Myopia (ie, nearsightedness) is becoming the most common eye disorder to cause blindness in younger persons in many parts of the world. Visual impairment due to myopia is associated with structural ...changes of the retina and the globe because of elongation of the eye axis. How axial length-a sum of the anterior chamber depth, lens thickness, and vitreous chamber depth-and myopia relate to the development of visual impairment over time is unknown.
To evaluate the association between axial length, spherical equivalent, and the risk of visual impairment and to make projections of visual impairment for regions with high prevalence rates.
This cross-sectional study uses population-based data from the Rotterdam Study I (1990 to 1993), II (2000 to 2002), and III (2006 to 2008) and the Erasmus Rucphen Family Study (2002 to 2005) as well as case-control data from the Myopia Study (2010 to 2012) from the Netherlands. In total, 15 404 individuals with data on spherical equivalent and 9074 individuals with data on axial length were included in the study; right eyes were used for analyses. Data were analyzed from September 2014 to May 2016.
Visual impairment and blindness (defined according to the World Health Organization criteria as a visual acuity less than 0.3) and predicted rates of visual impairment specifically for persons with myopia.
Of the 15 693 individuals included in this study, the mean (SD) age was 61.3 (11.4) years, and 8961 (57.1%) were female. Axial length ranged from 15.3 to 37.8 mm; 819 individuals had an axial length of 26 mm or greater. Spherical equivalent ranged from -25 to +14 diopters; 796 persons had high myopia (ie, a spherical equivalent of -6 diopters or less). The prevalence of visual impairment varied from 1.0% to 4.1% in the population-based studies, was 5.4% in the Myopia Study, and was 0.3% in controls. The prevalence of visual impairment rose with increasing axial length and spherical equivalent, with a cumulative incidence (SE) of visual impairment of 3.8% (1.3) for participants aged 75 years with an axial length of 24 to less than 26 mm and greater than 90% (8.1) with an axial length of 30 mm or greater. The cumulative risk (SE) of visual impairment was 5.7% (1.3) for participants aged 60 years and 39% (4.9) for those aged 75 years with a spherical equivalent of -6 diopters or less. Projections of these data suggest that visual impairment will increase 7- to 13-fold by 2055 in high-risk areas.
This study demonstrated that visual impairment is associated with axial length and spherical equivalent and may be unavoidable at the most extreme values in this population. Developing strategies to prevent the development of myopia and its complications could help to avoid an increase of visual impairment in the working-age population.
Summary
Background
Predictors for successful treatment are important for personalized medicine. Predictors for drug survival of biologics in psoriasis have been assessed, but not split for different ...biologics or for the reason of discontinuation.
Objectives
To compare long‐term drug survival between the outpatient biologics adalimumab, etanercept and ustekinumab in patients with psoriasis, and to elucidate predictors for overall survival and drug discontinuation due to ineffectiveness and side‐effects for each biologic separately.
Methods
Ten years of data were extracted from the prospective, multicentre, long‐term BioCAPTURE registry. Kaplan–Meier survival analyses and confounder‐corrected multivariate Cox regression analysis for drug survival (MCR‐DS) were performed to compare drug survival between biologics. To elucidate the predictors for different reasons of discontinuation for each biologic, univariate Cox regression analyses and multivariate Cox regression analyses for predictors (MCR‐P) with backward selection were performed.
Results
In total, 526 treatment episodes – 186 adalimumab, 238 etanercept and 102 ustekinumab – were included covering 1333 treatment years. MCR‐DS showed a significantly higher overall survival for ustekinumab compared with adalimumab and etanercept. MCR‐P showed that higher body mass index (BMI) was a predictor for discontinuation due to ineffectiveness for etanercept and ustekinumab and that female sex was a predictor for discontinuation due to side‐effects for adalimumab, etanercept and ustekinumab.
Conclusions
Ustekinumab has the highest confounder‐corrected long‐term drug survival in psoriasis treatment, compared with adalimumab and etanercept. Higher BMI is a predictor for discontinuation due to ineffectiveness in etanercept and ustekinumab, and female sex is a consistent predictor for discontinuation due to side‐effects in all three outpatient biologics.
What's already known about this topic?
Drug survival of biologics for psoriasis has been analysed, but few publications used prospective multicentre daily‐practice data.
These studies found that ustekinumab had the highest confounder‐corrected overall drug survival, but they did not split survival analysis for the different biologics or for different reasons of discontinuation.
Different predictors for overall drug survival were found in prospective and retrospective studies.
What does this study add?
This study reports on a longer period of drug survival than previous studies.
Ustekinumab has a higher confounder‐corrected drug survival and higher survival for discontinuation due to ineffectiveness and side‐effects than adalimumab and etanercept.
Higher body mass index (BMI) predicts discontinuation due to ineffectiveness in etanercept and ustekinumab, and female sex is a consistent predictor for discontinuation due to side‐effects in all three biologics.
Linked Comment: Egeberg. Br J Dermatol 2016; 175:247–248
Plain language summary available online
Global emissions of the ozone-depleting gas HCFC-141b (1,1-dichloro-1-fluoroethane, CH3CCl2F) derived from measurements of atmospheric mole fractions increased between 2017 and 2021 despite a fall in ...reported production and consumption of HCFC-141b for dispersive uses.
HCFC-141b is a controlled substance under the Montreal Protocol, and its phase-out is currently underway, after a peak in reported consumption and production in developing (Article 5) countries in 2013.
If reported production and consumption are correct, our study suggests that the 2017–2021 rise is due to an increase in emissions from the bank when appliances containing HCFC-141b reach the end of their life, or from production of HCFC-141b not reported for dispersive uses.
Regional emissions have been estimated between 2017–2020 for all regions where measurements have sufficient sensitivity to emissions.
This includes the regions of northwestern Europe, east Asia, the United States and Australia, where emissions decreased by a total of 2.3 ± 4.6 Gg yr−1, compared to a mean global increase of 3.0 ± 1.2 Gg yr−1 over the same period.
Collectively these regions only account for around 30 % of global emissions in 2020.
We are not able to pinpoint the source regions or specific activities responsible for the recent global emission rise.
Summary
Background
It is important to assess which patients with psoriasis are more likely to achieve high clinical responses on biologics.
Objectives
To assess the number of treatment episodes (TEs) ...that achieve a 100% improvement in Psoriasis Area and Severity Index (PASI 100), PASI 90 or PASI ≤ 5 at week 24 of biological treatment, and which baseline patient characteristics predict treatment response.
Methods
Data from patients with psoriasis treated with adalimumab, etanercept, infliximab or ustekinumab were extracted from a prospective cohort. TEs with high clinical responses were described. Uni‐ and multivariate regression analyses were performed with the generalized estimating equation method to elucidate which baseline patient characteristics were predictors for PASI 90 and PASI ≤ 5 at week 24.
Results
In total, 454 TEs were extracted (159 adalimumab; 193 etanercept; 19 infliximab; 83 ustekinumab) from 326 patients. At week 24, in 3%, 15% and 59% of TEs, respectively, PASI 100, PASI 90 and PASI ≤ 5 was reached. In TEs without a PASI 100 or PASI 90 response, PASI ≤ 5 was still achieved in 58% and 52%, respectively. Baseline PASI ≥ 10 was a strong predictor for achieving PASI 90; baseline PASI < 10 and a lower baseline body mass index (BMI) were significant predictors for PASI ≤ 5 at week 24.
Conclusions
A limited number of patients achieved PASI 100 or PASI 90 at 24 weeks of biological treatment. Including an absolute PASI score in the assessment of psoriasis severity is important. Baseline BMI was an important, modifiable predictor for a high response.
What's already known about this topic?
A high clinical response in patients with psoriasis is shifting towards a 90% improvement compared with baseline Psoriasis Area and Severity Index (PASI 90).
To date, no studies have assessed which patients with psoriasis are more likely to achieve a high clinical response at week 24 of biological treatment.
What does this study add?
We focused on high responders, defined as achieving PASI 100, PASI 90 or PASI ≤ 5.
Frequency of reaching high clinical responses at 24 weeks of biological treatment was assessed, as were predictors that could identify patients with the ability to respond well to biological treatment.
In only a limited number of treatment episodes are PASI 90 (15%) or PASI 100 (3%) achieved.
Lower baseline body mass index is a predictor for achieving PASI ≤ 5.
Linked Comment: Zheng. Br J Dermatol 2017; 176:576.
Background
Female sex has been reported as a predictor for treatment discontinuation with biological therapies for psoriasis, although reasons remain unclear. It can be hypothesized that lower ...satisfaction with biological treatment in women might add to the lower drug survival rates.
Objectives
To identify possible differences in satisfaction with biological treatment between female and male patients using the Treatment Satisfaction Questionnaire for Medication (TSQM).
Methods
Data of psoriasis patients treated with biologics were obtained from the prospective, multicentre, daily‐practice BioCAPTURE registry. Longitudinal TSQM data were analysed by linear mixed models. Relevant patient characteristics were incorporated as possible confounding factors. Post hoc analysis of adverse events was performed in order to investigate differences between sexes.
Results
We included 315 patients with 396 corresponding treatment episodes (137 adalimumab, 90 etanercept, 137 ustekinumab, 24 secukinumab and 8 infliximab). Almost forty per cent of the patients were female. Women had significantly lower baseline PASI scores (P = 0.01). Longitudinal analyses demonstrated lower TSQM scores for ‘side‐effects’ (P = 0.05) and ‘global satisfaction’ (P = 0.01) in female patients compared with male patients over 1 year of treatment. Women reported more relevant adverse events in the context of biologic treatment compared to men (rate ratio 1.79; P < 0.001), with more fungal (rate ratio 2.20; P = 0.001) and herpes simplex infections (rate ratio 3.25; P = 0.005).
Conclusions
This study provides a prospective, longitudinal analysis of treatment satisfaction with biologics in female and male patients with psoriasis. Women were slightly less satisfied with treatment regarding side‐effects and global satisfaction. Differences in treatment satisfaction and side‐effects might add to the fact that women discontinue biological treatments more often.
Summary
Background
Drug survival is a marker for treatment success. To date, no analyses relating dermatological quality‐of‐life measures to drug survival have been published.
Objectives
(i) To ...describe 1‐year drug survival for adalimumab, etanercept and ustekinumab in a daily practice psoriasis cohort, and (ii) to introduce the concept of ‘happy’ drug survival, defined as Dermatology Life Quality Index (DLQI) ≤ 5 combined with being ‘on drug’ at a specific time point.
Methods
Data were extracted from a prospective registry. Drug survival was analysed using Kaplan–Meier estimates. ‘Happy’ drug survival was calculated, with data split into ‘happy’ (DLQI ≤ 5) vs. ‘unhappy’ (DLQI > 5) at baseline and months 3, 6, 9 and 12.
Results
249 treatment episodes were included (101 adalimumab, 82 etanercept, 66 ustekinumab). The 1‐year drug survival rates for ustekinumab, adalimumab and etanercept were 85%, 74% and 68%, respectively. Ustekinumab showed a better confounder‐corrected drug survival vs. etanercept hazard ratio (HR) 3·8, P = 0·02 and a trend towards better survival vs. adalimumab (HR 2·3, P = 0·1). At baseline, the majority (n = 115, 73%) was considered ‘unhappy’ and a minority ‘happy’ (n = 42, 27%) (ratio ‘happy’:‘unhappy’ was 1 : 2.7). The percentage of treatment episodes with ‘happy’ on‐drug patients increased to 79% after 1 year.
Conclusions
Ustekinumab showed a better overall drug survival than etanercept, and a trend towards a better overall drug survival than adalimumab. After 1 year, patients reported to be ‘happy’ in 79% of episodes and ‘unhappy’ in 21%. We introduced the new concept of ‘happy’ drug survival because the proportion of on‐drug patients with good quality of life is an important indicator for treatment success.
What's already known about this topic?
The Dermatology Life Quality Index is a validated score for dermatology‐specific quality‐of‐life measurements.
Drug survival studies of biologics for psoriasis show varying results and differ in study design and population.
To date, studies including drug survival rates for ustekinumab are scarce.
What does this study add?
The introduction of a concept named ‘happy’ drug survival, which combines drug survival rates with dermatology‐specific quality‐of‐life measures to evaluate treatments for psoriasis.
Analysis of ‘happy’ drug survival showed that the proportion of ‘on‐drug’ biologic users with a good quality of life increased from 27% to 79% after 1 year of treatment.
Ustekinumab showed a better overall drug survival vs. etanercept and a trend towards a better survival vs. adalimumab.
Background
Psoriasis is a common inflammatory disease in any age group, but also in older patients (≥ 65 years of age). Since older patients are often excluded from clinical trials, limited data ...specifically on this growing population are available, e.g. regarding the safety and performance of biological treatment.
Aims
We aimed to give insight into this specific population by comparing the drug survival and safety of biologics in older patients with that in younger patients.
Methods
In this real-world observational study, data from 3 academic and 15 non-academic centers in The Netherlands were extracted from the prospective BioCAPTURE registry. Biologics included in this study were tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-12/23, and IL-23 inhibitors. Patients were divided into two age groups: ≥ 65 years and < 65 years. The Charlson Comorbidity Index (CCI) was used to measure comorbid disease status, and all adverse events (AEs) that led to treatment discontinuation were classified according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. All AEs that led to treatment discontinuation were studied to check whether they could be classified as serious AEs (SAEs). Kaplan–Meier survival curves for overall 5-year drug survival and split according to reasons of discontinuation (ineffectiveness or AEs) were constructed. Cox regression models were used to correct for possible confounders and to investigate associations with drug survival in both age groups separately. Psoriasis Area and Severity Index (PASI) scores during the first 2 years of treatment and at the time of treatment discontinuation were assessed and compared between age groups.
Results
A total of 890 patients were included, of whom 102 (11.4%) were aged ≥ 65 years. Body mass index, sex, and distribution of biologic classes (e.g. TNFα, IL12/23) were not significantly different between the two age groups. A significantly higher CCI score was found in older patients, indicative of more comorbidity (
p
< 0.001). The 5-year ineffectiveness-related drug survival was lower for older patients (44.5% vs. 60.5%;
p
= 0.006), and the 5-year overall (≥ 65 years: 32.4% vs. < 65 years: 42.1%;
p
= 0.144) and AE-related (≥ 65 years: 82.1% vs. < 65 years: 79.5%;
p
= 0.913) drug survival was comparable between age groups. Of all AEs (
n
= 155) that led to discontinuation, 16 (10.3%) were reported as SAEs but these only occurred in younger patients. After correcting for confounders, the same trends were observed in the drug survival outcomes. Linear regression analyses on PASI scores showed no statistical differences at 6, 12, 18, and 24 months of treatment between age groups.
Conclusions
This study in a substantial, well-defined, prospective cohort provides further support that the use of biologics in older patients seems well-tolerated and effective. Biologic discontinuation due to AEs did not occur more frequently in older patients. Older patients discontinued biologic treatment more often due to ineffectiveness, although no clear difference in PASI scores was observed. More real-world studies on physician- and patient-related factors in older patients are warranted.
Summary
Background
The efficacy of etanercept and ustekinumab in psoriasis has been compared in one randomized controlled trial. Comparison of the long‐term effectiveness of biologics in ...daily‐practice psoriasis treatment is currently lacking.
Objectives
To compare the effectiveness between the three widely used outpatient biologics adalimumab, etanercept and ustekinumab in daily‐practice psoriasis treatment and to correct for confounders.
Methods
Data were extracted from the prospective, multicentre BioCAPTURE registry. Multilevel linear regression analyses (MLRAs) and generalized estimating equation (GEE) analyses were performed on the course of mean Psoriasis Area and Severity Index (PASI) and PASI 75 (≥ 75% reduction vs. baseline). Both models were corrected for confounders. Subgroup analyses for biological dose were performed.
Results
We included 356 patients with 513 treatment episodes: 178 adalimumab, 245 etanercept and 90 ustekinumab. MLRA showed a similar effectiveness between adalimumab, etanercept and ustekinumab after 1 year, but the highest effectiveness for ustekinumab during 5 years of treatment (P = 0·047; ustekinumab vs. etanercept, P = 0·019). GEE analysis revealed a higher chance of attaining PASI 75 with adalimumab and ustekinumab than with etanercept at 1 year of treatment. A higher than label dose was more often used in patients treated with etanercept (adalimumab, etanercept and ustekinumab: respectively 31·5%, 55·1% and 17% after 1 year, P < 0·001; 39·3%, 71·4% and 24% after 5 years, P < 0·001).
Conclusions
Compared with etanercept, ustekinumab had the highest effectiveness during 5 years of treatment. Patients receiving adalimumab and ustekinumab more often reached PASI 75 than those on etanercept at 1 year of treatment. Dose escalation was more frequent in etanercept and adalimumab than in ustekinumab.
What's already known about this topic?
Randomized controlled clinical trials (RCTs) have shown that biologics are effective in treating selected patients with psoriasis.
RCTs comparing ustekinumab with adalimumab or etanercept with adalimumab have not been performed.
Patients from RCTs differ from patients in daily practice, and this might influence the effectiveness of biologics in the clinic.
What does this study add?
This prospective daily‐practice study compared the 1‐ and 5‐year effectiveness of adalimumab, etanercept and ustekinumab in psoriasis, corrected for confounders.
We showed a significantly higher confounder‐corrected Psoriasis Area and Severity Index (PASI) decrease for ustekinumab vs. etanercept over 5 years.
At 1 year of treatment, patients treated with adalimumab and ustekinumab had a higher chance of attaining PASI 75 than patients on etanercept after correction for confounders.
Etanercept was the agent most often prescribed in high doses in daily practice.
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Linked Comment: Ormerod. Br J Dermatol 2017; 176:856–857
Adult congenital heart disease (ACHD) predisposes to infective endocarditis (IE). Surgical advancements have changed the ACHD population, whereas associated prosthetic material may constitute ...additional IE targets. We aimed to prospectively determine contemporary incidence, risk factors, and predictors of IE in a nationwide ACHD cohort, focusing on the presence of prosthetics.
We identified 14 224 patients prospectively followed in the CONCOR ACHD registry (50.5% female, median age 33.6years). IE incidence was determined using Poisson regression, risk factors and predictors using Cox regression. Overall incidence was 1.33 cases/1000 person-years (124 cases in 93 562 person-years). For risk-factor analysis, presence of prosthetics was forced-as separate time-updated variables for specific prosthetics-into a model with baseline characteristics univariably associated with IE. Valve-containing prosthetics were independently associated with greater risk both short- and long term after implantation 0-6 months: hazard ratio (HR) = 17.29; 7.34-40.70, 6-12 months: HR = 15.91; 6.76-37.45, beyond 12 months: HR = 5.26; 3.52-7.86, non-valve-containing prosthetics, including valve repair, only in the first 6 months after implantation (HR = 3.34; 1.33-8.41), not thereafter. A prediction model was derived and validated using bootstrapping techniques. Independent predictors of IE were baseline valve-containing prosthetics, main congenital heart defect, multiple defects, previous IE, and sex. The model had fair discriminative ability and provided accurate predictions up to 10 years.
This study provides IE incidence estimates, and determinants of IE risk in a nationwide ACHD cohort. Our findings, essentially informing IE prevention guidelines, indicate valve-containing prosthetics as a main determinant of IE risk whereas other prosthetics, including valve-repair, are not associated with increased risk long term after implantation.
Emissions of the potent greenhouse gas perfluorocyclobutane
(c-C4F8, PFC-318, octafluorocyclobutane) into the global atmosphere
inferred from atmospheric measurements have been increasing sharply ...since
the early 2000s. We find that these inferred emissions are highly correlated
with the production of hydrochlorofluorocarbon-22 (HCFC-22, CHClF2) for
feedstock (FS) uses, because almost all HCFC-22 FS is pyrolyzed to produce
(poly)tetrafluoroethylene ((P)TFE) and hexafluoropropylene (HFP), a process
in which c-C4F8 is a known by-product, causing a significant
fraction of global c-C4F8 emissions. We find a global emission
factor of ∼0.003 kg c-C4F8 per kilogram of HCFC-22 FS
pyrolyzed. Mitigation of these c-C4F8 emissions, e.g., through
process optimization, abatement, or different manufacturing processes, such
as refined methods of electrochemical fluorination and waste recycling,
could reduce the climate impact of this industry. While it has been shown
that c-C4F8 emissions from developing countries dominate global
emissions, more atmospheric measurements and/or detailed process statistics
are needed to quantify c-C4F8 emissions at country to facility
levels.
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