The final CRISP Statement and CRISP Checklist are published at:
Phillips WR, Sturgiss E, Glasziou P, olde Hartman TC, Orkin AM, Prathivadi P, Reeve J, Russell GM, van Weel C. Improving the reporting of primary care research: Consensus Reporting Items for Studies in Primary Care—the CRISP Statement. Annals of Family Medicine 2023, 21(6):549-555; DOI: https://doi.org/10.1370/afm.3029
We appreciate the authors for their interesting article, but we want to highlight issues regarding the interpretation and reproducibility of the research results. The key problems lie in the documentation of measurements and the reporting of essential aspects of the study.
First, the article does not provide sufficient detail on how ventilation in the participating daycare centers is implemented – whether it is mechanical, gravity-based, or reliant solely on window ventilation. Fundamental information concerning the baseline ventilation is crucial for evaluating and reproducing the study results. When assessing the effectiveness of air purification against airborne infections, it is necessary to establish 1) what is the baseline ventilation capacity which dictates the reference airborne infection risk level and 2) what is the augmented ventilation capacity after introducing air purifiers which, in turn, dictate the expected reduction in the risk level (Rehva 2020; Auvinen et al. 2022; Buonanno et al. 2022). Without knowing the baseline ventilation rates and how they differ between intervention and control groups, it is impossible to assess whether the introduced air purification improves the overall ventilation performance sufficiently to bring the risk level low enough to justify expectations for an observable improvement. After all, it is possible that even after introducing air purifiers the infection risk levels remain high nonetheless (Rehva 2023).
We appreciate the authors for their interesting article, but we want to highlight issues regarding the interpretation and reproducibility of the research results. The key problems lie in the documentation of measurements and the reporting of essential aspects of the study.
First, the article does not provide sufficient detail on how ventilation in the participating daycare centers is implemented – whether it is mechanical, gravity-based, or reliant solely on window ventilation. Fundamental information concerning the baseline ventilation is crucial for evaluating and reproducing the study results. When assessing the effectiveness of air purification against airborne infections, it is necessary to establish 1) what is the baseline ventilation capacity which dictates the reference airborne infection risk level and 2) what is the augmented ventilation capacity after introducing air purifiers which, in turn, dictate the expected reduction in the risk level (Rehva 2020; Auvinen et al. 2022; Buonanno et al. 2022). Without knowing the baseline ventilation rates and how they differ between intervention and control groups, it is impossible to assess whether the introduced air purification improves the overall ventilation performance sufficiently to bring the risk level low enough to justify expectations for an observable improvement. After all, it is possible that even after introducing air purifiers the infection risk levels remain high nonetheless (Rehva 2023).
Second, the study introduces unpredictability through variable factors such as window ventilation. Depending on opening rate, and e.g. on window placement and weather conditions, window ventilation can significantly enhance overall ventilation (Park et al. 2021). The use of window ventilation was significantly higher in the control group as reported, possibly biasing the conclusion on the effectiveness of air purifiers.
Third, the article mentions a baseline test aerosol experiment, but lacks documentation on the test conditions and results. Information on the test space size, baseline ventilation, added ventilation, and measurement configuration is essential. However, it is not reported whether or not the clean air delivery rates (CADR) used in the test scenarios were equivalent or comparable with the study conditions.
For the monitoring period, understanding the effect of designed air purifier capacity is crucial for the interpretation and reproducibility. Was the decision for the chosen air purifier capacity based on their maximum CADR (and assumed maximum noise levels) or were the purifiers operated at lower CADR for operational comfort? What was the targeted gain of the added ventilation? This directly determines the expected reduction in infection risk, and whether this is in line with the presented 15% reduction in the significance estimation? Additionally, knowing if the designed CADR capacity aligned with the actual usage is vital. While acknowledging the challenge of for example noise levels, the pandemic has seen the emergence of effective, cost-efficient, and quiet air purifiers.
To interpret the study results, documentation of the above information is necessary. Unfortunately, the manuscript offers little analysis and omits crucial pieces of information relating to the baseline risk levels and obtained risk levels after augmenting the ventilation with air purifiers. This leaves the reader with the responsibility to guess whether there ever was a good reason to expect a significant change between the test and control groups. Appeal to real-world scenarios and their complexity does not negate the need to lay down the underlying assumptions and hypothesized outcomes. Without this information and analysis, the study cannot substantiate its claim that intervention daycares had a relatively lower viral load while showing no change in infections.
References
Auvinen, Mikko, Joel Kuula, Tiia Grönholm, Matthias Sühring, and Antti Hellsten. 2022. “High-Resolution Large-Eddy Simulation of Indoor Turbulence and Its Effect on Airborne Transmission of Respiratory Pathogens-Model Validation and Infection Probability Analysis.” Physics of Fluids (Woodbury, N.Y.: 1994) 34 (1): 015124.
Buonanno, Giorgio, Luca Ricolfi, Lidia Morawska, and Luca Stabile. 2022. “Increasing Ventilation Reduces SARS-CoV-2 Airborne Transmission in Schools: A Retrospective Cohort Study in Italy’s Marche Region.” Frontiers in Public Health 10 (December): 1087087.
Park, Sowoo, Younhee Choi, Doosam Song, and Eun Kyung Kim. 2021. “Natural Ventilation Strategy and Related Issues to Prevent Coronavirus Disease 2019 (COVID-19) Airborne Transmission in a School Building.” The Science of the Total Environment 789 (October): 147764.
Rehva. 2020. “COVID-19 Guidance Document: How to Operate HVAC and Other Building Service Systems to Prevent the Spread of the Coronavirus (SARS-CoV-2) Disease ….” Federation of European Heating, Ventilation and Air Conditioning Associations. https://www.rehva.eu/fileadmin/user_upload/REHVA_COVID-19_guidance_docum....
Rehva. 2023. “Health-Based Target Ventilation Rates and Design Method for Reducing Exposure to Airborne Respiratory Infectious Diseases.” Rehva - Federation of European Heating, Ventilation and Air Conditioning Associations. https://www.rehva.eu/activities/post-covid-ventilation.
The authors have conducted a thorough analysis of the existing literature on this crucial topic and have provided valuable insights into the effectiveness of various interventions for improving mental health outcomes among adolescents in sub-Saharan Africa (SSA).
The systematic review employed the Grades of Recommendation, Assessment, Development, and Evaluation approach, ensuring a robust evaluation of the evidence. The researchers conducted a comprehensive search across multiple databases, including Cochrane Library, MEDLINE, EMBASE, PSYCINFO, and Web of Science, and identified 30 studies for inclusion in the review.
The findings of this review highlight the significance of multi-level interventions in addressing mental health disorders among adolescents in SSA. The synthesis of the studies revealed that interventions comprising economic empowerment, peer support, and cognitive behavioral therapy (CBT) were particularly effective in improving mental health outcomes among vulnerable adolescents. Moreover, community-level interventions delivered to community groups demonstrated significant positive changes in mental health outcomes.
While the results of this review are promising, the authors acknowledge the need for further research to understand the reliability and sustainability of these interventions in different African contexts. They rightfully point out the variability in intervention components and study participants among the included studies, emp...
The authors have conducted a thorough analysis of the existing literature on this crucial topic and have provided valuable insights into the effectiveness of various interventions for improving mental health outcomes among adolescents in sub-Saharan Africa (SSA).
The systematic review employed the Grades of Recommendation, Assessment, Development, and Evaluation approach, ensuring a robust evaluation of the evidence. The researchers conducted a comprehensive search across multiple databases, including Cochrane Library, MEDLINE, EMBASE, PSYCINFO, and Web of Science, and identified 30 studies for inclusion in the review.
The findings of this review highlight the significance of multi-level interventions in addressing mental health disorders among adolescents in SSA. The synthesis of the studies revealed that interventions comprising economic empowerment, peer support, and cognitive behavioral therapy (CBT) were particularly effective in improving mental health outcomes among vulnerable adolescents. Moreover, community-level interventions delivered to community groups demonstrated significant positive changes in mental health outcomes.
While the results of this review are promising, the authors acknowledge the need for further research to understand the reliability and sustainability of these interventions in different African contexts. They rightfully point out the variability in intervention components and study participants among the included studies, emphasizing the importance of scaling up these interventions and evaluating their long-term impact.
One noteworthy aspect of the review is the focus on individual needs when designing interventions for highly vulnerable populations, such as adolescents affected by HIV, war-affected adolescents, and orphans. Engaging young people in the development of these interventions can help ensure their relevance and effectiveness. However, the authors also stress the limited application of youth engagement approaches in SSA and advocate for its increased utilization.
The review highlights the varied nature of community-level interventions, with economic empowerment interventions, family coaching or parenting interventions, and theory-based interventions such as CBT and interpersonal therapy (IPT) being particularly effective. Schools are identified as favorable settings for implementing interventions relevant to adolescents, and previous research supports the integration of school-based mental health interventions into education programs. Nonetheless, it is essential to avoid excluding out-of-school youth by overly targeting efforts on school settings. Peer-led community-based and digital mental health interventions, including internet-based CBT, are presented as potential solutions to reach a broader range of young people.
However, there are some limitations to consider in this review. The reliance on published studies and the exclusion of unpublished and qualitative studies may have resulted in some valuable evidence being overlooked. The heterogeneity in intervention components, study participants, and duration prevented the reporting of summary effect measures. Additionally, the absence of studies focusing on individual-level interventions restricted the ability to compare them with multi-level interventions. The age range limitation to adolescents aged 10-24 years may have also excluded important information.
In conclusion, this systematic review provides compelling evidence for the effectiveness of multi-level interventions in improving mental health outcomes among young people in SSA. The authors recommend combining individual-level and community or family-level interventions, tailoring them to the specific needs of adolescents. Economic empowerment, peer support, and CBT interventions have demonstrated positive results, either when delivered alone or in combination with other interventions.
However, further research is needed to replicate these promising interventions in different settings and ascertain their long-term effects and reliability under varied circumstances. Preventive interventions focused on universal mental health in SSA, such as economic empowerment and family strengthening interventions, are deemed crucial for reducing the social determinants of poor mental health in adolescents.
Overall, this review enhances our understanding of mental health interventions for adolescents and emphasizes the importance of addressing mental health in SSA's vulnerable youth population. It serves as a valuable resource for researchers, practitioners, and policymakers working towards supporting the mental well-being of young people in sub-Saharan Africa.
Eine interessante Studie mit einem klaren Ergebnis
Zur Schlußfolgerung: "Es ist bekannt, dass die Ansteckung hauptsächlich über den direkten Luftaustausch von Angesicht zu Angesicht während des Spiels erfolgt und dass die kontaminierte Luft nicht unbedingt vor dem Luftaustausch zwischen Kindern durch den Filter strömt. Die Verwendung von HEPA-Filtern kann auch zu einem Sicherheitsgefühl führen, was zu einem verringerten vorbeugenden Verhalten führt."
Die Studie enthält keine Untersuchung über den Verhaltensvergleich in den Kindergärten der zwei Kohorten (Mit/Ohne Filter).
Insofern vermisse ich in der Schlußfolgerung diese Aussage als eine Vermutung kenntlich zu machen.
Ich finde, daß "Ergebnis" und "Schlußfolgerung" zwei verschiedene Themen sind. Die Schlußfolgerung müßte meines Erachtens lauten: HEPA Filter bringen keinen Vorteil.
Ich finde die Schlußfolgerung eher in Brosa formuliert und somit abweichend vom vorhergehenden Text der Studie. Für mich macht dies die Qualität der Studie zunichte wenn Vermutungen angestellt werden welche nicht Umfang der Studie waren. Mithin viele Studien nur nach Abstrakt, Ergebnis & Schlußfolgerung lesen.
Wenn die Studienverfasser einen Beweis nahelegen, dann muß das Verhalten der Kinder in den Kohorten überprüft und nachgewiesen werden.
We appreciate the interest and questions posed by Professor Richards regarding the FORGE trial. The PREVENTT trial was a well-designed and executed trial, however the primary limitation of the trial is the “Two-week rule” described by the author in their letter and discussed in our introduction. It is well known that the biochemical response to all iron replacement improves with time, with most studies noting a larger response at 3 to 4 weeks post infusion[1,2]. In the PREVENTT study, the median time from infusion to surgery was 14 days in the iron infusion group, with an interquartile range (IQR) of 12-21 days. This is perhaps an explanation as to why the study demonstrated a hemoglobin increase of only 4.7g/L while other studies with median time from infusion to surgery demonstrated greater responses[1]. The study by Derman and colleagues found that at 2 weeks only 30% of patients obtained an increase of hemoglobin concentration greater than 20g/L in response to IV ferric derisomaltose (FDI), while at 3 weeks this increased to nearly 50% of patients[2]. Similarly, the work by Froessler and colleagues in 2016 found only an 8g/L difference in hemoglobin when IV iron (ferric carboxymaltose) was administered a median of 8 days (IQR 6-13 days) prior to surgery[3].
Although expedited surgery for malignancies is often the ideal, in many jurisdictions, this is not feasible, or advisable based on patient, disease, and health system factors. The COVID-19 pandemic afforded a...
We appreciate the interest and questions posed by Professor Richards regarding the FORGE trial. The PREVENTT trial was a well-designed and executed trial, however the primary limitation of the trial is the “Two-week rule” described by the author in their letter and discussed in our introduction. It is well known that the biochemical response to all iron replacement improves with time, with most studies noting a larger response at 3 to 4 weeks post infusion[1,2]. In the PREVENTT study, the median time from infusion to surgery was 14 days in the iron infusion group, with an interquartile range (IQR) of 12-21 days. This is perhaps an explanation as to why the study demonstrated a hemoglobin increase of only 4.7g/L while other studies with median time from infusion to surgery demonstrated greater responses[1]. The study by Derman and colleagues found that at 2 weeks only 30% of patients obtained an increase of hemoglobin concentration greater than 20g/L in response to IV ferric derisomaltose (FDI), while at 3 weeks this increased to nearly 50% of patients[2]. Similarly, the work by Froessler and colleagues in 2016 found only an 8g/L difference in hemoglobin when IV iron (ferric carboxymaltose) was administered a median of 8 days (IQR 6-13 days) prior to surgery[3].
Although expedited surgery for malignancies is often the ideal, in many jurisdictions, this is not feasible, or advisable based on patient, disease, and health system factors. The COVID-19 pandemic afforded an opportunity to assess and standardize timeframes for surgery for gynecologic oncology. Our health system, in line with The Society of Gynecologic Oncology guidelines, has targeted surgery for the majority of gynecologic malignancies within a 4-week time frame[4]. This affords an opportunity for patient optimization, which we hope to explore in FORGE. With our listed inclusion criteria of 21 day minimum from time to surgery, nearly three quarters of the patients from PREVENTT would not be eligible. As this is a pilot trial, we hope to demonstrate that in our population, and with sufficient time for onset of action, that FDI can be feasibly administered to these patients in this window of opportunity, with subsequent trials planned and powered for patient-centered outcomes including those suggested by the secondary results of the PREVENTT study.
Regarding the dosage of ferric derisomaltose, the regulatory approval from FDI in Canada for simplified fixed dosing based on patient weight is a maximum of 1000mg with reassessment in 4 weeks with a recommendation that a single dose not exceed 1500mg. This also coincides with the dose used in the PREVENTT trial and although the improved response found by Keeler and colleagues may be related solely to an increased dose of iron, the other studies listed above as well as the FERWON-IDA trial by Auerbach and colleagues would suggest that a sufficient (>10g/L) response can be obtained at 21 days from 1000mg of FDI[5]. As a pilot/feasibility study, FORGE will assess clinical and laboratory effects of repletion of iron stores in the perioperative course and will yield information as to whether further iron repletion/redosing might be needed in subsequent studies.
Based on the results of PREVENTT many have questioned the usefulness of preoperative iron infusions, suggesting instead postoperative treatment. Our goal, as a mature Enhanced Recovery After Surgery program[7] is to improve surgical outcomes for our patients; providing patients with proven iron deficiency with timely iron repletion has the potential to improve their surgical outcomes beyond improving hemoglobin concentration and rates of allogenic blood transfusion alone. The FORGE trial has the potential to clarify the role of preoperative iron repletion in the gynecologic oncology population prior to abandoning the practice entirely, as has been suggested following the results of the PREVENTT study[8,9]. Furthermore, Professor Richards suggested this line of research in the reference provided “Other future trials might examine particular diagnoses, such as surgery for cancer, and focus on cancer outcomes, such as tolerance on adjuvant treatment or patient-reported outcomes, as well as rate of recurrence” in addition to suggesting further studies on postoperative and patient-reported outcomes[9]. We hope that the FORGE trial can answer some of these unanswered questions.
[1] Keeler BD, Simpson JA, Ng O, Padmanabhan H, Brookes MJ, Acheson AG, et al. Randomized clinical trial of preoperative oral versus intravenous iron in anaemic patients with colorectal cancer. Br J Surg 2017;104:214–21. https://doi.org/10.1002/bjs.10328.
[2] Derman R, Roman E, Modiano MR, Achebe MM, Thomsen LL, Auerbach M. A randomized trial of iron isomaltoside versus iron sucrose in patients with iron deficiency anemia. Am J Hematol 2017;92:286–91. https://doi.org/10.1002/ajh.24633.
[3] Froessler B, Palm P, Weber I, Hodyl NA, Singh R, Murphy EM. The important role for intravenous iron in perioperative patient blood management in major abdominal surgery. Ann Surg 2016;264:41–6. https://doi.org/10.1097/SLA.0000000000001646.
[4] Fader AN, Huh WK, Kesterson J, Pothuri B, Wethington S, Wright JD, et al. When to Operate, Hesitate and Reintegrate: Society of Gynecologic Oncology Surgical Considerations during the COVID-19 Pandemic. Gynecol Oncol 2020;158:236–43. https://doi.org/10.1016/j.ygyno.2020.06.001.
[5] Auerbach M, Henry D, Derman RJ, Achebe MM, Thomsen LL, Glaspy J. A prospective, multi-center, randomized comparison of iron isomaltoside 1000 versus iron sucrose in patients with iron deficiency anemia; the FERWON-IDA trial. Am J Hematol 2019;94:1007–14. https://doi.org/10.1002/ajh.25564.
[6] Wolf M, Rubin J, Achebe M, Econs MJ, Peacock M, Imel EA, et al. Effects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia: Two Randomized Clinical Trials. JAMA - J Am Med Assoc 2020;323:432–43. https://doi.org/10.1001/jama.2019.22450.
[7] Bisch SP, Wells T, Gramlich L, Faris P, Wang X, Tran DT, et al. Enhanced Recovery After Surgery (ERAS) in gynecologic oncology: System-wide implementation and audit leads to improved value and patient outcomes. Gynecol Oncol 2018;151:117–23. https://doi.org/10.1016/j.ygyno.2018.08.007.
[8] Miles LF. The end of the beginning: pre‐operative intravenous iron and the PREVENTT trial. Anaesthesia 2021;76:6–10. https://doi.org/10.1111/anae.15268.
[9] Richards T, Baikady RR, Clevenger B, Butcher A, Abeysiri S, Chau M, et al. Preoperative intravenous iron for anaemia in elective major open abdominal surgery: the PREVENTT RCT. Health Technol Assess (Rockv) 2021;25:1–58. https://doi.org/10.3310/hta25110.
there are several limitations that should be considered:
Sampling Bias: The study relies on blood samples collected for unrelated tests, which may introduce a sampling bias. Patients who undergo routine testing may differ from those who do not, potentially affecting the generalizability of the findings to the broader population.
Cross-Sectional Design: The study design is cross-sectional, meaning it captures data at a single point in time. This limits the ability to establish causation or assess changes over time. Longitudinal studies would provide more robust evidence of the effectiveness of opportunistic screening.
Exclusion Criteria: The study excludes samples from patients with a previous diagnosis of diabetes or those who underwent diabetes screening in the past 12 months. However, the accuracy of this exclusion depends on the completeness and accuracy of medical records, which might not capture all instances of diabetes diagnoses.
Age Discrepancies: The study finds age-related differences in HbA1c levels but adjusts for these differences. However, age alone may not capture the complexity of diabetes risk factors. Other factors such as lifestyle, family history, and comorbidities could contribute to variations in HbA1c levels.
Limited Generalizability: The study is conducted in a specific Australian setting, and the findings may not be directly applicable to other regions with different demographics, healthcare systems, or diabetes p...
there are several limitations that should be considered:
Sampling Bias: The study relies on blood samples collected for unrelated tests, which may introduce a sampling bias. Patients who undergo routine testing may differ from those who do not, potentially affecting the generalizability of the findings to the broader population.
Cross-Sectional Design: The study design is cross-sectional, meaning it captures data at a single point in time. This limits the ability to establish causation or assess changes over time. Longitudinal studies would provide more robust evidence of the effectiveness of opportunistic screening.
Exclusion Criteria: The study excludes samples from patients with a previous diagnosis of diabetes or those who underwent diabetes screening in the past 12 months. However, the accuracy of this exclusion depends on the completeness and accuracy of medical records, which might not capture all instances of diabetes diagnoses.
Age Discrepancies: The study finds age-related differences in HbA1c levels but adjusts for these differences. However, age alone may not capture the complexity of diabetes risk factors. Other factors such as lifestyle, family history, and comorbidities could contribute to variations in HbA1c levels.
Limited Generalizability: The study is conducted in a specific Australian setting, and the findings may not be directly applicable to other regions with different demographics, healthcare systems, or diabetes prevalence rates.
Limited Clinical Outcomes: The study focuses on the prevalence of undiagnosed diabetes based on HbA1c levels but does not assess the clinical outcomes or the impact of early detection on patient outcomes. Understanding the long-term effects of opportunistic screening would provide a more comprehensive perspective.
Cost Considerations: While the study mentions the potential cost-effectiveness of opportunistic screening, it does not provide a detailed cost-benefit analysis. Further research is needed to assess the economic implications, including the costs associated with false-positive results and subsequent confirmatory testing.
Ethical Considerations: The study obtained ethical approval for testing without participant consent, citing impracticability. However, this raises ethical concerns regarding autonomy and informed consent, especially when testing is performed for a condition unrelated to the initial purpose of the blood sample.
Dear editor
The treatment of asthma is based on four fundamental pillars: patient education, dealergenization or environmental control measures aimed at avoiding the allergen, symptomatic pharmacological treatment and allergen-specific immunotherapy.
In each country there must be political will from the state, which does not exist in underdeveloped countries, to successfully control asthma and avoid the numerous crises of the disease that deteriorate the quality of life of patients.
Adequate health education is necessary, establishing simplified treatment plans and promoting shared decision-making with asthmatics themselves and their family, in addition to the necessary knowledge on the part of the professionals who attend consultations in primary care to improve the control of these patients.
It is very important to emphasize the use of inhaled corticosteroids, essential medications for controlling the disease, as well as explaining and showing their proper handling because when this fails it leads to non-control of asthma. It is also very important to take into account the ages of the patients and their characteristics, collected in their medical history to personalize each of the behaviors to be taken and improve the quality of life of each patient.
Regarding immunotherapy, it has been shown in numerous studies that it is the only way capable of modifying the course of the disease, controlling it. There are several allergenic extracts in Cu...
Dear editor
The treatment of asthma is based on four fundamental pillars: patient education, dealergenization or environmental control measures aimed at avoiding the allergen, symptomatic pharmacological treatment and allergen-specific immunotherapy.
In each country there must be political will from the state, which does not exist in underdeveloped countries, to successfully control asthma and avoid the numerous crises of the disease that deteriorate the quality of life of patients.
Adequate health education is necessary, establishing simplified treatment plans and promoting shared decision-making with asthmatics themselves and their family, in addition to the necessary knowledge on the part of the professionals who attend consultations in primary care to improve the control of these patients.
It is very important to emphasize the use of inhaled corticosteroids, essential medications for controlling the disease, as well as explaining and showing their proper handling because when this fails it leads to non-control of asthma. It is also very important to take into account the ages of the patients and their characteristics, collected in their medical history to personalize each of the behaviors to be taken and improve the quality of life of each patient.
Regarding immunotherapy, it has been shown in numerous studies that it is the only way capable of modifying the course of the disease, controlling it. There are several allergenic extracts in Cuba, manufactured by BIOCEN, patented and with numerous studies that support their safety and effectiveness for the control of asthma, especially at this time when our country is going through a significant economic siege and we have large shortages of medications due to that its raw material is exported from abroad and cannot be manufactured in Cuba, especially asthma controllers.
We read with interest the proposal for the FORGE trial. We are concerned that the authors are repeating work that has already been undertaken, without learning from previous trials. The authors criticise the PREVENTT trial, but fail to elaborate their reasons and then proceed to essentially duplicate the very same protocol.
In summary, the PREVENTT RCT (1) was the largest multicentre RCT to assess the role of IV iron compared to placebo in patients before major abdominal surgery. Included were 138 patients undergoing gynaecological surgery and most common operation was a Wertheim’s hysterectomy, a debulking procedure in gynaecological oncology. Of note about two thirds had Tsats < 20% (table 10), essentially representing the same PICO (and size) as proposed in the FORGE trial. There are a couple of key aspects of relevance to FORGE aside from the key question of why they need to repeat the data powered for change in haemoglobin?
A. A key limitation in recruitment was the ‘2-week rule’ whereby patients listed for cancer surgery are mandated to have their operation within 2 weeks (Chapter 4 of the NIHR report (1)). How do the authors propose to overcome this hurdle in FORGE?
B. The benefit of modern IV iron is the ability to give a full treatment dose, normally 20mg/kg, why are the authors proposing a lower dose?
We applaud the authors undertaking a randomised controlled trial but urge them to learn from existing studies to avoid future mist...
We read with interest the proposal for the FORGE trial. We are concerned that the authors are repeating work that has already been undertaken, without learning from previous trials. The authors criticise the PREVENTT trial, but fail to elaborate their reasons and then proceed to essentially duplicate the very same protocol.
In summary, the PREVENTT RCT (1) was the largest multicentre RCT to assess the role of IV iron compared to placebo in patients before major abdominal surgery. Included were 138 patients undergoing gynaecological surgery and most common operation was a Wertheim’s hysterectomy, a debulking procedure in gynaecological oncology. Of note about two thirds had Tsats < 20% (table 10), essentially representing the same PICO (and size) as proposed in the FORGE trial. There are a couple of key aspects of relevance to FORGE aside from the key question of why they need to repeat the data powered for change in haemoglobin?
A. A key limitation in recruitment was the ‘2-week rule’ whereby patients listed for cancer surgery are mandated to have their operation within 2 weeks (Chapter 4 of the NIHR report (1)). How do the authors propose to overcome this hurdle in FORGE?
B. The benefit of modern IV iron is the ability to give a full treatment dose, normally 20mg/kg, why are the authors proposing a lower dose?
We applaud the authors undertaking a randomised controlled trial but urge them to learn from existing studies to avoid future mistakes.
(1). Richards T, Baikady RR, Clevenger B, Butcher A, Abeysiri S, Chau M, et al. Preoperative intravenous iron for anaemia in elective major open abdominal surgery: the PREVENTT RCT. Health Technol Assess 2021;25(11).
I am writing to you regarding an amendment to the sample size section of the following 2021 published protocol paper: Mylrea-Foley B et al. TRUFFLE 2 Collaborators List. Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol. BMJ Open. 2022 Apr 15;12(4):e055543. doi: 10.1136/bmjopen-2021-055543. PMID: 35428631; PMCID: PMC9014041.
In light of a higher-than-expected overall rate of the primary outcome and based on advice from both the TRUFFLE 2 Independent Data Monitoring and the Trial Steering Committees, we have had to amend our sample size for the TRUFFLE 2 randomised trial. It is important for transparency, that the new section is published, and can be found below.
Yours sincerely,
Dr Rebecca Cannings-John, on behalf of the TRUFFLE 2 Trial Management Group
Statistics and data analysis
Sample size
The trial is powered to detect if immediate delivery following cerebral redistribution is superior to expectant management following cerebral redistribution on this outcome. The original sample size was based on a difference in the proportion with the primary outcome from 15% in the delayed delivery to 9% in the immediate delivery (based on the TRUFFLE 2 feasibility study) and demonstrated an odds ratio (OR) of 0.56. At two-sided 5% significance with 95% power, 780 participants per arm were required, giving 1560 in total.
I am writing to you regarding an amendment to the sample size section of the following 2021 published protocol paper: Mylrea-Foley B et al. TRUFFLE 2 Collaborators List. Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol. BMJ Open. 2022 Apr 15;12(4):e055543. doi: 10.1136/bmjopen-2021-055543. PMID: 35428631; PMCID: PMC9014041.
In light of a higher-than-expected overall rate of the primary outcome and based on advice from both the TRUFFLE 2 Independent Data Monitoring and the Trial Steering Committees, we have had to amend our sample size for the TRUFFLE 2 randomised trial. It is important for transparency, that the new section is published, and can be found below.
Yours sincerely,
Dr Rebecca Cannings-John, on behalf of the TRUFFLE 2 Trial Management Group
Statistics and data analysis
Sample size
The trial is powered to detect if immediate delivery following cerebral redistribution is superior to expectant management following cerebral redistribution on this outcome. The original sample size was based on a difference in the proportion with the primary outcome from 15% in the delayed delivery to 9% in the immediate delivery (based on the TRUFFLE 2 feasibility study) and demonstrated an odds ratio (OR) of 0.56. At two-sided 5% significance with 95% power, 780 participants per arm were required, giving 1560 in total.
In light of a higher than expected overall adverse event rate outcome of 36% (95% confidence interval = 28 to 44%) from 132 TRUFFLE-2 participants, and based on advice from both the Independent Data Monitoring and the Trial Steering Committees, on 30th June 2022 it was agreed to amend the trial sample size. Considering the 95% lower event rate limit of 28% as the benchmark to assume the control and intervention proportions for the sample size re-estimation, and assuming an OR of 0.56 remains the same, an event rate of 33.75% in the delayed delivery and 22.25% events in the immediate delivery was assumed. At two-sided 5% significance with 90% power, 319 participants per arm are required, giving 638 in total. Given the immediacy of this outcome, no loss to follow-up is expected.
An important non-inferiority secondary safety outcome is infant neurodevelopment, which is measured by parent completed questionnaire at 2 years using the PARCA-R, as recommended in NICE Guidance, supplemented by infant health information over the intervening 2 years. Assuming a loss to follow-up at 2 years of 20%, 2-year outcomes for approximately 510 infants are expected (255 per group assuming no difference in the lost to follow-up between the groups). The PARCA-R questionnaire provides a composite score for neurodevelopment with a standardised mean of 100 and SD of 15. With a one-sided significance level of 2.5%, under a non-inferiority hypothesis, a sample size of 255 in each group achieves an 85% power to detect a non-inferiority margin of difference in the mean PARCA-R score of no less than four points (0.25 of a SD). A margin of no less than three points can be detected with 62% power.
Dear Editor
The R21/Matrix-M vaccine is a new vaccine recommended by the World Health Organization (WHO) for the prevention of malaria in children below age 5 years , in pregnant women, in travellers and individuals with HIV and AIDS (1) . It is the second malaria vaccine recommended by WHO, following the first RTS,S/AS01 vaccine, which received a WHO recommendation in 2021 (1) . The R21 vaccine is shown to be safe and effective in preventing malaria in children and, when implemented broadly, is expected to have high public health impact (1) in the rainy season.
The R21/Matrix-M vaccine was developed by the University of Oxford and is a low-dose vaccine that can be manufactured at mass scale and modest cost, enabling as many as hundreds of millions of doses to be supplied to African countries which are suffering a significant malaria burden (3) . The vaccine targets the first form of the malaria parasite (the plasmodium sporozoite) to enter the body after a person is bitten by an infected mosquito (2)
The updated WHO malaria vaccine recommendation is informed by evidence from an ongoing R21 vaccine clinical trial and other studies, which showed high efficacy when given just before the high transmission season. In areas with highly seasonal malaria transmission (where malaria transmission is largely limited to 4 or 5 months per year as it is in Ghana and Nigeria), the R21 vaccine was shown to reduce symptomatic cases of malaria by 75%-77% during the 12...
Dear Editor
The R21/Matrix-M vaccine is a new vaccine recommended by the World Health Organization (WHO) for the prevention of malaria in children below age 5 years , in pregnant women, in travellers and individuals with HIV and AIDS (1) . It is the second malaria vaccine recommended by WHO, following the first RTS,S/AS01 vaccine, which received a WHO recommendation in 2021 (1) . The R21 vaccine is shown to be safe and effective in preventing malaria in children and, when implemented broadly, is expected to have high public health impact (1) in the rainy season.
The R21/Matrix-M vaccine was developed by the University of Oxford and is a low-dose vaccine that can be manufactured at mass scale and modest cost, enabling as many as hundreds of millions of doses to be supplied to African countries which are suffering a significant malaria burden (3) . The vaccine targets the first form of the malaria parasite (the plasmodium sporozoite) to enter the body after a person is bitten by an infected mosquito (2)
The updated WHO malaria vaccine recommendation is informed by evidence from an ongoing R21 vaccine clinical trial and other studies, which showed high efficacy when given just before the high transmission season. In areas with highly seasonal malaria transmission (where malaria transmission is largely limited to 4 or 5 months per year as it is in Ghana and Nigeria), the R21 vaccine was shown to reduce symptomatic cases of malaria by 75%-77% during the 12 months following a 3-dose series (1)
The addition of R21 to the list of WHO-recommended malaria vaccines is expected to result in sufficient vaccine supply to benefit all children living in areas where malaria is a public health risk (1) .
The R21/Matrix-M vaccine is a subunit CSP vaccine that targets the first form of the malaria parasite (the plasmodium sporozoite) to enter the body after a person is bitten by an infected mosquito( 4.)The vaccine contains parts of a protein secreted by the sporozoite that are bundled up with a part of the hepatitis B virus that is known to trigger a strong immune response( 4). The Matrix-M adjuvant, which is a saponin-based adjuvant, enhances the immune T cell system response, making it more potent and more durable. It stimulates the entry of antigen-presenting cells at the injection site and enhances antigen presentation in local lymph nodes (2).
The R21/Matrix-M vaccine has shown good safety and high efficacy in four countries with both seasonal and perennial malaria transmission( 5) .It is shown to be effective in reducing symptomatic cases of malaria by 75% during the 12 months following a 3-dose series given 4 weeks apart ,when given just before the high transmission season in areas with highly seasonal malaria transmission (5) followed by one booster dose after one year prior to malaria session
This R21/Matrix-M vaccine had a favorable safety profile and was well-tolerated. The majority of adverse events were mild, with the most common event being fever, pain and tenderness at site of injection. It is important to note that these are early reports and more data is needed to fully understand the safety profile of this vaccine. As with any vaccine, it is recommended that you speak with your healthcare provider if you have any concerns or questions about the R21/Matrix-M vaccine.
The efficacy of the vaccine is 75% following three doses for 12 months duration for plasmodium falciparum and plasmodium vivax infection but not for other species of plasmodium infections. This author still argue that, in combination with vaccination efforts, it is also crucial to maintain and possibly increase the intensity of existing malaria control measures to achieve greater protection for more children and eventually the eradication of the disease in Africa and also same in India. Enforcing existing control measures is a key part of the solution to preventing more children from contracting the disease, whilst the rollout of the vaccine is taking place in nations that have approved the vaccine, and deliberations are going on in other countries to determine the approval of the vaccine. Some of the malaria control measures the author shall propose should be reinforced, including those recommended by the Center for Disease Control that have been put in place in the past few years through the ministries of public health in different countries. This includes case management (diagnosing and treating people with malaria), the distribution of insecticide-treated nets (ITNs), indoor residual spraying (IRS), and intermittent preventive treatment of malaria in pregnant women, and infancy, amongst others
It is imperative to strengthen existing malaria control programmes and other preventive measures, especially in countries where the vaccine has not yet been approved.(6)
The R21/Matrix-M (R21) Phase 2 trial was conducted at one center in one country only. The study reported vaccine efficacy of 77% (95% CI: 66–84) in Nanoro, Burkina Faso, over 12-months of follow-up. The study was performed in a highly seasonal transmission setting, with vaccination coordinated to ensure peak immunity at the time of peak risk (so-called seasonal vaccination); peak risk occurred during the first 6 months of follow-up, followed by the low transmission dry season, with only a single clinical case observed in the control arm between days 200 and 300 of follow-up. It is therefore most appropriate to express these data as efficacy over one season and/or 6 months to align with the period of risk. Additional data, in settings of perennial transmission or over multiple seasons in regions of highly seasonal transmission, are needed to determine appropriately the efficacy of this vaccine candidate over longer follow-up periods and to enable more meaningful comparison to the RTS,S Phase 3 trial data.Also it is needed that how long the IGg antibodies against NANP repeat regions remains after final vaccination and how much protection it gives in adult people
The RTS,S Phase 3 trial was conducted at 11 centers across seven countries, including regions of both seasonal and perennial transmission. Aligned with the EPI schedule for dosing based on child age, the RTS,S vaccine delivery was not optimized to achieve peak immunity during the high transmission setting, nor do 6-month data occur during highest force of infection.The vaccine efficacy against clinical malaria, over 6 months of follow-up, across all 11 sites, was 68% (95% CI: 64–72); at the same Nanoro site, the vaccine efficacy was 72% (95% CI: 60–80).Direct comparisons of relatively short-acting vaccines or monoclonal antibodies employing different delivery strategies should be avoided, and hence the data available to date do not support the superiority of one vaccine over another(6)
6)Ashley Birkett, R. Scott Millerand Lorraine A. Soisson The Importance of Exercising Caution When Comparing Results from Malaria Vaccines Administered on the EPI Schedule and on a Seasonal Schedule The American journal of Tropical Medicine and hygiene vol 107 issue 6 page 1536
DOI: https://doi.org/10.4269/ https://www.ajtmh.org/view/journals/tpmd/107/6/article-p1356.xml
The final CRISP Statement and CRISP Checklist are published at:
Phillips WR, Sturgiss E, Glasziou P, olde Hartman TC, Orkin AM, Prathivadi P, Reeve J, Russell GM, van Weel C. Improving the reporting of primary care research: Consensus Reporting Items for Studies in Primary Care—the CRISP Statement. Annals of Family Medicine 2023, 21(6):549-555; DOI: https://doi.org/10.1370/afm.3029
We appreciate the authors for their interesting article, but we want to highlight issues regarding the interpretation and reproducibility of the research results. The key problems lie in the documentation of measurements and the reporting of essential aspects of the study.
First, the article does not provide sufficient detail on how ventilation in the participating daycare centers is implemented – whether it is mechanical, gravity-based, or reliant solely on window ventilation. Fundamental information concerning the baseline ventilation is crucial for evaluating and reproducing the study results. When assessing the effectiveness of air purification against airborne infections, it is necessary to establish 1) what is the baseline ventilation capacity which dictates the reference airborne infection risk level and 2) what is the augmented ventilation capacity after introducing air purifiers which, in turn, dictate the expected reduction in the risk level (Rehva 2020; Auvinen et al. 2022; Buonanno et al. 2022). Without knowing the baseline ventilation rates and how they differ between intervention and control groups, it is impossible to assess whether the introduced air purification improves the overall ventilation performance sufficiently to bring the risk level low enough to justify expectations for an observable improvement. After all, it is possible that even after introducing air purifiers the infection risk levels remain high nonetheless (Rehva 2023).
Sec...
Show MoreThe authors have conducted a thorough analysis of the existing literature on this crucial topic and have provided valuable insights into the effectiveness of various interventions for improving mental health outcomes among adolescents in sub-Saharan Africa (SSA).
Show MoreThe systematic review employed the Grades of Recommendation, Assessment, Development, and Evaluation approach, ensuring a robust evaluation of the evidence. The researchers conducted a comprehensive search across multiple databases, including Cochrane Library, MEDLINE, EMBASE, PSYCINFO, and Web of Science, and identified 30 studies for inclusion in the review.
The findings of this review highlight the significance of multi-level interventions in addressing mental health disorders among adolescents in SSA. The synthesis of the studies revealed that interventions comprising economic empowerment, peer support, and cognitive behavioral therapy (CBT) were particularly effective in improving mental health outcomes among vulnerable adolescents. Moreover, community-level interventions delivered to community groups demonstrated significant positive changes in mental health outcomes.
While the results of this review are promising, the authors acknowledge the need for further research to understand the reliability and sustainability of these interventions in different African contexts. They rightfully point out the variability in intervention components and study participants among the included studies, emp...
Eine interessante Studie mit einem klaren Ergebnis
Zur Schlußfolgerung: "Es ist bekannt, dass die Ansteckung hauptsächlich über den direkten Luftaustausch von Angesicht zu Angesicht während des Spiels erfolgt und dass die kontaminierte Luft nicht unbedingt vor dem Luftaustausch zwischen Kindern durch den Filter strömt. Die Verwendung von HEPA-Filtern kann auch zu einem Sicherheitsgefühl führen, was zu einem verringerten vorbeugenden Verhalten führt."
Die Studie enthält keine Untersuchung über den Verhaltensvergleich in den Kindergärten der zwei Kohorten (Mit/Ohne Filter).
Insofern vermisse ich in der Schlußfolgerung diese Aussage als eine Vermutung kenntlich zu machen.
Ich finde, daß "Ergebnis" und "Schlußfolgerung" zwei verschiedene Themen sind. Die Schlußfolgerung müßte meines Erachtens lauten: HEPA Filter bringen keinen Vorteil.
Ich finde die Schlußfolgerung eher in Brosa formuliert und somit abweichend vom vorhergehenden Text der Studie. Für mich macht dies die Qualität der Studie zunichte wenn Vermutungen angestellt werden welche nicht Umfang der Studie waren. Mithin viele Studien nur nach Abstrakt, Ergebnis & Schlußfolgerung lesen.
Wenn die Studienverfasser einen Beweis nahelegen, dann muß das Verhalten der Kinder in den Kohorten überprüft und nachgewiesen werden.
We appreciate the interest and questions posed by Professor Richards regarding the FORGE trial. The PREVENTT trial was a well-designed and executed trial, however the primary limitation of the trial is the “Two-week rule” described by the author in their letter and discussed in our introduction. It is well known that the biochemical response to all iron replacement improves with time, with most studies noting a larger response at 3 to 4 weeks post infusion[1,2]. In the PREVENTT study, the median time from infusion to surgery was 14 days in the iron infusion group, with an interquartile range (IQR) of 12-21 days. This is perhaps an explanation as to why the study demonstrated a hemoglobin increase of only 4.7g/L while other studies with median time from infusion to surgery demonstrated greater responses[1]. The study by Derman and colleagues found that at 2 weeks only 30% of patients obtained an increase of hemoglobin concentration greater than 20g/L in response to IV ferric derisomaltose (FDI), while at 3 weeks this increased to nearly 50% of patients[2]. Similarly, the work by Froessler and colleagues in 2016 found only an 8g/L difference in hemoglobin when IV iron (ferric carboxymaltose) was administered a median of 8 days (IQR 6-13 days) prior to surgery[3].
Although expedited surgery for malignancies is often the ideal, in many jurisdictions, this is not feasible, or advisable based on patient, disease, and health system factors. The COVID-19 pandemic afforded a...
Show Morethere are several limitations that should be considered:
Sampling Bias: The study relies on blood samples collected for unrelated tests, which may introduce a sampling bias. Patients who undergo routine testing may differ from those who do not, potentially affecting the generalizability of the findings to the broader population.
Cross-Sectional Design: The study design is cross-sectional, meaning it captures data at a single point in time. This limits the ability to establish causation or assess changes over time. Longitudinal studies would provide more robust evidence of the effectiveness of opportunistic screening.
Exclusion Criteria: The study excludes samples from patients with a previous diagnosis of diabetes or those who underwent diabetes screening in the past 12 months. However, the accuracy of this exclusion depends on the completeness and accuracy of medical records, which might not capture all instances of diabetes diagnoses.
Age Discrepancies: The study finds age-related differences in HbA1c levels but adjusts for these differences. However, age alone may not capture the complexity of diabetes risk factors. Other factors such as lifestyle, family history, and comorbidities could contribute to variations in HbA1c levels.
Limited Generalizability: The study is conducted in a specific Australian setting, and the findings may not be directly applicable to other regions with different demographics, healthcare systems, or diabetes p...
Show MoreDear editor
Show MoreThe treatment of asthma is based on four fundamental pillars: patient education, dealergenization or environmental control measures aimed at avoiding the allergen, symptomatic pharmacological treatment and allergen-specific immunotherapy.
In each country there must be political will from the state, which does not exist in underdeveloped countries, to successfully control asthma and avoid the numerous crises of the disease that deteriorate the quality of life of patients.
Adequate health education is necessary, establishing simplified treatment plans and promoting shared decision-making with asthmatics themselves and their family, in addition to the necessary knowledge on the part of the professionals who attend consultations in primary care to improve the control of these patients.
It is very important to emphasize the use of inhaled corticosteroids, essential medications for controlling the disease, as well as explaining and showing their proper handling because when this fails it leads to non-control of asthma. It is also very important to take into account the ages of the patients and their characteristics, collected in their medical history to personalize each of the behaviors to be taken and improve the quality of life of each patient.
Regarding immunotherapy, it has been shown in numerous studies that it is the only way capable of modifying the course of the disease, controlling it. There are several allergenic extracts in Cu...
We read with interest the proposal for the FORGE trial. We are concerned that the authors are repeating work that has already been undertaken, without learning from previous trials. The authors criticise the PREVENTT trial, but fail to elaborate their reasons and then proceed to essentially duplicate the very same protocol.
In summary, the PREVENTT RCT (1) was the largest multicentre RCT to assess the role of IV iron compared to placebo in patients before major abdominal surgery. Included were 138 patients undergoing gynaecological surgery and most common operation was a Wertheim’s hysterectomy, a debulking procedure in gynaecological oncology. Of note about two thirds had Tsats < 20% (table 10), essentially representing the same PICO (and size) as proposed in the FORGE trial. There are a couple of key aspects of relevance to FORGE aside from the key question of why they need to repeat the data powered for change in haemoglobin?
A. A key limitation in recruitment was the ‘2-week rule’ whereby patients listed for cancer surgery are mandated to have their operation within 2 weeks (Chapter 4 of the NIHR report (1)). How do the authors propose to overcome this hurdle in FORGE?
B. The benefit of modern IV iron is the ability to give a full treatment dose, normally 20mg/kg, why are the authors proposing a lower dose?
We applaud the authors undertaking a randomised controlled trial but urge them to learn from existing studies to avoid future mist...
Show MoreI am writing to you regarding an amendment to the sample size section of the following 2021 published protocol paper: Mylrea-Foley B et al. TRUFFLE 2 Collaborators List. Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol. BMJ Open. 2022 Apr 15;12(4):e055543. doi: 10.1136/bmjopen-2021-055543. PMID: 35428631; PMCID: PMC9014041.
In light of a higher-than-expected overall rate of the primary outcome and based on advice from both the TRUFFLE 2 Independent Data Monitoring and the Trial Steering Committees, we have had to amend our sample size for the TRUFFLE 2 randomised trial. It is important for transparency, that the new section is published, and can be found below.
Yours sincerely,
Dr Rebecca Cannings-John, on behalf of the TRUFFLE 2 Trial Management Group
Statistics and data analysis
Sample size
The trial is powered to detect if immediate delivery following cerebral redistribution is superior to expectant management following cerebral redistribution on this outcome. The original sample size was based on a difference in the proportion with the primary outcome from 15% in the delayed delivery to 9% in the immediate delivery (based on the TRUFFLE 2 feasibility study) and demonstrated an odds ratio (OR) of 0.56. At two-sided 5% significance with 95% power, 780 participants per arm were required, giving 1560 in total.
In light of a higher than expected overa...
Show MoreDear Editor
Show MoreThe R21/Matrix-M vaccine is a new vaccine recommended by the World Health Organization (WHO) for the prevention of malaria in children below age 5 years , in pregnant women, in travellers and individuals with HIV and AIDS (1) . It is the second malaria vaccine recommended by WHO, following the first RTS,S/AS01 vaccine, which received a WHO recommendation in 2021 (1) . The R21 vaccine is shown to be safe and effective in preventing malaria in children and, when implemented broadly, is expected to have high public health impact (1) in the rainy season.
The R21/Matrix-M vaccine was developed by the University of Oxford and is a low-dose vaccine that can be manufactured at mass scale and modest cost, enabling as many as hundreds of millions of doses to be supplied to African countries which are suffering a significant malaria burden (3) . The vaccine targets the first form of the malaria parasite (the plasmodium sporozoite) to enter the body after a person is bitten by an infected mosquito (2)
The updated WHO malaria vaccine recommendation is informed by evidence from an ongoing R21 vaccine clinical trial and other studies, which showed high efficacy when given just before the high transmission season. In areas with highly seasonal malaria transmission (where malaria transmission is largely limited to 4 or 5 months per year as it is in Ghana and Nigeria), the R21 vaccine was shown to reduce symptomatic cases of malaria by 75%-77% during the 12...
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