Disease-modifying therapies in systemic lupus erythematosus for extrarenal manifestations.

Our 2022 published working definition of disease modification in systemic lupus erythematosus (SLE) was 'minimising disease activity with the fewest treatment-associated toxicities and slowing or preventing organ damage progression'. The objective of this review was to classify current SLE treatments according to the proposed non-renal disease modification criteria excluding toxicities. Based on a review of select clinical trial (n=32) and observational study (n=54) publications for 14 SLE medications across different therapeutic classes, and the authors' clinical experience, we evaluated disease modification potential as per the proposed framework at three time points. Specific criteria used to determine disease modification potential included a drug's capacity to reduce: (1) non-renal disease activity, (2) severe flares, (3) use of steroids/immunosuppressants and (4) organ damage accrual. Criteria 1-3 were assessed at 1 year and 2-5 years and, when positive, were considered evidence for disease modification potential; criterion 4 was used to confirm disease modification at >5 years. Each treatment received one of four mutually exclusive designations at each time point: (a) criterion met, (b) indications of criterion met despite insufficient evidence in the literature, (c) inconclusive and (d) no available supportive data. This review excludes an assessment of potential toxicities. Eight of the 14 SLE treatments met ≥1 disease modification criteria up to year 5. Hydroxychloroquine improved overall survival at >5 years, suggesting long-term disease modification, but no data on specific organ systems were reported. Belimumab was the only treatment to meet all criteria. Belimumab and hydroxychloroquine met disease modification definitions across three time points. Evidence for other SLE therapies was incomplete, particularly at >5 years. Future studies are warranted for other treatments to meet the disease modification criteria. We discuss challenges to classification and possible updates to our published criteria.

Conceptual framework for defining disease modification in systemic lupus erythematosus: a call for formal criteria.

Disease modification has become a well-established concept in several therapeutic areas; however, no widely accepted definition of disease modification exists for SLE.We reviewed established definitions of disease modification in other conditions and identified a meaningful effect on 'disease manifestations' (ie, signs, symptoms and patient-reported outcomes) and on 'disease outcomes' (eg, long-term remission or progression of damage) as the key principles of disease modification, indicating a positive effect on the natural course of the disease. Based on these findings and the treatment goals and outcome measures for SLE, including lupus nephritis, we suggest a definition of disease modification based on disease activity indices and organ damage outcomes, with the latter as a key anchor. A set of evaluation criteria is also suggested.Establishing a definition of disease modification in SLE will clarify which treatments can be considered disease modifying, provide an opportunity to harmonise future clinical trial outcomes and enable comparison between therapies, all of which could ultimately help to improve patient outcomes. This publication seeks to catalyse further discussion and provide a framework to develop an accepted definition of disease modification in SLE.

Natural history of oral HPV infection: Longitudinal analyses in prospective cohorts from Australia.

Oral infection with human papillomavirus (HPV) is likely to underpin the rapidly rising incidence of oropharyngeal squamous cell carcinoma; however, there are few data describing the natural history of oral HPV infection. We recruited 704 participants aged 20 to 70 years from worksites, universities and primary care practices in Brisbane, Australia. Participants completed questionnaires at baseline, 12 and 24 months and donate four saliva samples at baseline, 6, 12 and 24 months for HPV polymerase chain reaction testing and typing. We estimated the prevalence of oral HPV infection at baseline, incidence of new infections among those HPV-negative at baseline, clearance rate and persistent infections. At baseline, 10.7% of participants had oral HPV infections from 26 different HPV types. Sexual behaviours were associated with oral HPV infection, including more partners for passionate kissing (29 or more; odds ratio [OR] 3.4, 95% confidence interval [CI] 1.5-8.0), and giving and receiving oral sex (16 or more; OR 5.4, 95% CI 1.6-17.7 and OR 5.6, 95% CI 1.6-18.7, respectively). Of 343 participants, HPV-free at baseline and with subsequent saliva samples, 87 (25%) acquired new infections over the 24 months. Sixty-eight of 87 people included in the clearance analysis (78%) cleared their oral HPV infections. Clearance was associated with being a nonsmoker (OR 12.7, 95% CI 1.3-122.8), and no previous diagnosis of a sexually transmitted infection (OR 6.2, 95% CI 2.0-19.9). New oral infections with HPV in this sample were not rare. Although most infections were cleared, clearance was not universal suggesting a reservoir of infection exists that might predispose to oropharyngeal carcinogenesis.

Surface waters as a sink and source of atmospheric gas phase ethanol.

This study reports the first ethanol concentrations in fresh and estuarine waters and greatly expands the current data set for coastal ocean waters. Concentrations for 153 individual measurements of 11 freshwater sites ranged from 5 to 598 nM. Concentrations obtained for one estuarine transect ranged from 56 to 77 nM and levels in five coastal ocean depth profiles ranged from 81 to 334 nM. Variability in ethanol concentrations was high and appears to be driven primarily by photochemical and biological processes. 47 gas phase concentrations of ethanol were also obtained during this study to determine the surface water degree of saturation with respect to the atmosphere. Generally fresh and estuarine waters were undersaturated indicating they are not a source and may be a net sink for atmospheric ethanol in this region. Aqueous phase ethanol is likely converted rapidly to acetaldehyde in these aquatic ecosystems creating the undersaturated conditions resulting in this previously unrecognized sink for atmospheric ethanol. Coastal ocean waters may act as either a sink or source of atmospheric ethanol depending on the partial pressure of ethanol in the overlying air mass. Results from this study are significant because they suggest that surface waters may act as an important vector for the uptake of ethanol emitted into the atmosphere including ethanol from biofuel production and usage.