Displaying 11-20 letters out of 408 published
I would like to make a correction to the funding list on our recently published paper "Association of 12 h shifts and nurses' job satisfaction, burnout and intention to leave: findings from a cross- sectional study of 12 European countries"
The correct list should be:
European Union's Seventh Framework Programme (FP7/2007-2013, grant agreement no. 223468; WS and LHA), National Institute of Nursing Research, National Institutes of Health (R01NR04513; LHA), the Norwegian Nurses Organisation and the Norwegian Knowledge Centre for the Health Services (IMH), Swedish Association of Health Professionals, the regional agreement on medical training and clinical research between Stockholm County Council and Karolinska Institutet, Committee for Health and Caring Sciences and Strategic Research Program in Care Sciences at Karolinska Institutet (CT), Spanish Ministry of Science and Innovation (FIS PI080599; TM-C). The current research was part funded by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care (NIHR CLAHRC). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.
Conflict of Interest:
Lack of transparency
In their article, Milliken et al point to the absence of transparency in the pan-Canadian Pharmaceutical Alliance (pCPA). However, their analysis also lacks clarity. First, they do not provide details of the drugs included in their pre-pCPA group so that it is impossible to assess whether they are comparing apples with oranges, which is a common failing of before/after study designs.
A second and more important lack of transparency results from aggregating drugs given full listing status with those that received coverage subject to special criteria. Unless a drug is a 'me-too' product joining a class of drugs that already has full coverage (e.g. Lodalis in Milliken et al's Appendix 1), almost all drugs selected for listing only receive financial coverage subject to specific clinical conditions (a situation that applies to all the other drugs in Appendix 1). If the access conditions are well designed with the participation of all appropriate stakeholders, they allow a new drug to be targeted to patients most likely to receive benefit.
However, access criteria are often not established with input from physicians and patients and, as a result, few patients are eligible for insurance coverage under the respective provincial government plan. All too often this situation occurs with expensive new drugs for rare disorders. For example, Kuvan for phenylketonuria in Milliken et al's Appendix 1, which is now listed in the Ontario and Saskatchewan drug plans, has access criteria that are extremely restrictive and not evidence -based and no patient has yet to meet the criteria. Thus, provinces may 'list' a drug as having restrictive coverage, but this does not necessarily equate with patient access. Future analyses need to separate drugs with restricted access from those with full coverage.
As Milliken et al note, the pCPA needs to improve the transparency of its policies, processes, decisions, criteria and timelines. The pCPA does not have its own website, just a page on the site used by Canada's provincial premiers to communicate a variety of issues to their constituents. The premiers report that pCPA negotiations have 'resulted in over $315 million in combined savings annually'. It is not known where these savings go. They should be used to improve provincial drug plan access, especially access to drugs for rare disorders.
1. Milliken D, Venkatesh J, Yu R, et al. Comparison of drug coverage in Canada before and after the establishment of the pan-Canadian Pharmaceutical Alliance. BMJ Open 2015; 5:e008100.
2. Update: what's happening with Ontario's Interim Funding for eculizumab. Brampton, ON: aHUS Canada, 2015. Available online at: http://www.ahuscanada.org/update- whats-happening-with-ontarios-interim-funding-for-eculizumab (Last accessed 25th September 2015).
3. Adams J. No patient access to only drug for PKU: have government drug plans been ignoring CDR? Poster presentation, Canadian Agency for Drugs and Technologies in Health Symposium, Saskatoon, April 2015.
4. Rawson NSB. Access delayed, transparency denied. Vancouver: Fraser Institute, 2014. Available online at: http://www.fraserinstitute.org/article/access- delayed-transparency-denied (Last accessed 25th September 2015).
5. The pan-Canadian Pharmaceutical Alliance. Ottawa: Council of the Federation Secretariat, 2015. Available online at: http://www.pmprovincesterritoires.ca/en/initiatives/358-pan-canadian- pharmaceutical-alliance. (Last accessed 25th September 2015).
Conflict of Interest:
Re:Harmful consumption of alcohol among people aged 50 or over in England
Martin Frisher in his letter 'Harmful consumption of alcohol among people aged 50 or over in England' (http://bmjopen.bmj.com/content/5/7/e007684.abstract/reply#bmjopen_el_9271) in response to my article 'Socioeconomic determinants of risk of harmful alcohol drinking among people aged 50 or over in England' (http://bmjopen.bmj.com/content/5/7/e007684.full) notes that in a careful study published shortly after mine (http://www.biomedcentral.com/1471- 2458/15/703), he and his co-authors failed to find any significant association between any pattern of current alcohol consumption and poor self-rated health, implicitly casting doubt about the usefulness of guidelines and recommendations regarding limits, and categorisations often used in academic and non-academic literature including 'harmful', 'hazardous', or 'sensible' drinking. Frisher cites an official document published in 1995 by the UK Government (Department of Health) when acknowledging that 'harmful' drinking is defined in relation to a given threshold. This is still the case: the former Coalition government published what to this day is the latest official policy paper on the topic: '2010 to 2015 government policy: harmful drinking', first published in 2013 but updated in May 2015. In that document, 'harmful drinking' is defined in terms of daily alcohol units consumed. Furthermore, as also detailed in my paper, NICE (the National Institute for Health and Care Excellence) also defines risk in relation to units. Nevertheless, in my paper, I also mention that resorting to a fixed number of units is not without problems but explain that I have adopted it because one of the objectives of the paper was to influence 'policymakers and practitioners in England who have to follow NICE guidelines' (p.4). Regarding Frisher et al's main result, that 'there were no drinking profiles associated with significantly higher rates of poor self-rated health relative to occasional drinkers', I do not see it as a contradiction with or a refutation of the results reported in my paper. An informative result in itself, it may as well suggest that self-rated health status does not necessarily reflect either risk or the actual presence of a health condition. That is, the risk or the harm may be present but is not captured by self-reported levels of health status. This is not new. Just to mention one example, Fink et al (http://onlinelibrary.wiley.com/doi/10.1046/j.1532-5415.2002.50467.x/pdf) reported that in their sample only 17 per cent of people aged 65 or over reported fair or poor subjective health, whilst one hundred percent of them had at least one morbidity potentially caused or worsened by alcohol use. I would encourage Frisher's team and other researchers to look into longitudinal effects of alcohol consumption above different thresholds on health conditions, not just on self-reported health.
Conflict of Interest:
There is a small mistake in the abstract of this manuscript.
The hazards ratios (HR) for mortality in the abstract are not consistent with the result section and Table 5. The correct sentence would be:
Mortality of UBC was not increased for patients with either type 1 (HR = 0.79 (95% CI 0.32 to 1.94)) or type 2 diabetes (HR = 1.05 (95% CI 0.83 to 1.33)).
Conflict of Interest:
Mistaken EquationEquation 2 that describes the change in the pure tone average of 2000, 3000, and 4000 Hz appears to be mistaken. The correct equation should be Women: PTA234 = (0.0002222*(Age.^3)) - (0.02262*(Age.^2)) + (0.9563*Age) - 10.99; The quadratic coefficient as published "-0.0262" yields a curve that does not fit the Annex B4 ISO 1999:2013 data.
Conflict of Interest:
Assessing knowledge and attitudes regarding HPV vaccination among those who have never heard of it
This article by Cunningham et al. on cervical cancer screening and HPV vaccine acceptability is a large population based study that collected self-reported responses - the authors mentioned the same as a study limitation. However, by detailed reading of Table 4, it appears that respondents who had not heard of the HPV vaccine were asked about attitudinal questions like 'willing to definitely accept the HPV vaccine', 'believes husband/partner will definitely accept HPV vaccine', 'believes family/friends will support the HPV vaccine', 'believes they are able to access a clinic/doctor for vaccination', 'believes vaccines are beneficial', 'willing to pay for vaccines', etc. Response against these questions are invalid. Therefore the interpretation of Table 4 is erroneous. Moreover these responses are going to introduce various biases, such as yes saying bias, faking bad bias, faking good bias, etc. All these were not mentioned in the study. Further examination of the study tool, i.e. the interview schedule will confirm the validity of this study.
Conflict of Interest:
Publication in BMJ Open: Onakpoya IJ, et al. BMJ Open 2015;5:e007199 - Inaccurate information and Comment
We read this article with great interest and would like to congratulate the authors on conducting an evidence based study on effectiveness, safety and cost of orphan medicinal products. Laboratoires CTRS is a pharmaceutical company specialising in orphan medicinal products.
We would like to correct certain inaccurate information within this article concerning Laboratoires CTRS' medicinal product Orphacol (cholic acid):
- In the Appendix 1, Orphacol is not listed as an approved medicinal product, although it is licensed since 12 September 2013.
- In the same table, a different medicinal product containing cholic acid, i.e., Cholic acid FGK, is listed. However, the reference associated with that product (number 13) concerns Orphacol.
- In the Appendix 2 table, Orphacol is listed with a wrong indication. Orphacol is approved for the treatment of inborn errors in primary bile acid synthesis due to 3beta-Hydroxy-delta5-C27-steroid oxidoreductase deficiency or delta4-3-Oxosteroid-5beta-reductase deficiency in infants, children and adolescents aged 1 month to 18 years and adults. In addition, the "Summary of main results" is very unclear, as the evaluated parameter is not specified.
- We note that the marketing authorisation for Cholic acid FGK (renamed to Kolbam) has recently been withdrawn following a judgement of the General Court of the European Union.
We would like to take this opportunity to comment on two main aspects of this article, i.e. the level of evidence available for very rare conditions and the treatment cost, from the specific perspective of Orphacol.
The diseases treated by Orphacol are extremely rare: In the United Kingdom, there are a total of 8 to 10 patients and in the European Union, we estimate that there are about 90 patients with 3beta-Hydroxy-delta5-C27 -steroid oxidoreductase deficiency and 15 patients with delta4-3- Oxosteroid-5beta-reductase deficiency. The treatment with cholic acid had been established as effective and safe in over 15 years of clinical use at the time of application for marketing authorisation. While the extremely small patient numbers already make the conduct of any clinical study very challenging, a controlled clinical trial would be unethical as withholding the effective cholic acid treatment exposes patients to a risk of liver damage or even death.
In this context, which is common for ultra-orphan conditions such as those treated by Orphacol, applying a "one size fits all" application of OCEBM and GRADE criteria for the assessment of clinical evidence is not meaningful. The Orphacol marketing authorisation application included data on each of the approximately 60 patients identifiable and described in the literature, and detailed treatment data (albeit not from a prospective clinical study) for 15 of them. The treatment effects were strong and highly consistent, demonstrating that cholic acid treatment changed the patients' prognosis from a certain need for a liver transplantation to a completely normal life. We believe that within the context of the disease, the quality and strength of the overall body of evidence for Orphacol was as strong as it could possibly be. The French Health Technology Assessment body (the Commission de la Transparence at the Haute Autorite de la Sante) has notably shared this approach as well as conclusion and has recognised Orphacol as a major improvement of patient care. In addition, the reputable journal Prescrire, specialised in the evaluation of medicinal products, did the same and has declared Orphacol a major therapeutic progress.
The article cites the cost of orphan medicinal products for which similar generic or unlicensed drugs (known as "Specials" in the UK) exist (see Figure 5 and related paragraphs). It must not be surprising that unlicensed medicines are cheaper as compared with the licensed medicines as the EU marketing authorisation obligatory for designated orphan medicinal products come with substantial obligations, designed to safeguard patient safety, for the licence holder. In addition, there is a significant cost associated with the licensing process itself. Orphacol is an example of an ultra-orphan medicinal product for which unlicensed versions exist or have existed. Laboratoires CTRS does not claim Orphacol's price to be justified by research and development costs, as the application for Orphacol was based on literature data. The price differential is rather justified by the costs of producing extremely small volumes of a medicinal product that complies with the applicable rules of Good Manufacturing Practice; of complying with the post-approval obligation of maintaining a treatment database including all patients treated with Orphacol; and of the applicable pharmacovigilance obligations. In particular the obligations related to pharmacovigilance are very onerous, as they apply within the entire European Union, irrespective of the existence of patients affected in any given member state or of whether the medicinal product is marketed. The resulting aggregate costs can only be spread over a very small overall sales volume. In the case of Orphacol, we estimate that these aggregate costs are about ten times higher than the costs of producing an unlicensed version (such as a "Special" in the United Kingdom) which does not have to follow all the regulatory obligations mentioned above. Laboratoires CTRS needs to make a medicinal product that complies with all regulatory obligations available, doing so in a financially sustainable manner.
The inaccuracies that we have pointed out should be corrected. We believe that supporting evidence and cost of orphan medicinal products should be considered in more detail in further investigations, taking into consideration the additional aspects that we have outlined.
Conflict of Interest:
The authors are employees and stockholder (A. Ferry) of Laboratoires CTRS.
Re:Are DPP-4 inhibitors free from risk of hospitalization for heart failure?
Having carefully read the letter by Donzelli et al., we would like to thank the writers for the comments. It is our intention to stick strictly to the results of our analysis and not to address topics such as glycemic targets and benefit of vegetarian diet in type 2 diabetes which have nothing to do with our paper. By using a validated epidemiological methodology in a real life population, our analysis aimed to see whether any greater risk of HF hospitalization could be detected in DPP-4i users as compared to patients on other type-2 diabetes treatments. We found no such increased risk, in accordance with Fadini et al who, some weeks later, published similar results in the European Heart Journal (1) and with the TECOS TRIAL (2) (which can not be reported as a commercial trial because it was requested and in part designed by the American agency FDA). By the way, even though all-cause mortality was not the objective of our work, we also found that it was 6% lower in DPP-4i users, whereas insulin users showed an excess of risk for any type of hospital admission (19%) and death (20%). These results support many speculative explanations in favor (or against) DPP-4i utilization. We thought it could make sense to remember that specialty care is associated with reduced mortality and since DPP-4i are mostly prescribed by diabetologists, this should be considered. In favor of DPP-4i class, we could have speculated that these medications, before the SAVOR TIMI negative findings on HF, were on purpose prescribed in patients at higher risk of cardiovascular disease because they were held safe. We acknowledge that the specialty could also have blunted a possible slight negative effect on HF of DPP-4i, however we would like to stress that our findings (OR for admission for HF 1.00 [0.94-1.07], incident HF1.01 [0.92-1.11], recurrent HF 1.02 [0.84-1.22]) can not be defined "...slightly increased OR..." but neutral, non-significant ORs. Our statistician is back on duty from September 14th and we are willing to share the databases for further analysis. However, as it seems that the authors of the letter intend to calculate ORs adjusted for insulin use, we wonder if they have misunderstood the results presented in our paper. ORs are already adjusted for insulin/glimepiride/glibenclamide use, as well as for other confounders reported in table 2.
1. Fadini GP, Avogaro A, Degli Esposti L, Russo P, Saragoni S, Buda S, Rosano G, Pecorelli S, Pani L; OsMed Health-DB Network. Risk of hospitalization for heart failure in patients with type 2 diabetes newly treated with DPP-4 inhibitors or other oral glucose-lowering medications: a retrospective registry study on 127,555 patients from the Nationwide OsMed Health-DB Database. Eur Heart J. 2015 Jun 25. pii: ehv301. [Epub ahead of print]
2. Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR; TECOS Study Group. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2015 Jul 16;373(3):232-42. doi: 10.1056/NEJMoa1501352. Epub 2015 Jun 8.
Conflict of Interest:
APPEAL beyond medical school
We would like to congratulate Briggs et al (1) for their work highlighting a lack of dedicated pain teaching in undergraduate medical studies. In light of the results it is unsurprising that pain is inadequately managed in the hospital setting (2,3), with only 4% of UK medical schools providing compulsory pain modules.
Whilst causes for a high prevalence of in-hospital patient pain are multifactorial, it is important to note that this is partly a function of the management delivered by all of the doctors responsible for the patients' care, not just those recently graduated from medical school. Inadequate assessment and treatment must therefore also relate to senior doctor input, suggesting that the education gap established in medical school fails to be addressed in the postgraduate setting. Awareness of how medical schools fall short in providing pain teaching should prompt us to address this problem in two ways: not just as the authors suggest by developing the undergraduate curriculum, but also through addressing pain education in postgraduate training and beyond.
In the UK the foundation program curriculum includes a comprehensive section on pain, yet specialist training pathways vary in further pain education requirements. Curriculum aside, it can be construed that methods of delivering effective postgraduate pain education are likely ineffective. The foundation program curriculum currently focuses on functional prescribing of analgesia however this fails to necessarily translate to safe knowledge on its use (4).
We were not surprised that methods of teaching at medical school were principally classroom based, despite evidence to support alternative methods (1). The meagre pain teaching sessions that junior doctors receive in the hospital setting probably use similar classroom based methods and may be inadequate to change practice and improve patient care. Our own work has demonstrated that whilst knowledge based teaching in acute pain management for foundation doctors improved their perceived confidence in using morphine in an acute pain setting, it failed to change their attitudes to strong opioids (5). These attitudes are a potential barrier to effective prescribing of opioids (6), the mainstay of severe pain management. Purely knowledge based interventions, which have been highlighted by Briggs et al (1) as inadequate in the undergraduate setting, are seemingly ineffective in changing doctor attitudes and practices, and are failing to improve patient care. Novel approaches such as inter- professional training (7) and interventions that address emotional and reflective development (8) would be useful additions to pain education in the postgraduate setting.
We have an obligation to our patients to ensure their pain is managed to the best of our ability, yet this may be hindered by a lack undergraduate education and training which remains wanting throughout our medical careers. Perhaps it is time for us to see pain education as part of continuous professional development. Briggs et al (1) have highlighted that an excellent start is needed to put doctors on the right track. However this could be entirely fruitless if early learning is not maintained and supported throughout one's career as a whole.
1. Briggs E V, Battelli D, Gordon D, et al. Current pain education within undergraduate medical studies across Europe: Advancing the Provision of Pain Education and Learning (APPEAL) study. BMJ Open. 2015;5(8):e006984.
2. Helfand M, Freeman M. Assessment and management of acute pain in adult medical inpatients: a systematic review. Pain Med. 2009;10(7):1183-99.
3. Dix P. Pain on medical wards in a district general hospital. Br J Anaesth. 2004;92(2):235-7.
4. Harding S, Britten N, Bristow D. The performance of junior doctors in applying clinical pharmacology knowledge and prescribing skills to standardized clinical cases. Br J Clin Pharmacol. 2010;69(6):598-606.
5. Laycock H, Casely E, Bantel C. Knowledge, skills but not attitudes change with pain education. In: Conference abstracts for Association for Medical Education Europe Conference 2013: Colouring outside the lines. 2013 August 24-28; Prague, Czechoslovakia. Dundee: MedEdWorld: 2013. Available from: http://www.amee.org/getattachment/Conferences/AMEE-Past- Conferences/AMEE-Conference-2013/AMEE-2013-ABSTRACT-BOOK-updated- 190813.pdf
6. Kim M-H, Park H, Park EC, Park K. Attitude and knowledge of physicians about cancer pain management: young doctors of South Korea in their early career. Jpn J Clin Oncol. 2011;41(6):783-91.
7. Salam T, Saylor JL, Cowperthwait AL. Attitudes of Nurse and Physician trainees towards an interprofessional simulated education experience on Pain Assessment and Management. J Interprof Care. 2015;29(3):276-8.
8. Murinson BB, Nenortas E, Mayer RS, et al. A New Program in Pain Medicine for Medical Students?: Integrating Core Curriculum Knowledge with Emotional and Reflctive Development. Pain Med. 2011;12(2):186-95.
Conflict of Interest:
The link between alcohol consumption defined as harmful among older people in England and adverse health outcomes
I read with interest, the paper on alcohol use, socioeconomic deprivation and ethnicity in older people . The study found that 21.4% of people aged 65 and over from an inner-city population, drank above "safe limits" (men <21 units; women <14 units ), yet the study found no association between unsafe drinking and a range of illnesses including hypertension, respiratory disease, heart disease, chronic kidney, disease, stroke, cancer, thyroid disease, dementia and depression.
Another recent study in BMJ Open reported that "the problem of harmful alcohol drinking among people aged 50 or over in England" is associated with people in better health and higher income . In this study harmful drinking was again defined with reference to units; increasing-risk drinking: 22-50 units per week (adult men) or 15-35 units per week (adult women) and higher risk drinking: >50 alcohol units per week) (adult men) or >35 units per week (adult women).
Thus these two studies classify drinking above a certain threshold as harmful or unsafe, yet neither study demonstrates a link with poor health.
A further recent study of people aged 50 or over in England found that even people who drank heavily at baseline (men >50 units; women >35 units) had similar self-rated health ten years later as those drinking below the threshold deemed to be harmful (men <21 units; women <14 units) .
There is clearly a link between levels of alcohol use and increased morbidity . However the link is not straightforward and the evidence from the three recent studies indicates that defining a level of alcohol use as harmful or unsafe does not equate to demonstrating adverse outcomes. Given the extensive media coverage about harmful drinking, these studies raise questions about how evidence-based research in this area is translated into public health messages.
1. Rao R, Schofield P, Ashworth M. Alcohol use, socioeconomic deprivation and ethnicity in older people. BMJ Open 2015;5:e007525.doi:10.1136/bmjopen-2014-007525
2. Department of Health. Sensible drinking: report of an inter- departmental working group. London, UK, 1995.
3. Iparraguirre J. Socioeconomic determinants of risk of harmful alcohol drinking among people aged 50 or over in England. BMJ Open 2015;5:e007684. doi:10.1136/bmjopen-2015-007684
4. Frisher M, Mendonca M, Shelton N, Pikhart H, de Oliveira C, Holdsworth C. Is alcohol consumption in older adults associated with poor self-rated health? Cross-sectional and longitudinal analyses from the English longitudinal study of ageing. BMC Public Health BMC Public Health (2015) 15:703 DOI 10.1186/s12889-015-1993-x
5. Rehm J, Room R, Graham K, Monteiro M, Gmel G, Sempos CT. The relationship of average volume of alcohol consumption and patterns of drinking to burden of disease-An overview. Addiction. 2003 Sep;98(9):1209- 28.
Conflict of Interest: