1516 e-Letters

  • PACE in COPD - change to primary endpoint of protocol

    Due to low recruitment into our trial, we have amended the primary endpoint of our study. The sections affected are summarised below:

    1. Primary and secondary outcomes

    The primary outcome is no longer the “time” to composite outcome but will now be a composite outcome of the following that will be categorised into a hierarchy according to clinical importance, to be used in the Win ratio analysis below:

    • Death - any cause of death
    • Severe COPD exacerbation -hospitalised and treated with OCS/Abx or both
    • MACE (defined as non-fatal MI, nonfatal stroke and cardiovascular death)
    • Hospitalisation with a primary cardiac cause - ischemia, arrythmia, or heart failure
    • Moderate COPD exacerbation - not hospitalised but treated with OCS /Abx or both
    • Cardiac Hospitalisation - hospitalisation for a cardiac cause other than ischemia, arrythmia or heart failure
    • Respiratory Hospitalisation - hospitalisation for a respiratory cause other than COPD exacerbation
    • Decrease in FEV1 or greatest FEV1 % drop - largest decrease in FEV1 from post-bronchodilator spirometry at baseline
    • Mild COPD exacerbation - treated with increased inhalers / inhaler technique / addition of theophylline
    • Higher SGRQ score at 12m and 24m (clinically important change > 4)
    • Higher CAT score at 12m and 24m (clinically important change >2)

    The secondary outcomes will remain the same, but...

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  • Standardization and automation can improve healthcare quality

    Dear Editor,

    We thank Dr. Rodriguez for his interest in our article. Dr. Rodriguez raises some questions which were carefully considered by the authors during the development and implementation of this quality improvement initiative. Some of these issues have, in fact, been mentioned in the original manuscript, while others were intentionally not included because the authors felt that they were outside the scope of the paper.

    First, we would like to clarify that our use of the adjective “low-value” refers to the definition of Sorenson et al (1), who describe low-value care as “those medical services that provide little or no clinical benefit or may even cause harm to patients” (not, as Dr. Rodriguez seems to have understood, as services provided for patients with arguably trivial presenting complaints). In line with this definition, our quality improvement initiative has proven to reduce low-value appointments by eliminating unnecessary first appointments. It is obvious that such appointments do not provide clinical benefit to patients and may even potentially cause harm through prolonged diagnostic workup, unnecessary disruptions to patients’ schedules, and avoidable travel. Our initiative was implemented in four hospitals which provide tertiary-level services to a population of over 1 million inhabitants in the Madrid area, thus ensuring that the data-driven selection of test order sets was based on a representative sample of the overall population. Given...

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  • Distribution of intranasal naloxone and overdose mortality - response to the comment made by Dr Littorin

    Dear Editor,

    Dr Littorin has published a response to our paper entitled ‘Distribution of intra-nasal naloxone to potential opioid overdose bystanders – effects on overdose mortality in a full region-wide study’. We thank Dr Littorin for his interest in our paper, and we note that he appreciates the fact that we acknowledged a number of limitations in our paper. Our paper described mortality rates in drug overdose after the introduction of a region-wide, large-scale naloxone distribution program aiming to prevent overdose deaths. Our paper reported that the number of fatal overdose cases, calculated per 100,000 inhabitants, was significantly lower during the years following the start of the intervention, compared to a historic time period when the intervention was not available (and both in the whole population and within the narrower group of patients with registered substance use disorder diagnoses). The significant decrease in number of fatal overdoses was seen in men, but not in women. In the absence of randomized controlled trials, which for example are challenging to conduct from an ethical standpoint, the present study lends supports to one previous observational study design where positive findings were seen when regions with higher or lower penetration of the intervention were compared (1).

    Dr Littorin argues that the overall decrease in overdoses in 2019-2021, compared to 2013-2017, is likely not associated with the introduction of naloxone, but ins...

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  • Response to Keenan et al comment

    We are grateful to Niall Keenan, Matthew Knight, Domenique Auger, Martin Hawkings, and Andrew Barlow for their careful consideration of our article.

    However, we firmly reject the characterisation of our article as a 'misleading economic analysis’.

    Although virtual ward occupancy information is not included in the abstract, it was originally reported in the Discussion. This stated that, ‘This means that for a hospital with 100% occupancy (therefore providing 365 hospital bed days per bed) and 40 virtual ward beds at the capacity found in this study (24%), the virtual ward effect is an increase in the hospital capacity of 3.08 hospital beds per day (1123.62/365).’

    Furthermore, in the same section of the article, we explicitly mentioned that ‘increasing the capacity to use the 40 virtual ward beds and reducing the time from hospital admission to virtual ward admission can reduce the cost of a freed-day hospital bed’.

    We encourage readers not to solely rely on the abstract but to peruse the full article for a comprehensive understanding of the findings, recommendations, and limitations.

  • Low-value appointments or low-value test-ordering?

    This study shows nicely the problems of digitalized healthcare and related data interpretation. The study has great strength analyzing data of patient referral for a first appointment (FA) in four medium-sized hospitals in Madrid, applying algorithms for test orders prior to the appointment with a specialist in many different pathologies. But these quantitative parameters should be interpreted with caution, as the study fails to give any qualitative measurements that could shed light on the most important question, i.e. if patient care meets the same quality standards in this digitalized setting of reducing backlogs for FA in outpatient care.
    The authors claim that the algorithms are applied to “low-value appointments” citing Sorensen et al., 2020 [1] (p. 1), but this article uses the given definition for complaints other than those used for test order algorithms here. The authors define many potentially important symptoms as of “low-value”, instead of targeting the referring physician as modifiable variable to reduce low-value appointments in specialized care, as in fact does one of the cited studies. [2]
    Both the primary and the secondary endpoints of the study try to show efficiency and efficacy of the implemented algorithms, but do not give any information about the accuracy of diagnosis and treatment in this patient group, nor does it reveal patients or healthcare professionals satisfaction, need of repetition of ill-suited tests or a second referral from...

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  • Misleading economic analysis

    We read with interest this assessment of the virtual ward at Wrightington, Wigan and Leigh (WWL) Hospitals by Jalilian et al. While we welcome the development of the literature on virtual ward and hospital at home models of care, we do not agree with the economic analysis in the paper which as presented in the abstract has the potential to be highly misleading.

    The authors say that they spent £1.051 million for 40 virtual ward beds in 2022. They then calculate that because they had looked after 366 patients and the mean reduction in length of stay was 3.07 days that the cost per bed day saved was £935 (=£1 051 150/ (3.07 days×366 patients)). However they go on to state: “… £935 is calculated based on the WWL’s capacity to use the virtual beds, which was 24% of the potential 14 600 (24-hour) beds per year provided by 40 virtual ward beds… reference to 3508 total days spent by virtual ward patients).”
    What this actually means is that they spent £1,051,000 to staff and run 40 virtual beds for a year, only used 10 of them, and then found that this was not cost effective. This is hardly surprising; however because this detail is not given in the abstract it runs the risk of making the paper seriously misleading – as some of the coverage in the medical press has demonstrated. “Virtual ward costs twice that of inpatient care, study finds” Lawrence L, HSJ 25 January 2024..

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  • Limitations to consider in this systematic review

    Dear editor,
    I have read with great interest Al-Wardat et al.'s recent systematic review entitled “Prevalence of attention-deficit hyperactivity disorder in children, adolescents, and adults in the Middle East and North Africa region: a systematic review and meta-analysis." 1. Well-conducted systematic reviews of prevalence and incidence data are generally considered to provide the best evidence for health care planning and resource allocation 2 3.
    I have following concerns about methodology of the aforementioned systematic review:
    1- In systematic reviews of prevalence and incidence data, the inclusion of gray literature (through specialized databases such as ProQuest), ranging from clinical registries to government reports, census data, and national administrative datasets, is recommended 2. Furthermore, to improve the comprehensiveness of literature searches, additional significant databases, such as PsycINFO and CINAHL, and all related keywords (e.g., attention deficit disorder, ADD, attention-deficit/hyperactivity disorder, etc.), should be considered.
    2- The majority of nations in the Middle East and North Africa (MENA) region have official languages other than English, and many scholarly works originating from these regions are published in their respective native languages 4. Restricting inclusion criteria solely to studies in the English language may have inadvertently overlooked a significant portion of relevant literature (i.e....

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  • RE: Cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients without diabetes

    The hypothesized mechanisms for reduction of cardiovascular risk by sodium-glucose cotransporter-2 (SGLT2) inhibitors are multifactorial. Among these mechanisms, Professor Tomoyuki Kawada made a comment on the relative contribution of two clinically important markers, serum uric acid and kidney function, to SGLT2 inhibitors-driven risk reduction of cardiovascular disease.
    Inzucchi et al. explored the potential underlying mechanisms behind the empagliflozin on cardiovascular benefit by conducting post hoc mediation analysis of data from the EMPA-REG OUTCOME trial. 1 The authors demonstrated that changes in plasma volume status (hematocrit or hemoglobin) had the largest impact (mediated around 50% of the treatment effect) on the cardiovascular death with empagliflozin versus placebo. In line with Professor Tomoyuki Kawada’s point of view, the authors reported that changes in uric acid had a greater mediation effect on the treatment effect of empagliflozin on cardiovascular risk reduction, whereas changes in kidney function had no or negligible effects (percentage mediation was 24.6% for uric acid, 11.1% for logUACR, and 5.3% for eGFR). The uricosuric effect of the SGLT2 inhibitors is linked to urinary glucose excretion and caused by blockage of renal tubular uric acid transporters. 2
    The relationship between changes in albuminuria and reduction in cardiovascular risk with SGLT2 inhibitors therapy depends on baseline albuminuria status. Waijer el al. assessed whet...

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  • RE: Cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients without diabetes

    Tsai et al. conducted a meta-analysis to evaluate the cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients without diabetes (1). Risk ratios (RRs) (95% confidence intervals [CIs]) of SGLT2 inhibitors for the composite cardiovascular outcome, cardiovascular death, hospitalization for heart failure, and the composite renal outcome were 0.79 (0.71 to 0.87), 0.85 (0.74 to 0.99), 0.72 (0.62 to 0.82), and 0.64 (0.48 to 0.85), respectively. The authors clarified that SGLT2 inhibitors had cardiorenal benefits and increased risk for urinary tract and genital infection in patients without diabetes. I present comments with special reference to the level of serum uric acid and kidney function.

    Zhao et al. conducted a meta-analysis to evaluate the effects of SGLT2 inhibitors on serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM) (2). Any of the SGLT2 inhibitors significantly decreased SUA levels against controls, and empagliflozin presented a predominant reduction in SUA. Increase of the urinary excretion of uric acid by SGLT2 inhibitor is not simply caused by the increased urinary volume, but the inhibition of uric acid reabsorption by SGLT2 inhibitor would be made at the collecting duct in the renal tubule (3). I suspect that the urinary excretion rate of uric acid would be increased by SGLT2 inhibitor-induced glycosuria plus active uric acid reabsorption mechanism via insulin resistance.

    Tang e...

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  • Reduction i mortality part of national trend, may not be attributed to Naloxone

    Dear editor,
    According to the authors, the "study lends support to the hypothesis that a large-scale naloxone programme in a region may decrease rates of overdose deaths in the population, in comparison to a historic control period when naloxone distribution was unavailable".
    They found that the rate of opioid overdoses in Skåne, the southernmost Swedish region, dropped significantly in three years ensuing the implementation of a Naloxone take home program (2019–2021) for opioid addicts, compared to "a historic control period” (2013–2017).
    The authors correctly state the risk of biases in observational retrospective studies. Their results should be interpreted with caution. However, even with such assurances, their results may be questioned. The years 2013-2017 happens to represent the peak of the Swedish opioid epidemic when Sweden as a whole experienced high rates of overdose deaths in the population (1).
    The years 2019-2021, on the other hand, represents a period when Sweden experienced a significant drop in overdose deaths (2). The present study specifically evaluates a local Naloxone take home programme, the first of its kind in Sweden. The observed decline in death rates may be part of a national trend that in turn may have many different explanations. For instance, in 2018 two Swedish brothers were convicted of manslaughter for selling Fentanyl online, in an unprecedented verdict. Fentanyl associated deaths dropped sharply th...

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