In the study of Huang C, et al. on BMJ Open 2018;8:e018070. doi:10.1136/bmjopen-2017-018070: “ MicroRNA-17 and the prognosis of human carcinomas: a systematic review and meta-analysis” the manuscript from Robaina et al. entitled “miR-17-92 cluster components analysis in Burkitt lymphoma: overexpression of miR-17 is associated with poor prognosis. Ann Hematol 2016;95:881–91.” was mentioned (citation number 38). We would like to point out some mistakes regarding the citation of our study as below:
1.Table 1 on page 4, the assay performed in our study was quantitative RT-PCR (q-PCR) instead of ISH assay as described on the table 1 and 2 of the Huang et al. publication. The same mistake is observed on the figure 3 C.
2. Discussion on page 7: The sentence: In the subgroup analysis, we found that the potential heterogeneity may have originated from the Caucasian group in the study conducted by Robaina et al.38 Unlike the commonly used RT-PCR, ISH technique was used to detect miR-17 .
There is a great misunderstanding on this sentence. Neither our Brazilian patients were classified by race as " Caucasian ", nor the analysis of miR-17 expression levels in our study was performed by ISH. All the assays were performed by qRT-PCR.
It is important to mention that the term " Caucasian " is not applied in Brazilian for race/ethnicity classification. The Brazilian population is formed by extensive admixture from three different ances...
In the study of Huang C, et al. on BMJ Open 2018;8:e018070. doi:10.1136/bmjopen-2017-018070: “ MicroRNA-17 and the prognosis of human carcinomas: a systematic review and meta-analysis” the manuscript from Robaina et al. entitled “miR-17-92 cluster components analysis in Burkitt lymphoma: overexpression of miR-17 is associated with poor prognosis. Ann Hematol 2016;95:881–91.” was mentioned (citation number 38). We would like to point out some mistakes regarding the citation of our study as below:
1.Table 1 on page 4, the assay performed in our study was quantitative RT-PCR (q-PCR) instead of ISH assay as described on the table 1 and 2 of the Huang et al. publication. The same mistake is observed on the figure 3 C.
2. Discussion on page 7: The sentence: In the subgroup analysis, we found that the potential heterogeneity may have originated from the Caucasian group in the study conducted by Robaina et al.38 Unlike the commonly used RT-PCR, ISH technique was used to detect miR-17 .
There is a great misunderstanding on this sentence. Neither our Brazilian patients were classified by race as " Caucasian ", nor the analysis of miR-17 expression levels in our study was performed by ISH. All the assays were performed by qRT-PCR.
It is important to mention that the term " Caucasian " is not applied in Brazilian for race/ethnicity classification. The Brazilian population is formed by extensive admixture from three different ancestral roots: Amerindians, Europeans and Africans. For more details see (Pena SD, Di Pietro G, Fuchshuber-Moraes M, et al. PLoS One. 2011 F;6 (2):e17063. In addition, The Instituto Brasileiro de Geografia e Estatıstica (IBGE) classifies the racial groups in Brazil by self-report as White (‘‘branca’’), Brown (‘‘parda’’), Black (‘‘preta’’), Yellow (“amarela”) and Indigenous (‘‘indigena”), based on a subjective phenotypic evaluation according to the skin pigmentation, and also hair pigmentation and type, eye melanization and facial features such as nose and lip shape. See details in IBGE:https://www.ibge.gov.br/.
Thus, the correction of the online article version is required because the results presented by Huang et al. on BMJ Open provided incorrect information of our study.
It would be satisfying if all papers gave a summary of the part played by PPI in the work. It is clear that they do not, despite it being editorial policy to seek it. We may conclude that either PPI does not occur to the extent foreseen, or that the authors do not rate it highly reportable in comparison to the rest of the content. Given the increased requirement to build PPI into grant applications, it seems likely that it is the second scenario that is predominant, and this leads to a consideration of the authors' motivation in writing. Ideally, the prime mover would be the altruism of wishing to get knowledge or a change in practice into the public arena, where it will have the greatest chance of creating patient benefit. Then would come the personal spur of academic reputation and all that follows from that. Maybe an up-coming REF exercise is being thought about in some cases. Whatever these motivations are, PPI appears to have no place among them, except that good manners require it should be acknowledged, along with other help received. If reporting PPI has no discernible utility, it will not generally happen without an enforceable requirement.
We agree with Shah et al. that caring for patients with acute kidney injury (AKI) is complicated, particularly when it comes to medication management (1). It is important to remember that AKI is a heterogenous condition with multiple etiologies and different degrees of severity. In some cases then, prioritization of other chronic diseases over AKI may be reasonable and even beneficial for patients.
On this background, we would caution against the conclusion that physicians view AKI as a low priority concern. More qualitative research is needed first to understand physician experiences with AKI during both the inpatient and outpatient setting. This information is necessary to develop and support the use of quality improvement tools for patients with AKI, such as the medication checklists referenced by Shah et al (2).
References:
1. Phipps DL, Morris RL, Blakeman T, Ashcroft DM. What is involved in medicines management across care boundaries? A qualitative study of healthcare practitioners' experiences in the case of acute kidney injury. BMJ Open 2017;7:e011765.
2. Griffith K, Ashley C, Blakeman T, Fluck R, Lewington A, Selby N, et al. ‘Sick day’ guidance in patients at risk of Acute Kidney Injury: An Interim Position Statement from the Think Kidneys Board 2015.
REPLY - CoMiSS validation study protocol
Letter to the Editor of BMJ Open - 8 August 2018
We thank MM Vanderschuren et al. for their interest in our published protocol for a validation study of the Cow’s Milk-related Symptom Score (CoMiSS®) [1] and would like to provide our reply to the concerns raised.
CoMiSS was designed in 2015 by a paediatric expert group in order to provide an easy-to-use tool to facilitate a greater awareness for cow’s milk protein allergy (CMPA), particularly in regions where allergy services are not easily accessed or where community awareness for CMPA is low. [2] Since its introduction, CoMiSS has been translated into 14 languages and is used in 16 countries around the world. A pooled data analysis of three cross-sectional studies in children with CMPA confirmed that the CoMiSS score is useful in monitoring the response to treatment with hypoallergenic formula or a cow’s milk protein (CMP)-free elimination diet in infants and children with CMPA. [3]
It is important to highlight that CoMiSS was not designed as a diagnostic tool for CMPA and has not been validated for this purpose. [2] The published protocol outlines a prospective, single-blinded study which aims to assess the sensitivity and specificity of a change in CoMiSS score from baseline to 2 weeks after commencing a hypoallergenic diet, using a single-blinded oral food challenge (OFC) with cow’s milk-based formula as the diagnostic reference. [1] While a double-bli...
REPLY - CoMiSS validation study protocol
Letter to the Editor of BMJ Open - 8 August 2018
We thank MM Vanderschuren et al. for their interest in our published protocol for a validation study of the Cow’s Milk-related Symptom Score (CoMiSS®) [1] and would like to provide our reply to the concerns raised.
CoMiSS was designed in 2015 by a paediatric expert group in order to provide an easy-to-use tool to facilitate a greater awareness for cow’s milk protein allergy (CMPA), particularly in regions where allergy services are not easily accessed or where community awareness for CMPA is low. [2] Since its introduction, CoMiSS has been translated into 14 languages and is used in 16 countries around the world. A pooled data analysis of three cross-sectional studies in children with CMPA confirmed that the CoMiSS score is useful in monitoring the response to treatment with hypoallergenic formula or a cow’s milk protein (CMP)-free elimination diet in infants and children with CMPA. [3]
It is important to highlight that CoMiSS was not designed as a diagnostic tool for CMPA and has not been validated for this purpose. [2] The published protocol outlines a prospective, single-blinded study which aims to assess the sensitivity and specificity of a change in CoMiSS score from baseline to 2 weeks after commencing a hypoallergenic diet, using a single-blinded oral food challenge (OFC) with cow’s milk-based formula as the diagnostic reference. [1] While a double-blind, placebo-controlled food challenge (DBPCFC) is considered superior to an OFC [4], the difference in validity mainly applies to older children and adults where subjective symptoms are more prevalent. [5, 6] In infants under 2 years of age, an OFC based on objective symptoms and protocolised outcome criteria is an accepted approach which minimises the burden for infants. [7] A DBPCFC would require 2 challenges while not necessarily providing additional clinical accuracy in this age group. For example, in the EuroPrevall study of infants with probable CMPA a correct diagnosis of non-IgE-mediated CMPA was not adequately captured despite use of the DBPCFC in the diagnostic process. [8, 9] Weighing up these factors, we have opted to include an OFC in the current study design which is in line with current clinical guidelines. [7]
As any clinical tool, CoMiSS has its limitations. During the design process, several clinical conditions were deliberately not included. For example, rectal bleeding as a mono-symptomatic presentation was omitted as it should prompt an urgent paediatric assessment. Similarly, growth failure in early infancy requires a specialist referral for a more detailed assessment, and CoMiSS was not deemed useful in this scenario. Furthermore, as CoMiSS was not designed as a diagnostic tool it cannot provide a differential diagnosis between CMPA and other common paediatric conditions. However, it may prompt the primary health care provider to consider CMPA in the diagnostic process.
At the time of study conception, CoMiSS was already a widely used clinical tool and modifications of the score for the purposes of a validation study were not practical. The validation study was therefore designed to gain further insights into CoMiSS in its current form as a possible diagnostic tool, if interpreted in conjunction with the clinical response to a trial of a CMP-free elimination diet. The main hypothesis of the trial is that a significant fall in CoMiSS, in parallel with improved symptoms on a CMP-free diet, would support a diagnosis of CMPA. As a secondary endpoint, the usefulness of the baseline CoMiSS as a diagnostic marker for CMPA will also be assessed. Finally, the relative contribution of each individual score component in identifying infants with CMPA will be assessed. Once these data are available, informed decisions can be made on possible refinements and design modifications of the CoMiSS tool.
Authors:
1. Yvan Vandenplas, Vrije Unversiteit Brussel, Brussels, Belgium
2. Christophe Dupont, Université Paris Descartes, Paris, France
3. Philippe Eigenmann, University Hospitals of Geneva, Geneva, Switzerland
4. Arne Høst, Odense University Hospital, Odense, Denmark
5. Mikael Kuitunen, University of Helsinki, Helsinki, Finland
6. Carmen Ribes-Koninkx, La Fe University Hospital, Valencia, Spain
7. Neil Shah, Great Ormond Street Hospital for Children, London, United Kingdom
8. Hania Szajewska, The Medical University of Warsaw, Warsaw, Poland
9. Andrea von Berg, Marien-Hospital, Wesel, Germany
10. Ralf G Heine, Nestlé Health Science, Vevey, Switzerland
REFERENCES
1. Vandenplas Y, Mukherjee R, Dupont C, Eigenmann P, Høst A, Kuitunen M, Ribes-Koninkx C, Shah N, Szajewska H, von Berg A, Heine RG, Zhao ZY, on behalf the Chinese CoMiSS Investigator Team. Protocol for the validation of sensitivity and specificity of the Cow's Milk-related Symptom Score (CoMiSS) against open food challenge in a single-blinded, prospective, multicentre trial in infants. BMJ Open 2018;8:e019968.
2. Vandenplas Y, Dupont C, Eigenmann P, Host A, Kuitunen M, Ribes-Koninckx C, Shah N, Shamir R, Staiano A, Szajewska H, Von Berg A. A workshop report on the development of the Cow's Milk-related Symptom Score awareness tool for young children. Acta Paediatr 2015;104:334-9.
3. Vandenplas Y, Steenhout P, Järvi A, Garreau AS, Mukherjee R. Pooled Analysis of the Cow's Milk-related-Symptom-Score (CoMiSS) as a Predictor for Cow's Milk Related Symptoms. Pediatr Gastroenterol Hepatol Nutr 2017;20:22-26.
4. Sampson HA, Gerth van Wijk R, Bindslev-Jensen C, Sicherer S, Teuber SS, Burks AW, Dubois AE, Beyer K, Eigenmann PA, Spergel JM, Werfel T, Chinchilli VM. Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma & Immunology-European Academy of Allergy and Clinical Immunology PRACTALL consensus report. J Allergy Clin Immunol 2012;130:1260-74.
5. Koletzko S, Niggemann B, Arato A, Dias JA, Heuschkel R, Husby S, Mearin ML, Papadopoulou A, Ruemmele FM, Staiano A, Schäppi MG, Vandenplas Y, European Society of Pediatric Gastroenterology Hepatology and Nutrition. Diagnostic approach and management of cow's-milk protein allergy in infants and children: ESPGHAN GI Committee practical guidelines. J Pediatr Gastroenterol Nutr 2012;55:221-9.
6. Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Beyer K, Bindslev-Jensen C, Cardona V, Dubois A, duToit G, Eigenmann P, Fernandez Rivas M, Halken S, Hickstein L, Høst A, Knol E, Lack G, Marchisotto MJ, Niggemann B, Nwaru BI, Papadopoulos NG, Poulsen LK, Santos AF, Skypala I, Schoepfer A, Van Ree R, Venter C, Worm M, Vlieg-Boerstra B, Panesar S, de Silva D, Soares-Weiser K, Sheikh A, Ballmer-Weber BK, Nilsson C, de Jong NW, Akdis CA; EAACI Food Allergy and Anaphylaxis Guidelines Group. EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy. Allergy 2014;69:1008-25.
7. Fiocchi A, Brozek J, Schünemann H, Bahna SL, von Berg A, Beyer K, Bozzola M, Bradsher J, Compalati E, Ebisawa M, Guzman MA, Li H, Heine RG, Keith P, Lack G, Landi M, Martelli A, Rancé F, Sampson H, Stein A, Terracciano L, Vieths S. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines. World Allergy Organ J 2010;3:57-161.
8. Schoemaker AA, Sprikkelman AB, Grimshaw KE, Roberts G, Grabenhenrich L, Rosenfeld L, Siegert S, Dubakiene R, Rudzeviciene O, Reche M, Fiandor A, Papadopoulos NG, Malamitsi-Puchner A, Fiocchi A, Dahdah L, Sigurdardottir ST, Clausen M, Stanczyk-Przyluska A, Zeman K, Mills EN, McBride D, Keil T, Beyer K. Incidence and natural history of challenge-proven cow's milk allergy in European children - EuroPrevall birth cohort. Allergy 2015;70:963-72.
9. Koletzko S, Heine RG. Non-IgE mediated cow's milk allergy in EuroPrevall. Allergy 2015;70:1679-80.
In the south Brazilian city of Porto Alegre - where about 1.5 million people live – two primary care units added out-of-hours (OOH) services in March and April of 2017 to increase patient access, as described by Kelly et al(1,2). OOH appointments in these two facilities are offered from 6 to 10pm. Differently from the traditional primary care model in Brazil, in which units serve people living in a specific catchment area with pre-scheduled appointments, during OHH all patients are welcomed without the need for scheduling. Medical, nursing, and dental care, as well as immunizations, are offered.
In the first 14 months since the start of the program, we recorded 33,964 appointments in the two clinics during OOH. During the same period, 51,181 consultations were provided in the same two units during traditional hours (and about 1.7 million primary care consultations in the city). Even though women are the most frequent users of both daytime and OOH services, the proportion of men ( 35.5% vs. 32.4% during the day) and of people of working age (54.96% vs. 47,7% during the day) was higher in OOH vs. regular daytime services.
However, the most interesting aspect of OOH services is the high number of rapid testing for HIV, syphilis, and hepatitis performed during these extended hours: 3,868 tests during OOH vs. 3,405 tests during usual hours – or 11.3% of the overall appointments during OOH vs. 6.6% during regular hours. Since the regular shift lasts 11 hours (...
In the south Brazilian city of Porto Alegre - where about 1.5 million people live – two primary care units added out-of-hours (OOH) services in March and April of 2017 to increase patient access, as described by Kelly et al(1,2). OOH appointments in these two facilities are offered from 6 to 10pm. Differently from the traditional primary care model in Brazil, in which units serve people living in a specific catchment area with pre-scheduled appointments, during OHH all patients are welcomed without the need for scheduling. Medical, nursing, and dental care, as well as immunizations, are offered.
In the first 14 months since the start of the program, we recorded 33,964 appointments in the two clinics during OOH. During the same period, 51,181 consultations were provided in the same two units during traditional hours (and about 1.7 million primary care consultations in the city). Even though women are the most frequent users of both daytime and OOH services, the proportion of men ( 35.5% vs. 32.4% during the day) and of people of working age (54.96% vs. 47,7% during the day) was higher in OOH vs. regular daytime services.
However, the most interesting aspect of OOH services is the high number of rapid testing for HIV, syphilis, and hepatitis performed during these extended hours: 3,868 tests during OOH vs. 3,405 tests during usual hours – or 11.3% of the overall appointments during OOH vs. 6.6% during regular hours. Since the regular shift lasts 11 hours (from 7am to 6pm) and OOH lasts 4 hours, this also shows that rapid testing was performed twice as fast during OOH. Therefore, it seems that there is a specific demand for rapid testing during OOH, suggesting an important role of these extended hours managing communicable diseases, still a very serious problem in our country(3).
Another important difference is OOH resolvability. While in the traditional format the number of consultations that result in a referral to a medical specialty is on average 16.9%, in OOH this number is 10.64%.
As reported by Kelly et al.(1), implementation of the OOH strategy in Porto Alegre aimed to attract to the primary care setting those people who sought emergency departments without needing urgent care. Not many primary care facilities offer extended hours in Brazil, and thus we need to keep monitoring our OOH units. However, our goal is to have eight working OOH units (one per district of the municipality) by the year 2020 (a third unit was added in June 2018), increasing access and strengthening primary health care in our city.
References
1. Kelly SJ, Piercy H, Ibbotson R, Fowler Davis SV. Who attends out-of-hours general practice appointments? Analysis of a patient cohort accessing new out-of-hours units. BMJ Open. 2018 Jun 9;8(6):e020308. doi: 10.1136/bmjopen-2017-020308.
2. Harzheim E, Marchezan Júnior N, Pfeil JN, Molina-Bastos CG, Frank T, Nascimento DM, Sturmer PL. Extending primary care hours in Brazil as health policy [comment]. Available at https://www.bmj.com/content/357/bmj.j2142/rr
3. Souza MFM, França EB, Cavalcante A. Burden of disease and health situation analysis: results of the Global Burden of Disease (GBD) Brazil network. Rev Bras Epidemiol. 2017 May;20Suppl 01(Suppl 01):1-3. doi: 10.1590/1980-5497201700050001.
We have read with great interest the article “What insights do patients and caregivers have on acute kidney injury and post-hospitalisation care? A single-center qualitative study from Toronto, Canada” by Silver et al.
The article sheds light on the fact that most of its participants prioritised chronic conditions that ‘progress over time’ over AKI. These co-morbidities often include heart failure, hypertension and Type 2 diabetes mellitus, which are treated with non-steroidal anti-inflammatory drugs, diuretics and metformin respectively( 1). There is considerable data that these drugs are nephrotoxic and should therefore, be deprescribed or temporarily with-held or dose-adjusted in patients with AKI.
However, from unpublished research at our hospital, there is often reluctance to stop these drugs, suggesting that this misconception may be shared by physicians as well. As this is a common clinical problem with considerable morbidity, Think Kidneys Campaign (NHS collaboration of various trusts) have developed a checklist for medication optimization in patients with AKI (2), but its use is sparse at least from our experience.
Studies have shown that in-hospital mortality due to AKI far exceeds that due to these long-standing, chronic conditions. In a large nation-based study, in-hospital mortality of AKI was found to be 12.32% (3), with an increase in number of absolute deaths from 2001 to 2011. This is in contrast to the 3% in-...
We have read with great interest the article “What insights do patients and caregivers have on acute kidney injury and post-hospitalisation care? A single-center qualitative study from Toronto, Canada” by Silver et al.
The article sheds light on the fact that most of its participants prioritised chronic conditions that ‘progress over time’ over AKI. These co-morbidities often include heart failure, hypertension and Type 2 diabetes mellitus, which are treated with non-steroidal anti-inflammatory drugs, diuretics and metformin respectively( 1). There is considerable data that these drugs are nephrotoxic and should therefore, be deprescribed or temporarily with-held or dose-adjusted in patients with AKI.
However, from unpublished research at our hospital, there is often reluctance to stop these drugs, suggesting that this misconception may be shared by physicians as well. As this is a common clinical problem with considerable morbidity, Think Kidneys Campaign (NHS collaboration of various trusts) have developed a checklist for medication optimization in patients with AKI (2), but its use is sparse at least from our experience.
Studies have shown that in-hospital mortality due to AKI far exceeds that due to these long-standing, chronic conditions. In a large nation-based study, in-hospital mortality of AKI was found to be 12.32% (3), with an increase in number of absolute deaths from 2001 to 2011. This is in contrast to the 3% in-hospital mortality of T2DM (4). Hence, it only seems logical that immediate and effective treatment of AKI take precedence over treatment of chronic, stable conditions in the short-term.
In summary, we believe that the finding of your study that AKI is a ‘low-priority concern’ holds true not just for patients, but potentially also for physicians, and therefore, does have considerable consequences in terms of safe prescribing.
1. Farooqi S, Dickhout JG. Major comorbid disease processes associated with increased incidence of acute kidney injury. World Journal of Nephrology 2016; 5(2): 139–146.
2. Griffith K, Ashley C, Blakeman T, Fluck R, Lewington A, Selby N, et al. ‘Sick day’ guidance in patients at risk of Acute Kidney Injury: an Interim Position Statement from the Think Kidneys Board 2015.
3. Chertow GM, Burdick E, Honour M et al. Acute Kidney Injury, Mortality, Length of Stay, and Costs in Hospitalized Patients. Journal of the American Society of Nephrolog 2005; 16(11): 3365-3370
4. Hyperglycemia: An Independent Marker of In-Hospital Mortality in Patients with Undiagnosed Diabetes. The Journal of Clinical Endocrinology & Metabolism 2002, 87(3): 978–982
To the editor:
We read with interest the protocol for the validation of the Cow’s Milk-related Symptom Score (CoMiSS) against open food challenge by Vandenplas et al.(1) They have proposed this symptom score as a resource for primary healthcare providers, aiming to increase awareness of cow’s milk allergy (CMA)-related symptoms to facilitate an earlier diagnosis. The score was developed to increase awareness of mainly non-IgE mediated CMA, a disorder of increasing interest in recent literature publications.(2,3) However, dysmotility, dysmotility-related symptoms, blood in stool and failure to thrive (weight ≤2.5 Z-scores, drift from growth curve of >2 percentiles over 6 months or weight-for-length -2 Z-scores)(4) are excluded from the score. These are considered key features in non-IgE mediated allergy.(5) In contrast, severe respiratory symptoms and urticaria are included in the score. In our opinion, using the CoMiSS for diagnosing CMA will therefore hamper diagnosing non-IgE mediated CMA. The authors stress that the design of this study might not enable a reliable distinguishment between IgE-mediated CMA, non-IgE mediated CMA and non-allergic cow’s milk-related symptoms. In addition, in our experience we believe that healthcare professionals might even get confused in the differential diagnosis regarding non-allergic cow’s milk-related symptoms. For example pyloric stenosis, gastroesophageal reflux disease, hemorrhagic disease of the newborn or infective gastro...
To the editor:
We read with interest the protocol for the validation of the Cow’s Milk-related Symptom Score (CoMiSS) against open food challenge by Vandenplas et al.(1) They have proposed this symptom score as a resource for primary healthcare providers, aiming to increase awareness of cow’s milk allergy (CMA)-related symptoms to facilitate an earlier diagnosis. The score was developed to increase awareness of mainly non-IgE mediated CMA, a disorder of increasing interest in recent literature publications.(2,3) However, dysmotility, dysmotility-related symptoms, blood in stool and failure to thrive (weight ≤2.5 Z-scores, drift from growth curve of >2 percentiles over 6 months or weight-for-length -2 Z-scores)(4) are excluded from the score. These are considered key features in non-IgE mediated allergy.(5) In contrast, severe respiratory symptoms and urticaria are included in the score. In our opinion, using the CoMiSS for diagnosing CMA will therefore hamper diagnosing non-IgE mediated CMA. The authors stress that the design of this study might not enable a reliable distinguishment between IgE-mediated CMA, non-IgE mediated CMA and non-allergic cow’s milk-related symptoms. In addition, in our experience we believe that healthcare professionals might even get confused in the differential diagnosis regarding non-allergic cow’s milk-related symptoms. For example pyloric stenosis, gastroesophageal reflux disease, hemorrhagic disease of the newborn or infective gastroenteritis all of which cannot be distinguished by this current published score.
The authors indicate that they based the trial design on current best clinical practice. That is, in their opinion, a cow’s milk protein-free elimination diet followed by an open food challenge (OFC).(6) However, in current clinical guidelines, double blind placebo controlled challenges (DBPCFC) are considered the gold standard to prove or exclude allergy.(5,7,8) Although the authors point out this limitation themselves, it remains unclear why the OFC was chosen over the DBPCFC. To solve this, they single-blinded the study so OFC and CoMiSS results will not be determined by the same investigator. This, however, causes a substantial risk of inter-observer variability, especially regarding atopic dermatitis.(9) Since the primary study objective is to validate the difference in CoMiSS before and after treatment with an amino-acid based formula against the OFC as a predictor of CMA, this inter-observer variability is undesirable. Of further importance, the score will not be validated against the gold standard DBPCFC. The secondary study objectives are to determine the sensitivity and specificity of the change in CoMiSS and to investigate whether the CoMiSS at baseline can predict the OFC outcome. Since the primary objective is to validate the score to the OFC outcome, it seems contradictory to investigate whether the score can predict the OFC outcome as a secondary objective.
We congratulate the authors in their development of a symptom score as a clinical resource for primary healthcare providers in this allergic disorder of infancy and childhood. However, the symptom score appears to have been validated in paediatric departments in secondary and tertiary care institutions against an inadequate reference standard. The primary healthcare providers should be educated, not only in paediatrics and allergy, but also in using the score, and be able to subsequently educate the patients’ parents. The eventual conversion of these results to primary healthcare and the possible increased awareness of non-IgE mediated CMA therefore remain major sources of concern and perhaps further development of this symptom score is required.
References
1. Vandenplas, Y. et al. Protocol for the validation of sensitivity and specificity of the Cow’ s Milk-related Symptom Score (CoMiSS) against open food challenge in a single-blinded, prospective, multicentre trial in infants. BMJ Open 8, (2018).
2. Candy, D. C. A. et al. A synbiotic-containing amino acid-based formula improves gut microbiota in non-IgE-mediated allergic infants. Pediatr. Res. 0, 1–10 (2017).
3. Berni Canani, R. et al. Formula selection for management of children with cow’s milk allergy influences the rate of acquisition of tolerance: A prospective multicenter study. J. Pediatr. 163, 771–777.e1 (2013).
4. van den Elzen, A., Sibbles, B. & Niewenhuis, E. Failure to thrive: van symptoom naar diagnose. Prakt. Pediatr. 48–52 (2007).
5. Venter, C. et al. Better recognition, diagnosis and management of non-IgE-mediated cow’s milk allergy in infancy: iMAP—an international interpretation of the MAP (Milk Allergy in Primary Care) guideline. Clin. Transl. Allergy 7, 26 (2017).
6. Koletzko, S. et al. Diagnostic Approach and Management of Cowʼs-Milk Protein Allergy in Infants and Children. J. Pediatr. Gastroenterol. Nutr. 55, 221–229 (2012).
7. Muraro, a. et al. EAACI Food Allergy and Anaphylaxis Guidelines: Diagnosis and management of food allergy. Allergy Eur. J. Allergy Clin. Immunol. 69, 1008–1025 (2014).
8. Richtlijn Diagnostiek van Koemelkallergie bij Kinderen in Nederland. NVK (2012).
9. Schmitt, J. et al. Assessment of clinical signs of atopic dermatitis: A systematic review and recommendation. J. Allergy Clin. Immunol. 132, 1337–1347 (2013).
The difference in levels of sugar in very similar foods that this study has revealed is shocking, but it does show that if one manufacturer can reduce sugar levels in their products, then it is possible for other manufacturers to do the same. We now need the government to take stronger action and make it compulsory for food manufacturers and retailers to reduce sugar levels in their products. Eating too much sugar leads to overweight and obesity, which our latest cancer prevention report shows is a cause of 12 different types of cancer. Healthy lifestyle patterns depend not only on individual choices but also on governments creating an environment that encourages people to eat healthily and do more exercise. WCRF calls on the government to prioritise cancer prevention through the development and implementation of effective policies to address the rising burden of obesity and cancer in the UK.
Gill Rapley makes some useful points about our recent paper (Daniels, L., Taylor, R.W., Williams, S.M., Gibson, R.S., Fleming, E.A., Wheeler, B.J., Taylor, B.J., Haszard, J.J. and Heath, A-L.M. (2018) Impact of a modified version of baby-led weaning on iron intake and status: a randomised controlled trial, BMJ Open, 8: e019036).
In particular, she points out that:
(a) While our Baby-Led Introduction to Solids (BLISS) intervention group was given specific advice on increasing iron intake, the Control group received only standard care.
(b) It is not clear whether the infants in the BLISS group would have had equivalent iron status to that of the Controls even without the additional advice.
(c) Infants following a traditional approach to infant feeding may also need advice to improve their iron intake, particularly now that complementary feeding should ideally be delayed to 6 months of age.
There are many interesting questions that can be asked about baby-led approaches to complementary feeding, and their impact on infant nutrient status. Each of these questions would need a different study design. In our case, we were interested in answering the pragmatic question – Is it possible to follow a baby-led approach to infant feeding instead of traditional feeding without negatively impacting on iron status? This required that we have an intervention group (our BLISS group) and a group representing the status quo, i.e. what is happening in the commu...
Gill Rapley makes some useful points about our recent paper (Daniels, L., Taylor, R.W., Williams, S.M., Gibson, R.S., Fleming, E.A., Wheeler, B.J., Taylor, B.J., Haszard, J.J. and Heath, A-L.M. (2018) Impact of a modified version of baby-led weaning on iron intake and status: a randomised controlled trial, BMJ Open, 8: e019036).
In particular, she points out that:
(a) While our Baby-Led Introduction to Solids (BLISS) intervention group was given specific advice on increasing iron intake, the Control group received only standard care.
(b) It is not clear whether the infants in the BLISS group would have had equivalent iron status to that of the Controls even without the additional advice.
(c) Infants following a traditional approach to infant feeding may also need advice to improve their iron intake, particularly now that complementary feeding should ideally be delayed to 6 months of age.
There are many interesting questions that can be asked about baby-led approaches to complementary feeding, and their impact on infant nutrient status. Each of these questions would need a different study design. In our case, we were interested in answering the pragmatic question – Is it possible to follow a baby-led approach to infant feeding instead of traditional feeding without negatively impacting on iron status? This required that we have an intervention group (our BLISS group) and a group representing the status quo, i.e. what is happening in the community without any intervention on our part (the Control group). This meant that the Control group needed to receive only the standard care currently offered to New Zealand families.
Dr Rapley is correct in saying that we do not know whether iron status would have been the same in the baby-led infants without our iron intervention. There are, however, some reasons to believe that it is likely their iron status would have been lower. In our earlier, small, observational study of Baby-Led Weaning (BLW), infants following unmodified BLW had significantly lower intakes of iron than their traditionally fed counterparts (Morison BJ, Taylor RW, Haszard JJ, Schramm CJ, Williams Erickson L, Fangupo LJ, Fleming EA, Luciano A, Heath A-LM (2016). How different are Baby-Led Weaning and conventional complementary feeding? A cross-sectional study of infants 6-8 months. BMJ Open 6:e010665). Also, BLISS infants were consuming more iron in the BLISS study than the BLW infants were in the earlier study. We do, however, agree that there is an urgent need to investigate iron status in infants following unmodified BLW. This study is needed so that we can determine whether it is necessary to roll out the intervention used in the BLISS study for parents following BLW.
The government-funded standard Well Child care provided to all New Zealand infants (including those in the BLISS study) includes advice on offering puréed sources of iron at six months – particularly iron-fortified infant cereal and red meat. Our two main approaches for increasing iron intake in the infants following BLISS were: specific advice on ways to offer iron-fortified infant cereal and red meat as handheld foods (i.e. making the standard Well Child advice feasible for infant self-feeding), and offering an iron-rich food with each meal. While one of our approaches was, therefore, a baby-led equivalent of current advice for the spoonfed infant, we would also be very interested to see whether encouraging parents to offer their traditionally spoonfed infant an iron-rich food with each meal would help improve their iron status. After all, 74% of the Control, as well as BLISS, infants had inadequate iron intakes at 7 months.
บทคัดย่อ
Show Moreบทนำ การใช้ยาปฏิชีวนะในประเทศที่มีรายได้น้อยและปานกลางยังคงเพิ่มขึ้นถึงแม้จะทราบว่าการใช้ยาปฏิชีวนะมากเกินไปอาจทำให้เกิดความดื้อยาปฏิชีวนะได้ ซึ่งข้อมูลรายละเอียดเหล่านี้มีความเกี่ยวข้องกับการใช้ยาปฏิชีวนะในหน่วยบริการปฐมภูมิที่มีอยู่อย่าง จำกัด
วัตถุประสงค์ อธิบายถึงอาการและอาการแสดงของการติดเชื้อเฉียบพลันและข้อบ่งชี้สำหรับการสั่งยาปฏิชีวนะ
รูปแบบการศึกษา การทบทวนข้อมูลที่เก็บเป็นประจำย้อนหลัง 2 ปี
ขอบเขตการศึกษา หน่วยบริการปฐมภูมิทั้งหมด 32 แห่งในอำเภอแห่งหนึ่ง ของภาคเหนือ ประเทศไทย
ผู้เข้าร่วมการศึกษา ผู้ป่วยที่เข้ารับการบริการหน่วยปฐมภูมิที่มีประวัติไข้ มีการบันทึกอุณหภูมิ และระบุ ICD 10 สำหรับการติดเชื้อหรือการสั่งยาปฏิชีวนะในระบบโดยไม่รวมผู้ป่วยที่เข้าร่วมทำการศึกษาเกี่ยวกับการทดสอบ C-reactive protein ใน หน่วยปฐมภูมิ 4 แห่ง
ผลลัพธ์ที่ได้ คือ สัดส่วนของผู้ป่วยที่ได้รับยาปฏิชีวนะและความถี่ของอาการและอาการแสดงทางคลินิก
ผู้ป่วยที่เข้ารับการรักษาที่หน่วยบริการสุขภาพ 762,868 คน ซึ่งอยู่ในเกณฑ์การคัดเลือก จำนวน 103,196 ราย และไม่เข้าเกณฑ์จำนวน 5,966 รายทำให้เหลือจำนวนผู้ป่วย 97,230 ราย ประกอบด้วย 83,661 ครั้งที่มีการเจ็บป่วย
ผู้ป่วย 46.9% (39,242 ราย) ได้รับยาปฏิชีวนะในช่วงป่วย ซึ่งค่าดัชนีของการใช้ยาปฏิชีวนะในการวิเคราะห์ถดถอยโลจิสติก ในหลายตัวแปร ได้แก่ เพศชาย(aOR 1.21 [CI 1.16-1.28], p <0.001), ผู้ใหญ่ (aOR 1.77 [CI 1.57-2, p <0.001]) และอุณหภูมิ> 37.5 องศาเซลเซียส (aOR 1.24 [CI 1.03-1.48, p 0.020]) 77.9% ของการศึกษานี้ แสดงให้เห็นถึง ความสัมพันธ์กับโรคระบบทางเดินหายใจ ซึ่ง 98.6% เป็นการติดเชื้อทางเดิ...
In the study of Huang C, et al. on BMJ Open 2018;8:e018070. doi:10.1136/bmjopen-2017-018070: “ MicroRNA-17 and the prognosis of human carcinomas: a systematic review and meta-analysis” the manuscript from Robaina et al. entitled “miR-17-92 cluster components analysis in Burkitt lymphoma: overexpression of miR-17 is associated with poor prognosis. Ann Hematol 2016;95:881–91.” was mentioned (citation number 38). We would like to point out some mistakes regarding the citation of our study as below:
1.Table 1 on page 4, the assay performed in our study was quantitative RT-PCR (q-PCR) instead of ISH assay as described on the table 1 and 2 of the Huang et al. publication. The same mistake is observed on the figure 3 C.
2. Discussion on page 7: The sentence: In the subgroup analysis, we found that the potential heterogeneity may have originated from the Caucasian group in the study conducted by Robaina et al.38 Unlike the commonly used RT-PCR, ISH technique was used to detect miR-17 .
There is a great misunderstanding on this sentence. Neither our Brazilian patients were classified by race as " Caucasian ", nor the analysis of miR-17 expression levels in our study was performed by ISH. All the assays were performed by qRT-PCR.
It is important to mention that the term " Caucasian " is not applied in Brazilian for race/ethnicity classification. The Brazilian population is formed by extensive admixture from three different ances...
Show MoreIt would be satisfying if all papers gave a summary of the part played by PPI in the work. It is clear that they do not, despite it being editorial policy to seek it. We may conclude that either PPI does not occur to the extent foreseen, or that the authors do not rate it highly reportable in comparison to the rest of the content. Given the increased requirement to build PPI into grant applications, it seems likely that it is the second scenario that is predominant, and this leads to a consideration of the authors' motivation in writing. Ideally, the prime mover would be the altruism of wishing to get knowledge or a change in practice into the public arena, where it will have the greatest chance of creating patient benefit. Then would come the personal spur of academic reputation and all that follows from that. Maybe an up-coming REF exercise is being thought about in some cases. Whatever these motivations are, PPI appears to have no place among them, except that good manners require it should be acknowledged, along with other help received. If reporting PPI has no discernible utility, it will not generally happen without an enforceable requirement.
Dear Editor,
We agree with Shah et al. that caring for patients with acute kidney injury (AKI) is complicated, particularly when it comes to medication management (1). It is important to remember that AKI is a heterogenous condition with multiple etiologies and different degrees of severity. In some cases then, prioritization of other chronic diseases over AKI may be reasonable and even beneficial for patients.
On this background, we would caution against the conclusion that physicians view AKI as a low priority concern. More qualitative research is needed first to understand physician experiences with AKI during both the inpatient and outpatient setting. This information is necessary to develop and support the use of quality improvement tools for patients with AKI, such as the medication checklists referenced by Shah et al (2).
References:
1. Phipps DL, Morris RL, Blakeman T, Ashcroft DM. What is involved in medicines management across care boundaries? A qualitative study of healthcare practitioners' experiences in the case of acute kidney injury. BMJ Open 2017;7:e011765.
2. Griffith K, Ashley C, Blakeman T, Fluck R, Lewington A, Selby N, et al. ‘Sick day’ guidance in patients at risk of Acute Kidney Injury: An Interim Position Statement from the Think Kidneys Board 2015.
REPLY - CoMiSS validation study protocol
Letter to the Editor of BMJ Open - 8 August 2018
We thank MM Vanderschuren et al. for their interest in our published protocol for a validation study of the Cow’s Milk-related Symptom Score (CoMiSS®) [1] and would like to provide our reply to the concerns raised.
Show MoreCoMiSS was designed in 2015 by a paediatric expert group in order to provide an easy-to-use tool to facilitate a greater awareness for cow’s milk protein allergy (CMPA), particularly in regions where allergy services are not easily accessed or where community awareness for CMPA is low. [2] Since its introduction, CoMiSS has been translated into 14 languages and is used in 16 countries around the world. A pooled data analysis of three cross-sectional studies in children with CMPA confirmed that the CoMiSS score is useful in monitoring the response to treatment with hypoallergenic formula or a cow’s milk protein (CMP)-free elimination diet in infants and children with CMPA. [3]
It is important to highlight that CoMiSS was not designed as a diagnostic tool for CMPA and has not been validated for this purpose. [2] The published protocol outlines a prospective, single-blinded study which aims to assess the sensitivity and specificity of a change in CoMiSS score from baseline to 2 weeks after commencing a hypoallergenic diet, using a single-blinded oral food challenge (OFC) with cow’s milk-based formula as the diagnostic reference. [1] While a double-bli...
In the south Brazilian city of Porto Alegre - where about 1.5 million people live – two primary care units added out-of-hours (OOH) services in March and April of 2017 to increase patient access, as described by Kelly et al(1,2). OOH appointments in these two facilities are offered from 6 to 10pm. Differently from the traditional primary care model in Brazil, in which units serve people living in a specific catchment area with pre-scheduled appointments, during OHH all patients are welcomed without the need for scheduling. Medical, nursing, and dental care, as well as immunizations, are offered.
In the first 14 months since the start of the program, we recorded 33,964 appointments in the two clinics during OOH. During the same period, 51,181 consultations were provided in the same two units during traditional hours (and about 1.7 million primary care consultations in the city). Even though women are the most frequent users of both daytime and OOH services, the proportion of men ( 35.5% vs. 32.4% during the day) and of people of working age (54.96% vs. 47,7% during the day) was higher in OOH vs. regular daytime services.
However, the most interesting aspect of OOH services is the high number of rapid testing for HIV, syphilis, and hepatitis performed during these extended hours: 3,868 tests during OOH vs. 3,405 tests during usual hours – or 11.3% of the overall appointments during OOH vs. 6.6% during regular hours. Since the regular shift lasts 11 hours (...
Show MoreDear Editor,
We have read with great interest the article “What insights do patients and caregivers have on acute kidney injury and post-hospitalisation care? A single-center qualitative study from Toronto, Canada” by Silver et al.
The article sheds light on the fact that most of its participants prioritised chronic conditions that ‘progress over time’ over AKI. These co-morbidities often include heart failure, hypertension and Type 2 diabetes mellitus, which are treated with non-steroidal anti-inflammatory drugs, diuretics and metformin respectively( 1). There is considerable data that these drugs are nephrotoxic and should therefore, be deprescribed or temporarily with-held or dose-adjusted in patients with AKI.
However, from unpublished research at our hospital, there is often reluctance to stop these drugs, suggesting that this misconception may be shared by physicians as well. As this is a common clinical problem with considerable morbidity, Think Kidneys Campaign (NHS collaboration of various trusts) have developed a checklist for medication optimization in patients with AKI (2), but its use is sparse at least from our experience.
Studies have shown that in-hospital mortality due to AKI far exceeds that due to these long-standing, chronic conditions. In a large nation-based study, in-hospital mortality of AKI was found to be 12.32% (3), with an increase in number of absolute deaths from 2001 to 2011. This is in contrast to the 3% in-...
Show MoreTo the editor:
Show MoreWe read with interest the protocol for the validation of the Cow’s Milk-related Symptom Score (CoMiSS) against open food challenge by Vandenplas et al.(1) They have proposed this symptom score as a resource for primary healthcare providers, aiming to increase awareness of cow’s milk allergy (CMA)-related symptoms to facilitate an earlier diagnosis. The score was developed to increase awareness of mainly non-IgE mediated CMA, a disorder of increasing interest in recent literature publications.(2,3) However, dysmotility, dysmotility-related symptoms, blood in stool and failure to thrive (weight ≤2.5 Z-scores, drift from growth curve of >2 percentiles over 6 months or weight-for-length -2 Z-scores)(4) are excluded from the score. These are considered key features in non-IgE mediated allergy.(5) In contrast, severe respiratory symptoms and urticaria are included in the score. In our opinion, using the CoMiSS for diagnosing CMA will therefore hamper diagnosing non-IgE mediated CMA. The authors stress that the design of this study might not enable a reliable distinguishment between IgE-mediated CMA, non-IgE mediated CMA and non-allergic cow’s milk-related symptoms. In addition, in our experience we believe that healthcare professionals might even get confused in the differential diagnosis regarding non-allergic cow’s milk-related symptoms. For example pyloric stenosis, gastroesophageal reflux disease, hemorrhagic disease of the newborn or infective gastro...
The difference in levels of sugar in very similar foods that this study has revealed is shocking, but it does show that if one manufacturer can reduce sugar levels in their products, then it is possible for other manufacturers to do the same. We now need the government to take stronger action and make it compulsory for food manufacturers and retailers to reduce sugar levels in their products. Eating too much sugar leads to overweight and obesity, which our latest cancer prevention report shows is a cause of 12 different types of cancer. Healthy lifestyle patterns depend not only on individual choices but also on governments creating an environment that encourages people to eat healthily and do more exercise. WCRF calls on the government to prioritise cancer prevention through the development and implementation of effective policies to address the rising burden of obesity and cancer in the UK.
Gill Rapley makes some useful points about our recent paper (Daniels, L., Taylor, R.W., Williams, S.M., Gibson, R.S., Fleming, E.A., Wheeler, B.J., Taylor, B.J., Haszard, J.J. and Heath, A-L.M. (2018) Impact of a modified version of baby-led weaning on iron intake and status: a randomised controlled trial, BMJ Open, 8: e019036).
In particular, she points out that:
(a) While our Baby-Led Introduction to Solids (BLISS) intervention group was given specific advice on increasing iron intake, the Control group received only standard care.
(b) It is not clear whether the infants in the BLISS group would have had equivalent iron status to that of the Controls even without the additional advice.
(c) Infants following a traditional approach to infant feeding may also need advice to improve their iron intake, particularly now that complementary feeding should ideally be delayed to 6 months of age.
There are many interesting questions that can be asked about baby-led approaches to complementary feeding, and their impact on infant nutrient status. Each of these questions would need a different study design. In our case, we were interested in answering the pragmatic question – Is it possible to follow a baby-led approach to infant feeding instead of traditional feeding without negatively impacting on iron status? This required that we have an intervention group (our BLISS group) and a group representing the status quo, i.e. what is happening in the commu...
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