
Data management plan | PMC10030347 | |||
The survey, biomedical and clinical data | Data are being entered by the research team into the RedCap database at SCTIMST servers. The database has validation checks for the values. Skip patterns are included using branching logic functions. Each team member double-checks the data s/he entered before synchronization. The project manager checks the entered data on weekly basis. Any data entry issues are rectified against the questionnaire. At 25%, 50%, 75%, and 100% of the data entry, the project manager re-checks 10% of the data for quality. After data cleaning is complete, a master copy of the dataset will be created and backed up. All data transformations (derivation of new variables) will be documented in the data dictionary. All hardcopy and electronic data will be properly secured at SCTIMST offices and servers. Data sharing will be based on the guidelines stipulated by the Data Management and Publications committee of the project. | PMC10030347 | ||
Retinal data | Image quality is being continuously monitored throughout the study. Initially, the day’s images were reviewed on site and feedback was provided to the photographer(s) immediately and appropriate measures have been taken to ensure that the images are captured accurately. During subsequent camps / data acquisition during the study, a few images per day are being sent for evaluation and any concerns while taking the photograph will be sent along with the images and a feedback is sent with comments and suggestions within 48 h. In case of any emergency, the contact persons can be contacted for problem resolutions.Images are being stored on the laptop computer and backed up at the end of each day onto the external hard drive and institutional repository. Each back-up is being labelled by the date of back-up. Apart from quality control images, image transfer is be performed at the end of the study by physical transfer of an external USB hard drive. The best image for each eye will be uploaded into the software for gradeability for each view and then all measurement indices will be obtained.The data from grading of retinal images will be entered into the RedCap database of the K-DPP Follow-up study. The Participant ID will be used to link the retinal imaging data and the rest of the data from the K-DPP Follow-up study. All data cleaning will be conducted in the same database. | PMC10030347 | ||
Statistical analysis | tortuosity, diabetes | CVD, REGRESSION, DIABETES | The two co-primary outcomes are diabetes incidence and CVD risk. The analyses will observe the intention-to-treat principle. A generalized estimating equation [To evaluate the treatment effect on continuous outcomes, a repeated measures mixed-effects linear regression model, adjusting for the baseline measures, will be fitted. Any skewed continuous outcome variable may be transformed before fitting this model. The model will specify treatment, time-point, and treatment by time-point interaction as fixed effects. Random effects will be specified for polling areas, to account for the clustered study design, and for participants, to account for correlation between the repeated measurements on the same participant. The estimated treatment effect (e.g., the absolute difference in means between the treatment arms) at nine years and two-sided 95% CI will be obtained. Binary other outcomes (e.g., diabetes) will be analyzed using GEE models similar to that of the co-primary outcomes.The retinal image measurements will be compared between the treatment and control groups on the impact of a lifestyle modification program on pre-clinical changes in the retinal microvasculature and its correlation with cardiometabolic risk factors. Retinal imaging measures will include measures retinal architecture such as arteriolar and venular diameters and tortuosity.The economic evaluation will consist of a cost-effectiveness analysis that will compare the incremental costs and 9-year effects (QALYs) between the study groups. Generalized linear models (GLM) with gamma family and log link components will be used to estimate the incremental costs and QALYs and the results will be presented as incremental cost-effectiveness ratios (ICERs) [Quantitative descriptive analyses will use key indicators—participation in group activities, maintenance of contact with peer leaders, interest to participate in group activities and recent effors made to improve lifestyle factors—to examine the extent of program sustainability from program participants perspectives. Statistical analyses will characterize the relationships among these indicators and the patterns of maintenance of other outcome measures over time. | PMC10030347 |
Ethics approvals | For the K-DPP Follow-up study, we obtained Ethics approval from the Institutional Review Board of SCTIMST (ID: SCT/IEC/1349/APRIL-2019) and the Alfred Human Research Ethics Committee (ID: 463/21). Local approvals from HMSC and State Health Departments have been obtained before the start of data collection. A participant information sheet that describes the objectives of the study and the study procedures are being provided to participants along with the informed consent form. Participants provided written informed consent for each phase of the study. | PMC10030347 | ||
Discussion | diabetes, Diabetes | DIABETES, TYPE 2 DIABETES, DIABETES | This paper describes the protocol for the nine-year follow-up of a cluster randomized controlled trial of a peer-led lifestyle intervention program – the Kerala Diabetes Prevention Program—to reduce the incidence of type 2 diabetes among individuals at high risk of developing type 2 diabetes at baseline. The study will generate evidence that could establish the long-term effectiveness, cost-effectiveness, and sustainability of lifestyle intervention programs to prevent diabetes in India and other resource-constrained settings. Moreover, evidence on the progressive development of various multimorbidities over time among people with or at high risk of diabetes would inform policies and practice in the prevention and management of diabetes in India and other low-resource settings. | PMC10030347 |
Acknowledgements | Diabetes | HEART, DIABETES | K-DPP follow-up study is funded by the National Health & Medical Research Council (Grant ID: 1160283). We acknowledge Dr Yingting Cao, Dr GK Mini, Professor Sivasubramonian Sivasankaran, Kate Chalmers, Ameera Katar, and Rebecca Gracey for their contribution in the preparatory phase of the study. We also acknowledge Sree Chitra Trunal Institute for Medical Sciences and Technology the Melbourne School of Population and Global at the University of Melbourne, and Baker Heart and Diabetes Institute for their contribution to this study. | PMC10030347 |
Authors’ contributions | JP | RECRUITMENT | TH, SJ, NK and TS contributed to the study design, coordination of the recruitment and data collection and prepared the first draft of the manuscript. BO, JP, KRT, EBF, PA, AM, RT, NK and TS contributed to the study design and involved in writing the original grant proposal. LT is managing the project and contributed to the preparation of the first draft of the manuscript. RT and SJ led the designing the retinal imaging sub-study and contributed to the writing of the manuscript. All authors reviewed and approved the final manuscript for submission. | PMC10030347 |
Funding | This study is funded by the Australian National Health and Medical Research Council (NHMRC) (Grant ID: 1160283). The funding body has no role in the design of the study and the writing the study protocol. | PMC10030347 | ||
Availability of data and materials | Not applicable. | PMC10030347 | ||
Declarations | PMC10030347 | |||
Ethics approval and consent to participate | The study obtained Ethics approval from the Institutional Review Board of Sree Chitra Tirunal Institute for Medical Sciences & Technology (ID: SCT/IEC/1349/APRIL-2019) and the Alfred Human Research Ethics Committee (ID: 463/21). Informed consent was obtained from all study participants. All methods will be carried out in accordance with relevant guidelines and regulations. | PMC10030347 | ||
Consent for publication | Not applicable. | PMC10030347 | ||
Competing interests | The authors declare no competing interests. | PMC10030347 | ||
References | PMC10030347 | |||
Background | Fecal microbiota transplantation (FMT) has become an important treatment method in recurrent | PMC10594821 | ||
Methods | enema | In eight participants, we administered contrast fluid (CF) with viscosity similar to an FMT in a crossover study design. First, CF was administered by colonoscopy, followed by an abdominal X-ray to visualize the CF distribution. Next, after four to eight weeks, participants were given CF, but as an enema, followed by a positioning procedure. X-rays were obtained before (enema ÷) and after (enema +) the positioning procedure. | PMC10594821 | |
Conclusion | CF, enema | ADVERSE EVENTS | Proportion of participants with CF in cecum were 100% after colonoscopy, 50% after enema + and 38% after enema ÷. In the transverse colon, proportions were 100% (colonoscopy), 88% (enema +) and 63% (enema ÷). There were no adverse events. | PMC10594821 |
Interpretation | enema | This study shows proof of concept for the distribution of FMT to proximal colon when delivered by enema. A positioning procedure after the enema slightly improves the proximal distribution. However, colonoscopy is the only method that ensures delivery to the cecum. Studies are needed to see if FMT colon distribution correlates with treatment effectiveness. | PMC10594821 | |
Trial registration | The study was retrospectively registered at ClinicalTrials.gov (NCT05121285) (16/11/2021). | PMC10594821 | ||
Supplementary Information | The online version contains supplementary material available at 10.1186/s12876-023-02979-x. | PMC10594821 | ||
Keywords | Open access funding provided by UiT The Arctic University of Norway (incl University Hospital of North Norway) | PMC10594821 | ||
Introduction | enema | Fecal microbiota transplantation (FMT) involves transfer of feces from a healthy donor to the gastrointestinal tract of a recipient and has proven to be very effective in treatment of recurrent FMT administration methods vary, and none have consistently shown to be superior to the others [FMT by colonoscopy require highly specialized personnel and facilities and is an invasive procedure that can be unpleasant for the recipient. Enema, on the other hand, can be given at the patient´s bedside, is less invasive and put less strain on hospital resources. It is believed that FMT delivered by enema only reach the rectum and sigmoid colon [Our hypotheses are that FMT delivered as an enema with positioning (enema +) is superior to enema without positioning (enema ÷) in reaching the transverse colon and cecum, and that FMT distribution after enema + is similar to the distribution when FMT is delivered by colonoscopy. | PMC10594821 | |
Method | PMC10594821 | |||
Trial design | enema | This was an assessor blinded, open labeled, single center crossover trial performed at the University Hospital of North-Norway Harstad, Norway. We used contrast fluid (CF) (Barium sulfate suspension 105% w/v, Liquid Polibar Plus, E-Z-EM Canada Inc) as a surrogate liquid for FMT produced in accordance with current European recommendations [The viscosity of the CF was compared to the viscosity of an FMT-treatment (appendix
Timeline and characteristics of each visit, created with BioRender.comOn the first visit, the examiner finished a complete examination of the colon before delivering CF in cecum, followed by an abdominal X-ray (Fig.
Contrast fluid delivered by colonoscopy, created with BioRender.comAfter a washout period of four to eight weeks, participants underwent a bowel lavage with Sodiumpicosulphate/Magnesiumcitrate (Picoprep/Ferring) before returning to the hospital to receive CF, now delivered as an enema (Fig.
Contrast fluid delivery by enema before and after the positioning procedure, created with BioRender.comImmediately after enema delivery, participants were (with minimal movement) lifted to another table for an X-ray (enema ÷). Next, lying on the bench, participants were instructed to follow the positioning procedure described in Fig. | PMC10594821 | |
Participants | cardiovascular or lung disease, malignancy, asthma, obstructive gastrointestinal disease | KIDNEY FAILURE, ASTHMA, INFLAMMATORY BOWEL DISEASE | Patients 18 to 70 years old (median 67) scheduled for a colonoscopy at the gastroenterology outpatient clinic were screened for eligibility. Patients were excluded if they had malignancy, inflammatory bowel disease or obstructive gastrointestinal disease suspected in advance or confirmed during colonoscopy. Other exclusion criteria were use of anticoagulants, symptomatic cardiovascular or lung disease, kidney failure, contraindications to the trial positioning procedure or contrast fluid (Barium sulfate suspension 105% w/v, Liquid Polibar Plus, E-Z-EM Canada Inc), asthma, breastfeeding or ongoing or planned pregnancy. All participants signed informed consent before trial inclusion. | PMC10594821 |
Outcome and analysis | CF | Our primary outcome was the proportion of participants with CF in the cecum after each administration method. Secondary outcome was the proportion of participants with CF in the transverse colon after each administration method. Proportions were compared using a Fischer Exact test with a significance level of 0·05. We used SPSS [28·0·1·0 (142)] to perform the calculations.All X-rays were evaluated by two independent radiologists blinded to administration method or procedure (assessor blinding). When the radiologists’ reports differed, a third (blinded) radiologist re-evaluated the X-ray images. | PMC10594821 | |
Ethics | enema, anaphylactic reactions | ANAPHYLACTIC REACTION | CF was delivered during scheduled colonoscopies necessary for medical purposes. The enema procedure is less invasive compared to a colonoscopy and therefore unlikely to cause any harm in healthy individuals such as our trial participants. Study personnel were trained and equipped to handle any case of anaphylactic reactions to the CF. Participants were exposed to a low radiation dose: one abdominal X-ray is equal to 10 days of background radiation. The trial is registered at ClinicalTrials.gov (NCT05121285). | PMC10594821 |
Results | malignancy, enema, asthma, CF | ADVERSE EVENTS, ASTHMA | A total of 31 participants were assessed for eligibility and ten were found to be eligible. Main medical reasons for exclusion were suspected malignancy (n = four), asthma (n = four), and history of trouble with bowel preparation in earlier colonoscopies (n = two). Among the ten eligible participants, two declined to participate, while the remaining eight participants were included and completed the trial, between 26. October 2021 and 4. April 2022. The study population consisted of three men and five women with median age 67 years. Dilution of CF at 1:2 in water resulted in similar shear viscosity to FMT.Proportion of participants with CF visualization in the cecum were 100% after colonoscopy, 50% after enema + and 38% after enema ÷ (Fig.
Percentage of participants with visualization of CF by different delivery methods. A: CF visualization in the cecum. B: CF visualization in the transverse colon. * p < 0·05
X-ray pictures from two study participants after colonoscopy, enema (-) and enema (+), created with BioRender.comAll participants tolerated the enema procedure well and there were no adverse events. One of the participants experienced some soiling of CF after the enema insertion, before the first X-ray was performed. During digital exam before enema insertion the sphincter tone was identified as weak. CF was still visualized in the patient’s cecum in both X-ray images. | PMC10594821 |
Discussion | enema, CF | ADVERSE EVENTS | To our knowledge, this is the first trial to evaluate how fluid similar to FMT is distributed in the colon immediately after delivery by colonoscopy or enema. CF delivered to the cecum by colonoscopy is indeed distributed across colon, which we saw in all participants. Following CF by enema, most patients had CF distributed to the transverse colon, and some even to the cecum, which contradicts the assumption that FMT delivered as enema is only distributed to the distal colon (i.e. rectum and sigmoid colon) [It is reasonable to believe that better FMT distribution increases the chance of donor microbiota engraftment, which has been shown to be associated with treatment outcome [Treatment cost, procedure invasiveness and risk of adverse events should be considered when choosing administration method. FMT by enema have the advantage that it can be given bedside, requires little training of the healthcare personnel performing the procedure and involves fewer adverse events than colonoscopy [The distribution of FMT delivered by enema may vary because of individual differences in colon anatomy. Studies have shown that the transverse colon is the major determinant of colonic length and that longer transverse colon is more tortuous with sharp-angles [Strengths of our trial is the use of a fluid proven to have the same viscosity as FMT, direct comparison of different methods in the same individual (i.e. same anatomy), standardized procedure for administration methods and outcome assessor blinding (X-ray evaluation).The main limitationAnother limitation is that the enema probe was visualized on the abdominal x-rays in a few patients, which could compromise blinding (i.e. probe was only inserted at enema). As the outcome assessors were not familiar with the enema procedures it is unlikely that this interfered with the blinding. Further, the enema + procedure used in our trial deviates slightly from how we recommend performing the procedure outside the trial: To obtain an abdominal X-ray from both enema ÷ and enema + procedures from one enema delivery, patients were lifted in a supine position after CF delivery by enema and returned to a supine position after the first X-ray (Fig. | PMC10594821 |
Conclusion | enema | This study shows proof of concept for the distribution of FMT to proximal colon when delivered by enema. Positioning the patient slightly improves the proximal distribution. However, colonoscopy is the only method that ensures delivery to the cecum. Studies are needed to see if FMT colon distribution correlates with treatment effectiveness. | PMC10594821 | |
Electronic supplementary material | Below is the link to the electronic supplementary material.
Supplementary Material 1
Supplementary Material 2
Supplementary Material 3
Supplementary Material 4 | PMC10594821 | ||
Acknowledgements | enema | The authors would like to thank Marthe Hammervår Rasmus, research nurse at the medical department at the University Hospital of North Norway, Harstad, for her expertise and excellent work regarding the enema procedure. | PMC10594821 | |
Authors’ contributions | HMH and LCKS contributed equally to this paperPHJ, HMH, PCV and LCKS conceived and developed the idea for the project. PHJ, HMH and LCKS wrote the study protocol. PHJ was responsible for all communication with the ethical committee. HMH and LCKS planned and organized the procedures. PCV performed the colonoscopies. PCV, LCKS and HMH screened the potential participants. ØA performed the viscosity measurementsMarianne Hovig, Martin Myreng and Roy Vestjord at the radiology department at the University Hospital of North Norway Harstad, performed all the X-ray pictures in the study. Pål Løvhaugen (Competence center for diagnostic physics) calculated the radiation dose for the X-ray pictures.PHJ, LCKS and HMH wrote the manuscript. PHJ, PCV, LCKS, HMH, FEJ, ØA and RG performed critical revision for important intellectual content and approved the final version of the manuscript. | PMC10594821 | ||
Funding | The study was funded by Northern Norway Regional Health Authority (HNF1604-21), the funder had no other role in the study.Open access funding provided by UiT The Arctic University of Norway (incl University Hospital of North Norway) | PMC10594821 | ||
Data Availability | The data supporting the findings in this research project will be delivered to researchers who provide a sound proposal, on request. The lead authors affirm that the manuscript is an honest, accurate and transparent account of the study being reported. That no important aspects of the study have been omitted. For request of the data please contact Peter Holger Johnsen at peter.holger.johnsen@unn.no. | PMC10594821 | ||
Declarations | PMC10594821 | |||
Ethics approval | The study was approved by the regional committee of medical ethics in Northern Norway (Regional Etisk Komité (REK)-NORD:267433). All participants signed informed consent before trial inclusion. The study was performed in accordance with the Declaration of Helsinki. | PMC10594821 | ||
Consent for publication | Not applicable. | PMC10594821 | ||
Dissemination | Results from this study will be presented at national and international conferences. | PMC10594821 | ||
Competing interests | obesity, enema | OBESITY, IRRITABLE BOWEL SYNDROME, SEVERE OBESITY, CLOSTRIDIOIDES DIFFICILE INFECTION | PHJ: North Norway Health trust - Personal fee as physician at dep. of internal medicine and researcher in a 50/50% position. South Eastern Norway Health Trust - Personal fee as researcher in a 20% position Principal investigator in REFIT 2 trial, An investigator-initiated and –run randomized trial investigating fecal microbiota transplantation by enema in patients with irritable bowel syndrome. PCV: Principal investigator in the study “Fecal microbiota transplantation in severe obesity”, The study is a RCT addressing FMT by enema in patients with severe obesity, initiated and run by the investigator and co-investigator. LCKS: The Research Council of Norway - Personal fee as a Ph.d. research fellow. Coordinating Investigator in the comeback study - An investigator-initiated and –run randomized trial investigating fecal microbiota transplantation by enema in patients with chronic fatigue syndrome/myalgic encephalomyelitis. Study co-worker in «the obesity study” - An investigator-initiated and –run randomized trial investigating fecal microbiota transplantation by enema in patients with severe obesity. Member scientific committee in the REFIT-2 trial - An investigator-initiated and –run randomized trial investigating fecal microbiota transplantation by enema in patients with irritable bowel syndrome. Member scientific committee in the C.O.L.O.N.I.Z.E trial - An investigator-initiated and –run randomized trial investigating fecal microbiota transplantation by enema versus oral vancomycin for primary Clostridioides difficile infection. HMH: Health Fund of Regional Health North Norway - Personal fee as a Ph.d. research fellow. Co-prinsipal investigator in “fecal microbiota transplantation in severe obesity” - A randomized controlled trial investigating fecal microbiota transplantation in patients with severe obesity. Subinvestigator in “fecal microbiota transplantation in CFS/ME” - An randomized controlled trial investigating fecal microbiota transplantation in patients with CFS/ME. Member scientific committee in REFIT2 trial - An investigator-initiated and –run randomized trial investigating fecal microbiota transplantation by enema in patients with irritable bowel syndrome. Member scientific committee in COLONIZE trial - An investigator-initiated and –run randomized trial investigating fecal microbiota transplantation by enema versus oral vancomycin for primary Clostridioides difficile infection. FEJ: South Eastern Norway Health Trust - Personal fee as a Ph.d. research fellow. Principal investigator in REFIT 2 trial - An investigator-initiated and –run randomized trial investigating fecal microbiota transplantation by enema in patients with irritable bowel syndrome. Co-Principal investigator in COLONIZE trial - An investigator-initiated and –run randomized trial investigating fecal microbiota transplantation by enema versus oral vancomycin for primary Clostridioides difficile infection.ØA: Non declared. RG: Non declared. | PMC10594821 |
References | PMC10594821 | |||
Background | hypermobility, hereditary connective tissue disorders | CHRONIC PAIN | Joint hypermobility is a common clinical finding amongst hereditary connective tissue disorders that is observed in pediatric rheumatological settings, and often associated with chronic pain. Joint hypermobility may also contribute to deficits in physical functioning and physical activity, but previous findings have been inconsistent. It is possible that physical activity impairment in joint hypermobility may be due to chronic aberrant movement patterns subsequent to increased joint laxity. | PMC10626644 |
Method | fibromyalgia, hypermobility, pain | FIBROMYALGIA, SECONDARY | As part of a larger randomized pilot trial of juvenile onset fibromyalgia (JFM), a secondary analysis was conducted to explore whether adolescents with JFM and joint hypermobility differed from non-joint hypermobility peers in terms of pain, daily functioning, and biomechanics (i.e., kinetics and kinematics) during a moderately vigorous functional task. | PMC10626644 |
Results | From the larger sample of adolescents with JFM ( | PMC10626644 | ||
Conclusions | decreased joint stiffness, hypermobility | In this exploratory study, there were small but notable differences in biomechanics between patients with JFM who also had joint hypermobility versus those without joint hypermobility during a landing and jumping task (e.g., DVJ). These differences may indicate decreased joint stiffness during landing, associated with increased joint laxity and decreased joint stability, which may put them at greater risk for injury. Further study with a larger sample size is warranted to examine whether these biomechanical differences in patients with JFM and joint hypermobility affect their response to typical physical therapy or exercise recommendations. | PMC10626644 | |
Keywords | PMC10626644 | |||
Background | hypermobility, musculoskeletal pain | SECONDARY | Joint hypermobility, characterized by excessive rangeof movement, is observed in 7–36% of children and adolescents [Joint hypermobility does not appear to be directly linked to physical activity impairment but is associated with repetitive use injuries [Joint hypermobility may also be a risk factor for the development of widespread musculoskeletal pain during later adolescence, such as exhibited in JFM [The aim of this study was to better understand how joint hypermobility may affect functioning in a sample of adolescents with JFM, given the high degree of clinical overlap. We performed a secondary analysis of data collected as part of a pilot randomized clinical trial [ | PMC10626644 |
Findings | PMC10626644 | |||
Methods | PMC10626644 | |||
Participants | pain | Adolescents (between 12 and 18 years of age), that met criteria for JFM, and had at least moderate functional disability and pain, were recruited as part of a larger pilot randomized clinical trial for teens with JFM, which tested a combined cognitive-behavioral therapy and neuromuscular exercise training program; only baseline data were included in this study [ | PMC10626644 | |
Measures | PMC10626644 | |||
Hypermobility | The Beighton Score [ | PMC10626644 | ||
Pain intensity | chronic pain, pain | CHRONIC PAIN | Participants rated their average pain intensity over the past 2 weeks using a 0–10 cm Visual Analog Scale (VAS) ranging from 0 (no pain) to 10 (worst possible pain). The VAS has been well-validated among youth with chronic pain [ | PMC10626644 |
Functional disability | The Functional Disability Inventory (FDI) is a 15-item, 5-point Likert scale (0 – no trouble; 4 – impossible) that assesses adolescents’ perceived difficulty with daily activities due to their physical health (e.g., “Doing chores at home”) [ | PMC10626644 | ||
Functional biomechanical assessment | The methodology for biomechanical assessment, data processing, andanalyses used in the pilot randomized trial are fully described in prior publications [
Drop vertical jump task | PMC10626644 | ||
Data analyses | Descriptive statistics are presented in Table Descriptive statistics among study variables – non-hypermobile vs. hypermobileScatterplot of Beighton and FDI scoresScatterplot of Beighton and knee flexion angleScatterplot of Beighton and internal hip rotation angleScatterplot of Beighton and hip abductor moment | PMC10626644 | ||
Results | PMC10626644 | |||
Descriptive statistics | Of the 36 patients enrolled in the larger study [ | PMC10626644 | ||
Relations between hypermobility, and biomechanics, pain, and functional disability | functional disability | Beighton scores decreased as functional disability increased (Fig. | PMC10626644 | |
Hypermobility group comparisons | Functional disability, joint hypermobility | Functional disability was lower for those with joint hypermobility ( | PMC10626644 |
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