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Sample size calculation | Although there is some uncertainty regarding the standard deviations (SD) of the “delta’s” (changes from before to after the intervention) of the parameters that were studied (because these have not been reported in previous studies), these were expected to be smaller than the SD’s at either baseline or after the intervention reported in previous studies [ | PMC10160212 | ||
Transthoracic echocardiography | Interventricular septal thickness, obesity, Diastolic dysfunction | OBESITY, DIASTOLIC DYSFUNCTION, DECUBITUS | Two-dimensional grayscale harmonic images were obtained in the left lateral decubitus position using a commercially available ultrasound system (EPIQ 7, Philips, the Netherlands), equipped with a broadband (1-5 MHz) X5-1 transducer. Diastolic dysfunction and reduced ejection fraction (≤ 54% in females, and ≤ 52% in males) were defined according to the current guidelines [Interventricular septal thickness (IVSd), posterior wall thickness (PWd), and LV dimension (LVEDD) were all measured at end-diastole. The LV mass (LVM) was calculated according to the Deveraux formula using these measurements: LVM (g) = 0.80 × {1.04[(IVSd + LVEDD + PWd)To optimize speckle tracking echocardiography, apical images were obtained at a frame rate of 60 to 80 frames/s. Three consecutive cardiac cycles were acquired from all apical views (4-chamber, 2-chamber, and 3-chamber). Subsequently, these cycles were transferred to a QLAB workstation (version 10.2, Philips, the Netherlands) for off-line speckle tracking analysis. Peak regional longitudinal strain was measured in 17 myocardial regions and a weighted mean was used to derive global longitudinal strain (GLS) (Fig.
Measurement of global longitudinal strain (GLS) by speckle tracking analysis in an obesity patient (45 year old female, BMI 38.4 kg/m | PMC10160212 |
Statistical analysis | SD | The normality of the data was checked by the Shapiro–Wilk test. The unpaired Student’s t-test for continuous variables was used to compare parameters between groups with normal distributions, the non-parametric Mann-Whitney U test for continuous parameters with skewed distributions, and the χ2 test/Fisher’s exact test for categorical variables. Continuous values were expressed as mean ± SD and categorical values as percentages.Patients who completed follow-up were added to the following analyses. Repeated-measure analyses of variance (ANOVA) was used for continuous variables, to assess the relationship of changes at follow-up between groups. Generalized linear mixed models were used to compare the categorical data. The categorical parameters were entered subsequently as the dependent variable, and group (standard CR vs. OPTICARE XL CR) and follow-up as the independent variables. Random intercepts were used to account for the patient ID.All statistical tests were 2-sided and a p-value of 0.05 was considered statistically significant. The analyses were performed with SPSS version 25 and R version 3.6.0 (glm package). | PMC10160212 | |
Results | PMC10160212 | |||
One-year follow-up; comparison between groups | Weight loss, left ventricular hypertrophy | DIASTOLIC DYSFUNCTION, LEFT VENTRICULAR HYPERTROPHY | Weight loss was comparable between groups (Table
Changes pre- and post-cardiac rehabilitation in mean weight (a), heart rate (b), global longitudinal strain (c), and ejection fraction (d). (Error bars represent 95% CI, Significant at p < 0.05, NS = non significant)
Comparison of percentage of diastolic dysfunction, reduced ejection fraction, reduces global longitudinal strain, and left ventricular hypertrophy between both standard cardiac rehabilitation, OPTICARE XL CR, and baseline and follow-up. (LV = left ventricular) | PMC10160212 |
Discussion | obesity, weight loss, LVH | OBESITY, LVH | The main finding of the current study is that cardiac function as measured with echocardiography in patients with obesity did not improve one-year after a novel state of the art CR program (OPTICARE XL CR) as compared to standard CR.Although there was a significant and promising reduction in weight and thereby BMI in both groups at one-year follow-up, this reduction was relatively small and does not meet the definition of clinically significant weight loss [The current study is the first in which echocardiographic parameters of cardiac function were investigated in patients with obesity who participated in standard CR or in a CR program specifically designed for patients with obesity. However, a few small studies have been performed in patients with obesity in which the impact of There are several studies in which echocardiographic parameters of LV function, such as GLS, were assessed in patients who participated in standard CR. However, the focus of none of the studies was on patients with obesity. First, Malfatto et al. [Finally, both groups showed a mild but non-significant decrease of LVH after rehabilitation. Nevertheless, the proportion of patients with LVH was significantly more decreased in the OPTICARE XL CR group. This finding suggests that the more intensive program of the OPTICARE XL CR may have a positive contribution to the reduction of LVH. However, more research is needed to conform this. | PMC10160212 |
Limitations | obesity | OBESITY | Although echocardiographic parameters of cardiac function did not improve in patients undergoing CR in our study, one may hypothesize that such parameters would even have worsened without any CR. However, because a control group of patients with obesity not undergoing any CR is lacking in the current study, this remains to be investigated. The number of subjects in this study was small. Studies with a larger sample size would be necessary for further evaluation of some of the trends that have been observed. Also, a more intensified echocardiographic follow-up with measurements for example also at six months would have allowed better comparison with the other studies with shorter follow-up described before. Nevertheless, the long term follow-up is also a major strength of our study. | PMC10160212 |
Author contributions | All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Sanne M Snelder. The first draft of the manuscript was written by Sanne M Snelder and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. | PMC10160212 | ||
Funding | This work was supported by the Dutch Organisation for Health Research and Development (ZonMw, Grant number 843001792) and Capri Cardiac Rehabilitation. | PMC10160212 | ||
Declarations | PMC10160212 | |||
Conflict of interest | None declared. | PMC10160212 | ||
Competing interests | The authors declare no competing interests. | PMC10160212 | ||
References | PMC10160212 | |||
2. Materials and Methods | PMC10608202 | |||
2.1. Ethical Considerations | Ethical approval was awarded by the institutional ethical review board at the Faculty of Dentistry, Riphah International University, Islamabad, Pakistan (Approval no: IIDC/IRC/2020/01/012). The trial protocol was registered with the Iranian Registry of Clinical Trials ( | PMC10608202 | ||
2.2. Trial Design | The design of the current randomized controlled trial (RCT) was single-centered, prospective, parallel, double-blinded, and phase III. The RCT was conducted in accordance with “The Preferred Reporting Items for Randomized Trials in Endodontics (PRIRATE)” guidelines [ | PMC10608202 | ||
2.3. Sample Size Calculation | A sample size (SS) of 152 participants was determined by utilizing the WHO SS calculator with confidence interval = 95%; significance level ≤ 0.05; study power = 80%, anticipated population proportion 1 (P1) = 0.65; and anticipated population proportion 2 (P2) = 0.45 [ | PMC10608202 | ||
2.4. Eligibility Criteria | The participants for the trial were selected at the screening clinic of the Department of Endodontics, Faculty of Dentistry, Riphah International University, Islamabad, Pakistan. The participants were recruited from 1 January to 30 June 2021, over a period of six months. The participants were fully informed about the purpose of the clinical trial and written consent ( | PMC10608202 | ||
2.4.1. Inclusion Criteria | pulpal necrosis | ASYMPTOMATIC IRREVERSIBLE PULPITIS, COLD | The trial included healthy (American Society of Anesthesiologists class I) Pakistani males and females with ages ranging from 25 to 35 years. The patients manifested symptomatic irreversible pulpitis (SIP) in mandibular premolar/molar teeth and depicted normal apical tissue, radiographically. Pulp Sensibility Testing (cold test, utilizing Endo-Ice) was conducted prior to the administration of LA to rule out pulpal necrosis. | PMC10608202 |
2.4.2. Exclusion Criteria | allergic | SYSTEMIC DISEASE | Patients who were allergic to amides, suffering from systemic diseases, were pregnant, and those who had taken analgesics within the 24 h preceding the commencement of the endodontic procedure were not included in the RCT. | PMC10608202 |
2.5. Randomization and Blinding | PMC10608202 | |||
2.5.1. Random Allocation SEQUENCE Generation | One hundred and fifty-two patients, who satisfied the criteria for inclusion, were randomly assigned to the control and experimental groups in 1:1. Randomization was carried out by a simple randomization technique. Online randomization software OpenEpi, ( | PMC10608202 | ||
2.5.2. Allocation Concealment | The current RCT was a double-blind trial in which both the operator and the patients were blinded to the randomized intervention that was administered. Allocation concealment, intervention preparation, and randomization were performed by an independent individual before the onset of the RCT. The investigators were blinded to the group of trial participants by securing assignment order in an opaque secured envelope. The preparation of intervention was carried out by dividing the local anesthetic medication cartridges (LAMC) into 152 (76 for each group) opaque sealed envelopes that were labeled with alphabetical symbols (A, B). Each envelope contained the LAMC, and the label of the cartridge was concealed by an opaque tap with alphabetical symbols (A or B) written on it. All LAMCs were packaged and labeled by the Septodont company and were acquired at the same time. | PMC10608202 | ||
2.5.3. Implementation | pain | CAVITY | After the confirmation of SIP, the independent individual informed the single operator (SH) of which intervention should be administered. The clinician was informed about the appropriate intervention by utilizing the assigned labels (A, B) to ensure the clinician’s blinding. The researchers utilized online randomization software to assign eligible patients to either control or experimental groups (A, B). During the visit, the operator provided a standardized explanation of HP-VAS both verbally and in a written format to familiarize and train the patients in the study instrument. The patients documented the intensity of pain on HP-VAS by marking a vertical line on HP-VAS three times: pretreatment, after access cavity preparation (ACP), and after initial instrumentation. All the pre- and post-intervention research data were evaluated by a trained clinician (AA). | PMC10608202 |
2.6. Intervention | pulpal bleeding, tooth, pulpal pain, pain | ENDO, COLD | The patients were diagnosed with SIP based on pain history (spontaneous, and lingering pulpal pain), and confirmed by exaggerated response of the offending tooth to cold sensibility testing utilizing Endo-Ice. The offending tooth’s response to cold sensibility testing was compared to a similar unaffected contralateral tooth (Control), and the diagnosis was verified clinically by directly observing the pulpal bleeding upon access opening. Only the teeth with normal periapical tissues (verified with periapical radiographs), and negative responses to palpation and percussion tests were included in the study.The patients were assigned to the control group or experimental group, containing 76 patients each, according to the previously explained methodology. Before receiving the anesthetic injection, the patients were taught and then requested to score their pain levels using the Heft–Parker Visual Analogue Scale (HP-VAS) (Initial instrumentation (Local II) and ACP were done using a high-speed handpiece and diamond round and Endo Z burs. Successful blocks were denoted as mild to no pain on II and during endodontic ACP, scored using HP-VAS [A total of 170 patients were initially assessed for eligibility. Out of those, 18 patients were excluded: 10 did not fulfill the criteria for inclusion and 8 refused to take part in the RCT. The final participant count for the trial was 152 with 98 males and 54 females. The participants were allocated randomly, to either the control or the experimental group (n = 76 each group), to assess the efficacy of the anesthetic agents under investigation. | PMC10608202 |
2.6.1. Control Group | The control group consisted of patients who received 1.7 mL of 2% Lidocaine Hydrochloride with 1:100,000 epinephrine (Septodont—Lignospan standard) and were labeled as A. | PMC10608202 | ||
2.6.2. Experimental Group | The experimental group comprised patients who received 1.7 mL of 4% Articaine Hydrochloride with 1:100,000 epinephrine (Septodont—Septanest SP) and were labeled as B. | PMC10608202 | ||
2.7. Outcome Assessment | pain | The primary outcome assessed was the comparative efficacy of two LAA, Lidocaine and Articaine, during II and ACP. The effectiveness of LA was described as a value of <54 mm on HP-VAS (No pain: 0 mm.Mild pain: between 0 and 54 mm.Moderate pain: between 54 and 114 mm.Severe pain: ≥114 mm.The HP-VAS, through its clear categories and descriptive language, facilitates accurate pain level assessment. | PMC10608202 | |
2.8. Statistical Analysis | pain | The data analysis was carried out with SPSS version 23.0. Descriptive variables (pain, and gender) were recorded as percentages and frequencies. Numerical variables (e.g., age) were documented as mean + SD. The intention to treat analysis was performed. The Shapiro–Wilk test was used to check the normality of the data. Subsequently, the AE of control and experimental groups in terms of pain control during ACP and initial instrumentation was compared by using the Chi-square test. The baseline demographic characteristics such as age and gender were also compared between the two groups using the Chi-square test. The level of significance for the Chi-square test was set at | PMC10608202 | |
4. Discussion | pulpitis | PULPITIS | The discovery of LAA led to the advent of pain-free dentistry. These agents have now become an indispensable part of endodontics. Without their use, routine procedures cannot be carried out optimally, primarily because of patient discomfort. The effectiveness of anesthesia, particularly the IANB, is subject to multiple factors, mainly anatomical considerations, clinical expertise, and formulation of the anesthetic agent used [The present study revealed no statistically significant difference between the effectiveness of 2% Lidocaine and 4% Articaine. These results align with those of prior research carried out by Philips et al. and Simon et al. [Although the results are statistically insignificant, Lidocaine demonstrated a 93% success rate during ACP whereas Articaine displayed a slightly higher rate of 97%. These efficacy rates are consistent with earlier studies in which the findings, while statistically insignificant, indicated a slightly better success rate for Articaine compared to Lidocaine. In an RCT on irreversible pulpitis, Brunetto and colleagues reported a 63.6% success rate for Articaine and a 54.5% success rate for Lidocaine, with no statistically significant difference in the AE of the two agents [Certain studies have posited that Articaine may possess superior AE to Lidocaine. The trials conducted in Pakistan have compared the anesthetic effectiveness of Articaine and Lidocaine. Sheba et al. found insignificant difference between the two aforementioned agents [Whether Articaine demonstrates anesthetic effectiveness superior to or on par with Lidocaine, it may emerge as a potential alternative to the conventionally employed Lidocaine. Although Lidocaine remains the anesthetic of choice in dentistry, and is still considered the gold standard worldwide, many reports and editorials have favored the use of Articaine. A survey conducted among dentists in New Zealand in 2016 revealed that Articaine was the most popular anesthetic agent among the majority [A distinctive aspect of the current research is that it compared the effectiveness of both types of anesthesia across different types of teeth, including molars and premolars. This contrasts with previous studies conducted by Henry et al. and Q Khan et al., which focused solely on the molar teeth [ | PMC10608202 |
4.1. Strengths of the Study | pulpal necrosis | SYMPTOMATIC IRREVERSIBLE PULPITIS | The present research is among the few randomized controlled trials that were conducted to compare the efficacy of Lidocaine, and Articaine during ACP and root canal II, when administered as IANB in a Pakistani sub-population. Another distinctive point is that the current RCT has compared the effectiveness of both types of anesthetic agents across mandibular molar as well as premolar teeth. Therefore, despite being statistically insignificant, the results of this study offer a more extensive database for comparing and analyzing the effectiveness of anesthetic agents across various types of teeth. Furthermore, patients with asymptomatic irreversible pulpitis as well as those with pulpal necrosis were excluded from the sample to prevent the possibility of error regarding AE. | PMC10608202 |
4.2. Limitations of the Study | pain | The effectiveness of anesthesia was measured using the VAS, which uses patients’ self-assessment of the extent of the pain they experience [ | PMC10608202 | |
5. Conclusions | SYMPTOMATIC IRREVERSIBLE PULPITIS, COMPLICATIONS | The AE of Articaine is comparable to that of Lidocaine in patients with symptomatic irreversible pulpitis. Articaine may, therefore, be a suitable alternative to Lidocaine for obtaining pulpal anesthesia during endodontic therapy, via IANB. However, it is prudent to conduct further research to determine the AE of Articaine in pediatric and geriatric patients, and to rule out the possibility of post-operative complications. | PMC10608202 | |
6. Future Recommendations | ADVERSE EFFECTS, COLD | It is recommended to conduct multi-center trials involving a study population that encompasses diverse age groups and to employ methodologies that incorporate patient follow-up. This will lead to an improved comprehension of the efficacy and possible post-injection adverse effects of different anesthetic agents. Moreover, objective measures, like Electric Pulp Testing or Cold Testing using liquid nitrogen or ethyl chloride, should be utilized for more reliable results regarding complete pulpal anesthesia. Lastly, during the training of patients, it is recommended to perform the calibration tests and report the findings in the methods. | PMC10608202 | |
Supplementary Materials | The following supporting information can be downloaded at: Click here for additional data file. | PMC10608202 | ||
Author Contributions | S.R.H. | Conceptualization, S.H. and A.A.; methodology, S.H. and M.Q.J.; validation, S.R.H., M.Q.J. and A.M.A.; formal analysis, A.A. and W.S.; investigation, S.H.; resources, S.H. and S.R.H.; data curation, A.A.; writing—original draft preparation, S.H., M.Q.J. and A.A.; writing—review and editing, M.Q.J., W.S., S.R.H. and A.M.A.; visualization, S.H., A.M.A. and M.Q.J.; supervision, A.A.; project administration, W.S. and S.H. All authors have read and agreed to the published version of the manuscript. | PMC10608202 | |
Institutional Review Board Statement | Ethical approval was awarded by the institutional ethical review board at Faculty of Dentistry, Riphah International University, Islamabad, Pakistan. (Approval no: IIDC/IRC/2020/01/012). | PMC10608202 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. | PMC10608202 | ||
Data Availability Statement | The study data is kept in password protected departmental computer as instructed by ethical committee. The data is accessible to principal investigator and statistician, only. Therefore, due to privacy concerns patients’ data can’t be shared. | PMC10608202 | ||
Conflicts of Interest | The authors have no conflict of interest to declare. | PMC10608202 | ||
References | tooth | PRIRATE 2020 flowchart showing the design of the current RCT.Heft–Parker Visual Analogue Scale.Comparison of anesthetic efficacy of Lidocaine vs. Articaine.* Measured using Heft–Parker Visual Analogue Scale—a reading of less than 54 mm denotes effective anesthesia. Comparison of Lidocaine and Articaine efficacy with respect to different tooth types.* Chi-square test. | PMC10608202 | |
Abstract | PMC10620739 | |||
Objectives | urinary tract infections | URINARY TRACT INFECTIONS | To evaluate whether a multimodal intervention in general practice reduces the proportion of second line antibiotic prescriptions and the overall proportion of antibiotic prescriptions for uncomplicated urinary tract infections in women. | PMC10620739 |
Design | Parallel, cluster randomised, controlled trial. | PMC10620739 | ||
Setting | General practices in five regions in Germany. Data were collected between 1 April 2021 and 31 March 2022. | PMC10620739 | ||
Participants | General practitioners from 128 randomly assigned practices. | PMC10620739 | ||
Interventions | Multimodal intervention consisting of guideline recommendations for general practitioners and patients, provision of regional data for antibiotic resistance, and quarterly feedback, which included individual first line and second line proportions of antibiotic prescribing, benchmarking with regional or supra-regional practices, and telephone counselling. Participants in the control group received no information on the intervention. | PMC10620739 | ||
Main outcome measures | urinary tract infections | ADVERSE EVENT, SECONDARY, URINARY TRACT INFECTIONS, UTI | Primary outcome was the proportion of second line antibiotics prescribed by general practices, in relation to all antibiotics prescribed, for uncomplicated urinary tract infections after one year between the intervention and control group. General practices were randomly assigned in blocks (1:1), with a block size of four, into the intervention or control group using SAS version 9.4; randomisation was stratified by region. The secondary outcome was the prescription proportion of all antibiotics, relative within all cases (instances of UTI diagnosis), for the treatment of urinary tract infections after one year between the groups. Adverse events were assessed as exploratory outcomes. | PMC10620739 |
Results | urinary tract infections, −0.21, fever | URINARY TRACT INFECTIONS, COMPLICATIONS, PYELONEPHRITIS | 110 practices with full datasets identified 10 323 cases during five quarters (ie, 15 months). The mean proportion of second line antibiotics prescribed was 0.19 (standard deviation 0.20) in the intervention group and 0.35 (0.25) in the control group after 12 months. After adjustment for preintervention proportions, the mean difference was −0.13 (95% confidence interval −0.21 to −0.06, P<0.001). The overall proportion of all antibiotic prescriptions for urinary tract infections over 12 months was 0.74 (standard deviation 0.22) in the intervention and 0.80 (0.15) in the control group with a mean difference of −0.08 (95% confidence interval −0.15 to −0.02, P<0.029). No differences were noted in the number of complications (ie, pyelonephritis, admission to hospital, or fever) between the groups. | PMC10620739 |
Conclusions | urinary tract infections | URINARY TRACT INFECTIONS | The multimodal intervention in general practice significantly reduced the proportion of second line antibiotics and all antibiotic prescriptions for uncomplicated urinary tract infections in women. | PMC10620739 |
Trial registration | German Clinical Trials Register (DRKS), DRKS00020389 | PMC10620739 | ||
Introduction | UTIs | URINARY TRACT INFECTIONS | Urinary tract infections (UTIs) in women lead to frequent consultation in primary care.Various strategies to improve antibiotic prescribing behaviours (ie, to align to recommendations more closely) by healthcare providers in primary care have been explored but none has been identified as the most successful strategy.Therefore, we aimed to investigate whether a multimodal intervention could reduce the number of prescriptions of second line antibiotics that GPs prescribe for women with UTIs. The intervention consisted of guideline recommendations for GPs and patients, provision of regional resistance data, and quarterly feedback that includes information on individual antibiotic prescribing proportions of first and second line antibiotics, benchmarking, and telephone counselling. | PMC10620739 |
Methods | PMC10620739 | |||
Trial design and setting | This cluster randomised controlled trial was conducted between 1 September 2019 and 31 December 2022. Data were collected between 1 April 2021 and 31 March 2022. Details of the study protocol have been published.The primary target population were general practitioners in these regions in the south and east of Germany: Baden-Wurttemberg, Bavaria, Berlin, Brandenburg, and Thuringia. Funding requirements for this study did not align with the inclusion of private practices. Dedicated study teams enrolled participating practices using registers of affiliated practices, GP networks, and regional contacts. | PMC10620739 | ||
Randomisation and trial interventions | UTIs, urinary tract infections | URINARY TRACT INFECTIONS, UTI | General practices were randomly assigned in blocks (1:1), with a block size of four, into the intervention or control group using SAS version 9.4; randomisation was stratified by region. Randomisation lists were generated by the Institute of Clinical Epidemiology and Biometry (University of Wurzburg).The multimodal intervention consisted of guideline recommendations on UTI management for GPs and patients; provision of regional resistance data and feedback that included information about the proportions of individual first line and second line antibiotic prescriptions; benchmarking with regional (practices from the participating federal state) or supra-regional practices (from all participating federal states); and telephone counselling to discuss further questions. Feedback was offered on a quarterly basis (a quarter comprised three months).In preparation for this project, data for regional resistance in uncomplicated urinary tract infections were collected in 136 primary care practices who did not participate in the randomised controlled trial. The resulting 2553 urine samples from women with uncomplicated UTIs were analysed and used to build the database to inform the intervention group on regional resistance data. As a result of expected relevant differences in resistance rates, | PMC10620739 |
Trial procedures | Study procedures were adapted to meet daily practice routine during a six month pilot phase in five non-participating practices in a region not participating in the trial. Additionally, acceptance and feasibility of the interventional procedures were assessed in two qualitative studies. | PMC10620739 | ||
Data collection | UTI | Electronic health record systems in Germany are diverse and not standardised, therefore, an automated extraction of patient files was not feasible. Instead, a medical practice assistant in each practice was trained by the research team to follow a detailed, standardised procedure for data extraction (supplementary material S1) to identify cases (instances of UTI diagnosis) and prescribed antibiotics from the electronic medical record. Data extraction was carried out at the end of each quarter over a 12 month period (Q1-Q4) in the intervention group and after 12 months in the control group. We documented first, second, and third antibiotic prescription for each instance of UTI. Information about non-antibiotic treatments such as painkiller, phytotherapy, or no documented treatment was also collected. Baseline data (Qb) was collected retrospectively using the data of the first quarter of 2020, one year before the study start. All data were verified by the relevant GPs. Data validation was performed once in the first quarter in each intervention practice. Research nurses randomly selected 10% of the UTI cases (three to five patients per practice) and compared all information in the patient file with the extracted data (supplementary material S2). Any inconsistency was clarified through personal contact with the medical practice assistants or, if required, with the GP.All data were collected at practice level and transferred in an aggregated form each quarter to the coordinating study site. Data were extracted from the control practices 12 months after inclusion of the practice in the study. Data collection and analysis was unblinded.Female patients with a documented uncomplicated UTI were identified via ICD 10 German modification-2020 code (N30.0, N30.9, N39.0, R30.0, R30.9). The GP’s clinical diagnosis of UTI was accepted in keeping with the pragmatic nature of the trial. | PMC10620739 | |
Outcomes | UTIs, urosepsis | COMPLICATIONS, SECONDARY, UTI, PYELONEPHRITIS, UROSEPSIS | The primary outcome was the proportion of second line antibiotics prescribed in relation to all antibiotics prescribed for uncomplicated UTIs after one year, calculated as the absolute difference in the mean proportion of the prescriptions between the control and intervention group. According to national guidelines, second line drugs were all antibiotics other than trimethoprim, pivmecillinam, nitrofurantoin, fosfomycin, or nitroxoline, which are first line treatments.The secondary outcome was the proportion of all antibiotics prescribed for the treatment of UTIs after 12 months, calculated as the absolute difference in the mean proportion of all antibiotics prescribed between the intervention and control group. The prescription proportion of all antibiotics was defined as the proportion of first line and second line antibiotics within all UTI cases. Other exploratory outcomes were the proportion of high and low prescribers, the changes of prescribing behaviour over time and factors associated with low performance (defined as >10% of second line antibiotic prescriptions).After publication of the study protocol, we added women with UTIs who were treated with any antibiotic after 12 months as an exploratory outcome to assess whether any changes could be observed with the intervention. For this outcome, we calculated the mean difference in the proportion of UTI cases treated with antibiotics in all UTI cases. Furthermore, we added cases with recurrent UTI and complications (eg, pyelonephritis, urosepsis, and hospital admissions) as exploratory outcomes. | PMC10620739 |
Data analysis | UTIs | SECONDARY, COMPLICATION, COMPLICATIONS | Data analysis followed the intention-to-treat principle on the full analysis set, which is as close as possible to an ideal intention-to-treat population. All randomly assigned practices remained in the allocated arm for analysis. Practices for which prescription data at baseline and from Q4 were available, formed the full analysis set. Prescription data were available and analysed as aggregated data for each practice and each quarter from Qb to Q4. Depending on the data type, descriptive statistics were used to summarise central tendencies (eg, means; variability, such as standard deviations; and frequencies of participant characteristics, prescribing patterns, and complications). For the primary and secondary hypotheses, analysis of covariance (ANCOVA) was used to adjust for the baseline proportion of prescribing and for region as defined a priori. Assumptions were examined before conducting ANCOVA to ensure the appropriateness of the statistical method.Primary and secondary outcomes were treated as a continuous variable because the assumptions were met and we had aggregated data only. Complication rates were analysed as a nominal variable.Like the exploratory outcomes, the secondary outcome was considered exploratory. Thus, no adjustment for multiple testing was made. Two sided tests such as t-test or χThe proportions of two practices in Qb and one practice in Q4 that had no prescribed antibiotics or any treatment in the intervention group were set to zero to keep them in the full analysis set for the primary and secondary analyses. In sensitivity analyses, primary and secondary outcomes were assessed after excluding these three practices. Further sensitivity analyses were conducted to evaluate the robustness of the means of the primary analysis including: (univariate) weighting by the inverse variance method; excluding practices with smaller numbers of diagnoses of UTIs (less than 5, 15, or 25); adjusting for region as well as for number of patients in a mixed effects meta-regression and applying multiple imputation that replaced missing data for prescription proportions in Qb or Q4. For the multiple imputation, missing data were assumed to be missing completely at random. A thousand iterations using predictive mean matching were done and effect estimates were pooled. Missing data in Qb, Q4, age, and years in practice were imputed by using information on these variables (if available) in addition to physician’s gender, practice location (region, community), average number of patients per quarter, and whether the practice was run by a GP with or without any partners. The data analyses were performed using R version 4.0.2. | PMC10620739 |
Sample size calculation | The sample size calculation for this study was based on our primary aim to reduce the proportion of second line antibiotics by 10 percent points per practice. To account for differing baseline prescribing proportions, the primary analysis used ANCOVA, with baseline prescribing proportions as the only covariate. Assumptions were made based on the findings of Dicheva and colleagues in 2015, | PMC10620739 | ||
Patient and public involvement | We established a collaboration with a citizens’ forum consisting of 10 participants, established at the Department of General Practice, University of Wurzburg, Germany.An external study advisory board consisting of a GP, a pharmacist, a lay person, and a scientist with experience in this field was also involved to increase practice feasibility and to discuss the results. This advisory board did not lead to further changes in the study materials. | PMC10620739 | ||
Results | PMC10620739 | |||
Participants | On 1 April 2021, we randomly assigned 128 practices (64 practices to the intervention group and 64 to the control group), representing 203 GPs. Eleven practices in the intervention group did not extract data from Qb or Q4, or both, and seven did not extract data at all (Flow diagram of participating practices throughout the trial. The final analysis included 57 practices in the intervention group and 53 practices in the control group. Q=quarterBaseline characteristics of the practices, number (percentage) | PMC10620739 | ||
Outcomes | UTIs, urinary tract infection | REGRESSION, SECONDARY, URINARY TRACT INFECTION, UTI | Overall, we identified 10 323 cases of UTIs from five quarters (ie, 15 months) in 110 practices included in the final analyses and to be analysed for the outcomes. The mean preintervention prescription proportions (Qb) for second line antibiotics in relation to all antibiotics for UTIs treatment were 0.27 (standard deviation 0.29) in the intervention group and 0.31 (0.25) in the control group (Proportions of second line antibiotic prescriptions in Qb-Q4. Percentiles: 10th (dashed line), 50th (solid line), and 90th percentile (dotted line). Q=quarter; Qb=baseline quarterPrimary, secondary, and exploratory outcomes in quarter four for the intervention group (n=57) and the control group (n=53)CI=confidence interval; SD=standard deviation; RR=relative reduction (ratio of adjusted means).Adjusted for baseline prescribing proportions and region.Welch Two Sample t-test.ANCOVA (Analysis of Covariance).Relevant within all antibiotic prescriptions.Relative within all cases (instances of urinary tract infection diagnosis). The mean proportion of all antibiotic prescriptions for UTIs in relation to all UTI instances after 12 months was 0.74 (standard deviation 0.22) in the intervention and 0.80 (0.15) in the control group, with a mean difference of −0.08 (95% confidence interval −0.15 to −0.02, P<0.029; supplementary table 2). The ratio of adjusted means for the treatment group and control group was 0.90 (95% confidence interval 0.81 to 0.98), corresponding to a relative reduction of 10% (Fosfomycin and pivmecillinam were the first line antibiotics most frequently used, while fluoroquinolones and trimethoprim-cotrimoxazole had the highest share in the group of second line antibiotics (Relative frequencies of antibiotic agents in the control and intervention group in Qb and Q4. GPs=general practices; Q=quarter; Qb=baseline quarter*Sensitivity analyses support the robustness of the primary results. When excluding the three intervention practices without prescriptions in the quarters Qb and Q4, the estimates remained stable (supplementary table 4). When weighting the means by the number of cases in the practices, the reduction of the second line antibiotics remained stable (supplementary table 5). This pattern was also present in practices that had at least 25 diagnoses of UTI in Qb and Q4, in which more precise proportion estimates were available. The results also remained consistent when applying the meta regression, accounting for baseline prescribing, region, and the number of UTI diagnoses within the same model (supplementary table 6). The assumptions for ANCOVA were checked (supplementary figure 2) and one outlier was detected during the assumption checks of the ANCOVA but this datapoint did not alter the results relevantly when excluded. After multiple imputation for 11 practices with missing values in Q4 or Qb, or both, results were similar to the original data (adjusted mean difference 0.13, P<0.001). | PMC10620739 |
Complication rates | urosepsis, fever, pain | URINARY TRACT INFECTIONS, COMPLICATIONS, UTI, PYELONEPHRITIS, COMPLICATIONS, UROSEPSIS | The rate of complications (ie hospital admissions, recurrent UTI, fever, pyelonephritis, flank pain, or urosepsis) in 12 months, documented within 14 days after the initial diagnosis, was very low overall (Complications in all cases of urinary tract infectionsQ=quarter.Fisher's exact test; Pearson's χPearson's χ | PMC10620739 |
High and low prescribing practices | REGRESSION | Comparing high and low prescribing practices of second line antibiotics, we found a marked decrease of practices that were deemed to be prescribing a high amount (90th percentile) in the intervention group without similar changes in the control group (Mean prescription proportions of second line antibiotics by quarterIn the negative binomial regression (supplementary table 7), we sought to explain the pattern of prescribing of second line antibiotics. The model shows that single doctor practices are more likely to prescribe second line antibiotics compared with joint practices at an incidence rate ratio of 1.48 (95% confidence interval 1.05 to 2.08, P=0.026). | PMC10620739 | |
Discussion | PMC10620739 | |||
Principal findings | cystitis, UTIs | DISEASE, CYSTITIS, COMPLICATIONS, UTI | The multimodal intervention consisting of guideline recommendations for GPs and patients, provision of regional resistance data, and quarterly feedback of individual antibiotic prescribing proportions, benchmarking, and telephone counselling resulted in a decrease in prescription proportions of second line antibiotics for uncomplicated UTIs in women. Additionally the intervention group noted a reduction of all antibiotics prescribed for this indication, with no evidence for an increase in complications.Disease specific quality indicators for outpatient antibiotic prescribing in Europe recommend a prescription rate of less than 5% for quinolones in adult women who were diagnosed with cystitis.Our study showed a reduction of antibiotic prescription proportions and an increase of UTI cases treated without antibiotics, which is in line with the recommendation of many guidelines. | PMC10620739 |
Comparison with other studies | respiratory tract infections | SCHWARTZ, RESPIRATORY TRACT INFECTIONS | The intervention was found to be sustained over the one year period and was most effective in practices with high proportions of second line prescriptions. The results are in line with Schwartz and colleagues who were able to show a reduction in antibiotic prescription rates for respiratory tract infections in high prescribing GPs using a single letter. | PMC10620739 |
Complications | UTIs | COMPLICATION | Despite a lower proportion of antibiotic prescriptions in the intervention group, complication rates within the 12 month period were similar in both groups. The rate of admissions to hospital in our study (0.2%) was identical to the results of a nationwide, register cohort study in Sweden including 752 289 women with acute uncomplicated UTIs.Our exploratory analysis showed differences in the rates of recurrent UTIs ( | PMC10620739 |
Strengths and limitations | UTIs, fever, pain | UTI | The main strength of our study comprises data for regional resistance rates as a component of the multimodal intervention that has not been used in intervention studies to improve prescribing patterns in UTI before.Our rigorous data extraction allowed us to focus on uncomplicated UTIs by using additional information from the electronic medical record to exclude complicating factors such as fever, flank pain, or immunosuppression at inclusion. This method is an advantage over routinely collected data that does not allow for accurate identification of uncomplicated UTIs. However, implementation of the project on a larger scale is limited because of the resources needed.During the intervention phase, 18 (14%) of 128 practices could not be included in the full analysis set because of insufficient or no data extraction. The most frequent reason for this was the high workload during the pandemic.The lack of blinding in the practice teams may have affected the validity of the results. Reporting bias and a contamination bias were possible because intervention and control practices were located in the same area. We believe the reporting bias was minimised by use of an objective endpoint, training of medical practice assistants, and validation of data by the study team. Contamination could have influenced prescribing behaviour. The prescription proportions in the control group, however, argue against a substantial impact from no blinding because this would have tended to reduce the effect size of the intervention. To mitigate the risk of systematic errors in data extraction, research nurses randomly checked data in the practices. Nevertheless, we cannot rule out an observer bias due to awareness of the intervention. Blinding of the statistician was also not possible at the analysis stage, because the regular analysis of the data was necessary to implement components of the interventions, for example, for the feedback analysis described. However, all statistical analyses were agreed on in advance in a detailed statistical analysis plan. Moreover suggestions from current practice and guidelines of blinding statisticians in clinical trials varies widely and is uncertain.We acknowledge the reliance on expert opinion for the estimation of the standard deviation as a limitation of our study. Yet, the standard deviation observed in our study was found to be consistent with the estimated standard deviation, suggesting that the expert opinion was reasonably aligned with the actual variability in the prescription proportions among the participating practices. This alignment indicates that the estimated standard deviation accurately captured the dispersion of the data and supports the validity of the power calculation.Another limitation is that we could not identify delayed prescriptions because these were not routinely documented in the electronic medical record. Therefore, the proportion of non-antibiotic treatment may be different than reported because delayed prescriptions are an accepted treatment option for women with uncomplicated UTI.We were not able to consider the number of patients in the practice and could not determine a denominator for our analyses because no fixed patient lists are available in German general practices and the number of patients varies from quarter to quarter. Numbers are likely to have varied at random in both groups of practices. Therefore, we could not gain information about whether consultation rates changed with the intervention or not. | PMC10620739 |
Implications for practice | UTIs | UTI | The study could show that the multifaceted intervention works and we assume that all components can be easily implemented in countries where the level of digitalisation allows an automated data extraction and feedback is possible. In Germany, implementing of the materials is possible for example within the continuous postgraduate medical education or work in quality circles. We do not expect relevant barriers in implementing resistance data but they have to be collected and presented at regional level because they are affected by different antibiotic recommendations or policies.After our study showed high resistance rates in women with recurrent UTIs, the current update of the German guidelines for the treatment of uncomplicated UTIs, which has not yet been published, will recommend against trimethoprim in women with recurrent UTI. | PMC10620739 |
Conclusions | UTI | The multimodal intervention comprising the provision of guideline recommendations, information about regional resistance data, and individualised feedback on antibiotic prescription proportions, increased GPs’ guideline adherence and reduced antibiotic prescribing in women with uncomplicated UTI in German general practices. If implemented on a larger scale, our results are likely to have a sustainable positive impact on antibiotic stewardship programmes for uncomplicated UTI in primary care. | PMC10620739 | |
What is already known on this topic | URINARY TRACT INFECTIONS | In uncomplicated urinary tract infections, symptomatic (non-antibiotic) treatment is an option that is recommended by current guidelinesDespite explicit recommendations, second line antibiotics are still often used in uncomplicated urinary tract infectionsInterventions including educational programmes and prescribing feedback have shown a reduction of inappropriate prescribing, encouraging a non-antibiotic treatment has not been addressed by intervention programmes so far | PMC10620739 | |
What this study adds | Competing interests | FRANK, URINARY TRACT INFECTIONS | A multimodal intervention including guideline information, individual prescribing feedback, and provision of regional resistance data might reduce the proportion of second line antibiotics and antibiotic prescriptions in uncomplicated urinary tract infectionsWe thank all participating practice teams, Christiane Wagner, Judith Kraft, Karin Scheeser, Mandy Böhme, and Liliana Rost for coordinating the project at the local sites; Wolfgang Schneider-Rathert for technical support of the data extraction and the members of the Advisory Board (Stanislava Dicheva-Radev, Ernst Engelmayr, Kerstin Kamm, and Florian Salm) for their project support; and members of the citizens forum for their supportive feedback. We also thank the thorough review of the article to Frank Sullivan.Extra material supplied by authorsWeb appendix: Online appendixContributors: IG, GS, AM, CH, and JB conceived the idea of the study. AG, AK, TE, AS, AME, and VM acquired data and supervised data collection in the practices. AG, AK, TE, AS, AME, and VM were involved in the statistical concept and analysis. All authors analysed and interpreted the data. IG and GS drafted the manuscript. The guarantor (IG) accepts full responsibility for the work and the conduct of the study, had access to the data, and controlled the decision to publish. The corresponding author (AG) attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.Funding: Funded by Innovation Fund coordinated by the Innovation Committee of the Federal Joint Committee (G-BA) in Germany (grant no. 01VSF18053). The funders had no role in considering the study design; nor in the collection, analysis, and interpretation of data, the writing of the report and in the decision to submit the article for publication; we confirm the independence of researchers from funders and that all authors, external and internal, had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.Competing interests: All authors have completed the ICMJE uniform disclosure form at Patient consent: Informed consent was only obtained from the physicians; patient informed consent was not needed because only aggregated and anonymised data were collected.The lead author (the manuscript's guarantor IG) affirms 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; and that any discrepancies from the study as originally planned (and, if relevant, registered) have been explained.Dissemination to participants and related patient and public communities: Study results will be presented to all participating practices and all information developed (patient information in various languages, posters, data on resistance rates) including the study homepage will be accessible to the public. Resistance rates are already included in the current update of the national guideline on urinary tract infections. The material developed will also be included in continuous medical education programmes.Provenance and peer review: Not commissioned; externally peer reviewed. | PMC10620739 |
Ethics statements | PMC10620739 | |||
Ethical approval | The local institutional review and ethics board (Clinical Ethics Committee of the University Wurzburg) judged that the project does not involve any medical or epidemiological research on humans and, as such, adopted a simplified assessment protocol (proposal number 20191106 01). We attest that we have obtained appropriate permissions for use of copyright protected materials. | PMC10620739 | ||
Data availability statement | The datasets (anonymised aggregated data at practice level) used and analysed during this study will be available from the corresponding author on reasonable request. | PMC10620739 | ||
Background | With the increased availability of access to prenatal ultrasound in low/middle-income countries, there is opportunity to better characterize the association between fetal growth and birth weight across global settings. This is important, as fetal growth curves and birthweight charts are often used as proxy health indicators. As part of a randomized control trial, in which ultrasonography was utilized to establish accurate gestational age of pregnancies, we explored the association between gestational age and birthweight among a cohort in Western Kenya, then compared our results to data reported by the INTERGROWTH-21st study. | PMC9993805 | ||
Methods | This study was conducted in 8 geographical clusters across 3 counties in Western Kenya. Eligible subjects were nulliparous women carrying singleton pregnancies. An early ultrasound was performed between 6 + 0/7 and 13 + 6/7 weeks gestational age. At birth, infants were weighed on platform scales provided either by the study team (community births), or the Government of Kenya (public health facilities). The 10 | PMC9993805 | ||
Results | MISCARRIAGE | A total of 1291 infants (of 1408 pregnant women randomized) were included. Ninety-three infants did not have a measured birth weight. The majority of these were due to miscarriage ( | PMC9993805 | |
Conclusions | A comparison of birthweight percentiles by gestational age estimation, among a sample of infants from rural Kenya, revealed slight differences as compared to those from the global population (INTERGROWTH-21 | PMC9993805 | ||
Trial registration | This is a single site sub-study of data collected in conjunction with the Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas (ASPIRIN) Trial, which is listed at | PMC9993805 | ||
Keywords | PMC9993805 | |||
Background | PERINATAL MORBIDITY | Pediatricians, obstetricians, and public health workers have become accustomed to using fetal growth curves to assess risk for perinatal morbidity and mortality. The widespread use of obstetrical ultrasound early in gestation, particularly within high-income settings, has allowed very accurate and precise estimation of gestational age [While early prenatal ultrasound is common in high resource countries, it is less common or even nonexistent in low resource settings. This has made the development of fetal growth curves difficult in these settings. Growing access to low-cost ultrasound (US) devices in these settings may begin to increase access to antenatal sonography for populations in low-to-middle income countries [The Global Network for Women’s and Children’s Health Research recently completed a multi-site global clinical trial of low dose aspirin administered to women throughout pregnancy, beginning between 6–14 weeks gestation [One of the largest, most comprehensive set of studies on multinational birth weight are those of the INTERGROWTH-21st trial [ | PMC9993805 | |
Methods | death | The data presented in this paper were acquired at the Kenya site as part of the Global Network for Women’s and Children’s Health Research ASPIRIN trial. Detailed study methods are described in Hoffman et al. [Map of the study region, located in Busia, Bungoma, and Kakamega counties of western Kenya. Study clusters are outlined in gray. County locations within Kenya are depicted in the inset mapEligible subjects were pregnant nulliparous women carrying singleton pregnancies. An early ultrasound was performed between 6 + 0/7 and 13 + 6/7 weeks gestational age for accurate pregnancy dating. From this ultrasound, the estimated day of delivery was determined using the ACOG algorithm [Infants born to subjects were weighed on platform scales either at a delivery in a health facility, or if born outside of a facility, at the home of the local village elder [For subjects experiencing either a stillbirth or an infant death before the 42-day follow-up period, the assumed cause of death was determined using a previously published algorithm [Statistical analyses were performed using JMP software and SAS version 9.4 (SAS Inc, Cary, NC USA). The 10A signed rank test was used to quantify the comparison of the percentiles generated in this study with those of the INTERGROWTH-21st study. This test was performed twice within each gestational week – once testing the null hypothesis that the Kenya Male median equals the reported median of the INTERGROWTH-21st Male data, and once testing the null hypothesis that the Kenya Female median equals the reported median of the INTERGROWTH-21st Female data. This analysis was non-directional and performed at the alpha = 0.05 significance level. | PMC9993805 | |
Discussion | malaria, deaths, prematurity | MALARIA, MISCARRIAGES, NAIROBI | Our data complements that reported by INTERGROWTH-21st, in that our Kenyan subjects were recruited from a rural agricultural setting with a significant malaria burden, whereas the Kenyan subjects in the INTERGROWTH-21st trial were recruited from the Parklands area of suburban Nairobi. Parklands is considered a middle to upper socioeconomic urban area, while the area of our study is largely defined as a World Bank rural poverty area. Thus, our population demographics are considerably different than those of the Kenyan subjects included in the INTERGROWTH-21st study. Despite these in-country geographical variations, our results, from rural Western Kenya, are quite similar to those reported for INTERGROWTH-21The incidence of prematurity and low birth weight are important public health indicators for a population. In addition, the construction of birth weight percentiles for gestational age are crucial for establishing the intrauterine growth of an infant, which is then used to track postnatal growth. Abnormal postnatal growth, as evidenced by deviations from the expected weight for age percentile that are established by the assessment of birth weight for gestational age, is then used as a warning sign for the need for nutritional intervention. However, it is known that the birth weight distribution curve varies among populations. In addition, despite extensive study, it has been challenging for clinicians and public health practitioners to find accurate prenatal surrogate markers that correlate reliably with actual birthweight [Birth weight and gestational age are intertwined, and it is crucial in evaluating a population to be able to separate low birth weight due to prematurity and low birth weight due to fetal factors, either constitutional or nutritional. Therefore, fetal growth curves with accurate birth weights are important tools for evaluating public health interventions designed to reduce rates of stillbirth [The INTERGROWTH-21st study found that for most gestational weeks, median birthweights differed for male and female infants. The signed rank test used for this analysis was performed separately for male and female data but was limited by sample size disparities. Although this analysis had limitations and was based on a single metric (median), the observed significant differences at lower gestational ages for females and higher gestational ages for males warrant further investigation in the rural, western Kenyan population. A major strength of our cohort is the data originated from a prospectively designed study. Subjects were enrolled early in pregnancy as part of the ASPIRIN trial, and tracked prospectively through delivery to 42 days postpartum, as part of our established, population-based maternal newborn health registry, which employs rigorous quality assurance procedures [In the present study, another strength was our very low loss-to-follow up rate; we lost only 22 subjects (1.56%) to follow-up before birth. Another key strength is the rigorous quality-assurance standards that were utilized to train, monitor, and evaluate the sonographers in this study [There are several limitations of our study. First, the sample size is relatively small, especially for infants born below 36 weeks and of less than 2500 g. Furthermore, we used data only from women who had qualified for and enrolled in the ASPIRIN study, as these women all had accurate ultrasound gestational dating. This limited our subjects to primagravidas, and to singleton pregnancies, consistent with the ASPIRIN eligibility requirements. It is well established that multiple gestation pregnancies are more likely to result in low birthweight infants. Birth spacing can also impact the birthweights of subsequently born sibling infants, as compared to first born infants [Similar to challenges faced by other groups (e.g., EN-INDEPTH; Blencowe, et al., 2021) [As mentioned previously, we had a very low loss-to-follow-up rate, overall. However, an additional 93 subjects, while not lost to follow-up, did not have measured birth weights. Of these, 49 pregnancies ended before 20 weeks and were considered miscarriages. Of the remaining subjects, 27 were stillbirths, 5 were neonatal deaths, and 12 had unknown status. A final challenge faced in this study is the limited precision of the scales used to determine birth weights. In general, these scales were graduated at 50-g increments. Combined with documented “digit preference” bias from other settings, including within the East African region [ | PMC9993805 |
Conclusions | PREMATURE BIRTH, FETAL GROWTH RESTRICTION | Premature birth continues to be a major problem in sub-Saharan Africa, including Kenya. The comparison of our data, with INTERGROWTH-21st results, found preliminary signals that this rural-dwelling population may have birthweight by gestational age percentiles that differ from that currently reported in global data sources. These results further indicate that continued efforts by clinicians and public health practitioners are needed to develop timely, accurate, effective, acceptable, and feasible evidence-based methods to accurately detect and predict regionally-specific rates of fetal growth restriction and low birthweight [ | PMC9993805 | |
Acknowledgements | We are grateful to the women who consented to participate in this study, and to the leaders, communities, and health facilities in Western Kenya with whom we collaborate to improve maternal-newborn-child health. | PMC9993805 | ||
Authors’ contributions | SB and EL served as the US-based co-PIs for the study, and drafted the manuscript, including the narrative sections, tables, and figures. SB was responsible for obtaining human ethics approval from Indiana University. KN performed statistical analysis and helped draft the Methods and Results section, including revision of tables and figures. KO provided overall study coordination for the Global Network site in Kenya, and served as the Senior Data Manager for the study. CT and IM serve as co-Investigators for the study, as well as for the Maternal Newborn Health Registry. They oversaw study operations, particularly in regards to ensuring that all participating village elders and health facilities had operational weighing scales. FR was the Cluster Coordinator and organized all study operations, as well as monitored the quality assurance procedures for the Maternal Newborn Registry attendants and quality assurance personnel. MK was the field-based data manager and statistician. EA was the ASPIRIN Trial study coordinator, and provided supervision for all study personnel under the direction of the Senior Foreign Investigator, FE. EA was also responsible for ensuring that the ultrasonography quality assurance milestones were attained, and maintained for the duration of the study period. OE served as a co-Investigator, and provided clinical technical assistance on the project in regards to newborn health. PN was the Kenyan-based co-PI on the study, and oversaw all study operations, Moi University ethical approvals, and data collection under the direction of FE. FE serves as the Senior Foreign Investigator for the IU-Kenya Global Network site. He is responsible for all Kenya-based study operations, including fiscal matters, human study ethics approvals, data collection, data analysis, and dissemination of research products. All authors reviewed the final manuscript, and provide approval for publication. | PMC9993805 | ||
Funding | Funding was provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant number 5UG1HD076461-10). | PMC9993805 | ||
Availability of data and materials | The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. | PMC9993805 | ||
Declarations | PMC9993805 | |||
Ethics approval and consent to participate | This study was conducted in accordance with the Declaration of Helsinki, and approved by the Indiana University Institutional Review Board (#1507246903) and the Moi University Institutional Research Ethics Committee (#0001429). The research study was conducted in accordance with all the relevant guidelines and regulations regarding protection of human populations, including pregnant women, fetuses, and newborns. No research was conducted in regards to embryos, gametes, or stem cells. All adult participants provided written informed consent for themselves and their infants to participate in the study. | PMC9993805 | ||
Consent for publication | Not applicable. | PMC9993805 | ||
Competing interests | The authors declare no competing interests. | PMC9993805 | ||
References | PMC9993805 | |||
Objectives | T2DM, Infection, Cancer | INSULIN RESISTANCE, TYPE 2 DIABETES MELLITUS, INFECTION, CANCER | Edited by: Qinglong Wu, Baylor College of Medicine, United StatesReviewed by: Bo Zhu, University of Texas MD Anderson Cancer Center, United States; Ravi Verma, Department of Pathology and Immunology, Baylor College of Medicine, United States†These authors have contributed equally to this work‡ORCID: Yongsong Chen, This article was submitted to Intestinal Microbiome, a section of the journal Frontiers in Cellular and Infection MicrobiologyRecent studies have shown that fecal microbiota transplantation (FMT) improved the metabolic profiles of patients with type 2 diabetes mellitus (T2DM), yet the effectiveness in reversing insulin resistance and increasing metformin sensitivity in T2DM patients have not been reported. In this study, we evaluated the improvements of T2DM patients and their gut microbiota by FMT alone and FMT plus metformin. | PMC9872724 |
Methods | T2DM | BLOOD | A total of 31 patients with newly diagnosed T2DM were randomized to intervention by metformin, FMT, or FMT plus metformin in the study. Patients were followed up at baseline and week 4 after treatment. Blood and stool samples were collected and subject to analyze clinical parameters and microbial communities by metagenomic sequencing, respectively. | PMC9872724 |
Results | T2DM, fasting blood glucose, postprandial blood glucose | FMT alone and FMT plus metformin significantly improved the clinical indicators HOMA-IR and BMI in T2DM, besides fasting blood glucose, postprandial blood glucose, and hemoglobin A1c that were also controlled by metformin. Donor microbiota effectively colonized in T2DM with slightly higher colonization ration in FMT than FMT plus metformin within 4 weeks, resulting in increased microbial diversity and community changes from baseline after treatment. A total of 227 species and 441 species were significantly alerted after FMT and FMT plus metformin, respectively. FMT were significantly associated with the clinical parameters. Among them, | PMC9872724 |
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