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PubMed · 9558300

Editorial

Abstract

As clinical dermatologists, we are all striving to achieve the highest possible accuracy in our clinical acumen and diagnostic skills. Over the past decade, one relatively simple advance, epiluminescence microscopy with the use of the dermatoscope, has significantly contributed to our diagnostic skills in the detection of benign versus pigmented lesions. In the paper by Kawabata and Tamaki, these authors delineate distinctive dermatoscopic features of acral lentiginous melanoma in situ, and contrast this with melanocytic nevi. The restructuring of healthcare delivery systems by third party payers and governmental programs is impacting on the pattern of our medical practices. In Canada, this has limited access to widespread use of techniques such as Mohs' micrographic surgery. The article by Arlette and colleagues has further supported the well-established studies indicating that Mohs' micrographic surgery for high-risk skin cancers has a dramatic benefit. Healthcare restructuring has also led to a decreased number of trainees in a number of subspecialties, including dermatology. This decrease in manpower has been an impetus to look at alternative forms of care for underserviced areas. Telemedicine, the use of telecommunications technology to provide healthcare services over a distance, has been examined as one attempt at solving this problem. In the Point-Counterpoint articles, we have two distinct views on the future of telemedicine as it applies to dermatology. Over the past decade, there have been dramatic advances in our understanding at a molecular nature of various disease processes. This rapid development has translated into a large number of therapies. Regulatory agencies such as the Food and Drug Administration in the United States, or the Health Protection Branch in Canada, are caught between demands to bring effective therapies to the market in an expedited fashion, and yet establish efficacy and maintain safety of new therapeutic entities. This occurs by a multistaged approval process. During the early phases, exposure is limited in order to accumulate preliminary data on pharmacology and toxicity. In the Critical Appraisal CME series, Muglia and DiGiovanna describe early testing processes in Phase 1 clinical trials. Calciphylaxis is a severe disease associated with calcification of the skin, subcutaneous tissue and potentially, internal organs. While the disease itself is relatively uncommon, the manifestations are quite distinctive. In this issue of the Journal, we have a review of calciphylaxis from Richard Worth, as well as a preamble by Dr. Goodall and a case report by Kalaaji et al. illustrating the consequences of this rare but distinctive entity.

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BibTeXRIS

DN Sauder. 1998. Editorial. https://doi.org/10.1177/120347549800200401

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Effectiveness of high-dose versus standard-dose influenza vaccines against hospitalisation according to frailty risk: a prespecified analysis of the randomised trial DANFLU-2.

BACKGROUND: Frailty is a major risk factor for influenza-related complications and can influence vaccine effectiveness. We aimed to assess the relative vaccine effectiveness (rVE) of high-dose (HD-IIV) versus standard-dose inactivated influenza vaccine (SD-IIV) in older adults aged 65 years or older according to frailty risk. METHODS: This study was a prespecified analysis of DANFLU-2, an open-label, individually randomised trial, conducted in Denmark during three consecutive influenza seasons (2022-23, 2023-24, and 2024-25). Adults aged 65 years or older were randomised (1:1) to the HD-IIV or SD-IIV group. The primary endpoint was hospitalisation for influenza or pneumonia. Frailty was defined according to the validated Hospital Frailty Risk Score (HFRS) based on ICD-10 codes within 10 years before randomisation. Participants were stratified into three HFRS categories, namely low (<5 points), intermediate (5-15 points), and high (>15 points) frailty risk. The rVE of HD-IIV versus SD-IIV against the primary endpoint was assessed across prespecified HFRS categories and treating HFRS as a continuous variable. Pearson's chi-square test was used to compare safety events across frailty risk groups and randomisation groups. FINDINGS: Among 332&#x2009;438 randomised participants (mean age 73&#xb7;7 years [SD 5&#xb7;8]; 161&#x2009;538 [48&#xb7;6%] were female), 276&#x2009;173 (83&#xb7;1%) had low frailty risk, 52&#x2009;395 (15&#xb7;8%) had intermediate frailty risk, and 3861 (1&#xb7;2%) had high frailty risk. The primary endpoint of hospitalisation for influenza or pneumonia occurred in 1424 (0&#xb7;5%) of 276&#x2009;173 participants with low frailty risk, 761 (1&#xb7;5%) of 52&#x2009;395 with intermediate frailty risk, and 163 (4&#xb7;2%) of 3861 with high frailty risk (relative risk [RR] for intermediate vs low frailty risk 2&#xb7;8 [95% CI 2&#xb7;6-3&#xb7;1]; RR for high vs low frailty risk 8&#xb7;2 [7&#xb7;0-9&#xb7;6]). HFRS as a continuous variable significantly modified the effect of HD-IIV versus SD-IIV against the primary endpoint with higher rVE estimates with increasing HFRS (pinteraction=0&#xb7;020). The rVE was 0&#xb7;2% (95% CI -10&#xb7;8 to 10&#xb7;2) among those with low frailty risk, 13&#xb7;1% (-0&#xb7;4 to 24&#xb7;8) among those with intermediate frailty risk, and 19&#xb7;9% (-10&#xb7;3 to 42&#xb7;1) among those with high frailty risk. No significant interaction was observed when HFRS was assessed according to the prespecified categorical frailty groups (pinteraction=0&#xb7;17). The proportion of participants with at least one serious adverse event increased across frailty risk groups (13&#x2009;366 [4&#xb7;8%] of 275&#x2009;795 for low frailty risk, 5475 [10&#xb7;5%] of 52&#x2009;315 for intermediate frailty risk, and 777 [20&#xb7;2%] of 3850 for high frailty risk; p<0&#xb7;0001), with similar proportions of serious adverse events in the HD-IIV and SD-IIV groups for each frailty risk group. INTERPRETATION: Among adults aged 65 years or older in Denmark, frailty risk might modify the effects of HD-IIV versus SD-IIV against hospitalisation for influenza or pneumonia, with higher rVE estimates with increasing frailty risk. These findings might support considering high-dose influenza vaccines for frail older adults. However, effect modification was not evident when frailty was assessed using prespecified categorical subgroups, and subgroup-specific estimates were imprecise, with 95% CIs crossing the null. These results should be considered exploratory, warranting further investigation. FUNDING: The DANFLU-2 trial was funded by Sanofi.

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