Sociodemographic and Disease Correlates of Body Image Distress among Patients with Systemic Sclerosis

Body image concerns are infrequently studied in systemic sclerosis (SSc), even though significant visible disfigurement is common. The objective of this study was to identify sociodemographic and disease-related correlates of dissatisfaction with appearance and social discomfort among people with SSc.SSc patients came from the 15-center Canadian Scleroderma Research Group Registry. Sociodemographic information was based on patient self-report. Disease characteristics were obtained via physician examinations. The Brief-SWAP was used to assess dissatisfaction with appearance and social discomfort. Structural equation models were conducted with MPlus to determine the relationship of dissatisfaction with appearance and social discomfort with age, sex, education, marital status, race/ethnicity, disease duration, skin involvement, telangiectasias, skin pigmentation changes, and hand contractures.A total of 489 SSc patients (432 female, 57 male) were included. Extent of skin involvement was significantly associated with both dissatisfaction with appearance and social discomfort (standardized regression coefficients = 0.02, p = 0.001; 0.02, p = 0.020, respectively), as was skin involvement in the face (0.18, p = 0.016; 0.23, p = 0.006, respectively). Greater social discomfort was robustly associated with younger age (-0.017, p<0.001) and upper-body telangiectasias (0.32, p = 0.021). Dissatisfaction with appearance was associated with hand contractures (0.07, p = 0.036).This study found that dissatisfaction with appearance and social discomfort were associated with numerous disfiguring characteristics of SSc, in addition to age. These results underline that there are multiple factors contributing to body image distress in SSc, as well as the need to attend to both disease and social contexts in understanding the impact of disfigurement among patients

The role of conversation in health care interventions: enabling sensemaking and learning

<p>Abstract</p> <p>Background</p> <p>Those attempting to implement changes in health care settings often find that intervention efforts do not progress as expected. Unexpected outcomes are often attributed to variation and/or error in implementation processes. We argue that some unanticipated variation in intervention outcomes arises because unexpected conversations emerge during intervention attempts. The purpose of this paper is to discuss the role of conversation in shaping interventions and to explain why conversation is important in intervention efforts in health care organizations. We draw on literature from sociolinguistics and complex adaptive systems theory to create an interpretive framework and develop our theory. We use insights from a fourteen-year program of research, including both descriptive and intervention studies undertaken to understand and assist primary care practices in making sustainable changes. We enfold these literatures and these insights to articulate a common failure of overlooking the role of conversation in intervention success, and to develop a theoretical argument for the importance of paying attention to the role of conversation in health care interventions.</p> <p>Discussion</p> <p>Conversation between organizational members plays an important role in the success of interventions aimed at improving health care delivery. Conversation can facilitate intervention success because interventions often rely on new sensemaking and learning, and these are accomplished through conversation. Conversely, conversation can block the success of an intervention by inhibiting sensemaking and learning. Furthermore, the existing relationship contexts of an organization can influence these conversational possibilities. We argue that the likelihood of intervention success will increase if the role of conversation is considered in the intervention process.</p> <p>Summary</p> <p>The generation of productive conversation should be considered as one of the foundations of intervention efforts. We suggest that intervention facilitators consider the following actions as strategies for reducing the barriers that conversation can present and for using conversation to leverage improvement change: evaluate existing conversation and relationship systems, look for and leverage unexpected conversation, create time and space where conversation can unfold, use conversation to help people manage uncertainty, use conversation to help reorganize relationships, and build social interaction competence.</p

Large-scale meta-genome-wide association study reveals common genetic factors linked to radiation-induced acute toxicities across cancer types

BACKGROUND: This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity across 4 cancer types (prostate, head and neck, breast, and lung). METHODS: A genome-wide association study meta-analysis was performed using 19 cohorts totaling 12 042 patients. Acute standardized total average toxicity (STATacute) was modelled using a generalized linear regression model for additive effect of genetic variants, adjusted for demographic and clinical covariates (rSTATacute). Linkage disequilibrium score regression estimated shared single-nucleotide variation (SNV-formerly SNP)-based heritability of rSTATacute in all patients and for each cancer type. RESULTS: Shared SNV-based heritability of STATacute among all cancer types was estimated at 10% (SE = 0.02) and was higher for prostate (17%, SE = 0.07), head and neck (27%, SE = 0.09), and breast (16%, SE = 0.09) cancers. We identified 130 suggestive associated SNVs with rSTATacute (5.0 × 10‒8 < P < 1.0 × 10‒5) across 25 genomic regions. rs142667902 showed the strongest association (effect allele A; effect size ‒0.17; P = 1.7 × 10‒7), which is located near DPPA4, encoding a protein involved in pluripotency in stem cells, which are essential for repair of radiation-induced tissue injury. Gene-set enrichment analysis identified 'RNA splicing via endonucleolytic cleavage and ligation' (P = 5.1 × 10‒6, P = .079 corrected) as the top gene set associated with rSTATacute among all patients. In silico gene expression analysis showed that the genes associated with rSTATacute were statistically significantly up-regulated in skin (not sun exposed P = .004 corrected; sun exposed P = .026 corrected). CONCLUSIONS: There is shared SNV-based heritability for acute radiation-induced toxicity across and within individual cancer sites. Future meta-genome-wide association studies among large radiation therapy patient cohorts are worthwhile to identify the common causal variants for acute radiotoxicity across cancer types

A Randomized Pilot Study of Four Dosing Schemes of Sublingual Methazolamide in Glaucoma Patients

Nicholas E Tan, Jennifer L Patnaik, Sara McWilliams, Leonard K Seibold, Malik Y Kahook Sue-Anschutz Rodgers Eye Center at the University of Colorado, Aurora, CO, USACorrespondence: Malik Y Kahook, Sue Anschutz-Rodgers Eye Center, 1675 Aurora Court, Aurora, CO, 80045, USA, Email [email protected]: To evaluate the safety and efficacy of sublingual methazolamide in patients with open-angle glaucoma (OAG) and inform future trial design.Methods: Fourteen participants (28 eyes) aged 50 to 90 years with bilateral OAG and intraocular pressure (IOP) between 18 and 35 mmHg after medication washout were included. Participants were randomized to receive either 25 mg or 50 mg of sublingual methazolamide once daily for one week, followed by twice-daily administration during the second week. The primary outcome was change in IOP from baseline to days 7 and 14. Secondary outcomes included changes in serum methazolamide levels, serum electrolytes, urine pH and electrolytes, and side effects.Results: After randomization, exclusion, and two dropouts, four patients in the 25 mg group and ten in the 50 mg group completed the study in full. Both doses of sublingual methazolamide resulted in significant reductions in IOP from the post-washout baseline at all follow-up points (all p < 0.05). Lowest mean IOPs were recorded 8 hours post-dose; after a week of daily dosing, the 25 mg and 50 mg groups achieved reductions of 6.6 mmHg (− 26.5%) and 4.2 mmHg (− 19.3%), respectively (both p < 0.001). Twice-daily dosing resulted in significantly lower morning IOPs compared to once-daily in each group (p = 0.05 for 25 mg; p = 0.003 for 50 mg). Serum methazolamide levels correlated with dose amount and frequency. Serum electrolyte levels were stable throughout, while urinary pH and urinary electrolytes fluctuated based on time since last dose. Side effects of mild headaches and/or fatigue were reported by 3 out of 14 (21.4%) participants, with no serious adverse events.Conclusion: Sublingual methazolamide demonstrated effective IOP reduction with a favorable safety profile. Twice-daily dosing may offer more sustained IOP control. These findings support further investigation into sublingual methazolamide as an alternative glaucoma treatment.Keywords: IOP, carbonic anhydrase inhibitor, pressure, compoundin

Longitudinal analysis of the peripapillary retinal nerve fiber layer thinning in patients with retinitis pigmentosa.

[Purpose]To investigate longitudinal changes in peripapillary retinal nerve fiber layer (RNFL) thickness in patients with retinitis pigmentosa (RP). [Methods]We re-examined 103 RP patients whose RNFL thickness was previously examined and reported. RNFL thickness was measured using Stratus optical coherence tomography and was compared with the previous measurements. The results were also compared with that of previously reported normal subjects. Association between the decrease rate and visual acuity, and visual field was also investigated. [Results]The mean follow-up period was 56.9 months. After excluding the patients in whom RNFL images were of poor quality, 88 patients were eventually analyzed. The average RNFL thickness decreased from 105.8 to 98.2 μm during the period, with the average rate of decrease being 1.6 μm/year. The decrease in RNFL was more evident in superior and inferior sectors. Cross-sectional linear regression analysis also revealed an age-dependent decrease in RNFL, with the slower rate of decrease being 0.94 μm/year. The decrease in RNFL thickness was significantly faster than that reported in normal subjects. The decrease rate was not associated with visual functions. [Conclusion]Age-dependent RNFL thinning occurs at a faster rate in RP patients as compared with that in normal subjects. The result supports the notion that pathologic changes involve inner retina as well as outer retina in eyes with RP. Considering the discrepancy in the rate of RNFL thinning estimated from trend analysis and longitudinal measurement, care should be taken when interpreting the result of cross-sectional analysis

A multicenter retrospective comparison of goniotomy versus trabecular bypass device implantation in glaucoma patients undergoing cataract extraction

Syril K Dorairaj,1 Malik Y Kahook,2 Blake K Williamson,3 Leonard K Seibold,4 Mohammed K ElMallah,5 Inder P Singh6 On behalf of the KDB Goniotomy Study Group 1Department of Ophthalmology, Mayo Clinic, Jacksonville, FL, 2School of Medicine, University of Colorado, Denver, CO, 3Williamson Eye Center, Baton Rouge, LA, 4School of Medicine, University of Colorado, Aurora, CO, 5Ocala Eye, Ocala, FL, 6The Eye Center of Racine and Kenosha, Kenosha, WI, USA Purpose: The aim of this study was to compare intraocular pressure (IOP) outcomes in eyes with cataract and glaucoma undergoing phacoemulsification (phaco) in combination with goniotomy using the Kahook Dual Blade (KDB) or implantation of a single iStent trabecular bypass device.Methods: Retrospective analysis of IOP and IOP-lowering medication reduction in eyes undergoing phaco-goniotomy with KDB (n=237) or phaco-iStent (n=198). Preoperative, intraoperative, and postoperative data were collected through 6&nbsp;months of follow-up. Outcome measures included mean IOP reduction, mean reduction in IOP-lowering medications, and the proportion of eyes achieving &ge;20% IOP reduction or &ge;1 medication reduction from baseline.Results: Mean IOP in the phaco-goniotomy with KDB group decreased from 17.9&plusmn;4.4&nbsp;mmHg at baseline to 13.6&plusmn;2.7&nbsp;mmHg at Month 6 (P&lt;0.001), with mean medication use decreasing from 1.7&plusmn;0.9 to 0.6&plusmn;1.0 (P&lt;0.001). In the phaco-iStent group, mean IOP decreased from 16.7&plusmn;4.4 mmHg to 13.9&plusmn;2.7&nbsp;mmHg (P&lt;0.001), with mean IOP-lowering medication use decreasing from 1.9&plusmn;0.9 to 1.0&plusmn;1.0 (P&lt;0.001). Mean IOP reduction from baseline was significantly greater in the phaco-goniotomy with KDB group at Month 6 (phaco-goniotomy with KDB &minus;4.2&nbsp;mmHg [23.7%] vs phaco-iStent &minus;2.7&nbsp;mmHg [16.4%]; P&lt;0.001). IOP-lowering medication reduction was greater in the phaco-goniotomy with KDB group compared to the phaco-iStent group (1.1 vs 0.9 medications, respectively; P=0.001). The most common adverse event was IOP spikes occurring in 12.6% of phaco-iStent eyes and 6.3% of phaco-goniotomy with KDB eyes (P=0.024).Conclusion: Goniotomy with the KDB combined with cataract surgery significantly lowers both IOP and the need for IOP-lowering medications compared to cataract extraction with iStent implantation in glaucomatous eyes through 6&nbsp;months of postoperative follow-up. Keywords: glaucoma, goniotomy, intraocular pressur

Safety and tolerability of nintedanib in patients with systemic sclerosis-associated interstitial lung disease: data from the SENSCIS trial

OBJECTIVES: To characterise the safety and tolerability of nintedanib and the dose adjustments used to manage adverse events in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). METHODS: In the SENSCIS trial, patients with SSc-ILD were randomised to receive nintedanib 150 mg two times per day or placebo. To manage adverse events, treatment could be interrupted or the dose reduced to 100 mg two times per day. We assessed adverse events and dose adjustments over 52 weeks. RESULTS: A total of 576 patients received nintedanib (n=288) or placebo (n=288). The most common adverse event was diarrhoea, reported in 75.7% of patients in the nintedanib group and 31.6% in the placebo group; diarrhoea led to permanent treatment discontinuation in 6.9% and 0.3% of patients in the nintedanib and placebo groups, respectively. In the nintedanib and placebo groups, respectively, 48.3% and 12.2% of patients had ≥1 dose reduction and/or treatment interruption, and adverse events led to permanent discontinuation of the trial drug in 16.0% and 8.7% of patients. The adverse events associated with nintedanib were similar across subgroups defined by age, sex, race and weight. The rate of decline in forced vital capacity in patients treated with nintedanib was similar irrespective of dose adjustments. CONCLUSIONS: The adverse event profile of nintedanib in patients with SSc-ILD is consistent with its established safety and tolerability profile in patients with idiopathic pulmonary fibrosis. Dose adjustment is important to minimise the impact of adverse events and help patients remain on therapy